Morphological brain plasticity induced by musical expertise is accompanied by modulation of functional connectivity at rest.
The aim of this study was to explore whether musical practice-related gray matter increases in brain regions are accompanied by modifications in their resting-state functional connectivity. 16 young musically experienced adults and 17 matched nonmusicians underwent an anatomical magnetic resonance imaging (MRI) and a resting-state functional MRI (rsfMRI). A whole-brain two-sample t test run on the T1-weighted structural images revealed four clusters exhibiting significant increases in gray matter (GM) volume in the musician group, located within the right posterior and middle cingulate gyrus, left superior temporal gyrus and right inferior orbitofrontal gyrus. Each cluster was used as a seed region to generate and compare whole-brain resting-state functional connectivity maps. The two clusters within the cingulate gyrus exhibited greater connectivity for musicians with the right prefrontal cortex and left temporal pole, which play a role in autobiographical and semantic memory, respectively. The cluster in the left superior temporal gyrus displayed enhanced connectivity with several language-related areas (e.g., left premotor cortex, bilateral supramarginal gyri). Finally, the cluster in the right inferior frontal gyrus displayed more synchronous activity at rest with claustrum, areas thought to play a role in binding sensory and motor information. We interpreted these findings as the consequence of repeated collaborative use in general networks supporting some of the memory, perceptual-motor and emotional features of musical practice.


Genome-wide transcriptional analysis of T cell activation reveals differential gene expression associated with psoriasis.
Psoriasis is a chronic autoimmune disease in which T cells have a predominant role in initiating and perpetuating the chronic inflammation in skin. However, the mechanisms that regulate T cell activation in psoriasis are still incompletely understood. The objective of the present study was to characterize the main genetic pathways associated with T cell activation in psoriasis. Gene expression profiles from in vitro activated T cells were obtained from 17 psoriasis patients and 7 healthy controls using Illumina HT-12 v4 microarrays. From a total of 47,321 analyzed transcripts, 42 genes were found to be differentially expressed between psoriasis and controls (FDR p-value < 0.1, absolute fold-change > 1.2). Using an independent cohort of 8 patients and 8 healthy controls we validated the overexpression of SPATS2L (p-value =0.0009) and KLF6 (p-value =0.0012) genes in activated T cells from psoriasis patients. Using weighted correlation analysis we identified SPATS2L and KLF6 coexpression networks, which were also significantly associated with psoriasis (p-value < 0.05). Gene Ontology analysis allowed the identification of several biological processes associated with each coexpression network. Finally, using Gene Set Enrichment Analysis over the global T cell transcriptome we also found additional genetic pathways strongly associated with psoriasis (p-value < 0.0001). This study has identified two new genes, SPATS2L and KLF6, strongly associated with T cell activation in psoriasis. Functional analyses of the gene expression profiles also revealed new biological processes and genetic pathways associated with psoriasis. The results of this study provide an important insight into the biology of this common chronic inflammatory disease.


Effect of the thromboxane synthetase inhibitor UK-37,248 (dazoxiben) upon platelet aggregation, coronary artery thrombosis and vascular reactivity.
The effects of the thromboxane synthetase inhibitor dazoxiben on thrombus formation, platelet aggregation and vascular reactivity have been studied in open-chest anesthetized dogs. Dazoxiben at 4 mg/kg prolonged the time required for occlusive thrombi to form at sites of electrical injury to the left circumflex coronary artery by 3-fold and also decreased venous thromboxane B2 concentrations by 45% within 30 min. The progressive decline in flow observed during thrombogenesis was interrupted by rapid and spontaneous reactive hyperemic responses, the frequency and number of which were diminished by dazoxiben. In vitro platelet aggregation responses to ADP and collagen determined during the course of these experiments also were inhibited to a variable extent. The effect of dazoxiben on coronary vascular responsiveness was examined using an in situ constant pressure perfused coronary vascular bed. Although basal left circumflex coronary blood flow was unaffected by the drug, vasodilation induced by arachidonic acid, but not prostacyclin, was potentiated. The data suggest that dazoxiben possesses in vivo antithrombotic activity due to modification of platelet reactivity and that it can enhance coronary vasodilator responses to exogenously administered arachidonic acid.


Presence of pRI1: a small cryptic mobilizable plasmid isolated from Enterococcus faecium of human and animal origin.
This study focused on the molecular characterization of a small cryptic, mobilizable plasmid (6038 bp) sequenced from an E. faecium 9631160-1 of poultry origin. Sequence analysis of pRI1 revealed seven open reading frames. pRI1 contained an IS 100% identical to ISEfa4. This insertion element disrupted a putative mobilization gene (mobA) which presented 99% similarity to the one described in plasmid pJS42 (NC_010291). pRI1 harbored a cluster of four coding sequences which exhibited a homology to those described in contig 658 (from nucleotide 8940 to nt 10515) of E. faecium DO. In addition, a rep almost identical to the repA from the pEFNP1 and pKQ10 plasmids from E. faecium was also identified. Presence of the pRI1 replication initiation gene (rep) was analyzed in a panel of 159 E. faecium isolates of human and animal origin from different European countries, of which 60 tested positive for the presence of pRI1-rep. Conjugation experiments verified transfer of the pRI1 together with conjugative plasmids harboring resistance to vancomycin and streptogramin. The presence of pRI1 in enterococcal isolates geographically separated and from different origin demonstrates the ability of enterococci to acquire and transfer mobile genetic elements, emphasizing the need for further studies to reveal the meaning and role that these cryptic plasmids play in nature.


Osseointegration improvement by plasma electrolytic oxidation of modified titanium alloys surfaces.
Titanium (Ti) is a material frequently used in orthopedic applications, due to its good mechanical properties and high corrosion resistance. However, formation of a non-adherent fibrous tissue between material and bone drastically could affect the osseointegration process and, therefore, the mechanical stability of the implant. Modifications of topography and configuration of the tissue/material interface is one of the mechanisms to improve that process by manipulating parameters such as morphology and roughness. There are different techniques that can be used to modify the titanium surface; plasma electrolytic oxidation (PEO) is one of those alternatives, which consists of obtaining porous anodic coatings by controlling parameters such as voltage, current, anodizing solution and time of the reaction. From all of the above factors, and based on previous studies that demonstrated that bone cells sense substrates features to grow new tissue, in this work commercially pure Ti (c.p Ti) and Ti6Al4V alloy samples were modified at their surface by PEO in different anodizing solutions composed of H2SO4 and H3PO4 mixtures. Treated surfaces were characterized and used as platforms to grow osteoblasts; subsequently, cell behavior parameters like adhesion, proliferation and differentiation were also studied. Although the results showed no significant differences in proliferation, differentiation and cell biological activity, overall results showed an important influence of topography of the modified surfaces compared with polished untreated surfaces. Finally, this study offers an alternative protocol to modify surfaces of Ti and their alloys in a controlled and reproducible way in which biocompatibility of the material is not compromised and osseointegration would be improved.


Relationships between advanced glycation end products (AGEs), vasoactive substances, and vascular function.
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key role in the development and progression of vasculopathies. Abnormal vascular responsiveness to vasoactive substances including vasoconstrictors and vasodilators has been observed in various arteries in diseases including diabetes, hypertension, chronic kidney diseases, and atherosclerosis. Several substances derived from ECs tightly control vascular function, such as endothelium-derived relaxing and contracting factors, and it is known that abnormal vascular signaling of these endothelium-derived substances is often observed in various diseases. Derangement of signaling in VSMCs and altered function influence vascular reactivity to vasoactive substances and tone, which are important determinants of vascular resistance and blood pressure. However, understanding the molecular mechanisms underlying abnormalities of vascular functions in pathological states is difficult because multiple substances interact in the development of these processes. Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to vascular dysfunction, which in turn cause the development of several diseases including diabetes, hypertension, stroke, and atherosclerosis. A growing body of evidence suggests that AGEs could affect these cells and modulate vascular function. This study is focused on the link between AGEs and functions of ECs and VSMCs, particularly the modulative effects of AGEs on vascular reactivities to vasoactive substances.


Coenzyme Q10 supplementation and diastolic heart functions in hemodialysis patients: a randomized double-blind placebo-controlled trial.
Coenzyme Q10 (CoQ10) supplementation has been shown to improve diastolic heart function in various patient cohorts. Systolic and diastolic dysfunctions are common in patients with end-stage renal disease. Favorable effects of CoQ10 on cardiac functions are yet to be seen in hemodialysis patients. We aimed to evaluate effect of CoQ10 supplementation on diastolic function in a cohort of maintenance hemodialysis patients. This was a prospective, double-blind, placebo-controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d during the 8 weeks in each phase, with a 4-week washout period. Participants underwent conventional and tissue Doppler echocardiography before and after each study phase. Parameters characterizing left ventricle diastolic function and other standard echocardiographic measurements were recorded. Twenty-eight patients were randomized, but 22 patients completed study protocol. Intraventricular septum (IVS) thickness and left ventricle mass were significantly decreased in CoQ10 group (P = 0.03 and P = 0.01, respectively). Myocardial peak systolic and early diastolic velocities derived from IVS were significantly increased (P = 0.048 and P = 0.04, respectively). Isovolumetric relaxation time and E/Em ratio calculated for IVS also significantly reduced in CoQ10 group (p = 0.02 and p = 0.04, respectively). There was no significant difference in any of the studied echocardiographic parameters in placebo group. The results of this study showed that CoQ10 supplementation did not significantly improved diastolic heart functions compared with placebo in maintenance hemodialysis patients.


Lipooligosaccharide locus class of Campylobacter jejuni: sialylation is not needed for invasive infection.
Campylobacter jejuni is a highly diverse enteropathogen that is commonly detected worldwide. It can sometimes cause bacteraemia, but the bacterial characteristics facilitating bloodstream infection are not known. A total of 73 C. jejuni isolates, consecutively collected from blood-borne infections during a 10-year period all over Finland and for which detailed clinical information of the patients were available, were included. We screened the isolates by PCR for the lipooligosaccharide (LOS) locus class and for the presence of the putative virulence genes ceuE, ciaB, fucP, and virB11. The isolates were also tested for γ-glutamyl transpeptidase production. The results were analysed with respect to the clinical characteristics of the patients, and the multilocus sequence types (MLSTs) and serum resistance of the isolates. LOS locus classes A, B, and C, which carry genes for sialylation of LOS, were detected in only 23% of the isolates. These isolates were not more resistant to human serum than those with the genes of non-sialylated LOS locus classes, but were significantly more prevalent among patients with underlying diseases (p 0.02). The fucose permease gene fucP was quite uncommon, but was associated with the isolates with the potential to sialylate LOS (p <0.0001). LOS locus classes and some of the putative virulence factors were associated with MLST clonal complexes. Although some of the bacterial characteristics studied here have been suggested to be important for the invasiveness of C. jejuni, they did not explain why the clinical isolates in the present study were able to cause bacteraemia.


Granulomatous reaction to hyaluronic acid filler material in oral and perioral region: A case report and review of literature.
The use of cosmetic fillers agents in orofacial region has become more often used for esthetic concern. Although adverse effects are rare, some patients may develop foreign body reaction to such fillers. Hyaluronic acid (HA) is a biomaterial in the spotlight, because it is normally present in several tissues of human body. The aim of this study was to report a case of a 54-year-old white woman with granulomatous reaction to the HA located in the lips. In addition, a review of the English-language literature of all previously described cases of this condition in oral and perioral region was performed. The location, clinical features, symptoms, time between injection and reaction, type of treatment and treatment outcome of 17 cases were summarized. The clinical and histopathological examination along with a detailed history about this condition is very important to management of patients with nodular lesions in maxillofacial region.


Long-term treatment of benign prostatic hyperplasia with alfuzosin: a 12-18 month assessment. BPHALF Group.
In order to assess the efficacy and safety of alfuzosin, an alpha-1 blocker, in symptomatic patients with benign prostatic hyperplasia (BPH), 131 patients who had completed a 6-month placebo-controlled trial conducted on parallel groups entered a 12-month open study; 122 patients were treated with alfuzosin for 12 months and 56 patients for 18 months. After 12 months, all obstructive and irritative symptoms assessed according to the Boyarsky scale were significantly improved, as were peak flow rates in obstructed patients and mean flow rates and residual urine in the whole population. Voiding symptoms showed sustained improvement after treatment for 12 to 18 months. Only 5.3% of patients experienced vasodilatory side effects, none of which led to withdrawal from the study. No side effect related to long-term administration was reported. Alfuzosin has a beneficial effect on voiding symptoms in patients with BPH and can be safely used in long-term administration.


[Comparative experimental study of microsurgical nerve suture. I. Immediate suture and delayed suture].
Impressed by multiplicity of theories and conceptions concerning nerve surgery and by the difficulty to draw grouded conclusions from the different and contradictory work available from the litterature on the subject, the author makes a revision of the biology of the nerve, to be used as a point of departure for investigation. Based on the fact that protheosynthesis capacity of the nerve cell is known to be at its top value during the first week after the lesion of the nerve, the author endeavours to compare immediate suture with delayed suture. This comparative study is based both on electrophysiological and histological data and show clearly enough the real advantage of trying nerve reconstruction as early as possible, to avoid progression of devitalisation and invasion by fibrosis of both stumps. The surgical procedures are made with the help of the operating microscope and the same technique is used in both groups.


Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size.
Clathrin-mediated endocytosis (CME) is the major mechanism for internalization in mammalian cells. CME initiates by recruitment of adaptors and clathrin to form clathrin-coated pits (CCPs). Nearly half of nascent CCPs abort, whereas others are stabilized by unknown mechanisms and undergo further maturation before pinching off to form clathrin-coated vesicles (CCVs). Phosphatidylinositol-(4,5)-bisphosphate (PIP(2)), the main lipid binding partner of endocytic proteins, is required for CCP assembly, but little is currently known about its contribution(s) to later events in CCV formation. Using small interfering RNA (siRNA) knockdown and overexpression, we have analyzed the effects of manipulating PIP(2) synthesis and turnover on CME by quantitative total internal reflection fluorescence microscopy and computational analysis. Phosphatidylinositol-4-phosphate-5-kinase cannot be detected within CCPs but functions in initiation and controls the rate and extent of CCP growth. In contrast, the 5'-inositol phosphatase synaptojanin 1 localizes to CCPs and controls early stabilization and maturation efficiency. Together these results suggest that the balance of PIP(2) synthesis in the bulk plasma membrane and its local turnover within CCPs control multiple stages of CCV formation.


Vaginal tolerance of CT based image-guided high-dose rate interstitial brachytherapy for gynecological malignancies.
Purpose of this study was to identify predictors of vaginal ulcer after CT based three-dimensional image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancies. Records were reviewed for 44 female (14 with primary disease and 30 with recurrence) with gynecological malignancies treated with HDR-ISBT with or without external beam radiation therapy. The HDR-ISBT applicator insertion was performed with image guidance by trans-rectal ultrasound and CT. The median clinical target volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy, doses of external-beam radiation therapy and brachytherapy were combined). For re-irradiation patients, median EQD2 of D(2cc) for rectum and bladder, D0.5cc, D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was 91.1 Gy, 100.9 Gy, 260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For those without prior radiation therapy, median EQD2 of D(2cc) for rectum and bladder, D(0.5cc), D(1cc), D(2cc), D(4cc), D(6cc) and D(8cc) for vaginal wall was 56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy, respectively. Among five patients with vaginal ulcer, three had prior pelvic radiation therapy in their initial treatment and three consequently suffered from fistula formation. On univariate analysis, re-irradiation and vaginal wall D(2cc) in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025, respectively). The ROC analysis revealed that vaginal wall D(2cc) is the best predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the patients with vaginal wall D(2cc) in EQD2 equal to or less than 145 Gy and over 145 Gy were 3.7% and 23.5%, respectively, with a statistically significant difference (p = 0.026). Re-irradiation and vaginal D(2cc) is a significant predictor of vaginal ulcer after HDR-ISBT for gynecologic malignancies. Three-dimensional image-guided treatment planning should be performed to ensure adequate target coverage while minimizing vaginal D(2cc) in order to avoid vagina ulcer.


[Comparative study of the biological utilization of beta-carotene from synthetic and natural sources in rats].
The purpose of this study was to evaluate the change in concentration of retinol and beta-carotene (BC) in blood serum and liver tissue of rats, after supplementation with synthetic BC and commonly consumed carotenoid-rich vegetables (carrot and spinach). Weanling male Wistar rats were randomly assigned in four groups of 16 rats each. The four groups of rats were supplemented according to the following feeding treatments: 1) Control group (0G), 0.2 mL corn oil; 2) Pure BC group (BCG), 60 micrograms RE in 0.2 mL corn oil; 3) Carrot group (CG), 60 micrograms RE in 0.2 mL corn oil; 4) Spinach group (SG), 60 micrograms RE in 0.2 mL corn oil. Analysis of retinol and BC contents in serum and liver was performed by HPLC procedures. The variance analysis showed no significant differences (a = 0.05) in the increase of weight of the animals and in the increase of retinol and BC levels in serum and in liver of the four treatments during the four weeks of supplementation. The correlation analysis between levels of retinol and BC in serum and in liver showed no relation between these two parameters. A regression analysis of liver BC levels in the four treatments showed the following slopes of the regression lines: BCG, 0.909; CG, 0.451; SG, 0.444, and 0G, 0.203. These results indicate that the highest BC absorption was in the BCG treatment, whereas the BC absorption in the CG and SG treatments was approximately one half.


Dynamic isomiR regulation in Drosophila development.
Several recent reports have demonstrated that microRNAs (miRNAs) can exhibit heterogeneous ends and post-transcriptional nontemplate 3' end additions of uridines or adenosines. Using two small RNA deep-sequencing data sets, we show here that these miRNA isoforms (isomiRs) are differentially expressed across Drosophila melanogaster development and tissues. Specifically, we demonstrate that: (1) nontemplate nucleotide additions of adenosines to miRNA 3' ends are highly abundant in early development; (2) a subset of miRNAs with nontemplate 3' Us are expressed in adult tissues; and (3) the size of at least eight "mature" (unmodified) miRNAs varies in a life-cycle or tissue-specific manner. These results suggest that subtle variability in isomiR expression, which is widely thought to be the result of inexact Dicer processing, is regulated and biologically meaningful. Indeed, a subset of the miRNAs enriched for 3' adenosine additions during early embryonic development, including miR-282 and miR-312, show enrichment for target sites in developmental genes that are expressed during late embryogenesis, suggesting that nontemplate additions increase miRNA stability or strengthen miRNA:target interactions. This work suggests that isomiR expression is an important aspect of miRNA biology, which warrants further investigation.


Bone mineral density among elderly patients with chronic obstructive pulmonary disease patients in India.
Osteoporosis is one of the major extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), which limits the physical activity. The present study was undertaken to study the bone mineral density (BMD) and osteoporosis in the elderly COPD patients. This was a cross-sectional study carried out among elderly COPD patients. After a detailed clinical history spirometry was done to stage the severity of COPD. DEXA scan of the lumbar spine was performed using bone densitometer to determine osteoporosis. Statistical analysis was based on Chi-square test. Risk factors were identified by univariate and multivariate logistic regression analysis. A total of 70 elderly COPD patients were included. Fourty-six patients (65.7%) had osteoporosis and 13 (18.6%) had osteopenia. Majority of the osteoporosis patients had stage III or stage IV COPD disease (77.2%). As the severity grade of COPD increased, the risk of osteoporosis also increased. Also, with the increasing severity of COPD, BMD decreased. Patients with lower body mass index (BMI) had higher prevalence of osteoporosis (45.7%). Using multivariate regression analysis, stage IV COPD, number of acute exacerbations >3 and steroid cumulative dose >1000 mg were independent risk factors for osteoporosis in elderly COPD patients. The prevalence of osteoporosis was 65.7%, and 18.6% had osteopenia. Stage III and IV patients had significantly lower BMI in elderly COPD patients. High clinical suspicion and early diagnosis and treatment are required in the evaluation of osteoporosis in elderly COPD patients.


MiSight Assessment Study Spain: A Comparison of Vision-Related Quality-of-Life Measures Between MiSight Contact Lenses and Single-Vision Spectacles.
Recent research has shown that concentric contact lenses (CLs) can be a way to control the progression of myopia. The purpose of the current study was to compare vision-related quality-of-life measures in children wearing distance single-vision (SV) spectacles versus MiSight CLs, a specific concentric design for myopia control. Subjects aged 8 to 12 with myopia from -0.75 to -4.00 diopters (D) of sphere and astigmatism less than 1.00 D of cylinder were allocated to the lenses study group (MiSight) or control group (SV). A Pediatric Refractive Error Profile (PREP) questionnaire was administered at 12- and 24-month intervals to evaluate children's perceptions in overall vision, near vision, far distance vision, symptoms, appearance, satisfaction, activities, academic performance, handling, and peer perceptions. The mean score of all items was calculated as the overall score. In total, 74 children completed the study: n=41 in the MiSight group and n=33 in the SV group. In the MiSight group, the ratings at 12 and 24 months for appearance, satisfaction, effect on activities, handling, and peer perceptions were significantly better than those given by children in the SV group (P<0.001), as was the overall score. However, near vision was significantly better in the SV group at both 12 and 24 months (P<0.001). MiSight CL wear for controlling myopia improves vision-related quality of life in children when compared with spectacle wear.


Cell death during luteal regression in the marmoset monkey (Callithrix jacchus).
The mechanism controlling luteal regression in primates is unknown but may involve cell death by apoptosis. Marmoset ovaries containing corpora lutea were studied at different stages of the normal ovarian cycle. Two additional groups of animals underwent induced luteolysis with either the prostaglandin F2 alpha analogue, cloprostenol, or the GnRH antagonist, antarelix, at the mid-luteal phase. Apoptosis in ovarian sections was estimated both by counting the number of cells exhibiting morphological features of apoptosis and by in situ labelling the 3' ends of the DNA fragments with digoxigenin-11-dUTP. Apoptosis was found to be significantly increased in corpora lutea in the early follicular phase (equivalent to the later stage of luteal lifespan) compared with the mid-luteal phase corpora lutea, as judged by either computerized morphometry or 3' end labelling. Apoptosis was also increased by the administration of either cloprostenol or antarelix when using the 3' end labelling end point, but only after cloprostenol when using computerized morphometry. A further form of cell death, characterized by the formation of cytoplasmic vacuoles, was also observed in corpora lutea undergoing both induced and spontaneous regression. These results demonstrate that apoptosis within the primate corpus luteum is increased in both physiological and induced luteal regression. In addition, they show that an alternative form of cell death is involved in both spontaneous and induced luteal regression, although the relative importance of the two mechanisms remains to be determined.


Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH).
Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.


Red Blood Cells' Area Deformation as the Origin of the Photoplethysmography Signal.
The origin of the photoplethysmography (PPG) signal is a debatable topic, despite plausible models being addressed. One concern revolves around the correlation between the mechanical waveform's pulsatile nature and the associated biomechanism. The interface between these domains requires a clear mathematical or physical model that can explain physiological behavior. Describing the correct origin of the recorded optical waveform not only benefits the development of the next generation of biosensors but also defines novel health markers. In this study, the assumption of a pulsatile nature is based on the mechanism of blood microcirculation. At this level, two interconnected phenomena occur: variation in blood flow velocity through the capillary network and red blood cell (RBC) shape deformation. The latter effect was qualitatively investigated in synthetic capillaries to assess the experimental data needed for PPG model development. Erythrocytes passed through 10 µm and 6 µm microchannel widths with imposed velocities between 50 µm/s and 2000 µm/s, according to real scenarios. As a result, the length and area deformation of RBCs followed a logarithmic law function of the achieved traveling speeds. Applying radiometric expertise on top, mechanical-optical insights are obtained regarding PPG's pulsatile nature. The mathematical equations derived from experimental data correlate microcirculation physiologic with waveform behavior at a high confidence level. The transfer function between the biomechanics and the optical signal is primarily influenced by the vasomotor state, capillary network orientation, concentration, and deformation performance of erythrocytes.


Regulation of gibberellin 20-oxidase and gibberellin 3beta-hydroxylase transcript accumulation during De-etiolation of pea seedlings.
Gibberellin (GA) 20-oxidase (GA 20-ox) and GA 3beta-hydroxylase (GA 3beta-hy) are enzymes that catalyze the late steps in the formation of active GAs, and are potential control points in the regulation of GA biosynthesis by light. We have investigated the photoregulation of the GA 20-ox and GA 3beta-hy transcript levels in pea (Pisum sativum L.). The GA 20-ox transcript level was higher in light-grown seedlings than in etiolated seedlings, whereas GA 3beta-hy mRNA accumulation was higher in etiolated seedlings. However, transfer of etiolated seedlings to light led to a 5-fold increase in the expression of both transcripts 4 h after transfer. GA 20-ox mRNA accumulation is regulated by both phytochromes A and B. Transfer to light also resulted in a 6-fold decrease in GA(1) levels within 2 h. These results suggest that the light-induced drop in GA(1) level is not achieved through regulation of GA 20-ox and GA 3beta-hy mRNA accumulation. The application of exogenous GA(1) to apical buds of etiolated seedlings prior to light treatments inhibited the light-induced accumulation of both GA 20-ox and GA 3beta-hy mRNA, suggesting that negative feedback regulation is an important mechanism in the regulation of GA 20-ox and GA 3beta-hy mRNA accumulation during de-etiolation of pea seedlings.


Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes.
The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.


Optical properties of mammalian tissue: introduction by the feature editors.
This issue of Applied Optics features twenty-two papers on the optical character of tissue, a topic of growing importance in the life sciences. The papers deal with theory and experiment and are contributed by a core of researchers active in the current development of this relatively new field. The complete description of the tissue's optical properties is fraught with problems due to the extraordinary nature of this difficult, varied, turbid, highly scattering medium. The solution of these optical problems promises important dividends in practical areas, such as cancer treatment and diagnosis.


Observation of periodic orbits on curved two-dimensional geometries.
We measure elastomechanical spectra for a family of thin shells. We show that these spectra can be described by a "semiclassical" trace formula comprising periodic orbits on geodesics, with the periods of these orbits consistent with those extracted from experiment. The influence of periodic orbits on spectra in the case of two-dimensional curved geometries is thereby demonstrated, where the parameter corresponding to Planck's constant in quantum systems involves the wave number and the curvature radius. We use these findings to explain the marked clustering of levels when the shell is hemispherical.


Antimicrobial Susceptibility of Neisseria gonorrhoeae Isolates in Baltimore, Maryland, 2016: The Importance of Sentinel Surveillance in the Era of Multi-Drug-Resistant Gonorrhea.
The increasing rates of gonorrhea infections and the global emergence and spread of multi-drug-resistant Neisseria gonorrhoeae (NG) threaten the successful management of gonorrhea. In the era of nucleic acid amplification tests (NAATs), surveillance projects are urgently needed to monitor prevalence and trends in the antimicrobial susceptibility of NG. In this study, we retrospectively determined the susceptibility profile of NG isolates to previously and currently prescribed antimicrobials. NG isolates collected in Baltimore, Maryland between January and October 2016 were evaluated by the E-test method and/or molecular methods for susceptibility to ceftriaxone, azithromycin, ciprofloxacin, tetracycline, gentamicin, and penicillin. One-hundred and forty-three NG isolates from African-American males (98.6%), primarily heterosexual (88.8%), ranging in age from 15 to 69 years of age were included in the study. Ciprofloxacin resistance was observed in 44.1% of isolates. Plasmid-mediated resistance to penicillin and tetracycline resistance was detected in 22.4% and 10.1% of isolates, respectively. Three isolates (2.1%) displayed high-level resistance to azithromycin (minimum inhibitory concentration (MIC) > 256 μg/mL). Forty-three percent of isolates were resistant or had decreased susceptibility to three antimicrobials (ciprofloxacin, tetracycline, and penicillin). All isolates were susceptible to ceftriaxone and gentamicin. Overall, the epidemiology of antimicrobial resistant NG in Baltimore continues to evolve, and the emergence of azithromycin resistance in this population emphasizes the need for continued sentinel surveillance programs to monitor susceptibility trends and aid in treatment recommendations.


Peroxynitrite Exposure of CXCL12 Impairs Monocyte, Lymphocyte and Endothelial Cell Chemotaxis, Lymphocyte Extravasation in vivo and Anti-HIV-1 Activity.
CXCL12 is a chemotactic cytokine that attracts many different cell types for homeostasis and during inflammation. Under stress conditions, macrophages and granulocytes produce factors such as peroxynitrite as a consequence of their oxidative response. After short incubations of CXCL12 with peroxynitrite, the gradual nitration of Tyr7, Tyr61, or both Tyr7 and Tyr61 was demonstrated with the use of mass spectrometry, whereas longer incubations caused CXCL12 degradation. Native CXCL12 and the nitrated forms, [3-NT61]CXCL12 and [3-NT7/61]CXCL12, were chemically synthesized to evaluate the effects of Tyr nitration on the biological activity of CXCL12. All CXCL12 forms had a similar binding affinity for heparin, the G protein-coupled chemokine receptor CXCR4 and the atypical chemokine receptor ACKR3. However, nitration significantly enhanced the affinity of CXCL12 for chondroitin sulfate. Internalization of CXCR4 and β-arrestin 2 recruitment to CXCR4 was significantly reduced for [3-NT7/61]CXCL12 compared to CXCL12, whereas β-arrestin 2 recruitment to ACKR3 was similar for all CXCL12 variants. [3-NT7/61]CXCL12 was weaker in calcium signaling assays and in in vitro chemotaxis assays with monocytes, lymphocytes and endothelial cells. Surprisingly, nitration of Tyr61, but not Tyr7, partially protected CXCL12 against cleavage by the specific serine protease CD26. In vivo, the effects were more pronounced compared to native CXCL12. Nitration of any Tyr residue drastically lowered lymphocyte extravasation to joints compared to native CXCL12. Finally, the anti-HIV-1 activity of [3-NT7]CXCL12 and [3-NT7/61]CXCL12 was reduced, whereas CXCL12 and [3-NT61]CXCL12 were equally potent. In conclusion, nitration of CXCL12 occurs readily upon contact with peroxynitrite and specifically nitration of Tyr7 fully reduces its in vitro and in vivo biological activities.


Evolution under changing climates: climatic niche stasis despite rapid evolution in a non-native plant.
A topic of great current interest is the capacity of populations to adapt genetically to rapidly changing climates, for example by evolving the timing of life-history events, but this is challenging to address experimentally. I use a plant invasion as a model system to tackle this question by combining molecular markers, a common garden experiment and climatic niche modelling. This approach reveals that non-native Lactuca serriola originates primarily from Europe, a climatic subset of its native range, with low rates of admixture from Asia. It has rapidly refilled its climatic niche in the new range, associated with the evolution of flowering phenology to produce clines along climate gradients that mirror those across the native range. Consequently, some non-native plants have evolved development times and grow under climates more extreme than those found in Europe, but not among populations from the native range as a whole. This suggests that many plant populations can adapt rapidly to changed climatic conditions that are already within the climatic niche space occupied by the species elsewhere in its range, but that evolution to conditions outside of this range is more difficult. These findings can also help to explain the prevalence of niche conservatism among non-native species.


Impact on enzyme activity as a new quality index of wastewater.
The aim of this study was to define a new indicator for the quality of wastewaters that are released into the environment. A quality index is proposed for wastewater samples in terms of the inertness of wastewater samples toward enzyme activity. This involves taking advantage of the sensitivity of enzymes to pollutants that may be present in the waste samples. The effect of wastewater samples on the rate of a number of different enzyme-catalyzed reactions was measured, and the results for all the selected enzymes were analyzed in an integrated fashion (multi-enzymatic sensor). This approach enabled us to define an overall quality index, the "Impact on Enzyme Function" (IEF-index), which is composed of three indicators: i) the Synoptic parameter, related to the average effect of the waste sample on each component of the enzymatic sensor; ii) the Peak parameter, related to the maximum effect observed among all the effects exerted by the sample on the sensor components; and, iii) the Interference parameter, related to the number of sensor components that are affected less than a fixed threshold value. A number of water based samples including public potable tap water, fluids from urban sewage systems, wastewater disposal from leather, paper and dye industries were analyzed and the IEF-index was then determined. Although the IEF-index cannot discriminate between different types of wastewater samples, it could be a useful parameter in monitoring the improvement of the quality of a specific sample. However, by analyzing an adequate number of waste samples of the same type, even from different local contexts, the profile of the impact of each component of the multi-enzymatic sensor could be typical for specific types of waste. The IEF-index is proposed as a supplementary qualification score for wastewaters, in addition to the certification of the waste's conformity to legal requirements.


Sperm function in vitro and fertility after antibiotic-free, hypothermic storage of liquid preserved boar semen.
The role of antibiotics (AB) in semen extenders as a potential contribution to the global antimicrobial resistance threat is emerging. Here, we establish an AB-free hypothermic preservation strategy for boar semen and investigate its impact on sperm function, microbial load and fertility after artificial insemination (AI). Spermatozoa (12 boars) preserved in AB-free AndroStar Premium extender at 5 °C maintained high motility, membrane integrity, and a low DNA-fragmentation index throughout 72 h storage and results did not significantly differ from controls stored at 17 °C in extender containing AB (p = 0.072). Likewise, kinetic response of spermatoza to the capacitation stimulus bicarbonate during 180 min incubation in Tyrode's medium did not differ from 17 °C-controls. In a competitive sperm oviduct binding assay, binding indices did not differ between semen stored for 72 h AB-free at 5 °C and 17 °C-controls (n = 6 boars). Bacterial load < 103 CFU/ml after 72 h was measured in 88.9% of samples stored at 5 °C AB-free compared to 97.2% in 17 °C-controls (n = 36 semen pools, 23 boars). Fertility traits of 817 females did not differ significantly between the two semen groups (p > 0.05). In conclusion, a hypothermic semen preservation strategy is presented which offers antibiotic-free storage of boar semen doses.


Serum-mediated activation of macrophages reflects TcVac2 vaccine efficacy against Chagas disease.
Chagas disease is endemic in Latin America and an emerging infectious disease in the United States. No effective treatments are available. The TcG1, TcG2, and TcG4 antigens are highly conserved in clinically relevant Trypanosoma cruzi isolates and are recognized by B and T cells in infected hosts. Delivery of these antigens as a DNA prime/protein boost vaccine (TcVac2) elicited lytic antibodies and type 1 CD8(+) T cells that expanded upon challenge infection and provided >90% control of parasite burden and myocarditis in chagasic mice. Here we determined if peripheral blood can be utilized to capture the TcVac2-induced protection from Chagas disease. We evaluated the serum levels of T. cruzi kinetoplast DNA (TckDNA), T. cruzi 18S ribosomal DNA (Tc18SrDNA), and murine mitochondrial DNA (mtDNA) as indicators of parasite persistence and tissue damage and monitored the effect of sera on macrophage phenotype. Circulating TckDNA/Tc18SrDNA and mtDNA were decreased by >3- to 5-fold and 2-fold, respectively, in vaccinated infected mice compared to nonvaccinated infected mice. Macrophages incubated with sera from vaccinated infected mice exhibited M2 surface markers (CD16, CD32, CD200, and CD206), moderate proliferation, a low oxidative/nitrosative burst, and a regulatory/anti-inflammatory cytokine response (interleukin-4 [IL-4] plus IL-10 > tumor necrosis factor alpha [TNF-α]). In comparison, macrophages incubated with sera from nonvaccinated infected mice exhibited M1 surface markers, vigorous proliferation, a substantial oxidative/nitrosative burst, and a proinflammatory cytokine response (TNF-α ≫ IL-4 plus IL-10). Cardiac infiltration of macrophages and TNF-α and oxidant levels were significantly reduced in TcVac2-immunized chagasic mice. We conclude that circulating TcDNA and mtDNA levels and macrophage phenotype mediated by serum constituents reflect in vivo levels of parasite persistence, tissue damage, and inflammatory/anti-inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies.


An immunoglobulin-like fold in a major plant allergen: the solution structure of Phl p 2 from timothy grass pollen.
Grass pollen allergens are the most important and widespread elicitors of pollen allergy. One of the major plant allergens which millions of people worldwide are sensitized to is Phl p 2, a small protein from timothy grass pollen. Phl p 2 is representative of the large family of cross-reacting plant allergens classified as group 2/3. Recombinant Phl p 2 has been demonstrated by immunological cross-reactivity studies to be immunologically equivalent to the natural protein. We have solved the solution structure of recombinant Phl p 2 by means of nuclear magnetic resonance techniques. The three-dimensional structure of Phl p 2 consists of an all-beta fold with nine antiparallel beta strands that form a beta sandwich. The topology is that of an immunoglobulin-like fold with the addition of a C-terminal strand, as found in the C2 domain superfamily. Lack of functional and sequence similarity with these two families, however, suggests an independent evolution of Phl p 2 and other homologous plant allergens. Because of the high homology with other plant allergens of groups 1 and 2/3, the structure of Phl p 2 can be used to rationalize some of the immunological properties of the whole family. On the basis of the structure, we suggest possible sites of interaction with IgE antibodies. Knowledge of the Phl p 2 structure may assist the rational structure-based design of synthetic vaccines against grass pollen allergy.


Clinical Characteristics and Risk Factors of Cardiac Involvement in COVID-19.
Background Increasing studies demonstrated that the cardiac involvements are related to coronavirus disease 2019 (COVID-19). Thus, we investigated the clinical characteristics of patients with COVID-19 and further determined the risk factors for cardiac involvement in them. Methods and Results We analyzed data from 102 consecutive laboratory-confirmed and hospitalized patients with COVID-19 (52 women aged 19-87 years). Epidemiologic and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, chest imaging findings, management methods, and clinical outcomes were collected. Patients were divided into acute cardiac injury, with and without cardiac marker abnormities groups according to different level of cardiac markers. In this research, cardiac involvement was found in 72 of the 102 (70.6%) patients: tachycardia (n=20), electrocardiography abnormalities (n=23), echocardiography abnormalities (n=59), elevated myocardial enzymes (n=55), and acute cardiac injury (n=9). Eight patients with acute cardiac injury were aged >60 years; seven of them had ≥2 underlying comorbidities (hypertension, diabetes mellitus, cardiovascular diseases, chronic obstructive pulmonary disease, and chronic kidney disease). Novel coronavirus pneumonia was much more severe in the patients with acute cardiac injury than in patients with nondefinite acute cardiac injury (P<0.001). Multivariate analyses showed that CRP (C-reactive protein) levels, old age, novel coronavirus pneumonia severity, and underlying comorbidities were the risk factors for cardiac abnormalities in patients with COVID-19. Conclusions Cardiac involvements are common in patients with COVID-19. Elevated CRP levels, old age, underlying comorbidities, and novel coronavirus pneumonia severity are the main risk factors for cardiac involvement in patients with COVID-19. More attention should be given to cardiovascular protection during COVID-19 treatment for mortality reduction. Registration URL: https://www.chictr.org; Unique identifier: ChiCTR2000029955.


Evidence that the N-terminal part of the S-layer protein from Bacillus stearothermophilus PV72/p2 recognizes a secondary cell wall polymer.
The S-layer of Bacillus stearothermophilus PV72/p2 shows oblique lattice symmetry and is composed of identical protein subunits with a molecular weight of 97,000. The isolated S-layer subunits could bind and recrystallize into the oblique lattice on native peptidoglycan-containing sacculi which consist of peptidoglycan of the A1gamma chemotype and a secondary cell wall polymer with an estimated molecular weight of 24,000. The secondary cell wall polymer could be completely extracted from peptidoglycan-containing sacculi with 48% HF, indicating the presence of phosphodiester linkages between the polymer chains and the peptidoglycan backbone. The cell wall polymer was composed mainly of GlcNAc and ManNAc in a molar ratio of 4:1, constituted about 20% of the peptidoglycan-containing sacculus dry weight, and was also detected in the fraction of the S-layer self-assembly products. Extraction experiments and recrystallization of the whole S-layer protein and proteolytic cleavage fragments confirmed that the secondary cell wall polymer is responsible for anchoring the S-layer subunits by the N-terminal part to the peptidoglycan-containing sacculi. In addition to this binding function, the cell wall polymer was found to influence the in vitro self-assembly of the guanidinium hydrochloride-extracted S-layer protein. Chemical modification studies further showed that the secondary cell wall polymer does not contribute significant free amino or carboxylate groups to the peptidoglycan-containing sacculi.


Negatively charged anabaena flavodoxin residues (Asp144 and Glu145) are important for reconstitution of cytochrome P450 17alpha-hydroxylase activity.
Catalysis by microsomal cytochromes P450 requires the membrane-bound enzyme NADPH-cytochrome P450 reductase (P450 reductase), which transfers electrons to the P450 heme via a flavodoxin-like domain. Previously, we reported that Escherichia coli flavodoxin (Fld), a soluble electron transfer protein, directly interacts with bovine cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) and donates electrons to this enzyme when reconstituted with NADPH-ferredoxin (flavodoxin) reductase (FNR) (Jenkins, C. M., and Waterman, M. R. (1994) J. Biol. Chem. 269, 27401-27408). To investigate whether flavodoxins can serve as useful models of the analogous domain in P450 reductase, we have examined the FNR-Fld system from the cyanobacterium Anabaena. Mutagenesis of two acidic Anabaena Fld residues (D144A and E145A) significantly decreased flavodoxin-supported P450c17 progesterone 17alpha-hydroxylase activity. Specifically, D144A exhibited only 15% of the activity of wild-type Fld, whereas the adjacent mutation, E145A, caused a 40% loss in activity. P450-dependent hydrogen peroxide/superoxide production by wild-type FNR-Fld was measurably higher than that generated by FNR-D144A or FNR-E145A, indicating that the mutations do not lead to P450 heme-mediated electron uncoupling. Interestingly, the D144A and E145A mutants bind with equal or even greater affinity to P450c17 than wild-type Fld. Furthermore, these mutations (D144A and E145A) actually increased cytochrome c reductase activity (35 and 100% higher than wild type). Anabaena Fld residues Asp144 and Glu145 align closely with rat P450 reductase residue Asp208, which has been shown by mutagenesis to be important in electron transfer to P4502B1 but not to cytochrome c (Shen, A. L., and Kasper, C. B. (1995) J. Biol. Chem. 270, 27475-27480). Thus, these residues in flavodoxins and P450 reductase appear to have similar functions in P450 recognition and/or electron transfer, supporting the hypothesis that flavodoxins represent valid models for the FMN-binding domain of P450 reductase.


Inhibiting LCN2 can suppress the development of NSCLC by promoting ferroptosis.
Tumor progression is intricately linked to ferroptosis, a recently discovered form of regulated cell death. However, the specific causes of ferroptosis in non-small cell lung cancer (NSCLC) remain unclear. In this study, we conducted transcriptome sequencing on NSCLC samples and identified Lipocalin-2 (LCN2) as a significantly differentially expressed gene associated with ferroptosis in NSCLC. Through the intersection of the set of significantly different genes with ferroptosis-related genes, we unveiled the relevance of LCN2 in NSCLC. To validate our findings, several cell lines (BEAS-2B, A549, H1299, PC-9, H1975) were utilized, and Western blot (WB) analysis was performed. We employed a variety of assays, including CCK8, EDU, scratch, Transwell, and specific assays targeting ferroptosis, to investigate the effects of LCN2 on NSCLC cell proliferation, migration, and ferroptosis. Additionally, LCN2 was evaluated in vivo using a mouse tumor xenograft model. In both NSCLC patients and cells, LCN2 exhibited upregulation and was associated with a poor prognosis. Inhibition of LCN2 promoted ferroptosis, resulting in the inhibition of NSCLC proliferation and migration. Conversely, the ferroptosis inhibitor Fer-1 promoted NSCLC cell proliferation and migration while inhibiting ferroptosis. Furthermore, down-regulating LCN2 reduced Fer-1's promotion of NSCLC cell migration and proliferation, as well as its prevention of ferroptosis. In vivo inhibition of LCN2 prevented NSCLC cell growth and enhanced ferroptosis. Based on our research, reducing LCN2 could effectively induce ferroptosis and hinder the growth of NSCLC.


Development of visual attention in West syndrome.
To study prospectively the evolution of visual attention in children with West syndrome to evaluate its development before the onset of spasms, its possible deterioration as a consequence of epileptic disorders, and its outcome at the age of 2 years, and the possible relation between the impairment of visual attention and cognitive development. Infants with symptomatic West syndrome were examined before the onset of spasms and until age 24 +/- 2 months. Visual attention study (through a clinical observation and the fixation-shift test), cognitive assessment, and complete clinical examination including brain magnetic resonance imaging were performed. A maturation defect of fixation shift skills was generally observed in infants with West syndrome. In some cases, the impaired visual-attention abilities paralleled a cognitive deterioration, even months before the onset of spasms. During the acute stage of West syndrome, infants lost the previously acquired visual and cognitive abilities, with a typical fluctuation of arousal. Usually at 2 years, there was a persistent defective visual attention detected with the fixation-shift test. The parallel defect of visual attention and of cognitive competencies is a constant finding in infants with West syndrome; these can precede the clinical onset of epileptic spasms. The severity and persistence of visual inattention might be explained by the age of visual maturation, corresponding to the usual onset of West syndrome.


Amplification of whole tumor genomes and gene-by-gene mapping of genomic aberrations from limited sources of fresh-frozen and paraffin-embedded DNA.
Sufficient quantity of genomic DNA can be a bottleneck in genome-wide analysis of clinical tissue samples. DNA polymerase Phi29 can be used for the random-primed amplification of whole genomes, although the amplification may introduce bias in gene dosage. We have performed a detailed investigation of this technique in archival fresh-frozen and formalin-fixed/paraffin-embedded tumor DNA by using cDNA microarray-based comparative genomic hybridization. Phi29 amplified DNA from matched pairs of fresh-frozen and formalin-fixed/paraffin-embedded tumor samples with similar efficiency. The distortion in gene dosage representation in the amplified DNA was nonrandom and reproducibly involved distinct genomic loci. Regional amplification efficiency was significantly linked to regional GC content of the template genome. The biased gene representation in amplified tumor DNA could be effectively normalized by using amplified reference DNA. Our data suggest that genome-wide gene dosage alterations in clinical tumor samples can be reliably assessed from a few hundred tumor cells. Therefore, this amplification method should lend itself to high-throughput genetic analyses of limited sources of tumor, such as fine-needle biopsies, laser-microdissected tissue, and small paraffin-embedded specimens.


Alcohol Use Among Never-Deployed U.S. Army Reserve and National Guard Soldiers: The Effects of Nondeployment Emotions and Sex.
Limited research shows that mental health problems are prevalent among never-deployed soldiers and many experience negative emotions related to their nondeployment. U.S. Army Reserve/National Guard (USAR/NG) soldiers are also at high risk for alcohol misuse. However, it is not known if nondeployment emotions contribute to an increased risk of alcohol misuse among never-deployed USAR/NG soldiers. Data are from Operation: SAFETY (Soldiers and Families Excelling Through the Years), an ongoing study of USAR/NG soldiers. We used regression models to examine the relations between nondeployment emotions, assessed by the Non-Deployment Emotions (NDE) Questionnaire, and a range of alcohol use outcomes, assessed by the Alcohol Use Disorders Identification Test and standard quantity and frequency questions, among a sample of never-deployed soldiers who were partnered at baseline (N = 174). Final models controlled for years of military service, current number of close military friends in the social network, marital satisfaction, and depression. We also tested for potential differences in these associations by sex. Nondeployment emotions were associated with frequency of getting drunk (adjusted risk ratio [aRR] = 1.02, 95% CI: 1.01, 1.04; p < 0.05) and typical number of drinks consumed during a drinking episode (aRR = 1.03, 95% CI: 1.01, 1.04; p < 0.01). Nondeployment emotions had a trend-level association with percent of days drinking (adjusted odds ratio = 1.05, 95% CI: 1.00, 1.11; p = 0.055). Nondeployment emotions had a significant interaction with sex (p < 0.05) on the likelihood of alcohol problems, such that only male soldiers experienced a greater likelihood of alcohol problems when they had highly negative nondeployment emotions. There was no relation between nondeployment emotions and alcohol problems among female soldiers. Findings demonstrate that greater nondeployment emotions are associated with increased alcohol use among never-deployed USAR/NG soldiers. The NDE Questionnaire may assist in identifying those at highest risk for alcohol problems.


[Analysis of spontaneous and ethylmethanesulfonate-induced visible mutations in the genetically unstable MS, w strain of Drosophila melanogaster].
We analyzed genetic effects of ethylmethanesulfonate (EMS) on mature sperm of males of the Drosophila melanogaster MS, w strain. The frequency of induced mutations was estimated in the X chromosome, in five loci of chromosome 2 (b, j, pr, cn, and vg), and in eight loci of chromosome 3 (ru, h, th, st, cu, sr, es, and ca). Mutability was significantly increased in the genetically unstable MS, w strain in comparison with the reference laboratory ss, w strain. In MS, w, genetic instability was characteristic of more than 50% EMS-induced mutations. Analysis of the mutation spectrum revealed a specific distribution along the chromosomes. In MS, w, exhibition of spontaneous and induced instability was shown to be similar. This could imply a common mechanism of control of mutability involving transpositions of mobile genetic elements.


Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells.
The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.


A viral lncRNA tethers HSV-1 genomes at the nuclear periphery to establish viral latency.
Herpes simplex virus 1 (HSV-1) establishes lifelong latency in neuronal cells. Following a stressor, the virus reactivates from latency, virus is shed at the periphery and recurrent disease can occur. During latency, the viral lncRNA termed the latency-associated transcript (LAT) is known to accumulate to high abundance. The LAT is known to impact many aspects of latency though the molecular events involved are not well understood. Here, we utilized a human neuronal cell line model of HSV latency and reactivation (LUHMES) to identify the molecular-binding partners of the LAT during latency. We found that the LAT binds to both the cellular protein, TMEM43, and HSV-1 genomes in LUHMES cells. Additionally, we find that knockdown of TMEM43 prior to infection results in a decreased ability of HSV-1 to establish latency. This work highlights a potential mechanism for how the LAT facilitates the establishment of HSV-1 latency in human neurons.


The Reproduction Rate of Peptide Transporter PEPT-1 Deficient C. elegans Is Dependent on Dietary Glutamate Supply.
Intestinal absorption of dietary amino acids is mediated via two routes. Free amino acids released by hydrolysis of dietary proteins are taken up by a multitude of amino acid transporters while di- and tripeptides released are taken up by the peptide transporter PEPT-1. Loss of PEPT-1 impairs growth, post-embryonic development and reproduction in Caenorhabditis elegans, and supplementation with a mixture of all L-amino acids only partially rescues fertility. In the present study, we demonstrate that dietary L-glutamate is the responsible amino acid that can increase fertility in hermaphrodite pept-1 worms. This effect was associated with a significantly higher uptake of glutamate/aspartate in pept-1 than in wildtype C. elegans. Furthermore, we found that the intestinal transporter proteins SNF-5 of the solute carrier SLC6 family of nutrient amino acid transporters (NAT) and AAT-6 of the SLC7 family as the light subunit of a heteromeric amino acid transporter (HAT) play a key role in glutamate homeostasis in pept-1 C. elegans. Genes encoding these transporters are highly expressed and upon silencing a 95% reduced fertility (snf-5) and sterility (aat-6) was observed. A subsequent L-glutamate supplementation failed to rescue these phenotypes. Dietary glutamate supplementation did neither influence the feeding frequency, nor did it improve mating efficiency of pept-1 males. Most strikingly, pept-1 were more prone to habituation to repeated gentle touch stimuli than wildtype C. elegans, and dietary glutamate supply was sufficient to alter this behavioral output by restoring the mechanosensory response to wildtype levels. Taken together, our data demonstrate a key role of L-glutamate in amino acid homeostasis in C. elegans lacking the peptide transporter in the intestine and demonstrate its distinct role in reproduction and for neural circuits mediating touch sensitivity.


Changes in gene expression linked with adult reproductive diapause in a northern malt fly species: a candidate gene microarray study.
Insect diapause is an important biological process which involves many life-history parameters important for survival and reproductive fitness at both individual and population level. Drosophila montana, a species of D. virilis group, has a profound photoperiodic reproductive diapause that enables the adult flies to survive through the harsh winter conditions of high latitudes and altitudes. We created a custom-made microarray for D. montana with 101 genes known to affect traits important in diapause, photoperiodism, reproductive behaviour, circadian clock and stress tolerance in model Drosophila species. This array gave us a chance to filter out genes showing expression changes during photoperiodic reproductive diapause in a species adapted to live in northern latitudes with high seasonal changes in environmental conditions. Comparisons among diapausing, reproducing and young D. montana females revealed expression changes in 24 genes on microarray; for example in comparison between diapausing and reproducing females one gene (Drosophila cold acclimation gene, Dca) showed up-regulation and 15 genes showed down-regulation in diapausing females. Down-regulation of seven of these genes was specific to diapause state while in five genes the expression changes were linked with the age of the females rather than with their reproductive status. Also, qRT-PCR experiments confirmed couch potato (cpo) gene to be involved in diapause of D. montana. A candidate gene microarray proved to offer a practical and cost-effective way to trace genes that are likely to play an important role in photoperiodic reproductive diapause and further in adaptation to seasonally varying environmental conditions. The present study revealed two genes, Dca and cpo, whose role in photoperiodic diapause in D. montana is worth of studying in more details. Also, further studies using the candidate gene microarray with more specific experimental designs and target tissues may reveal additional genes with more restricted expression patterns.


Satisfaction with nursing care and its related factors in patients with COVID-19: A descriptive correlational study.
Patients' satisfaction is a fundamental factor in the quality of nursing care. The emergence of the novel Coronavirus Disease 2019 (COVID-19) and the highly contagious virus can affect nursing care by increasing the number of care-seekers. This study aimed to determine the patients' satisfaction and related factors in patients with COVID-19 hospitalized in Taleghani Hospital, Urmia-Iran, in 2020. This descriptive, correlational study was conducted on 196 patients with COVID-19 hospitalized in Taleghani Hospital, Urmia. Purposive convenient sampling was used to recruit participants. Study participants completed Patient Satisfaction Instrument and demographics questionnaires. Data were analyzed with the SPSS software version 25.0. The majority of patients (68.9%) were moderately satisfied with nursing care. Based on Pearson Correlation Analysis, only residential status had a significant inverse relationship with satisfaction level in patients with COVID-19 (r = -0.0238, P = 0.001). The patients' satisfaction with nursing care was mostly at a moderate level. Thus, there is a need to educate health personnel and nurses in particular and motivate them to have active participation in achieving patients' satisfaction with COVID-19. Notably, only the institutes that take patients' satisfaction as a top priority can succeed in a competitive market of health services.


Neurological suppression of diaphragm electromyographs in hamsters infected with West Nile virus.
To address the hypothesis that respiratory distress associated with West Nile virus (WNV) is neurologically caused, electromyographs (EMGs) were measured longitudinally from the diaphragms of alert hamsters infected subcutaneously (s.c.) with WNV. The EMG activity in WNV-infected hamsters was consistently and significantly (P <or= .001) less than that of sham-infected animals, beginning with suppression at day 3 and continuing to beyond day 17 after viral challenge. Of the tissues known to affect respiration, i.e., lung, diaphragm, cervical spinal cord, brain stem, and the carotid or aortic bodies, foci of WNV-immunoreactive neurons were only observed in the brain stems and some cervical spinal cords from EMG-suppressed animals. To confirm the involvement of the brain stem and spinal cord, WNV was injected directly in the ventrolateral medulla containing respiratory functions using stereotaxic surgery and into the cervical cord at the C4 vertebral level. As with subcutaneous WNV challenge, hamsters developed EMG suppression of the diaphragm within 4 days. Because WNV-positive neurons were only sporadically identified in EMG-suppressed animals as early as day 3, a plausible mechanism of EMG suppression may involve regulation of diaphragm activity via vagal afferents acting on respiratory control system neurons in the brain stem. Brain auditory evoked response (BAER) was performed to determine if generalized brain stem neuropathy was the cause of diaphragmatic EMG suppression. Because deficiencies of BAER were only observed after day 11, which is long after diaphragm EMGs became suppressed, multiple phases of WNV-induced neurological disease are likely. These data establish that WNV infection of hamsters causes electrophysiological suppression of the diaphragm either directly by lesions in the brain stem and cervical spinal cord, or indirectly by altered vagal afferent function. This WNV-induced EMG suppression may be analogous to conditions leading to respiratory distress of WNV-infected human patients.


TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases.
The 43-kDa TAR DNA-binding protein (TDP-43) is known to be a major component of the ubiquitinated inclusions characteristic of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Although TDP-43 is a nuclear protein, it disappears from the nucleus of affected neurons and glial cells, implicating TDP-43 loss of function in the pathogenesis of neurodegeneration. Here we show that the knockdown of TDP-43 in differentiated Neuro-2a cells inhibited neurite outgrowth and induced cell death. In knockdown cells, the Rho family members RhoA, Rac1, and Cdc42 GTPases were inactivated, and membrane localization of these molecules was reduced. In addition, TDP-43 depletion significantly suppressed protein geranylgeranylation, a key regulating factor of Rho family activity and intracellular localization. In contrast, overexpression of TDP-43 mitigated the cellular damage caused by pharmacological inhibition of geranylgeranylation. Furthermore administration of geranylgeranyl pyrophosphate partially restored cell viability and neurite outgrowth in TDP-43 knockdown cells. In summary, our data suggest that TDP-43 plays a key role in the maintenance of neuronal cell morphology and survival possibly through protein geranylgeranylation of Rho family GTPases.


Medical students as EMTs: skill building, confidence and professional formation.
The first course of the medical curriculum at the Hofstra North Shore-LIJ School of Medicine, From the Person to the Professional: Challenges, Privileges and Responsibilities, provides an innovative early clinical immersion. The course content specific to the Emergency Medical Technician (EMT) curriculum was developed using the New York State Emergency Medical Technician curriculum. Students gain early legitimate clinical experience and practice clinical skills as team members in the pre-hospital environment. We hypothesized this novel curriculum would increase students' confidence in their ability to perform patient care skills and enhance students' comfort with team-building skills early in their training. Quantitative and qualitative data were collected from first-year medical students (n=97) through a survey developed to assess students' confidence in patient care and team-building skills. The survey was completed prior to medical school, during the final week of the course, and at the end of their first year. A paired-samples t-test was conducted to compare self-ratings on 12 patient care and 12 team-building skills before and after the course, and a theme analysis was conducted to examine open-ended responses. Following the course, student confidence in patient care skills showed a significant increase from baseline (p<0.05) for all identified skills. Student confidence in team-building skills showed a significant increase (p<0.05) in 4 of the 12 identified skills. By the end of the first year, 84% of the first-year students reported the EMT curriculum had 'some impact' to 'great impact' on their patient care skills, while 72% reported the EMT curriculum had 'some impact' to 'great impact' on their team-building skills. The incorporation of EMT training early in a medical school curriculum provides students with meaningful clinical experiences that increase their self-reported level of confidence in the performance of patient care skills early in their medical education.


Nurses' role in detecting deterioration in ward patients: systematic literature review.
This paper is a report of a review conducted to identify and critically evaluate research investigating nursing practice in detecting and managing deteriorating general ward patients. Failure to recognize or act on deterioration of general ward patients has resulted in the implementation of early warning scoring systems and critical care outreach teams. The evidence of effectiveness of these systems is unclear. Possible mechanisms for low effectiveness may be inconsistent recording of patient observations by ward staff, or inconsistent application of 'calling criteria' for outreach teams, even when observations have been recorded. The literature was searched between 1990 and 2007 using four sources: electronic databases, reference lists, key reports and experts in the field. Three broad search categories were used: nursing observations, physiological deterioration and general ward patients. All research designs describing nursing observations (vital signs) on deteriorating adult patients in general hospital wards were included. Fourteen studies met the inclusion and quality criteria. The findings were grouped into four main themes: recognition; recording and reviewing; reporting; and responding and rescuing. The main findings suggest that intuition plays an important part in nurses' detection of deterioration, and vital signs are used to validate intuitive feelings. The process is highly complex and influenced by many factors, including the experience and education of bedside nurses and their relationship with medical staff. Greater understanding of the context within which deterioration is detected and reported will facilitate the design of more effective education and support systems.


Editor's Highlight: OrganophosphateDiazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome.
The gut microbiome plays a key role in energy production, immune system development, and host resistance against invading pathogens, etc. Disruption of gut bacterial homeostasis is associated with a number of human diseases. Several environmental chemicals have been reported to induce alterations of the gut microbiome. Diazinon, one of important organophosphate insecticides, has been widely used in agriculture. Diazinon and its metabolites are readily detected in different environmental settings and human urine. The toxicity of organophosphates has been a long-standing public health concern. We recently demonstrated that organophosphate insecticide diazinon perturbed the gut microbiome composition of mice. However, the functional impact of exposure on the gut microbiome has not been adequately assessed yet. In particular, the molecular mechanism responsible for exposure-induced microbial profile and community structure changes has not been identified. Therefore, in this study, we used metatranscriptomics to examine the effects of diazinon exposure on the gut metatranscriptome in C57BL/6 mice. Herein, we demonstrated for the first time that organophosphate diazinon modulated quorum sensing, which may serve as a key mechanism to regulate bacterial population, composition, and more importantly, their functional genes. In addition, we also found that diazinon exposure activated diverse stress response pathways and profoundly impaired energy metabolism of gut bacteria. These findings provide new understandings of the functional interplay between the gut microbiome and environmental chemicals, such as organophosphates.


Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains.
Bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding ability of 28 strains of Lactobacillus gasseri were examined. There was significant variation among strains in growth in media containing bile and also variation in the ability to bind cholesterol. Cultures grown for 12 h at 37 degrees C bound significantly more cholesterol than did cells from a 48-h incubation. Variation among strains in the ability to deconjugate sodium taurocholate was not significantly different. Maximal deconjugation of sodium taurocholate was achieved with the cells during the stationary phase of growth (12 h). Statistical analysis showed no significant correlation between bile tolerance and sodium taurocholate deconjugation, bile tolerance and cholesterol-binding ability, or sodium taurocholate deconjugation and cholesterol-binding ability.


Risk of prostate, breast and colorectal cancer after skin cancer diagnosis.
Ultraviolet radiation is the major cause of skin cancer, but promotes vitamin D synthesis, and vitamin D has been inversely related to the risk of several common cancers including prostate, breast and colorectum. We therefore computed the incidence of prostate, breast and colorectal cancer following skin cancer using the datasets of the Swiss cancer Registries of Vaud and Neuchâtel. Between 1974 and 2005, 6,985 histologically confirmed squamous cell skin cancers, 21,046 basal cell carcinomas and 3,346 cutaneous malignant melanomas were registered, and followed up to the end of 2005 for the occurrence of second primary cancer of the prostate, breast and colorectum. Overall, 680 prostate cancers were observed versus 568.3 expected (standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI): 1.11-1.29), 440 breast cancers were observed versus 371.5 expected (SIR = 1.18; 95% CI: 1.08-1.30) and 535 colorectal cancers were observed versus 464.6 expected (SIR = 1.15; 95% CI: 1.06-1.25). When basal cell, squamous cell and skin melanoma were considered separately, all the SIRs for prostate, breast and colorectal cancers were around or slightly above unity. Likewise, the results were consistent across strata of age at skin cancer diagnosis and location (head and neck versus others), and for male and female colorectal cancers. These findings, based on a population with a long tradition of systematic histologic examination of all surgically treated skin lesions, do not support the hypothesis that prostate, breast and colorectal cancer risk is decreased following skin cancer.


Single-cell transcriptomics reveals pre-existing COVID-19 vulnerability factors in lung cancer patients.
COVID-19 and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that cancer patients are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathological conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory responses mediated by macrophages, increased T cell response suppression, and elevated fibrosis risk by pathological fibroblasts. These pre-existing conditions in lung cancer patients may lead to more severe inflammation, fibrosis, and weakened adaptive immune response upon COVID-19 infection. Our findings revealed potential molecular mechanisms driving an increased COVID-19 risk in lung cancer patients and suggested preventive and therapeutic targets for COVID-19 in this population. Implications: Our work reveals the potential molecular mechanisms contributing to the vulnerability to COVID-19 in lung cancer patients.


Cytokine mRNA expression and iron status in children living in a malaria endemic area.
Iron deficiency has been reported to affect both malaria pathogenesis and cell-mediated immune responses; however, it is unclear whether the protection afforded by iron deficiency is mediated through direct effects on the parasite, through immune effector functions or through both. We have determined cytokine mRNA expression levels in 59 children living in a malaria endemic area on the coast of Kenya who we selected on the basis of their biochemical iron status. Real-time quantitative reverse transcriptase polymerase chain reaction analysis of cytokine mRNA levels of peripheral blood mononuclear cells (PBMC) obtained from these children showed an association between interleukin-4 (IL-4) mRNA levels and all the biochemical indices of iron that we measured. Furthermore, IL-10 mRNA was higher in parasite blood smear-positive children than in blood smear-negative children irrespective of their iron status. This study suggests that IL-4 expression by PBMC may be affected by iron status.


Touch interacts with vision during binocular rivalry with a tight orientation tuning.
Multisensory integration is a common feature of the mammalian brain that allows it to deal more efficiently with the ambiguity of sensory input by combining complementary signals from several sensory sources. Growing evidence suggests that multisensory interactions can occur as early as primary sensory cortices. Here we present incompatible visual signals (orthogonal gratings) to each eye to create visual competition between monocular inputs in primary visual cortex where binocular combination would normally take place. The incompatibility prevents binocular fusion and triggers an ambiguous perceptual response in which the two images are perceived one at a time in an irregular alternation. One key function of multisensory integration is to minimize perceptual ambiguity by exploiting cross-sensory congruence. We show that a haptic signal matching one of the visual alternatives helps disambiguate visual perception during binocular rivalry by both prolonging the dominance period of the congruent visual stimulus and by shortening its suppression period. Importantly, this interaction is strictly tuned for orientation, with a mismatch as small as 7.5° between visual and haptic orientations sufficient to annul the interaction. These results indicate important conclusions: first, that vision and touch interact at early levels of visual processing where interocular conflicts are first detected and orientation tunings are narrow, and second, that haptic input can influence visual signals outside of visual awareness, bringing a stimulus made invisible by binocular rivalry suppression back to awareness sooner than would occur without congruent haptic input.


The extra-cytoplasmic function sigma factor sigX modulates biofilm and virulence-related properties in Pseudomonas aeruginosa.
SigX, one of the 19 extra-cytoplasmic function sigma factors of P. aeruginosa, was only known to be involved in transcription of the gene encoding the major outer membrane protein OprF. We conducted a comparative transcriptomic study between the wildtype H103 strain and its sigX mutant PAOSX, which revealed a total of 307 differentially expressed genes that differed by more than 2 fold. Most dysregulated genes belonged to six functional classes, including the "chaperones and heat shock proteins", "antibiotic resistance and susceptibility", "energy metabolism", "protein secretion/export apparatus", and "secreted factors", and "motility and attachment" classes. In this latter class, the large majority of the affected genes were down-regulated in the sigX mutant. In agreement with the array data, the sigX mutant was shown to demonstrate substantially reduced motility, attachment to biotic and abiotic surfaces, and biofilm formation. In addition, virulence towards the nematode Caenorhabditis elegans was reduced in the sigX mutant, suggesting that SigX is involved in virulence-related phenotypes.


Qualitative research on the Belgian Cancer Rehabilitation Evaluation System (CARES): An evaluation of the content validity and feasibility.
The systematic assessment of cancer patients well-being and care needs is internationally recommended to optimize comprehensive cancer care. The Cancer Rehabilitation Evaluation System (CARES) is a psychometrically robust quality of life and needs assessment tool of US origin, developed in the early 1990s. This article describes Belgian patients' view on the content validity and feasibility of the CARES for use in current cancer care. Participants were cancer patients recruited through media. Data were gathered in 4 focus groups (n = 26). The focus group discussions were facilitated with key questions. A moderator and an observer conducted and followed up the discussion. The audio file was transcribed verbatim and afterwards analyzed thematically. Participants experience concerns and needs in a wide range of life domains such as physical, emotional, cognitive, social, relational, sexual, financial, and work-related and in the interaction with care professionals. According to participants, the items of the CARES are all relevant to capture the possible life disruption that cancer patients and survivors experience. One important theme is missing in the CARES, namely, the well-being of loved ones. The completion time of the CARES was judged to be feasible, and according to participants, only a few items need a reformulation. In general, the results of this study support the content validity and feasibility of the CARES. However, little adjustments in formulation and a few extra items are needed. The instrument can be used to obtain a comprehensive assessment of a cancer patients' overall well-being and care needs to take dedicated action in care.


The hypoglycemic and antioxidant effects of polysaccharides from the petioles and pedicels of Euryale ferox Salisb. on alloxan-induced hyperglycemic mice.
The present study investigated the potential hypoglycemic and antioxidant effects of polysaccharides extracted from the petioles and pedicels of Euryale ferox Salisb. (EFPP) on alloxan-induced hyperglycemic mice. The EFPP had a total carbohydrate of 65.72 ± 2.81%, uronic acid of 4.56 ± 0.62% and protein of 0.58 ± 0.12%, with an average molecular weight from 1.02 kDa to 11.45 kDa and monosaccharide composition of Man, GlcA, Rha, Glc, Gal and Ara at a molar ratio of 0.12 : 0.01 : 9.57 : 0.41 : 1.00 : 0.24. Administration with EFPP, especially high dose EFPP, was beneficial to reverse body weight loss, reduce blood glucose levels, enhance serum insulin levels, improve oral glucose tolerance, increase hepatic glycogen content and GCK activity, and modulate the mRNA expression of GCK in the liver. Meanwhile, EFPP had protective effects against alloxan-induced oxidative injury in mice, via increasing the activities of SOD, CAT and GSH-Px and decreasing the MDA contents in the liver and kidney of the mice. EFPP ameliorated the damage in pancreas, kidney and liver tissues, which was confirmed by histopathological observation. The results suggested that EFPP possess hypoglycemic and antioxidant activities, and could be a potential source of natural hypoglycemic and antioxidant agents for functional foods or complementary medicines.


[Relationship of postoperative complications to the surgical approach in treating cancer of the proximal portion of the stomach].
The authors have analyzed the interrelationship between postoperative complications and surgical approach in the treatment of carcinoma of the proximal portion of the stomach. The radical operations were carried out upon 140 patients; in 93 of them the transperitoneal approach was applied and in 47-the transpleural one. It has been found that in the transpleural approach the insufficiency of anastomosis sutures and postoperative pancreatitis occur much more seldom, and bronchopulmonary complications rate the first. Such complications are not infrequent after the transperitoneal approach either. The disorders of bronchial permeability constitute the main cause in the occurrence of these complications.


Molecular dynamics simulation of octacosane for phase diagrams and properties via the united-atom scheme.
We used the united-atom scheme to build three types of crystalline structures for octacosane (C28H58) and carried out molecular dynamics simulations to investigate their phase properties. By gradually heating the three polymorphs, we managed to reproduce the sequence of experimentally reported crystalline phases and rotator phases. By studying the system density, molecule morphology, chain tilt angle and cell anisotropy, we hypothesized three mechanisms behind the observed system deformations and phase transformations during the annealing process. Furthermore, our model successfully predicted the melting temperature and heat of fusion. We also reproduced the characteristics of the rotator phases and the liquid phase, validating the transferability of the united-atom scheme among the different condensed phases of octacosane. Our methodology represents an effective and efficient means of numerical study for octacosane and may be used for other members of the n-alkane family.


Binding of (14C) parathion in soil: a reassessment of pesticide persistence.
A steady decrease of extractable [14C] parathion residues in soils over a 1-month incubation period was accompanied by an increase of unextractable, bound 14C-labeled residues, resulting finally in total recoveries of extracted plus bound residues of 80 to 87 percent of the applied radiocarbon. Soils containing bound residues were nontoxic to fruit flies. Binding of 14C-labeled residues was related to the activity of soil microorganisms; soil sterilization resulted in a reduction of binding by 58 to 84 percent. Under flooded (anaerobic) conditions, the binding of compounds labeled with 14C doubled, and parathion was reduced to aminoparathion. Reinoculation of sterilized flooded soil fully reinstated the binding capacity. [14C] Aminoparathion was preferentially bound to soil, since its binding within 2 hours was 30 times greater than that of [14C] parathion. Because of the existence of formerly "unseen," unextractable residues, the concept of "persistent" and "nonpersistent" pesticide residues might have to be reconsidered.


Expanding role of percutaneous ablative and consolidative treatments for musculoskeletal tumours.
Interventional approaches to musculoskeletal tumours have significantly changed over the last several years, and new treatments continue to be developed. All ablative modalities are currently applied to the treatment of bone tumours, including radiofrequency, cryo-, microwave, and laser ablation devices. Indications for ablation of bone and soft-tissue tumours have expanded beyond palliation of painful bone metastases and eradication of osteoid osteomas to the local control of oligometastatic disease from a number of primary tumours and ablation of desmoid tumours. In addition, tools for consolidation of bone tumours at risk of pathological fracture have also expanded. With these developments, ablation has become the primary treatment for osteoid osteomas and, at some institutions, desmoid tumours. It may be the primary or secondary treatment for palliation of painful bone tumours, frequently used in patients with pain refractory to or recurrent after radiation therapy. It is used as a treatment for limited metastatic disease or for metastases that grow disproportionately in patients with multifocal metastases, either in combination with systemic therapy or to reserve systemic therapy and its toxicity for more widespread disease progression. Moreover, percutaneous methods to consolidate bone at risk of fracture have become more commonplace, aided by techniques using materials beyond typical bone cement.


Ophthalmic manifestations of bartonella infection.
The eye is commonly affected in disseminated cat scratch disease (CSD) caused by Bartonella species. This article reviews recently published data on epidemiology of CSD, clinical features of ocular involvement, diagnosis and treatment. The annual incidence of CSD has been estimated as 4.7 per 100 000 in the United States. It occurs predominantly in the southern states, with a peak in January, and disproportionately affects children. Retinal infiltrates, neuroretinitis and branch retinal artery occlusions have been reported as common manifestations of ocular bartonellosis in recent series. The use of different antigens for serodiagnosis and new real-time PCR assays for molecular diagnosis have been described. Despite lack of a standard treatment, good visual outcomes were generally reported in patients with ocular bartonellosis. Bartonella infections continue to be a burden worldwide and epidemiologic features may guide preventive measures in high-risk regions and populations. An increased awareness of diverse posterior segment manifestations will lead to an early diagnosis of ocular bartonellosis. Laboratory diagnostic methods continue to evolve and may be applied to the investigation of ocular fluids for a definitive diagnosis of ocular bartonellosis. Well designed clinical trials are required to establish the optimum treatment of especially sight-threatening manifestations.


N-terminal truncated human RAG1 proteins can direct T-cell receptor but not immunoglobulin gene rearrangements.
The proteins encoded by RAG1 and RAG2 can initiate gene recombination by site-specific cleavage of DNA in immunoglobulin and T-cell receptor (TCR) loci. We identified a new homozygous RAG1 gene mutation (631delT) that leads to a premature stop codon in the 5' part of the RAG1 gene. The patient carrying this 631delT RAG1 gene mutation died at the age of 5 weeks from an Omenn syndrome-like T(+)/B(- )severe combined immunodeficiency disease. The high number of blood T-lymphocytes (55 x 10(6)/mL) showed an almost polyclonal TCR gene rearrangement repertoire not of maternal origin. In contrast, B-lymphocytes and immunoglobulin gene rearrangements were hardly detectable. We showed that the 631delT RAG1 gene can give rise to an N-terminal truncated RAG1 protein, using an internal AUG codon as the translation start site. Consistent with the V(D)J recombination in T cells, this N-terminal truncated RAG1 protein was active in a plasmid V(D)J recombination assay. Apparently, the N-terminal truncated RAG1 protein can recombine TCR genes but not immunoglobulin genes. We conclude that the N-terminus of the RAG1 protein is specifically involved in immunoglobulin gene rearrangements.