Imaging performance in guiding response to neoadjuvant therapy according to breast cancer subtypes: A systematic literature review.
Monitoring therapeutic response to neoadjuvant chemotherapy(NAC) is likely to improve NAC effectiveness in breast cancer(BC). Imaging performance seems to vary per tumour subtype(by ER and HER2 status), therefore we performed a systematic review on subtype specific imaging performance in monitoring NAC in BC. Studies examining imaging performance in predicting pathologic complete response(pCR) during NAC in BC subtypes were selected. Per study, negative- and positive predictive value, sensitivity(se) and specificity(sp), AUC and accuracy were derived. Fifteen/106 articles were included. Inter-study variability was revealed in: monitoring interval, response and pCR definitions. In ER-positive/HER2-negative BC, 181F FDG-PET/CT showed se/sp of 38%-89%/74%-100%, MRI showed se/sp of 35%-37%/87%-89%. In triple negative BC, 181F FDG-PET/CT showed se/sp of 0%-79%/95%-100%. 181F FDG-PET/CT showed in ER-positive/HER2-positive BC se/sp of 59%/80% and in ER-negative/HER2-positive 27%/88%. Evidence on imaging performance in monitoring NAC according BC subtypes is lacking. Consensus should be reached in: definitions of pCR, response and monitoring interval before starting well-designed studies.


Activity of plasma sprayed yttria stabilized zirconia reinforced hydroxyapatite/Ti-6Al-4V composite coatings in simulated body fluid.
Hydroxyapatite (HA)/yttria stabilized zirconia/Ti-6Al-4V bio-composite coatings deposited onto Ti-6Al-4V substrate through a plasma spray technique were immersed in simulated body fluid (SBF) to investigate their behavior in vitro. Surface morphologies and structural changes in the coatings were analyzed by scanning electron microscopy, thin-film X-ray diffractometer, and X-ray photoelectron spectroscopy. The tensile bond strength of the coatings after immersion was also conducted through the ASTM C-633 standard for thermal sprayed coatings. Results showed that carbonate-containing hydroxyapatite (CHA) layer formed on the surface of composite coatings after 4 weeks immersion in SBF solution, indicating the composite coating possessed excellent bioactivity. The mechanical properties were found to decrease with immersion duration of maximum 56 days. However, minimal variation in mechanical properties was found subsequent to achieving supersaturation of the calcium ions, which was attained with the precipitation of the calcium phosphate layers. The mechanical properties of the composite coating were found to be significantly higher than those of pure HA coatings even after immersion in the SBF solution, indicating the enhanced mechanical properties of the composite coatings.


Pericellular matrix formation by renal tubule epithelial cells in relation to crystal binding.
Retention of crystals in the kidney ultimately leads to renal stone formation. Hyaluronan (HA) has been identified as binding molecule for calcium oxalate monohydrate crystals. The association of high molecular mass (M(r)) HA with cell surface receptors such as CD44 gives rise to pericellular matrix (PCM) formation by many eukaryotic cells in culture. Here, we study the ability of several renal tubular cell lines to assemble PCMs and to synthesize high-M(r) HA during proliferation in relation to crystal retention. PCM assembly by MDCK-I, MDCK-II, and LLC-PK1 cells was visualized by particle exclusion assay. Metabolic labeling studies were performed to estimate the cellular production of HA. The expression of CD44 and HA was studied using fluorescent probes, and crystal binding was quantified with radiolabeled calcium oxalate monohydrate. PCMs were formed, and HA was expressed by most MDCK-I and some MDCK-II, but not by LLC-PK1 cells. All cell types expressed CD44 at their apical surface. MDCK-I and MDCK-II cells secreted, respectively, 14.7 +/- 1.6 and 0.5 +/- 0.2 pmol [3H]glucosamine incorporated in high-M(r) HA, whereas LLC-PK1 cells did not secrete HA. Streptomyces hyaluronidase treatment significantly decreased crystal binding (microg/cm2) to MDCK-I cells (from 8.6 +/- 0.4 to 3.9 +/- 0.9), but hardly to MDCK-II cells (from 10.2 +/- 0.2 to 9.6 +/- 0.1) or LLC-PK1 cells (from 10.2 +/- 0.8 to 9.9 +/- 0.3). There are various forms of crystal binding to renal tubular cells in culture. Crystal attachment to MDCK-I and some MDCK-II cells involves PCM assembly that requires high-M(r) HA synthesis. HA production and PCM formation do not play a role in crystal binding to LLC-PK1 and the majority of MDCK-II cells. It remains to be determined which form of binding is involved in renal stone disease.


Advances in Algomics technology: Application in wastewater treatment and biofuel production.
Advanced sustainable bioremediation is gaining importance with rising global pollution. This review examines microalgae's potential for sustainable bioremediation and process enhancement using multi-omics approaches. Recently, microalgae-bacterial consortia have emerged for synergistic nutrient removal, allowing complex metabolite exchanges. Advanced bioremediation requires effective consortium design or pure culture based on the treatment stage and specific roles. The strain potential must be screened using modern omics approaches aligning wastewater composition. The review highlights crucial research gaps in microalgal bioremediation. It discusses multi-omics advantages for understanding microalgal fitness concerning wastewater composition and facilitating the design of microalgal consortia based on bioremediation skills. Metagenomics enables strain identification, thereby monitoring microbial dynamics during the treatment process. Transcriptomics and metabolomics encourage the algal cell response toward nutrients and pollutants in wastewater. Multi-omics role is also summarized for product enhancement to make algal treatment sustainable and fit for sustainable development goals and growing circular bioeconomy scenario.


The inhibition mechanism of the SUR2A-containing KATP channel by a regulatory helix.
KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.


Outcomes of surgery in children with early-onset exotropia.
To evaluate the clinical characteristics and surgical outcomes of early-onset exotropia and to compare differences between constant and intermittent exotropia at presentation. The medical records of 45 exotropia patients with a reported onset before 1 year of age who were operated on between 2008 and 2011 were reviewed, and the clinical characteristics and surgical outcomes of these patients were analyzed retrospectively. Patients were then divided into two groups according to type of exotropia at presentation: a constant (XT) group and an intermittent (X(T)) group. Clinical features and surgical results of exotropia were then compared between these two groups. The mean age of onset of exodeviation in 45 patients was 9.3±3.8 months. Mean age at surgery was 4.5±2.4 years, and the mean postoperative follow-up period was 17.3 months (range, 6-37 months). Of the 45 patients, 67% showed alignment of less than±10 prism diopters (PD) at final visit. Gross stereopsis was achieved in all 34 testable patients, and bifixation developed in 10 patients (29%). Eleven patients were included in XT group and 34 patients in X(T) group. No significant intergroup difference was found between surgical success rates and binocularities. Surgical outcomes, both motor and sensory, were not poor in early-onset exotropia patients, even in patients with constant deviation. Good binocular results following surgery can be achieved in children presenting with apparently constant early-onset exotropia.


Three new species of Candida from apple cider: C. anglica, C. cidri and C. pomicola.
Three new anamorphic ascomycetous yeasts are described: Candida anglica (type strain NRRL Y-27079, CBS 4262), Candida cidri (type strain NRRL Y-27078, CBS 4241), and Candida pomicola (type strain NRRL Y-27083, CBS 4242). These three species were isolated from cider produced in the United Kingdom, and their identification was determined from unique nucleotide sequences in the species-specific D1/D2 domain of large subunit (26S) ribosomal DNA. Phylogenetic analysis of D1/D2 sequences placed C. anglica near Candida fragi, C. cidri near Pichia capsulata, and C. pomicola in the Pichia holstii clade.


Spaced learning versus massed learning in resuscitation - A systematic review.
Skill decay is a recognised problem in resuscitation training. Spaced learning has been proposed as an intervention to optimise resuscitation skill performance compared to traditional massed learning. A systematic review was performed to answer 'In learners taking resuscitation courses, does spaced learning compared to massed learning improve educational outcomes and clinical outcomes?' This systematic review followed the PRISMA guidelines. We searched bibliographic databases (Embase, MEDLINE and the Cochrane Library (CENTRAL)) from inception to 2 December 2019. Randomised controlled trials and non-randomised studies were eligible for inclusion. Two reviewers independently scrutinized studies for relevance, extracted data and assessed quality of studies. Risk of bias of studies and quality of evidence were assessed using RoB, ROBINS-I tool and GRADEpro respectively. Educational outcomes studied were skill retention and performance 1 year after completion of training; skill performance between completion of training and 1 year; and knowledge at course conclusion. Clinical outcomes were skill performance at actual resuscitation, patient survival to discharge with favourable neurological outcome. This systematic review was registered in PROSPERO (CRD42019150358). From 2,042 references, we included data from 17 studies (13 randomised studies, 4 cohort studies) in courses with manikins and simulation in the narrative synthesis. Eight studies reported results from basic life support training (with or without automatic external defibrillator); three studies reported from paediatric life support training; five were in neonatal resuscitation and one study reported results from a bespoke emergency medicine course which included resuscitation teaching. Fifteen out of seventeen studies reported improved performance with the use of spaced learning. The overall certainty of evidence was rated as very low for all outcomes primarily due to a very serious risk of bias. Heterogeneity across studies precluded any meta-analyses. There was a lack of data on the effectiveness of spaced learning on skill acquisition compared to maintaining skill performance and/or preventing skill decay. There was also insufficient data to examine the effectiveness of spaced learning on laypeople compared to healthcare providers. Despite the very low certainty of evidence this systematic review suggests that spaced learning can improve skill performance at 1 year post course conclusion and skill performance between course conclusion and 1 year. There is a lack of data from this educational intervention on skill performance in clinical resuscitation and patient survival at discharge with favourable neurological outcomes.


Corneal donor material selection.
Histologic study of eyes used as donor material for corneal transplant revealed one instance of massive leukemic infiltration with leukemic keratic precipitates on the fellow eye. In another eye, microabscesses composed of acute and chronic inflammatory cells containing Crytococcus neoformans were present. In a third patient metastatic anaplastic cells were present in the choroid. We think donor eyes are absolutely unacceptable if death was caused by any chronic neurologic disorder, unless clearly secondary to trauma. Eyes from patients with septecimia, hepatitis, jaundice and any evidence of any active viral infection, syphilis, and positive serology are also unacceptable. Extreme caution should be used in selecting eyes of patients with ocular or systemic malignancy, long-term diseases, particularly if immunosuppressive agents were used, where a history of eye disease exists, including corneal disease or dystrophy, iritis, absolute glaucoma or acute glaucoma, and eyes with a history of previous intraocular surgery.


Improved production of adipate with Escherichia coli by reversal of β-oxidation.
The linear C6 dicarboxylic acid adipic acid is an important bulk chemical in the petrochemical industry as precursor of the polymer nylon-6,6-polyamide. In recent years, efforts were made towards the biotechnological production of adipate from renewable carbon sources using microbial cells. One strategy is to produce adipate via a reversed β-oxidation pathway. Hitherto, the adipate titers were very low due to limiting enzyme activities for this pathway. In most cases, the CoA intermediates are non-natural substrates for the tested enzymes and were therefore barely converted. We here tested heterologous enzymes in Escherichia coli to overcome these limitations and to improve the production of adipate via a reverse β-oxidation pathway. We tested in vitro selected enzymes for the efficient reduction of the enoyl-CoA and in the final reaction for the thioester cleavage. The genes encoding the enzymes which showed in vitro the highest activity were then used to construct an expression plasmid for a synthetic adipate pathway. Expression of paaJ, paaH, paaF, dcaA, and tesB in E. coli BL21(DE3) resulted in the production of up to 36 mg/L of adipate after 30 h of cultivation. Beside the activities of the pathway enzymes, the availability of metabolic precursors may limit the synthesis of adipate, providing another key target for further strain engineering towards high-yield production of adipate with E. coli.


Clinical Features and Management of "Phlebitis-like Abnormal Reaction" After Cyanoacrylate Closure for the Treatment of Incompetent Saphenous Veins.
Cyanoacrylate closure for the treatment of incompetent saphenous veins does not cause thermal damage and demonstrates satisfactory outcomes with rapid recovery. However, the characteristics of phlebitis-like abnormal reaction (PLAR), the most common adverse event after cyanoacrylate closure, have not been clarified. Moreover, it differs from typical phlebitis after thermal ablation. The objective of our study is to investigate the clinical features of PLAR after cyanoacrylate closure and to report its management. A total of 160 patients with 271 incompetent saphenous veins (great saphenous veins, 201; small saphenous veins, 70) underwent cyanoacrylate closure with the VenaSeal™ system. We defined PLAR as any unusual skin condition that develops suddenly, such as erythema, itching, swelling, and pain/tenderness, over the treated veins several days after cyanoacrylate closure. Oral antihistamines and intravenous dexamethasone were administered to manage PLAR. Of the 271 treated veins, 69 experienced PLAR (25.4%). The mean time of occurrence was 13.6 ± 4.6 days after treatment. The rate of occurrence of erythema, itching, swelling, and pain/tenderness were 92.2%, 91.2%, 66.2%, and 48.5%, respectively. The occurrence of PLAR was significantly higher for great saphenous veins than for small saphenous veins (P < 0.001). Occurrences were more frequent in cases with a suprafascial great saphenous vein of length >10 cm than in cases with a subfascial great saphenous vein (P = 0.001). The proportion of patients who reported swelling decreased by more than half after the administration of oral antihistamine. The pain score on the 10th day also decreased significantly after the administration of antihistamine (P = 0.006). PLAR must be distinguished from classic phlebitis. We believe that PLAR is a type IV hypersensitivity reaction due to a foreign body, and in our experience, antihistamines or steroids are effective for the prevention and management of PLAR.


Daily temperature fluctuations can magnify the toxicity of pesticides.
We review the effect of daily temperature fluctuations (DTF), a key thermal factor predicted to increase under climate change, on pesticide toxicity. The effect of DTF on pesticide toxicity may be explained by: (i) a DTF-specific mechanism (caused by Jensen's inequality) and (ii) general mechanisms underlying an increased pesticide toxicity at both higher (increased energetic costs, pesticide uptake and metabolic conversion) and lower constant temperatures (lower organismal metabolic and associated elimination rates, increased sodium channel modulated nervous system vulnerability and energetic costs). Furthermore, DTF may enhance pesticide-induced reductions in heat tolerance due to stronger effects on oxygen demand (increase) and oxygen supply (decrease). Our literature review showed considerable support that DTF increase the negative impact of pesticides on insects, especially in terms of decreased survival. Therefore, we suggest that considering DTF in ecotoxicological studies may be of great importance to better protect biodiversity in our warming world.


A rapid method for the purification of extrachromosomal DNA from eukaryotic cells.
A simple and efficient procedure to purify the low molecular weight extrachromosomal DNA from eukaryotic cells is described. Gentle lysis of cells with urea and sodium dodecyl sulfate in 0.24 M phosphate buffer (pH 6.8) is followed by the removal of high molecular weight bulk DNA by centrifugation. Protein and RNA are removed from the supernatant by hydroxyapatite chromatography in urea/phosphate buffer. Urea is then removed with 0.15 M phosphate buffer and the extrachromosomal DNA, virtually free from protein and RNA, is finally eluted in 0.5 M phosphate buffer. The procedure allows the recovery of about 99% simian virus 40 (SV40) DNA from infected monkey kidney cells in the extrachromosomal fraction. In normal mouse, monkey, andhuman cells, approximately 1% of total cell DNA appears to be extrachromosomal.


Clinical validation of in-hospital stroke diagnosis.
In-hospital stroke cases occur during hospitalization for another diagnosis and reflect a clinically distinct cohort from community-onset stroke. The objective was to validate the diagnostic accuracy of in-hospital stroke identification in stroke audit data at a large teaching hospital. A retrospective clinical validation of in-hospital stroke diagnoses from two linked data sources was completed for a 2-year period from January 1st 2020 to December 31st 2021. The linked data sources include the Hospital Inpatient Enquiry system which assigns coded stroke diagnoses at discharge and/or the local stroke audit coordinators who work clinically in stroke teams and input additional specific clinical data. Diagnostic sensitivity, specificity and the level of agreement using an unweighted Cohen's Kappa were calculated. There were 597 strokes admitted during the 2-year period. The median age was 72 years and 55% occurred in males. In total, 88 cases of in-hospital stroke were clinically validated yielding an in-hospital stroke rate of 15%. The clinical audit coordinator identified in-hospital stroke with higher sensitivity (86%; 95% CI 77%-93%) whereas the coding process was more specific at 96% (95% CI 85% to 99%). Levels of agreement with the clinically validated gold standard sample were moderate for the audit coordinator and coding process with κ = 0.57 and K = 0.42 respectively. When both data sources were combined the level of agreement was substantial (κ = 0.65; p < .000). Clinical validation studies are required to reinforce data quality within stroke registers. Combining clinical and administrative data sources improves diagnostic accuracy for in-hospital stroke identification.


Genetic variation and structure of the endangered Lady Fern Athyrium viridescentipes based on ubiquitous genotyping.
To clarify the genetic status and provide effective information for the conservation of Athyrium viridescentipes, a critically endangered fern species with only 103 individuals remaining in the wild, we conducted ubiquitous genotyping to determine the genotypes of all remnant individuals of the target species. We analyzed the genetic variation of the 103 known individuals in four populations by using 13 microsatellite loci. The genotypes of single spores from a sporophytic individual were also determined in order to reveal the breeding system of this species. The level of allelic variation in A. viridescentipes was significantly lower than that of closely related Athyrium species. The genetic composition of the four populations was rather similar. Sixty-nine individuals (67%) possessed an identical pattern in the allele combinations at 13 microsatellite loci. The mean pairwise F (ST) among four populations was 0.018. The segregated pattern of alleles, determined by single-spore genotyping, revealed that allelic recombination occurs through meiosis. The results indicate that this species contains a low level of genetic variation, has low population differentiation, and maintains populations by sexual reproduction. These findings could lead to more effective conservation programs, the selection of the most appropriate individuals for ex situ conservation efforts, and separate management of extant populations.


Membrane potential of stored platelets and its effect on platelet functions.
Relationships among intracellular Ca2+ level, membrane potential in resting state and platelet functions were examined. Membrane potential of platelets was increased (hyperpolarized) during storage and decreased (depolarized) by 37 degrees C incubation with plasma after storage. The degree of depolarization was greater in fresh plasma than in stored plasma. Changes of platelet functions were reverse with the membrane potential change. Aggregation induced by ADP or collagen was enhanced by depolarization with increasing extracellular [K+]. Shrinkage ratio (hypotonic shock response) of stored platelet which were hyperpolarizing, exhibited optimal value when the membrane potential was slightly depolarized. Intracellular [Ca2+] was not affected by the extracellular [K+]. These results suggest that platelet sensitivity is controlled by the membrane potential in resting state.


Microalbuminuria is not a valuable marker for relapse in Crohn's disease.
Previous reports correlated microalbuminuria with disease activity in patients with Crohn's disease (CD). The aim of the present study is to determine the value of microalbuminuria as a marker for relapses in quiescent CD. In a 1-year prospective maintenance trial with oral budesonide in patients with CD in remission, microalbuminuria was measured at randomization, after 2, 6 and 12 months, plus at the time of a relapse. The association of microalbuminuria with the course of disease was analyzed with logistic regression analysis. Time-dependent Cox regression was undertaken to study the association between microalbuminuria and relapse. We included a total of 139 patients. At randomization, microalbuminuria was present in 8 patients. During a 1-year follow-up, 29 patients relapsed and in 11% (3/29), microalbuminuria was present during the relapse. We found no statistically significant association between microalbuminuria and relapse (odds ratio 0.92, 95% confidence interval (CI) 0.76-1.13). Time-dependent Cox regression analysis also revealed no statistical predictive value for microalbuminuria (hazard ratio 1.29, 95% CI 0.37-4.39, p = 0.68). Microalbuminuria was moderately prevalent in quiescent CD patients, but it could not be associated with disease characteristics or the type of medication before randomization, nor as a predictor for relapses.


Extrachromosomal gene systems in Streptococcus mutans.
1) Four of 86 S. mutans strains of human origin harbor a 3.6 Mdal multicopy plasmid while 2 of 13 strains of rat origin carry multiple copies of a 2.3 Mdal and 2.5 Mdal plasmid. 2) There is no evidence to support that any of these plasmids confers clinically or ecologically important phenotypes. 3) The restriction endonucleases Hind III and Bam HI cleave the 3.6 Mdal plasmid once, thus facilitating the use of this extrachromosomal element in gene cloning systems.


Influence of anti-androgens on the anterior horn cells of rat spinal cord: morphometric and in-situ hybridization studies.
To examine the roles of the androgens for growth and maintenance of anterior horn cells (AHCs) of the spinal cord, one of the two anti-androgen agents, flutamide or cyproterone, was injected into young rats. Morphometric analysis of the spinal cords after the injections showed that the average area occupied by an AHC was significantly smaller in the rats treated with the anti-androgens than in the controls. By contrast, neurons in the posterior horns did not show significant difference in their size. Moreover, an in-situ hybridization of choline acetyltransferase (CAT) messenger RNA revealed a significant reduction in the signal density in AHCs in the treated rats. These results show that androgens play an important role in the growth and maintenance of AHCs, and influence a wide range of protein synthesis, including that of CAT.


The first synthesis and immunomodulatory properties of p-hydroxyphenyl caffeate derived from Wedelia trilobata.
Herein, we report a concise and efficient method for the synthesis of p-hydroxyphenyl caffeate, a novel natural caffeic acid ester derivative isolated from Wedelia trilobata. The key feature of this synthesis is the Verley-Doebner modification of the Knoevenagel condensation of the p-hydroxyphenyl malonate intermediate. The synthesized p-hydroxyphenyl caffeate enhanced interleukin 2 production by murine lymph node T cells, and suppressed interleukin 13 production by murine epidermal T cells. This implies that p-hydroxyphenyl caffeate might be a novel immunomodulatory drug candidate, specifically targeting T helper 2 cell type responses in skin diseases such as atopic dermatitis and vitiligo. [Formula: see text].


Primary aneurysmal bone cysts in children: percutaneous sclerotherapy with absolute alcohol and proposal of a vascular classification.
Percutaneous sclerotherapy is an effective treatment for aneurysmal bone cysts (ABCs). The purpose of this study was to demonstrate the safety and efficacy of sclerotherapy with absolute alcohol and to propose a vascular classification of ABCs based on a retrospective review. This was a review of children treated with absolute alcohol sclerotherapy for ABC at a single institution from January 1995 until November 2009. Treatment response was evaluated radiographically and clinically. Cyst fluid was classified as clear, partially bloody, or bloody. Presence of any venous drainage of the cyst was assessed by injection of contrast medium into the cyst cavity. Twenty-nine children with ages ranging from 2 to 16 years were included. Treatment response was good in 17 (59%), partial in 9 (31%), and poor in 3 (10%) children. Venous drainage was absent in six out of seven clear-fluid cysts, which we classified as lymphatic. Drainage was present in all seven bloody-fluid cysts, which we classified as venous. In seven partially bloody-fluid cysts, venous drainage was seen in three. Sclerotherapy with absolute alcohol is a safe and effective treatment of ABC. We propose classifying ABC as lymphatic or venous and suggest considering ABC intraosseous slow-flow vascular malformations.


A novel cationic graphene modified cyclodextrin adsorbent with enhanced removal performance of organic micropollutants and high antibacterial activity.
The coexistence of pathogenic microorganisms and refractory organic chemicals in water nurtures certain biological and chemical risks to human beings and the water environment as a whole. For an environmentally friendly utilization of water cleaning and recycling technologies, a bifunctional cationic cyclodextrin material (GD-DTAC) with adsorption and bactericidal function was designed. By a simple crosslinking method, GD-DTAC was prepared with graphene supported citric acid-β-cyclodextrin polymer (GD) and dimethyldodecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DTAC). Following the introduction of rich quaternary ammonium groups by DTAC, GD-DTAC realized a double regulation of surface positive charge and wettability. The maximum adsorption capacities of Roxarsone (ROX), Methyl Orange (MO) and Bisphenol A (BPA) were 153.59 mg/g, 445.60 mg/g and 237.90 mg/g, respectively. Antibacterial activity tests showed the efficiency of DTAC not only for enhanced adhesion resistance, but it also realized the sterilization function. This work displays the potential of the prepared bifunctional materials for the removal of pollutants from wastewater as well as the suppression of micro-pollutants. The successful preparation of GD-DTAC provided a basis for the bifunctional material, which showed a great potential in adsorption and antibiosis.


Validation of growth enhancing, immunostimulatory and disease resistance properties of Achyranthes aspera in Labeo rohita fry in pond conditions.
The immunostimulatory and disease resistance properties of herb Achyranthes aspera L. (Amaranthaceae) were evaluated in rohu Labeo rohita in pond. Rohu fry (1.9 ± 0.08 g) were cultured in hapas (25 hapa-1) set inside a pond and were fed with two experimental diets containing 0.5% seeds (D1) and leaves (D2) of A. aspera and control diet (D3). Fish were challenged with Aeromonas hydrophila after 80 days. The cumulative mortality rate of fish was significantly (P < 0.05) higher in D3 (28-48%) compared to others. Average weight was significantly (P < 0.05) higher in D1 (6.5-12.5%) compared to other treatments. Myeloperoxidase and nitric oxide synthase levels were significantly (P < 0.05) higher in D1 and D2 compared to D3. Thiobarbituric acid reactive substances and carbonyl protein levels were significantly (P < 0.05) lower in hepatopancreas and kidney of D1 compared to others. In hepatopancreas, the expressions of lysozyme C, loysozyme G, TNF-α, IL-10 and IL-1β were significantly (P < 0.05) higher in D1 compared to others. This treatment was followed by D2. In kidney, lysozyme G and TNF-α levels were significantly (P < 0.05) higher in D1 and D2 compared to D3. Whereas, IL-10 and IL-1β were significantly (P < 0.05) down-regulated and up-regulated, respectively in kidney of D2. There was up-regulation (P < 0.05) of TLR-4 in hepatopancreas and kidney of D1 and D2 diets fed rohu, respectively compared to others.


Immunocytochemical localization of the myelin-associated glycoprotein. Fact or artifact?
Immune staining for the myelin-associated glycoprotein (MAG) by the peroxidase-antiperoxidase technique in vibratome, paraffin and Epon sections of peripheral nerve resulted in a periaxonal ring of immune reaction product and an absence of staining over compact myelin. The thickness of the periaxonal rings of staining in Epon sections were similar when axons were surrounded by single Schwann cell processes and when they were surrounded by compact myelin sheaths. Thicker rings of periaxonal staining were present when axons were surrounded by multiple layers of uncompacted Schwann cell membranes. When swelling of the Schwann cell periaxonal cytoplasm separated the periaxonal Schwann cell membrane from compact myelin by distances that could be readily resolved in the light microscope, immune staining for MAG was found over the periaxonal Schwann cell membrane but not over compact myelin. Biochemical experiments in which myelin or MAG was treated with sodium ethoxide and hydrogen peroxide, under conditions similar to those used for etching Epon sections prior to immune staining, showed that the immune reactivity of MAG was stable to these treatments. Finally, a pre-embedding technique for immune staining at the electron-microscopic level showed MAG reaction product on the cytoplasmic side of Schwann cell periaxonal membranes and the membranes of Schmidt-Lanterman incisures and paranodal loops. These results confirm and strengthen the evidence from previous reports indicating that MAG is confined to periaxonal membranes, Schmidt-Lanterman incisures, paranodal loops, and the outer mesaxon of myelinating Schwann cells and is absent from compact myelin. These results are discussed in reference to a recent report apparently showing the presence of MAG in compact CNS myelin. Based on the data presented and discussed in this paper, it is concluded that MAG is located in specific non-compact regions of central and peripheral myelin sheaths and not in compact myelin lamellae.


Biosynthesis of trialkyl-substituted aromatic polyketide NFAT-133 involves unusual P450 monooxygenase-mediating aromatization and a putative metallo-beta-lactamase fold hydrolase.
The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123 (1), veramycin A (2), NFAT-133 (3) and benwamycin I (4), which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities. Though the biosynthetic pathway of 1-3 was reported as a type I polyketide synthase (PKS), the PKS assembly line was interpreted inconsistently, and it remains a mystery how the compound 3 was generated. Herein, the PKS assembly logic of 1-4 was revised by site-mutagenetic analysis of the PKS dehydratase domains. Based on gene deletion and complementation, the putative P450 monooxygenase nftE1 and metallo-beta-lactamase (MBL) fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1-4. The absence of nftE1 led to abolishment of 1-4 and accumulation of new products (5-8). Structural elucidation reveals 5-8 as the non-aromatic analogs of 1, suggesting the NftE1-catalyzed aromatic core formation. Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected. As a rare MBL-fold hydrolase from type I PKSs, NftF1 potentially generates the compound 3 through two strategies: catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.


DUN1 encodes a protein kinase that controls the DNA damage response in yeast.
DNA damage induces the expression of many genes proposed to enhance DNA repair capacities. We investigated the mechanism by which DNA damage induces transcription of RNR3, a subunit of ribonucleotide reductase. Five complementation groups of DNA-damage uninducible (dun) mutants were identified. Each is sensitive to DNA damage. dun1 mutants are also defective for RNR1 and RNR2 induction but are proficient for induction of other genes, defining the existence of at least two distinct DNA damage induction pathways. DUN1 encodes a nuclear protein kinase that is also a phosphoprotein. Phosphorylation of Dun1 increases in response to DNA damage in a Dun1-dependent manner, suggesting an increase in autophosphorylation activity. These results establish the existence of a eukaryotic SOS response regulated by protein phosphorylation.


[Effectiveness and Cost-Effectiveness of Daily School Sport in the Primary School--Project: "fit for pisa"].
The "fit for pisa" intervention implemented daily physical education at five primary schools in Göttingen. The results of the evaluation show an increase in physical activity among the students participating in the programme. At the same time sedentary behaviour, like watching television, decreased remarkably. In the long run the promotion of an active lifestyle had improved the body mass index. The study emphasises the need for government funding to implement the programme across the country.


Ascites following prostatectomy: a rare presentation of comorbid disease.
We report a rare case of ascites developing in the early post-prostatectomy period due to a mass originating from the head of the pancreas. Comorbid diseases that are not documented preoperatively may emerge with signs mimicking the complication of prostate surgery.


An fMRI paradigm based on Williams inhibition test to study the neural substrates of attention and inhibitory control.
The purpose of this study is to present an fMRI paradigm, based on the Williams inhibition test (WIT), to study attentional and inhibitory control and their neuroanatomical substrates. We present an index of the validity of the proposed paradigm and test whether the experimental task discriminates the behavioral performances of healthy participants from those of individuals with acquired brain injury. Stroop and Simon tests present similarities with WIT, but this latter is more demanding. We analyze the BOLD signal in 10 healthy participants performing the WIT. The dorsolateral prefrontal cortex, the inferior prefrontal cortex, the anterior cingulate cortex, and the posterior cingulate cortex were defined for specified region of interest analysis. We additionally compare behavioral data (hits, errors, reaction times) of the healthy participants with those of eight acquired brain injury patients. Data were analyzed with GLM-based random effects and Mann-Whitney tests. Results show the involvement of the defined regions and indicate that the WIT is sensitive to brain lesions. This WIT-based block design paradigm can be used as a research methodology for behavioral and neuroimaging studies of the attentional and inhibitory components of executive functions.


Hybrid organic-inorganic two-dimensional metal carbide MXenes with amido- and imido-terminated surfaces.
Two-dimensional (2D) transition-metal carbides and nitrides (MXenes) combine the electronic and mechanical properties of 2D inorganic crystals with chemically modifiable surfaces, which provides an ideal platform for both fundamental and applied studies of interfaces. Good progress has been achieved in the functionalization of MXenes with small inorganic ligands, but relatively little work has been reported on the covalent bonding of various organic groups to MXene surfaces. Here we synthesize a family of hybrid MXenes (h-MXenes) that incorporate amido- and imido-bonding between organic and inorganic parts by reacting halogen-terminated MXenes with deprotonated organic amines. The resulting hybrid structures unite tailorability of organic molecules with electronic connectivity and other properties of inorganic 2D materials. Describing the structure of h-MXene necessitates the integration of concepts from coordination chemistry, self-assembled monolayers and surface science. The optical properties of h-MXenes reveal coherent coupling between the organic and inorganic constituents. h-MXenes also exhibit superior stability against hydrolysis.


Pathogenic Effects and Pathogenesis Processes in Vitro & in Vivo in Murine Cytomegalovirus Infected Rat Corneal Endothelial Cells.
To understand the pathogenesis in rat corneal endothelial cells (RCECs) induced by murine cytomegalovirus infection in vitro and in vivo. In vitro, cultured RCECs were infected with murine cytomegalovirus strain K181-eGFP (MCMV-eGFP). In vivo, experimental rats received intracameral injection of MCMV-eGFP. Replicating viruses and morphology change of RCECs in vivo were evaluated at several time points. In vitro, RCECs became necrosis at 6hpi. MCMV-eGFP began replicating at 12hpi. In vivo, the inflammatory reactions appeared at 12hpi, peaked at 72hpi and gradually subsided. Replicating MCMV-eGFP appeared in RCECs in vivo from 24hpi to 72hpi. RCECs enlarged after 12hpi and capsids in the nuclei were visible at 72hpi. A monocyte was found on a corneal endothelium at 120hpi. RCECs were sensitive to MCMV in vitro. Replication of MCMV-eGFP in vivo began at 24hpi and ended after 72hpi, later than the inflammatory reactions.


Phlebitis rate and time kinetics of short peripheral intravenous catheters.
An observational prospective cohort study was carried out on complication rates and time kinetics of phlebitis caused by short peripheral intravenous catheters (PIVCs) in inpatients on 15 hospital wards in four hospitals in Cologne, Germany. We observed 1,582 patients with 2,495 PIVCs daily using standardized questionnaires. Phlebitis was defined using modified Centers for Disease Control and Prevention (CDC) criteria. Average phlebitis rates were 27 per 100 patients and 104 per 1,000 catheter days. Median duration of PIVC was 2 days (25 percentile = 2 days; 75 percentile 3 days). Time kinetics (Kaplan-Meier) were linear. Linear time kinetics of PIVC phlebitis do not support CDC recommendations for an elective PIVC change after 72 hours, provided daily monitoring of the insertion site occurs.


Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and behavioural assessment in zebrafish model.
Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children. To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy. Suvarna Bhasma was characterised by physicochemical characterization techniques such as scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and atomic emission spectroscopy (ICP-AES). Toxicity of Suvarna Bhasma was studied in Holtzman rats with daily oral dose from 3 mg/kg (therapeutic dose, TD) up to 30 mg/kg (10 TD) body weight for 90 days. Behavioural study, such as motor and geotactic behaviour were examined in zebrafish model to find out any sign of neurotoxicity or behavioural changes due to Suvarna Bhasma administration. Suvarna Bhasma has two types of gold particles, large ones (~60 μm) having irregular shapes, and nano-sized spherical particles (starting from ~10 nm), the latter coated with Fe, Si, O, P and Na. XRD study revealed that all the peaks of Suvarna Bhasma match well with pure gold (face centred cube) with crystallites size 45 ± 2.8 nm. In rat studies, some change in biochemical parameters such as urea, creatinine and alanine aminotransferase (ALT) was observed mainly at the higher therapeutic dose; however, those parameters were within the normal range. There were no significant macroscopic as well as microscopic treatment-related alteration observed, in any of the organs and tissues evaluated. In zebrafish behavioural study, the motor parameters of Suvarna Bhasma treated fish showed normal behaviour analogous to the vehicle control group. Interestingly, the geotactic behaviour showed anxiolytic effects of Suvarna Bhasma as evidenced by the time spent in the upper zone, and average swimming height. The anxiolytic effects persisted for more than 30 days after withdrawing the Suvarna Bhasma treatment. Suvarna Bhasma contained spherical gold nanoparticles. It was nontoxic in rat model at the does tested. Suvarna Bhasma has anxiolytic effects in zebrafish behavioural model.


Effects produced by acute and chronic treatment with granisetron alone or in combination with haloperidol on midbrain dopamine neurons.
In this study, we examined the effects of acute and chronic administration of the 5-HT3 receptor antagonist granisetron (0.1, 1.0 or 10 mg/kg i.p.) alone or in combination with haloperidol (0.5 mg/kg i.p.) on the number of spontaneously active dopamine neurons in the substantia nigra pars compacta (SNC or A9) and the ventral tegmental area (VTA or A10). This was accomplished using the technique of extracellular single unit recording. Acute granisetron at 0.1 mg/kg, but not at higher doses, selectively decreased the number of spontaneously active A10 DA cells. Chronic administration of 0.1 or 1 mg/kg granisetron selectively decreased the number of spontaneously active A10 dopamine cells compared to controls, mimicking the effect produced by chronic treatment with the atypical neuroleptic drug clozapine. However, unlike the effect produced by neuroleptics, this granisetron-induced effect was not reversed by the systemic administration of apomorphine (50 micrograms/kg). These results suggest that the chronic granisetron-induced reduction of the number of spontaneous active dopamine cells is not the result of depolarization inactivation. Chronic coadministration of granisetron with haloperidol negates the effects produced by either compound alone. Acute coadministration of granisetron with haloperidol also attenuated or abolished haloperidol's action, particularly that on the A9 dopamine cells. Overall, it appears that at 0.1 and 1.0 mg/kg, chronic granisetron may possess atypical neuroleptic drug potential. However, the combination of haloperidol and granisetron nullifies changes in midbrain dopamine neurons observed with either agent alone.


Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study.
Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. Retrospectively registered at clinicaltrials.gov (NCT05655793).


Functional expression of human heme oxygenase-1 (HO-1) driven by HO-1 promoter in vitro and in vivo.
We developed a retrovirus-mediated human heme oxygenase-1 (HO-1) gene expression system and assessed the impact of heme on the inducibility of the HO-1 gene in rat lung microvessel (RLMV) endothelial cells and in newborn Sprague-Dawley (SD) rats. Overexpression of the HO-1 gene driven by HO-1 promoter (HOP) resulted in an increase in HO-1 protein and HO activity by 4.8- and 1.3-fold, respectively, compared to the viral LTR promoter. The increased HO-1 gene expression was associated with the enhancement of CO production. In cells transduced by HOP-driven HO-1 gene, there was a decrease in basal cyclooxygenase (COX) activity as measured by PGE(2). The degree of HO-1 expression and, consequently, the levels of cellular heme were directly related to COX activity. Supplementation with heme markedly increased PGE(2) and cGMP synthesis. In all (6/6) of newborn SD rats injected with retrovirus LSN-HOP-HO-1, both HO-1 and neo(r) transcripts were expressed in tissues. We hypothesize that degree of HO-1 gene expression resulted in a differential rate of cellular heme-dependent enzyme gene expression, which may play a vital role in maintaining cellular homeostasis.


Peroxynitrite stimulates pulmonary artery endothelial and smooth muscle cell proliferation: involvement of ERK and PKC.
There is evidence that peroxynitrite is generated in pulmonary hypertension and we have therefore investigated whether peroxynitrite can cause proliferation of pulmonary artery cells. Bovine pulmonary artery endothelial (PAEC) and smooth muscle cells (PASMC) were exposed to peroxynitrite solution or to the peroxynitrite generating compound, 3-morpholinosydnonimine (SIN-1). Vascular cell proliferation was determined by cell count and (3)H-thymidine incorporation. Protein biochemistry was by western blot analysis. Transient exposure to peroxynitrite stimulated the proliferation of PASMC (peroxynitrite 0.2 nM-2 μM) and PAEC (peroxynitrite 0.2 μM). Peroxynitrite 0.2 μM stimulated DNA synthesis in PASMC cell by 200 ± 22% and in PAEC by 137 ± 4%. DNA synthesis in PAEC and PASMC was also stimulated by the peroxynitrite generator SIN-1 2 μM. Cell proliferation was accompanied by activation of ERK, which peaked at 15 min and remained elevated for 12 h in PASMC. However peroxynitrite at the concentrations used in this study did not activate the stress pathways p38 mitogen activated protein kinase (MAPK) or Jun N-terminal kinase (JNK). Peroxynitrite-induced proliferation and ERK phosphorylation in PASMC were abolished by the peroxynitrite scavenger ebselen 5 μM. Peroxynitrite-induced proliferation and extracellular signal-regulated kinase (ERK) phosphorylation in PASMC was prevented by selective inhibitors of MAP kinase kinase (MEK) (U0126 5 μM, PD98059 50 μM), Raf-1 (Raf-1 kinase inhibitor 10 μM), Ras (FPT II and FPT III 10 μM) and protein kinase C (PKC) (GF109203X 10 μM). Inhibition of EGF or PDGF receptor signaling using AG-1296, AG-1478 or imatinib prevented peroxynitrite-induced cell proliferation and ERK phosphorylation in PASMC. Peroxynitrite can stimulate proliferation of pulmonary artery cells, involving ERK, PKC and EGF or PDGF receptors.


Towards a continuous population model for natural language vowel shift.
The Great English Vowel Shift of 16th-19th centuries and the current Northern Cities Vowel Shift are two examples of collective language processes characterized by regular phonetic changes, that is, gradual changes in vowel pronunciation over time. Here we develop a structured population approach to modeling such regular changes in the vowel systems of natural languages, taking into account learning patterns and effects such as social trends. We treat vowel pronunciation as a continuous variable in vowel space and allow for a continuous dependence of vowel pronunciation in time and age of the speaker. The theory of mixtures with continuous diversity provides a framework for the model, which extends the McKendrick-von Foerster equation to populations with age and phonetic structures. We develop the general balance equations for such populations and propose explicit expressions for the factors that impact the evolution of the vowel pronunciation distribution. For illustration, we present two examples of numerical simulations. In the first one we study a stationary solution corresponding to a state of phonetic equilibrium, in which speakers of all ages share a similar phonetic profile. We characterize the variance of the phonetic distribution in terms of a parameter measuring a ratio of phonetic attraction to dispersion. In the second example we show how vowel shift occurs upon starting with an initial condition consisting of a majority pronunciation that is affected by an immigrant minority with a different vowel pronunciation distribution. The approach developed here for vowel systems may be applied also to other learning situations and other time-dependent processes of cognition in self-interacting populations, like opinions or perceptions.


Systems Biology Approaches for Understanding Genome Architecture.
The linear and three-dimensional arrangement and composition of chromatin in eukaryotic genomes underlies the mechanisms directing gene regulation. Understanding this organization requires the integration of many data types and experimental results. Here we describe the approach of integrating genome-wide protein-DNA binding data to determine chromatin states. To investigate spatial aspects of genome organization, we present a detailed description of how to run stochastic simulations of protein movements within a simulated nucleus in 3D. This systems level approach enables the development of novel questions aimed at understanding the basic mechanisms that regulate genome dynamics.


National survey of surgical practices: Sacropexy in France in 2019.
Sacropexy is a reference surgical treatment for pelvic organ prolapse in women. The great variability in surgical techniques for this procedure is a source of bias that complicates analysis of the results of trials assessing it. Using the French guidelines issued in 2016 by the SCGP, AFU, SIFUD-PP, and CNGOF as a reference, we sought to inventory the surgical practices of the surgeons who perform these procedures. In November 2018, a questionnaire about the technical aspects of this procedure was distributed by email to the French physicians performing it. It was distributed to members of several professional societies (CNGOF, SCGP, and SIFUD) and to gynecologists practicing in clinics owned by the ELSAN group. Of the 273 responders, 92% reported that they perform most operations laparoscopically. Overall, 83% of gynecologic surgeons used polypropylene prostheses (mesh); 38% routinely placed a posterior mesh, while the rest did so only in cases of clinical rectocele with anorectal symptoms. A concomitant hysterectomy was performed by 51% of respondents when the uterus was bulky and/or associated with substantial uterine prolapse. Finally, half the surgeons suggested the placement of a suburethral sling for women with stress urinary incontinence. Although practices are largely consistent with the most recent guidelines, surgical techniques vary widely between surgeons, both in France and internationally.


[Determination by high performance chromatography, steroid saponins in a biologically active food supplements containing the extract of Tribulus terrestris].
Steroidal saponins are bioactive substances of Tribulus terrestris and can be used to assess the quality of raw materials and processed products from them. For this purpose has been developed the method of qualitative and quantitative determination of steroidal saponins by high performance liquid chromatography with spectrophotometric and mass-selective detection and optimal conditions of sample preparation (70% methanol extraction with sonication and heating); also has been studied steroidal saponins composition of Tribulus terrestris (protodioscin, tribulosaponin B, metilprotodiostsin, terrestrozin H, prototribestin, gracillin and others were found).


Liver function tests during treatment with desipramine in children and adolescents.
Results of liver function tests in 42 children and adolescents treated with desipramine for up to 24 months were unchanged. Although tricyclic-related hepatotoxicity cannot be ruled out with a small sample, it does not appear to be a dose- or time-related phenomenon in this age group.


Self-renewing human bone marrow mesenspheres promote hematopoietic stem cell expansion.
Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45- CD31- CD71- CD146+ CD105+ nestin+ cells but could also be simply grown from fetal and adult BM CD45--enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.


Kinetic adhesion test to determine particle surface energy.
A new hardware is described to quantify the particle surface energy by assuming that the Johnson Kendall and Roberts theory of elastic-adhesive contacts is applicable. The setup is used in the active section of the measurement, where newly designed elements provide the sharp impact needed to detach the particles under the action of their own kinetic energy. It employs a selection of sensors to provide the necessary measurements in a streamlined procedure, which lets the user complete one test in less than one minute. The temporal resolution is 1μs for the contact time measurement and the velocity has a repeatability of 1%. The surface energy is a significant parameter for the characterisation of particulate materials and is widely used in Discrete Element simulations of the bulk behaviour.


The incidence of deep venous thrombosis in patients undergoing abdominal aortic aneurysm resection.
Fifty consecutive patients undergoing abdominal aortic aneurysm resection were studied prospectively for the presence of deep venous thrombosis (DVT) after surgery. Bilateral venography was performed 5 days after surgery in all patients. There were 42 men and 8 women, with a mean age of 70 years (range 60 to 83 years). No patients received DVT prophylaxis before surgery. Nine (18%) of 50 patients had a venogram positive for acute DVT. Nine (21%) of 42 men and none of eight women had DVT. Six patients had DVT in the left leg and three patients in the right leg. No patients had symptoms to suggest DVT. Seven (78%) of the nine patients with DVT had thrombi in the calf veins and two patients (22%) had thrombi in the more proximal venous segments, representing 14% and 4% of the entire series, respectively. No clinically evident pulmonary emboli were observed. Eighteen percent of 50 consecutive patients undergoing abdominal aortic aneurysm resection had DVT. Because of this high incidence, a study should be undertaken to determine whether DVT prophylaxis can lower the incidence of DVT after abdominal aortic aneurysm resection.


Intracavitary Corynebacterium parvum for treatment of malignant effusions.
Intracavitary instillation of Corynebacterium parvum was used to treat recurrent malignant effusions in 15 patients. Eleven patients were treated for ascites, and four patients were treated for pleural effusion. Six patients (40%) had good response with no recurrence of effusions up to 3 months after treatment. Three patients responded but died before criteria for complete response could be fulfilled. Six patients were judged to have poor response, either because of death from tumor burden before evaluation could be made or because of recurrent effusions. There were no serious side effects directly attributed to intracavitary C. parvum therapy. Analysis of the results in this preliminary study suggests that patients who have had prior good response to chemotherapy, whose performance scale is adequate, whose tumor burden is not preterminal, and who have been previously treated with immunotherapy may be excellent candidates for definitive treatment of malignant effusions with intracavitary C. parvum.


Lack of a role of circulating bradykinin in the blood pressure response to acute angiotensin converting enzyme inhibition in rats.
The role of circulating bradykinin in blood pressure regulation was investigated in conscious normotensive rats using a competitive antagonist of bradykinin. The acute blood pressure effect of this antagonist was also evaluated after inhibition of angiotensin converting enzyme with captopril and during simultaneous infusion of exogenous angiotensin II. No evidence was found for a role of circulating bradykinin in rats studied under normal conditions. Endogenous bradykinin seemed however involved in blood pressure control during angiotensin II infusion. Acute angiotensin converting enzyme inhibition had no influence on the blood pressure response to the bradykinin antagonist.


Den1, den2 and den3, ATP-inhibited deoxyribonucleases from Dropsophila embryonic nuclei.
Three Drosophila embryonic deoxyribonucleases, designated den1, den2 and den3, are identified in nuclear extracts separated by glycerol density gradient centrifugation. Den1, removes short products from the 5'-ends of single-stranded DNA or double-stranded DNA with either blunt or 5'-recessed termini. Den2 is inactive with single-stranded DNA and acts as 3'-exonuclease with double-stranded DNA possessing either blunt or 3'-recessed termini. Den3 preferentially uses partial duplex DNA containing single-stranded gap and it catalyzes hydrolysis, in 3'-5' direction, of one of the shorter strands that flank the gap. Nucleolytic activities of den1, den2 and den3 are inhibited with ATP.


Enhanced Expression of miR-34c in Peripheral Plasma Associated with Diabetic Foot Ulcer in Type 2 Diabetes Patients.
To explore the correlation between the expression of miR-34c in peripheral blood of patients with type 2 diabetes mellitus (T2DM) and the onset of diabetic foot ulcer (DFU) and diabetic foot osteomyelitis (DFO). Sixty newly diagnosed patients with T2DM without DFU (T2DM group), 112 T2DM patients with DFU (DFU group) and 60 controls with normal glucose tolerance (NC group). The DFU group patients were subdivided into DFO (n=64) and NDFO (n=48) groups. Quantitative real-time PCR (qRT-PCR) method was used to determine miR-34c expression levels in the peripheral blood of subjects to analyze the clinical characteristics of DFU and DFO risk factors. MiR-34c expression level in the T2DM group was marked higher than the NC group [2.99 (1.45-6.22) vs 1.01 (0.89-1.52)] (P < 0.05). However, the expression level of miR-34c in the DFU group was significantly higher than the T2DM group [9.65 (6.15-18.63) vs 2.99 (1.45-6.22)] (P < 0.01). Compared with the NDFO group, the expression level of miR-34c in the DFO group was also obviously increased [13.46 (8.89-19.11) vs 6.02 (5.93-14.72)] (P < 0.01). The expression level of miR-34c in DFU patients was positively correlated with the amputation rate of foot ulcers (P=0.030) and was negatively correlated with the healing rate of foot ulcers after eight weeks (P=0.025). Multifactorial logistic regression analysis showed that increased expression of miR-34c was an independent risk factor for DFU and DFO (ORDFU=3.47, ORDFO=4.25, P < 0.01). Meanwhile, the ROC curve analysis indicated that the AUC of miR-34c for the diagnosis of DFU and DFO was 0.803 and 0.904, the optimum sensitivity being was 100% and 98.7%, the optimum specificity was 98.4% and 98.4%, respectively. The increased expression of miR-34c in peripheral blood of T2DM patients is closely related to the occurrence, development and prognosis of DFU and DFO.


Long-term follow up of visual acuity in eyes with stage 5 retinopathy of prematurity after closed vitrectomy.
This study was done to determine the efficacy of closed vitrectomy on long-term visual acuity of stage 5 retinopathy of prematurity. We studied the visual acuity of eyes that had undergone retinal reattachment by closed vitrectomy for stage 5 retinopathy of prematurity and were followed up for more than three years. Forty-nine eyes of 31 patients among a total of 71 eyes of 48 consecutive patients were operated on and followed up for more than three years. Retinal reattachment occurred in 29 (59%) of the 49 eyes. Six patients (eight eyes) did not respond to visual acuity testing because of mental retardation or cerebral palsy. Measured visual acuity in the remaining 21 eyes varied from no light perception in one eye, light perception in four eyes, Recognizable hand movement in three eyes, 20/2,000 to 20/200 in seven eyes, 20/200 to 20/25 in five eyes, and 20/25 in one eye. No correlation was seen between visual outcome and factors such as gestational age, birth weight, and configuration of retinal detachment. Markedly better visual acuity was obtained in eyes that underwent initial surgery within four months of birth. Useful vision can be obtained after reattachment of the retina by closed vitrectomy on some patients who have stage 5 retinopathy of prematurity. Better visual acuity may be obtained by earlier surgery.


The American Cancer Society guidelines for breast screening with magnetic resonance imaging: an argument for genetic testing.
The American Cancer Society (ACS) guidelines for screening with breast magnetic resonance imaging (MRI) recommend MRI for women who have a lifetime risk > or = 20% of developing breast cancer. Genetic testing for breast cancer gene (BRCA) mutations is offered to women who have a risk > or = 10% of carrying a mutation. The objectives of the current study were 1) to identify the number of women in a breast cancer screening population who had > or = 20% lifetime breast cancer risk and, thus, were candidates for screening MRI; and 2) to determine the number of women who had > or = 10% risk of BRCA mutation yet had <20% lifetime risk of breast cancer and, thus, may not have been identified as candidates for MRI screening. From 2003 to 2005, women who underwent screening mammography completed a self-administered questionnaire regarding breast cancer risk factors. For each patient, the lifetime breast cancer risk and the risk of BRCA mutation was determined by using the computerized BRCAPRO breast cancer risk-assessment model. Of 18,190 women, 78 (0.43%) had > or = 20% lifetime risk of breast cancer, all of whom had > or = 10% risk of carrying a BRCA mutation. An additional 374 women (2.06%) had <20% lifetime breast cancer risk but > or = 10% risk of mutation. Overall, there were 183 (1%) predicted mutation carriers, 27 women (0.15%) who had > or = 20% lifetime risk of breast cancer, and 62 women (0.34%) who had > or = 10% risk of mutation but <20% lifetime breast cancer risk. The ACS guidelines for breast MRI screening may systematically exclude MRI screening for many women who have a substantial risk for BRCA mutation. The current results demonstrated a need for greater awareness of breast cancer risk factors in the screening mammography population, so that high-risk women can be identified and given access to genetic testing and counseling regarding all risk-reducing interventions.


Labor market costs for long-term family caregivers: the situation of caregivers of persons with spinal cord injury in Switzerland.
Family members are key in the provision of care to persons facing disability. To undertake the role as caregivers, they face many costs, being the setback in the labor market one of the most relevant. We analyze comprehensive data from long-term family caregivers of persons with spinal cord injury (SCI) in Switzerland. Using information about their working situation before and after becoming caregivers, we estimated the reduction in working hours and the associated income loss. On average, family caregivers reduced their working hours by about 23% (8.4 h per week), which has a monetary value of CHF 970 per month (EUR 845). Women, older caregivers, and less educated caregivers have a much higher opportunity cost in the labor market: CHF 995 (EUR 867), CHF 1,070 (EUR 932), and CHF 1,137 (EUR 990) respectively. In contrast, family members who care for a person that works have a much lower impact on their working status, CHF 651 (EUR 567). Interestingly, the reduction in their working time is only a third of the extra work they face as caregivers. Health and social systems rely on the unpaid work of family caregivers. To guarantee their long-term involvement, family caregivers need to be recognized for their work and potentially compensated. Without family caregivers, it is very unlikely societies can cope with the increasing need for care, as professional services are limited and expensive.


Rheologic properties of erythrocytes in Duchenne muscular dystrophy.
The transformation of erythrocytes into echinocytes by suspension in isotonic phosphate buffer was increased in patients with Duchenne muscular dystrophy (DMD) as compared to healthy controls. The transformation was enhanced when glass slides instead of polystyrole slides were used for observation. Viscosity of erythrocyte suspensions with a hematocrit of 80% was the same in patients and controls. The mean flow rate of erythrocyte suspensions in autologous plasma was only slightly reduced in the patient group, but decreased markedly after suspension of the cells in phosphate buffer, without as well as after preincubation with 10 mM Na salicylate. The decreased flow rate in patients is probably due to the increased number of echinocytes and not to an increased membrane rigidity, because the membrane flexibility of isolated ghosts, measured in a viscosimeter, was normal at all shear rates. Echinocyte formation in patients with DMD is strongly dependent on the techniques applied and difficult to evaluate quantitatively by phase contrast microscopy. Filtration of erythrocyte suspensions seems to be a more reliable, quantitative test for increased erythrocyte vulnerability.


Captured at last: a catalyst-substrate adduct and a Rh-dihydride solvate in the asymmetric hydrogenation by a Rh-monophosphine catalyst.
The mechanism of asymmetric hydrogenation catalyzed by [Rh(NBD)((R)-PhenylBinepine)(2)]SbF(6)1 has been studied by NMR experiments and DFT computations. Either the low-temperature hydrogenation of the catalyst-substrate adduct 4 or the reaction of solvate dihydride 6 with MAC produced the hydrogenation product with over 99% ee (S).


Tryptophan residue of Trp-Ser-X-Trp-Ser motif in extracellular domains of erythropoietin receptor is essential for signal transduction.
The Trp-Ser-X-Trp-Ser motif commonly exists just outside the transmembrane domains of all cytokine receptors so far isolated. The role of this conserved motif in erythropoietin receptor was examined by assessing a series of mutant receptors on erythropoietin-induced signal transduction. Replacement of one of the two conserved Trp residues in the motif to Gly was found to completely abolish the binding of erythropoietin to the receptor and also to lose the ability to transduce the factor-dependent growth signal. While the mutants with one Ser residue converted to Gly or Ala retained full biological activities, the replacement of both conserved Ser residues diminished the functions of the receptor. Furthermore, the receptors lacking a part or all of the Trp-Ser-X-Trp-Ser motif did not respond to erythropoietin. The Trp-Ser-X-Trp-Ser motif, especially Trp residue, located in extracellular domains of the erythropoietin receptor thus appears to play a critical role in receptor-mediated signal transduction.


The effect of lower leg sensory impulses on the force sense of knee extensor muscles in healthy adults: The accuracy of sense-of-force studies.
Producing the target force of a muscle group by using visual feedback and reproducing the same force fully blind are regarded as a common approach for quantifying the sense of force. Force sense error is considered to be the difference between the produced target force and reproduced force. The present study aimed to evaluate the effects of tactile sensory feedback in the lower leg on the perceived magnitude of force sense. In this cross-sectional study, 18 healthy men (mean age 24.31 ± 3.94 years) were selected based on a simple randomized method. First, the quantity of force sense error of the knee extensor muscle group was measured before and after manipulating the tactile inputs of the leg. Then, methods A, B, and C were applied to measure force sense errors. In addition, the tactile impulses were manipulated in methods B and C by placing a piece of thick foam between the distal portion of lower leg among the subjects and the dynamometer. The tactile inputs remained intact during method A. The accuracy of the reproduced target force was significantly affected following the disturbance of tactile inputs in the lower leg in methods B and C, compared to method A (p < 0.05). Altering tactile inputs in the lower leg can affect the force sense of the knee extensor muscles. The received somatosensory inputs across the lower leg can affect the whole process of force perception at this joint.


A cryogenic machine for selective recovery of xenon from breathing system waste gases.
Xenon has many characteristics that make it very attractive as an anesthetic and therapeutic drug. Unfortunately, the supply of xenon is fixed, and therefore reclamation and recovery from even the most efficient breathing circuits is desirable. We built and evaluated a cryogenic device to recover xenon from waste anesthetic gases. Xenon was selectively frozen to -139.2 degrees C from test gas mixtures at ambient pressure (STP). The machine ran on standard 240 V 13 A electrical current without refrigerants that required replenishing, e.g., liquid nitrogen. A wide range of xenon/oxygen mixtures were processed over a range of freezing chamber temperatures. Efflux gas and thawed reclaimed xenon were collected separately. Xenon purity and yield (fraction recovered) were measured and calculated on each occasion. Gas was processed at 300 mL/min, and the operating temperature was -139.2 (0.096) degrees C [Mean (sd)]. Purity and yield were >90% and >70% for gas mixtures containing > or =20% xenon, increasing to >95% and >85%, respectively, with an input gas xenon fraction > or =40%. Efficiency improved linearly with reducing temperature. Xenon of high purity (>90%) and yield (>70%) for such a machine was recovered from all gas mixtures containing > or =20% xenon. The operating temperature of the freezing chamber is a major influence on the efficiency of recovery.


Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth.
Ceramides are known to be key players in intracellular signaling and are involved in apoptosis, cell senescence, proliferation, cell growth and differentiation. They are synthesized by ceramide synthases (CerS). So far, six different mammalian CerS (CerS1-6) have been described. Recently, we demonstrated that human breast cancer tissue displays increased activity of CerS2, 4, and 6, together with enhanced generation of their products, ceramides C(16:0), C(24:0), and C(24:1). Moreover, these increases were significantly associated with tumor dignity. To clarify the impact of this observation, we manipulated cellular ceramide levels by overexpressing ceramide synthases 2, 4 or 6 in MCF-7 (breast cancer) and HCT-116 (colon cancer) cells, respectively. Overexpression of ceramide synthases 4 and 6 elevated generation of short chain ceramides C(16:0), C(18:0) and C(20:0), while overexpression of ceramide synthase 2 had no effect on ceramide production in vivo, presumably due to limited substrate availability, because external addition of very long chain acyl-CoAs resulted in a significant upregulation of very long chain ceramides. We also demonstrated that upregulation of CerS4 and 6 led to the inhibition of cell proliferation and induction of apoptosis, whereas upregulation of CerS2 increased cell proliferation. On the basis of our data, we propose that a disequilibrium between ceramides of various chain length is crucial for cancer progression, while normal cells require an equilibrium between very long and long chain ceramides for normal physiology.


Anorexia nervosa, Felix Deutsch, and the associative anamnesis: a psychosomatic kaleidoscope.
An abiding mystery of the mind-body connection is that it should seem mysterious at all--an indication, perhaps, of how deeply conditioned we have been by "dualism." That doctrine, laid down more than three centuries ago by French philosopher Rene Descartes, sees mind and body as distinct entities, to be treated separately. It became the paradigm for medicine, and still dominates medical thinking.


Osteopenia in inhabitants with renal dysfunction induced by exposure to environmental cadmium.
Bone density was measured in 28 women with itai-itai disease, 92 men and 114 women with cadmium-induced renal dysfunctions and 44 men and 66 women living in the three different non-polluted areas using a microdensitometer. The values of both indices corresponding to cortical width and bone mineral content were significantly lower in itai-itai disease patients than the cadmium-exposed women with renal dysfunctions and the non-exposed subjects. The cadmium-exposed women also showed a decrease in bone density compared with the non-exposed subjects. A significant decrease in bone density was also observed between cadmium-exposed men and the non-exposed subjects, although the difference was not as clear as in the women. The present study indicates that exposure to cadmium could cause marked osteopenia, particularly in the women.


Comparison of Obesity, Physical Activity, and Sedentary Behaviors Between Adolescents With Autism Spectrum Disorders and Without.
Body mass index classification, physical activity (PA), and sedentary behaviors were compared in adolescents with autism spectrum disorder (ASD) to typically developing adolescents. Participants included 42,747 adolescents (ASD, n = 915) from the 2011-2012 National Survey of Children's Health. After controlling for covariates, adolescents were more likely to be overweight and obese, and less likely to engage in regular PA versus typically developing adolescents (p's < 0.05). Increased odds for overweight and obesity were attenuated after adjustment for PA. Higher autism severity was associated with increased odds of overweight and obesity and decreased odds of PA, sport, and club participation. These findings suggest adolescents with ASD are in need of targeted programs to decrease obesity and increase physical activity.


Surgical patient education related to smoking.
Estimates indicate that one million patients who smoke present annually in the United States for some form of surgical intervention. Smoking is a known cause of respiratory complications, hemodynamic fluctuations, and delayed wound healing. A literature search revealed a small number of available studies that address the education provided to surgical patients who smoke. Information about the effects of smoking on surgical outcomes is not routinely provided to smokers. Determining the best methods by which to provide smoking cessation counseling will help increase patients' chances for a positive surgical outcome.


Cellular and in vivo characterization of the MCR rat mammary tumor model.
The slowly growing, transplantable MCR-83 rat mammary tumor is estrogen-dependent and non-metastasizing. A rapidly growing, estrogen-independent, metastasizing subline (MCR-86) was subsequently isolated in vivo. We have established and characterized cell lines from both MCR rat mammary tumors. MCR cell lines and tumors were studied in vivo and in vitro. Analysis of DNA from tumors and cell lines showed that mutations had not occurred in codons 12, 13 and 61 of the Ha-ras and Ki-ras genes. Additionally, dominant transforming activity could not be detected by DNA transfection using NIH 3T3 focus-forming assay. No gene amplification was detected for either the EGF-receptor or c-erbB-2 genes. Differences in the tyrosine phosphorylation patterns were found between the 2 MCR cell lines. Addition of serum to starved cells resulted in the tyrosine phosphorylation of a 120-kDa protein, which was elevated in the MCR-86. The lack of ras activation in the MCR tumors differentiates this model from the widely studied, chemically induced rodent mammary tumors. In addition, the differences in the cellular phosphotyrosine patterns between MCR-83 and MCR-86 suggests the occurrence of alterations in signalling pathways that involve tyrosine protein kinases.


Flavonoid Nobiletin Attenuates Cyclophosphamide-Induced Cystitis in Mice through Mechanisms That Involve Inhibition of IL-1β Induced Connexin 43 Upregulation and Gap Junction Communication in Urothelial Cells.
Bladder inflammatory diseases cause various urinary symptoms, such as urinary frequency and painful urination, that impair quality of life. In this study, we used a mouse model of cyclophosphamide (CYP)-induced bladder inflammation and immortalized human urothelial (TRT-HU1) cells to explore the preventive potential of nobiletin (NOB), a polymethoxylated flavone enriched in citrus fruit peel, and investigate its mechanism of action in the bladder. Prophylaxis with PMF90 (60% NOB) attenuated the development of bladder inflammation and urinary symptoms in CYP-treated mice. PMF90 also reduced the upregulation of connexin 43 (Cx43), a major component of gap junction channels, in the bladder mucosa of CYP-treated mice. Stimulation of TRT-HU1 cells with the pro-inflammatory cytokine IL-1β increased Cx43 mRNA and protein expression and enhanced gap junction coupling-responses that were prevented by pre-treatment with NOB. In urothelium-specific Cx43 knockout (uCx43KO) mice, macroscopic signs of bladder inflammation and changes in voiding behavior induced by CYP treatment were significantly attenuated when compared to controls. These findings indicate the participation of urothelial Cx43 in the development of bladder inflammation and urinary symptoms in CYP-treated mice and provide pre-clinical evidence for the preventive potential of NOB through its anti-inflammatory effects on IL-1β signaling and urothelial Cx43 expression.


A meta-analysis of abnormal β-catenin immunohistochemical expression as a prognostic factor in lung cancer: location is more important.
The aim of the study was to evaluate the effect of β-catenin immunohistochemical expression on the prognosis of lung cancer. We searched Pubmed and Embase to identify eligible studies. The enrolled references were between January 1985 and January, 2015, with no lower date limit. The citation lists associated with the studies were used to identify additional eligible studies. The data of β-catenin immunohistochemical expression, clinical features and survival in each eligible article were recorded and analyzed as hazard ratio (HR) and odd ratio (OR). A total of 15 studies were identified and comprised 3404 cases. β-catenin expression was not significantly correlated with poor overall survival (OS) in lung cancer patients (HR 0.79, 95 % CI 0.47-1.34), but showed a significant degree of heterogeneity (I (2) = 95 %, P < 0.0001). Subgroup analysis indicated that accumulation in the nucleus or loss of membrane significantly influences the survival of lung cancer patients independently. But, the result indicated that β-catenin expression was not associated with clinicopathological features such as TNM stage (OR 1.22, 95 % CI 0.69-2.14), T stage (OR 0.86, 95 % CI 0.63-1.17), lymph node metastasis (0.85, 95 % CI 0.41-1.78), distant metastasis (OR 0.82, 95 % CI 0.31-2.18), grade of differentiation (OR 0.92, 95 % CI 0.47-1.80), or vascular invasion (OR 0.99, 95 % CI 0.04-24.10). Abnormal β-catenin immunohistochemical expression might be associated with tumor progression and could be a predictive factor of poor prognosis in patients with lung cancer based on more precise evaluation.


Status epilepticus following local anesthesia in a previously healthy adult.
Local anesthesia could result in lethal complications if injected in highly vascularized area. Dentist should take care to avoid such complications. We present a case of 15 year old girl with a coma following convulsive status epilepticus which developed after inferior alveolar nerve blockade by a dentist. The patient was admitted to the intensive care unit ICU and recovered within several days. This case is reported to tell both of dentists and medical staff that although it is uncommon, such complications of local anesthesia should be in mind to be avoided and managed promptly if happened.


Non-steroidal anti-inflammatory drug (NSAID)-induced colonic strictures and perforation: a case report.
Although non-steroidal anti-inflammatory drug-induced colopathy is well described, colonic perforations complicating non-steroidal anti-inflammatory drug intake are rare. We report a patient with rheumatoid arthritis who was on long-term diclofenac and presented with early colonic stricture formation and a caecal perforation, which to the best of our knowledge, has only been reported once before. It is important to suspect this diagnosis in patients on non-steroidal anti-inflammatory drug therapy who present with an acute abdomen.


Correlation between high-resolution computed tomography and galactomannan antigenemia in adult hematologic patients at risk for invasive aspergillosis.
To analyse the predominant radiological pattern of pulmonary lesions in adult hematologic patients at risk for invasive aspergillosis (IA) together with the results of serial serum Aspergillus galactomannan antigen testing (GM). In a prospective study for patients at high risk of aspergillus pulmonary infection, serum GM were performed 2-3 times per week during the periods of high risk for IA and high-resolution CT (HRCT) was performed in case of abnormal chest X-ray (CXR) and/or persistent fever after 5 days of antibiotic treatment. Changes on HRCT scan were classified as airway IA and angioinvasive IA. IA was classified as proven or probable in accordance with the definitions stated by the European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC-MS). Positive GM testing was not considered as microbiological criterion. 38 hematological patients were diagnosed of probable (n=28) or proven (n=10) IA. 55% patients had a neutrophil count less than 500 mm(-3) (n=21), and 37% patients > or =2 risk factors for IA. All probable IA were diagnosed by bronchoalveolar lavage (BAL). Proven IA was reached by positive histopathologic and culture results of samples obtained by autopsy (n=4), percutaneous (n=3) or transbronchial biopsy (n=3). 18 patients had airway IA, and 60% had a GM level > or =1.5. 20 patients were diagnosed of angioinvasive IA from which 80% had a GM level > or =1.5. Serum GM levels may be lower in patients with airway IA than in those with an angioinvasive form. HRCT and serum GM are complementary tests in the diagnosis of IA.


The RNA-binding protein Snd1/Tudor-SN regulates hypoxia-responsive gene expression.
Snd1 is an evolutionarily conserved RNA-binding protein implicated in several regulatory processes in gene expression including activation of transcription, mRNA splicing, and microRNA decay. Here, we have investigated the outcome of Snd1 gene deletion in the mouse. The knockout mice are viable showing no gross abnormalities apart from decreased fertility, organ and body size, and decreased number of myeloid cells concomitant with decreased expression of granule protein genes. Deletion of Snd1 affected the expression of relatively small number of genes in spleen and liver. However, mRNA expression changes in the knockout mouse liver showed high similarity to expression profile in adaptation to hypoxia. MicroRNA expression in liver showed upregulation of the hypoxia-induced microRNAs miR-96 and -182. Similar to Snd1 deletion, mimics of miR-96/182 enhanced hypoxia-responsive reporter activity. To further elucidate the function of SND1, BioID biotin proximity ligation assay was performed in HEK-293T cells to identify interacting proteins. Over 50% of the identified interactors were RNA-binding proteins, including stress granule proteins. Taken together, our results show that in normal growth conditions, Snd1 is not a critical factor for mRNA transcription in the mouse, and describe a function for Snd1 in hypoxia adaptation through negatively regulating hypoxia-related miRNAs and hypoxia-induced transcription consistent with a role as stress response regulator.


Stunting and Anemia in Children from Urban Poor Environments in 28 Low and Middle-income Countries: A Meta-analysis of Demographic and Health Survey Data.
Child malnutrition remains a global concern with implications not only for children's health and cognitive function, but also for countries' economic growth. Recent reports suggest that global nutrition targets will not be met by 2025. Large gaps are evident between and within countries. One of the largest disparities in child malnutrition within counties is between urban and rural children. Large disparities also exist in urban areas that have higher rates of child malnutrition in the urban poor areas or slums. This paper examines stunting and anemia related to an urban poverty measure in children under age 5 in 28 low and middle-income countries with Demographic and Health Survey data. We used the United Nations Human Settlements Programme (UN-HABITAT) definition to define urban poor areas as a proxy for slums. The results show that in several countries, children had a higher risk of stunting and anemia in urban poor areas compared to children in urban non-poor areas. In some countries, this risk was similar to the risk between the rural and urban non-poor. Tests of heterogeneity showed that these results were not homogeneous across countries. These results help to identify areas of greater disadvantage and the required interventions for stunting and anemia.


Multiblock polymers: panacea or Pandora's box?
Advances in synthetic polymer chemistry have unleashed seemingly unlimited strategies for producing block polymers with arbitrary numbers (n) and types (k) of unique sequences of repeating units. Increasing (k,n) leads to a geometric expansion of possible molecular architectures, beyond conventional ABA-type triblock copolymers (k = 2, n = 3), offering alluring opportunities to generate exquisitely tailored materials with unparalleled control over nanoscale-domain geometry, packing symmetry, and chemical composition. Transforming this potential into targeted structures endowed with useful properties hinges on imaginative molecular designs guided by predictive theory and computer simulation. Here, we review recent developments in the field of block polymers.


Unit-based clinical and organizational indicators for residential treatment.
A psychiatric residential treatment center has developed a system for monitoring and evaluating the quality of care provided. Administrators of the nine residential treatment units of the Devereux Foundation's Edward L. French Center use a standard form to report on a number of uniform clinical and organizational indicators. The data are evaluated monthly by the utilization review committee, quarterly by the quality assurance committee, and semiannually and annually by other administrators, committees, and the foundation's board of trustees. This process has been an effective mechanism for identifying trends and patterns in client care, for improving client care, and for providing clues to relationships among organizational problems.


The unfolded protein response: controlling cell fate decisions under ER stress and beyond.
Protein-folding stress at the endoplasmic reticulum (ER) is a salient feature of specialized secretory cells and is also involved in the pathogenesis of many human diseases. ER stress is buffered by the activation of the unfolded protein response (UPR), a homeostatic signalling network that orchestrates the recovery of ER function, and failure to adapt to ER stress results in apoptosis. Progress in the field has provided insight into the regulatory mechanisms and signalling crosstalk of the three branches of the UPR, which are initiated by the stress sensors protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α) and activating transcription factor 6 (ATF6). In addition, novel physiological outcomes of the UPR that are not directly related to protein-folding stress, such as innate immunity, metabolism and cell differentiation, have been revealed.


In vitro activities of the des-fluoro(6) Quinolone BMS-284756 against aerobic and anaerobic pathogens isolated from skin and soft tissue animal and human bite wound infections.
BMS-284756, a new des-fluoro(6) quinolone, was very active against 240 aerobic and 180 anaerobic isolates from bite victims. It inhibited 403 of 420 (96%) isolates, including those of Moraxella spp., CDC group EF-4, and Eikenella corrodens at < or = 2 microg/ml and those of all Pasteurella spp. and Bergeyella zoohelcum at < or = 0.015 microg/ml. Fusobacterium russii and 6 of 11 Fusobacterium nucleatum isolates of animal bite origin were resistant, but isolates of human bite origin were susceptible, which suggests that they were of a different subspecies.


Premixed vs Compounded Parenteral Nutrition: Effects of Total Parenteral Nutrition Shortage on Clinical Practice.
Drug shortages continue to impact our patients with intestinal failure and their ability to receive nutrition. ASPEN guidelines address the management of certain shortages in compounded total parenteral nutrition (TPN); however, some institutions have utilized premixed total parenteral nutrition (pTPN) in place of TPN. Premixed TPN appears to be as safe, if not safer, as compounded TPN when comparing the risk of bloodstream infection. However, there is an increased use of supplemental electrolytes to meet patient needs. Cost-effectiveness depends on multiple factors and should be evaluated by each institution when considering the use of TPN. In light of the published information on the use of pTPN compared to TPN, institutions and nutrition clinicians should consider their current practice and opportunities to consider when pTPN may be beneficial for their patients, not only from a safety perspective, but also considering cost savings. However, close monitoring and individual patient needs should be considered as these formulas may not meet all patient nutritional and electrolyte needs.


Cholesterol, GM1, and autism.
Disruption of cholesterol metabolism has been hypothesized to contribute to dementia, possibly due to its role in maintaining membrane fluidity as well as the integrity of lipid rafts. Previously, we reported an apparent inverse relationship between membrane cholesterol levels and those of GM1, another lipid that can be found in rafts. This paper describes the observation that red blood cell (RBC) membranes isolated from blood drawn from children diagnosed with autism have on the average significantly less cholesterol and significantly more GM1 than RBC membranes isolated from blood obtained from control children. While cholesterol in the circulation does not cross the blood brain barrier, a generalized defect in its synthesis could affect its concentration in the central nervous system and that, coupled with a change in ganglioside expression, could contribute to development of the behaviors associated with autism.


β-D-Arabinosyl 1-C-sulfonic acid.
A short synthetic route to β,d-arabinofuranosyl 1-C-sulfonic acid (7), a possible biomimetic for the arabinofuranosyl anomeric phosphate, is described. The furanosyl 1-C-sulfonate was prepared by buffered DMDO oxidation of an S-acetyl-1-thio-β-arabinofuranose derivative. Deprotection under mild conditions allowed isolation of the free sulfonic acid without desulfonylation.


Adaptation of a prefabricated post to dentin.
The adaptation of an inventive prefabricated post and core to dentin is presented as part of a series of research reports. The authors suggest that the imaginative design of the split shaft and its telescoping or collapsible apex reduces stress and the finely threaded shaft improves retention.


Lipoprotein assembly. Apolipoprotein B size determines lipoprotein core circumference.
Apolipoprotein B (apoB) is an essential structural protein for the two triglyceride-rich lipoproteins synthesized by humans: chylomicrons and very low density lipoproteins. Although much is known about the role of apoB in clearance of lipoproteins from the circulation, relatively little is known about its role in the assembly of nascent lipoproteins. Therefore, we have investigated the relationship between the length of various N-terminal apoB fragments and the characteristics of the lipoproteins with which these fragments were associated. After the addition of puromycin, HepG2 cells secreted a discrete series of C-terminally truncated apoB fragments on lipoprotein particles including apoB25, apoB29, apoB31, apoB33, apoB36, apoB38, apoB42, apoB45, apoB49, apoB51, apoB55, apoB70, and apoB80. Also, using plasmids encoding apoB26, apoB33, apoB37, apoB42, and apoB48, C-terminally truncated apoB fragments were expressed and secreted after transient transfection of HepG2 cells. Lipoproteins bearing the metabolically labeled apoB fragments were isolated from the cell culture media and characterized in terms of size, density, flotation coefficient, and composition. Lipoprotein radii, calculated from their flotation coefficients and buoyant densities, were used to derive the circumference of the non-polar core of each lipoprotein species. When plotted as a function of apoB size, core circumference defined a straight line of near-zero intercept. The slope of this line was approximately 1 A of core circumference/1 kDa of apoB molecular mass. A model for the mechanism of lipoprotein assembly in HepG2 cells, consistent with the concept that apoB size determines lipoprotein core circumference, is proposed.