Pattern of esophageal injuries and surgical management: A retrospective review.
The consequence of significant injury to the esophagus is devastating. The initial management when timely and appropriate is rewarding and often prevents lethal complications. The objective of this study is to describe the etiology of esophageal injury in our institution, the management procedures and the mid-term results. Consecutive patients diagnosed and managed for esophageal injury from January 2005 to March 2015 were retrospectively reviewed. One hundred and eleven patients were seen and treated during this period; 85 (76.6%) predominantly children were corrosive esophageal injuries who accidentally ingested caustic soda and 26 (24.4%) were traumatic esophageal injuries. Patients with corrosive esophageal injuries were predominantly male (2:1), mean age 12.8 ± 14.2 years (2-58 years) and predominantly children (53% ≤5 years; 18.8% ≥ 18 years). Patients with non-corrosive esophageal injury were also predominantly male (4:1) with a mean age of 34.4 ± 20.1 years (1-73 years). The treatment procedures for corrosive esophageal injuries included esophagocoloplasty 64 (75.3%), colopharyngoplasty 10 (11.8%), colon-flap augmentation pharyngo-esophagoplasty 4 (4.7%), colopharyngoplasty with tracheostomy 4 (4.7%) and esophagoscopy and dilatation 3 (3.5%). Mortality was 5.9% and 5 patients were lost to follow-up. In patients with noncorrosive esophageal injury, esophageal perforation from instrumentation accounted for 14 (53.9%), foreign body impaction 11 (42.3%) and spontaneous perforation 1 (3.8%) making up the rest. Management of these patients included esophagotomy and removal of foreign body 7 (26.9%), esophagectomy, cervical esophagostomy and feeding gastrostomy 10 (38.6%), primary repair 7 (26.9%), Ivor Lewis procedure 1 (3.8%) and emergency esophagectomy with colon replacement 1 (3.8%). Mortality in this group of patients was 7.7% and 4 patients were lost to follow-up. Corrosive esophageal injuries were the most frequent form of esophageal injury at our center due to unrestricted access to corrosive substances. Generally, appropriate surgical intervention in patients with esophageal injury based on individualization of care yields excellent early and mid-term results.


On- and Off-Cycle Catalyst Cooperativity in Anion-Binding Catalysis.
Chiral, neutral H-bond donors have found widespread use as catalysts in enantioselective reactions involving ion-pair intermediates. Herein, a systematic mechanistic study of a prototypical anion-binding reaction, the thiourea-catalyzed enantioselective alkylation of α-chloroethers, is detailed. This study reveals that the catalyst resting state is an inactive dimeric aggregate that must dissociate and then reassemble to form a 2:1 catalyst-substrate complex in the rate-determining transition structure. Insight into this mode of catalyst cooperativity sheds light on the practical limitations that have plagued many of the H-bond donor-catalyzed reactions developed to date and suggests design strategies for new, highly efficient catalyst structures.


HSPB7 gene polymorphism associated with anthropometric parameters of obesity and fat intake in a Central European population.
Heat shock proteins act as chaperones at the molecular level and therefore they have been investigated in numerous diseases associated with oxidative stress, including obesity. The aim of this study was to investigate the possible associations of genetic variability in the 3´-untranslated region of the HSPB7 gene (rs1048261) with anthropometric and dietary parameters in a cohort of lean and obese Central European subjects. A total of 708 Central European Caucasian individuals were enrolled in this study, 415 obese subjects and 293 non-obese subjects. The rs1048261 genotypes were established using a conventional PCR-based methodology. Significant differences were observed in the total daily fat intake between subjects with AT and TT genotypes (82.6 ± 29.2 g vs. 74.1 ± 31.3 g, p = 0.023) and also borderline significance in daily proportion of fat in the diet between AA and TT genotypes (36.0 ± 4.4% vs. 33.3 ± 5.9%, p = 0.061). Based on the linear regression model we found association between rs1048261 genotype and body fat percentage. To the best of our knowledge, this is the first study which reports an association of defined genetic variability in the HSPB7 gene, rs1048261, with obesity and its associated anthropometric characteristics and dietary composition.


The Effect of Kinesio Taping Combined with Virtual-Reality-Based Upper Extremity Training on Upper Extremity Function and Self-Esteem in Stroke Patients.
(1) Background: The purpose of this study is to investigate the effect of virtual-reality-based hand motion training (VRT) in parallel with the Kinesio Taping (KT) technique on upper extremity function in stroke patients and to present a more effective therapeutic basis for virtual reality training intervention. (2) Methods: First, 43 stroke patients were randomly assigned to two groups: 21 experimental subjects and 22 controls. The experimental group performed Kinesio Taping (KT) on the dorsal part of the hand along with virtual-reality-based hand motion training, and the control group performed only virtual-reality-based hand motion training. The intervention was conducted for a total of 30 sessions over 6 weeks. To evaluate changes in upper extremity function, the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), the Wolf Motor Function Test (WMFT), and the Motor Activity Log (MAL) (including amount of use (AOU) and quality of movement (QOM)) were evaluated. In addition, the Self-Efficacy Scale (SEF) was evaluated to examine the change in the self-esteem of the study subjects. (3) Results: The experimental group who participated in the virtual reality training in parallel with the KT technique showed statistically significant improvement (** p < 0.01) in the FMA-UE, WMFT, and MAL evaluations that investigate changes in upper extremity function. SEF evaluation also showed a statistically significant improvement (** p < 0.01). A statistically significant difference between the two groups was observed in the evaluation of FMA-UE, WMFT, MAL-QOM, and SEF (†p < 0.05), showing that that combined intervention was more effective at improving upper extremity function than the existing VRT intervention. There was no statistical difference between the two groups in the MAL-AOU item, which is an evaluation of upper extremity function (p > 0.05). There was a statistically significant difference between the two groups in the amount of change in upper limb function (††p < 0.01). (4) Conclusions: It was confirmed that virtual-reality-based hand motion training performed in parallel with the KT technique had a positive effect on the recovery of upper extremity function of stroke patients. The fact that the KT technique provided stability to the wrist by assisting the wrist extensor muscles appears to have improved the upper extremity function more effectively than VRT alone.


Restoring the patient's voice. The therapeutics of illness narratives.
Reflective and insightful autobiographical accounts of illness not only illuminate fundamental disruptions in selfhood and continuity of life that accompany illness, but authors of such accounts also maintain that narration is an important way to make sense of an illness episode, to restore personhood and connectedness, and to reclaim the illness experience from the medical meta-narrative. That witnessing and helping to order illness narratives can be a caring/healing nursing practice modality with significant healing potential is supported both by narrative theory and by nursing's theoretical and philosophical legacy. The challenge for the nurse guided by narrative ideas is to give primacy to the patient's voice, to listen for meaning rather than for facts, and to provide a relationship enabling the evolution of the patient's story.


Associative Agreement as a Predictor of Naming Ability in Alzheimer's Disease: A Case for the Semantic Nature of Associative Links.
We aimed to address the long-standing issue of the nature of the relationships that link a cue word to words associated with it. In keeping with a recently proposed neuropsychological model of semantic memory (Zannino et al., 2015), we provide support for the hypothesis that associative links are semantic in nature and not lexical. In support of this hypothesis, we demonstrate a relationship in healthy subjects between the probability of producing word X in response to cue word Y in a free association task and the probability of using word X to describe the meaning of word Y. Furthermore, we provide evidence that associative measures are altered in people suffering from Alzheimer's disease (AD) and predict their level of performance in a picture-naming task. We provide a parsimonious account of the experimental data gathered form these different sources of evidence according to the hypothesis that the links between a cue word and its associates can be viewed as binding a concept (the cue) to pieces of information regarding its meaning (the associates).


Association of pregnancy-related stigma and intimate partner violence with anxiety and depression among adolescents.
We explored the association between pregnancy-related stigma and intimate partner violence (IPV) with depression and anxiety among adolescents in Uganda. We interviewed a convenience sample of 100 adolescents (>18 years) who were pregnant (>3 months) or recently gave birth (<3 months) at Tororo District Hospital, Uganda. Symptoms of depression and anxiety were evaluated using the Hopkins Symptom Checklist (HSCL-25), physical and sexual IPV were assessed using the WHO violence against women instrument, and pregnancy-related stigma was captured with a questionnaire. Regression models were used to evaluate associations of pregnancy stigma and IPV with depression and anxiety. Mean age was 18 years, 84% were primiparous, 66% were married and 57% had only primary school-level education. About 48% women had clinically meaningful distress levels; 45% reported sexual IPV, 32% physical IPV, and 86% reported experiencing pregnancy-related stigma. Adjusted models showed that higher levels of depression and anxiety were associated with higher report of pregnancy-related stigma (β = .27, p = .03), physical IPV, (β = -.24, p < .01), or sexual IPV (β = -.19, p = .05), compared to those who did not. Unemployment (β = -.24, p = .01) and lower educational level (β = -.21, p = .05) were also independent predictors of depression and anxiety. Findings suggest that IPV is common among adolescents in Uganda, as is pregnancy-related stigma, and both are independent predictors of depression and anxiety. The implications of these findings and the need for clinical interventions for IPV among adolescents are discussed.


[A pharmacogenetic analysis of dopaminergic and opioidergic genes in opioid addicts treated with the combination of naltrexone and guanfacine].
To evaluate an effect of opioid receptor and dopamine system gene polymorphisms on the efficacy of combined treatment with oral naltrexone and guanfacine in a randomized double blinded double dummy placebo controlled clinical trial. Three hundred and one patients with opioid dependence were randomized into 4 treatment groups: naltrexone 50 mg/day + guanfacine 1 mg/day (N+G); naltrexone + placebo guanfacine (N+GP); placebo naltrexone + guanfacine (NP+G); double placebo (NP+GP). The primary outcome was treatment retention. All enrolled participants were genotyped for polymorphisms in the following genes: mu- (OPRM1), kappa-opioid receptors (OPRK1), catechol-O-methyltransferase (COMT), dopamine receptors types 2 (DRD2) and 4 (DRD4), dopamine-beta-hydroxylase, and dopamine transporter (SLC6A3, DAT1) and alpha-2-adrenoreceptor (ADRA2A) a pharmacological target of guanfacine. The efficacy of the combination of naltrexone and guanfacine was comparable to naltrexone monotherapy. Regardless of treatment, several gene polymorphisms were associated with higher chance to complete the treatment program: allele Т DRD4 - 521 С/Т (rs1800955) (р=0.039; OR (95% CI)=3.7 (1.1-12.7); log-rank test: р=0.01); allele С DRD2 С957Т (rs6277) (р=0.03; HR=0.6 (0.34-0.95); genotype combination: DRD4 VNTR (LL) + OPRM1 A118G (rs1799971) (AA), р=0.051; DRD2 C957T (ТТ) + OPRM1 (rs1074287) (СС), р=0.025; DRD2 - 141С (II) + OPRM1 (rs510769) (АА), р=0.035; DBH Fau(СС) + OPRM1 (rs1074287) (СС), р=0.0497. Regardless of treatment several polymorphisms were associated with high risk of relapse: allele Т (rs510769) OPRM1 (р=0.053), allele А (rs1799971, A118G) OPRM1 (р=0.056), allele S exon III 48 bp DRD4 VNTR (р=0.001; HR=3.1 (ДИ 95% 1.57-6.18); genotype combinations: DRD4 - 521 С/Т (ТТ) + DRD2 Nco I (TT), р=0.026; DRD4 -521 С/Т (ТТ) + DRD2 -141 С (II), р=0.011; DRD4 - 521 С/Т (ТТ) + OPRM1 A118G (rs1799971) (AA), р=0.011; DRD2 Nco I(ТТ) + ADRA2A (СС), р=0.012; DRD2 Nco I(ТТ) + OPRM1 A118G (AA), р=0.02. The effects dependent on the treatment group were as follows: 1) in the N+G group, patients with the DRD4 -521 С/Т TT genotype had higher probability of completion of treatment program in comparison with other genotypes (CC and CT) (log-rank test: p=0.002); 2) in NP + GP group, patients with the OPRM1 rs510769 T allele had higher risk of relapse compared to the genotype GG (p=0.008) (FDR p<0.0125). The additive effect of opioid receptor genes and dopaminergic system genes on outcomes of treatment opioid dependence with oral naltrexone and guanfacine was shown. Pharmacological effects of naltrexone and guanfacine were associated with genetic variants of the DRD4 - 521C/T polymorphism, since its effect was shown only in the N+G group. The effect of the OPRM1 rs510769 polymorphism was demonstrated in the double placebo group that was associated with personality traits (temperament, character) and determined compliance. Genetic analysis is useful for determining potential responders to treatment of opioid dependence; genotyping can increase the efficacy of pharmacotherapy.


Calcium-permeable glutamate receptors in horizontal cells of the mammalian retina.
Mechanisms that mediate the calcium influx in mammalian horizontal cells were studied. Horizontal cells (HCs) enzymatically dissociated from the rabbit retina were recorded by the whole-cell configuration of the patch-clamp technique and by calcium image ratioespectrophotometry of Fura-2 loaded cells. AMPA-preferring glutamate receptors were shown to permeate Ca2+ in mammalian HCs by ionic substitution experiments. Furthermore, after blocking the L-type calcium current with nifedipine (100 microM), calcium current through the AMPA-preferring glutamate receptors was measured. Calcium image ratioespectrophotometry was performed on the dissociated HCs in order to determine the changes in the intracellular calcium ([Ca2+]i). Fura-2 microspectrophotometry showed that in HCs, K+-induced cell depolarization promoted an increase in [Ca2+]i, mediated by the L-type calcium channels, since it was abolished in the presence of nifedipine. The increase in [Ca2+], upon cell depolarization was observed throughout each cell: however, it was maximal at the cell soma. Activation of glutamate receptors in dissociated HCs by glutamate, AMPA or kainate promoted an increase in [Ca2+]i. This increase in [Ca2+]i, was abolished in nominally Ca2+-free solution (0 mM Ca2+); in contrast, nifedipine decreased the glutamate-induced influx of calcium in ca. 50%. The present study demonstrates that calcium may permeate through glutamate receptors expressed in HCs of the rabbit retina.


Evolution of marginal populations of an invasive vine increases the likelihood of future spread.
The prediction of invasion patterns may require an understanding of intraspecific differentiation in invasive species and its interaction with climate change. We compare Japanese honeysuckle (Lonicera japonica) plants from the core (100-150 yr old) and northern margin (< 65 yr old) of their North American invaded range to determine whether evolution during invasion increases the probability of future expansion. Plants from populations in the core and margin were compared in two sites beyond the northern range edge to assess their potential to invade novel areas. Data were compared with previous work to assess the effect of latitudinal climate on L. japonica spread. Winter survival in current climates was modeled and projected for future climates to predict future spread. Margin plants were larger and had 60% greater survival than core plants at sites beyond the northern range edge. Overall, winter survival decreased with increasing latitude and decreasing temperature, and was greater in margin plants than core plants. Models suggested that greater winter tolerance in margin populations has increased L. japonica's northward spread by 76 km, and that this survival advantage will persist under future climates. These results demonstrate that evolution during invasion may increase spread beyond predictions using increasing global temperatures alone.


Synergistic inhibition of human immunodeficiency virus replication in vitro by combinations of 3'-azido-3'-deoxythymidine and 3'-fluoro-3'-deoxythymidine.
The antiviral activity against human immunodeficiency virus type 1 of the two structurally related thymidine analogs azidothymidine and fluorothymidine, both alone and in combination, was tested. Fluorothymidine was tenfold more active than azidothymidine. The selectivity indices of the two compounds were similar. The combination of azidothymidine and fluorothymidine showed clearly synergistic antiviral activity, and diminished cytotoxicity. The inhibition of reverse transcriptase from human immunodeficiency virus type 1 by the triphosphates of azidothymidine and fluorothymidine, both alone and in combination was also tested. Azidothymidine triphosphate was a fourfold stronger inhibitor than fluorothymidine triphosphate. The combination of the two showed only additive (and not synergistic) effects upon reverse transcriptase. The combination of azidothymidine and fluorothymidine showed both synergistic antiviral activity and diminished cytotoxicity, and may therefore represent a promising therapeutic strategy. The additive (and not synergistic) inhibition of reverse transcriptase by the combination of the triphosphates indicates that in cell culture additional factors other than inhibition of the reverse transcriptase by the triphosphates influence the antiviral activity of the combination. Such factors might include effects upon normal nucleoside metabolism or metabolism of the analogs. Alternatively, one of the nucleosides might have an additional mechanism of action besides inhibition of the reverse transcriptase.


Effect of external drive on strongly coupled Yukawa systems: a nonequilibrium molecular dynamics study.
Using nonequilibrium molecular dynamics (MD) simulations behavior of three-dimensional (3D) Yukawa system has been studied in the presence of a small amplitude drive along one direction (say z[over ] ). This drive has the general form V=V_{0} cos(k_{L}z)Theta(t-t_{0}) , where Theta(t-t_{0}) is a Heaviside step function in time at t=t_{0} and k_{L}=2pi/L , L being the size of the system; V0 is considered small compared to average interparticle potential energy. In particular, a 3D equilibrated Yukawa crystal (bcc) near solid-liquid transition is subjected to an external drive at times t> or =t_{0} at the largest possible scale. For a given k_{L} it is observed that there exists a critical amplitude (V_{0};{c}) of the external drive below which the crystalline order is preserved and above which (V_{0}> or =V_{0};{c}) the transition from bcc to strongly coupled Yukawa liquid is observed. This critical amplitude (V_{0};{c}) is sensitive to the location of the Yukawa solid in the (kappa,Gamma) phase space. Various signatures of melting, transients, and steady state in the presence of this drive are elucidated using extensive MD diagnostics such as loss of long-range crystalline order, change in diffusion from subnormal to normal, and the fall of transversal shear peak in the Fourier transform of the velocity autocorrelation function. The mechanism of heating in the transient state is attributed to the local heating of the system where the forces are maximum. It is shown that these local hot regions dissipate heat into surrounding regions ultimately leading to a uniform temperature throughout the system. Ion streaming due to external field has been neglected.


Pulmonary function and pathology in cats exposed 28 days to diesel exhaust.
Young adult male cats were exposed 28 days, 20 hrs per day, to a 1:14 dilution of diesel exhaust emissions. Following termination of exposure, the following pulmonary function measurements were carried out: lung volumes, maximum expiratory flow rates (MEF), MEF at 50%, 25% and 10% of vital capacity (VC): forced expiratory volume (FEV) after 0.2, 0.3 and 0.4 sec, dynamic compliance, resistance and helium washout at 25, 50, 75, and 100 breaths per min. The only significant functional change was a decrease in MEF at 10% of VC (P x .02). The lungs of the exposed cats appeared charcoal grey with frequent focal black spots visible on the pleural surface. Pathologic changes in the exposed cats included a predominantly peribronchiolar localization of black-pigmented macrophages within the alveoli producing a focal pneumonitis or alveolitis. In general, evidence of serious lung damage was not observed following the 28-day exposure period.


Comparison of Field and Laboratory-Based Tests for Behavioral Response of Aedes aegypti (Diptera: Culicidae) to Repellents.
The repellent and irritant effects of three essential oils-clove, hairy basil, and sweet basil-were compared using an excito-repellency test system against an insecticide-resistant strain of Aedes aegypti (L.) females from Pu Teuy, Kanchanaburi Province. DEET was used as the comparison standard compound. Tests were conducted under field and controlled laboratory conditions. The most marked repellent effect (spatial noncontact assay) among the three test essential oils was exhibited by sweet basil, Ocimum basilicum L. (53.8% escaped mosquitoes in 30-min exposure period) under laboratory conditions while hairy basil, Ocimum americanum L. and clove, Syzygium aromaticum (L.) Merill et. L.M. Perry from laboratory tests and sweet basil from field tests were the least effective as repellents (0-14%). In contrast, the contact assays measuring combined irritancy (excitation) and repellency effects found the best contact irritant response to hairy basil and DEET in field tests, whereas all others in laboratory and field were relatively ineffective in stimulating mosquitoes to move out the test chambers (0-5.5%). All three essential oils demonstrated significant differences in behavioral responses between field and laboratory conditions, whereas there was no significant difference in contact and noncontact assays for DEET between the two test conditions (P > 0.05).


Functional analysis of a cotton glucuronosyltransferase promoter in transgenic tobaccos.
The 5' fragment (1 647 bp) of the cotton glucuronosyltransferase gene (GhGlcAT1) was transcriptionally fused to the beta-glucuronidase (GUS) gene, and functionally analyzed for important regulatory regions controlling gene expression in transgenic tobacco plants. GUS activity analysis revealed that the full-length promoter drives efficient expression of the GUS gene in the root cap, seed coat, pollen grains and trichomes. Exposure of the transgenic tobacco to various abiotic stresses showed that the promoter was mainly responsive to the sugars (glucose and sucrose) as well as gibberellic acid. Progressive upstream deletion analyses of the promoter showed that the region from -281 to +30 bp is sufficient to drive strong GUS expression in the trichomes of shoot, suggesting that the 311 bp region contains all cis-elements needed for trichome-specific expression. Furthermore, deletion analysis also revealed that the essential cis-element(s) for sucrose induction might be located between -635 and -281 bp. In addition, sequence analysis of the regulatory region indicated several conserved motifs among which some were shared with previously reported seed-specific elements and sugar-responsive elements, while others were related with trichome expression. These findings indicate that a 1 647-bp fragment of the cotton GhGlcAT1 promoter contains specific transcription regulatory elements, and provide clues about the roles of GhGlcAT1 in cotton fiber development. Further analyses of these elements will help to elucidate the molecular mechanisms regulating the expression of the GhGlcAT1 gene during fiber elongation.


The role of gut microbiome in inflammatory skin disorders: A systematic review.
The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.


Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.
In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.


Pigment violet 19 - a test case to define a simple method to simulate the vibronic structure of absorption spectra of organic pigments and dyes in solution.
A typical quinacridone pigment, PV19, has been used to analyze the impact of several computational parameters on the UV/vis absorption band shape in solution, simulated using density functional theory and time-dependent density functional theory levels of approximation. These encompass, (i) the choice of exchange-correlation functional, (ii) the basis set, (iii) the method for non-equilibrium optimization of the excited state geometry, (iv) the approach for evaluating the vibronic band structure, (v) the peak broadening, and (vi) the scaling of the harmonic vibrational frequencies. Among these, the choice of exchange-correlation functional is certainly of the most importance because it can drastically modify the spectral shape. In the case of PV19, the M05-2X and to a lesser extent CAM-B3LYP XC functionals are the most efficient to reproduce the vibronic structure, confirming the important role of exact Hartree-Fock exchange. Still, these functionals are not the most reliable to predict the excitation energies and oscillator strengths, for which M05, a functional with less HF exchange, performs better. For evaluating the vibronic structure, the simple gradient method, where only one step of geometry optimization of the excited state is carried out and the gradients are used to evaluate the Huang-Rhys factors as well as to determine the excited state geometries produces a spectrum that is very similar to the ones obtained with the more involved Duschinsky and geometry methods, opening the way to a fast simulation of the UV/vis absorption spectra of pigments and dyes. Then, the effect of scaling the calculated vibrational frequencies to account for anharmonicity effects as well as for limitation of the method also impacts the shape of the vibronic spectrum and this effect depends on the method used to determine the Huang-Rhys factors. Indeed, scaling the vibrational frequencies by a factor which is typically smaller than 1.0 results in a relative decrease of the 0-1 peak intensity with respect to the 0-0 band when optimizing the geometry of the excited state whereas the effect is opposite and magnified if using the gradient method.


The effect of sleep deprivation on retrieval of emotional memory: a behavioural study using film stimuli.
Although the deleterious effects of sleep deprivation on memory consolidation are well documented, it is still unclear how the facilitating effect of emotions on memory consolidation processes could be modulated by the lack of sleep. In this study, we investigated the effects of sleep deprivation on episodic memory using emotional and non-emotional film stimuli. Forty-eight healthy subjects, divided into a sleep group (SG) and a sleep-deprived (SD) group, completed an Encoding and a Recall phase. Participants in the SD group were sleep deprived the night immediately following the Encoding phase, whereas the control group slept at home. The Recall phase was administered to all subjects 48 h after the Encoding. During the Encoding phase, six film clips of different valence (two positive, two neutral and two negative) were presented to the participants. During the Recall phase, episodic memory was assessed by a recognition task. Results showed that the SD group had a lower discrimination memory performance for all stimuli compared to the SG, confirming the deleterious effect of sleep deprivation on episodic memory consolidation. Therefore, lack of sleep severely impairs the consolidation of both emotional and neutral memories, as valence-related effects on memory consolidation were not observed after sleep deprivation.


Development of cortical orientation selectivity in the absence of visual experience with contour.
Visual cortical neurons are selective for the orientation of lines, and the full development of this selectivity requires natural visual experience after eye opening. Here we examined whether this selectivity develops without seeing lines and contours. Juvenile ferrets were reared in a dark room and visually trained by being shown a movie of flickering, sparse spots. We found that despite the lack of contour visual experience, the cortical neurons of these ferrets developed strong orientation selectivity and exhibited simple-cell receptive fields. This finding suggests that overt contour visual experience is unnecessary for the maturation of orientation selectivity and is inconsistent with the computational models that crucially require the visual inputs of lines and contours for the development of orientation selectivity. We propose that a correlation-based model supplemented with a constraint on synaptic strength dynamics is able to account for our experimental result.


Festivals and medical relevance (with special reference to medieval Andhra society).
The physicians of indigenous medical science believed that the climatic changes are one of the causes for diseases. They observed that severity of a disease depends on the movements of the planets. Thus, they prescribed ritucharya as a remedy to their evil influence and also, made the people to follow some of the important regulations for the maintenance of health by incorporating them into the religious rituals by instituting some new festivals and customs like Vinayakachaturthi, Ugadi and Dasara etc., in course of time. The primary data regarding the subject can be found available in the contemporary literary works, medical texts, travellers accounts, inscriptions and the temple monuments.


Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.
Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice. The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5 μg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1 day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2 days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured. ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4 days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8 days after cisplatin injection. ANP significantly increased serum G-CSF levels 1 day after cisplatin injection. ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.


Risk factors for drug-resistant tuberculosis among non-US-born persons in New York City.
New York City (NYC). To examine the extent to which prior tuberculosis (TB) treatment, length of residence in the United States and other factors are associated with the occurrence of drug resistance among non-US-born persons in NYC. Cases were non-US-born persons diagnosed with TB in NYC from 1998-1999 and from 2001-2002, with an initial Mycobacterium tuberculosis isolate resistant to any first-line anti-tuberculosis drug. Controls were randomly selected from non-US-born persons whose isolates were susceptible to all first-line anti-tuberculosis drugs. Overall, cases with multidrug-resistant (MDR) TB were more likely to have had prior TB treatment; other drug resistance was not associated with prior TB treatment. In a multivariate model, the relationship between MDR-TB and prior treatment remained significant for non-US-born persons regardless of length of time in the U.S. The findings underscore the utility of monitoring trends in drug resistance among the non-US-born by time in the US and prior treatment to determine where or when drug resistance may be occurring.


Acousto-optical interaction of surface acoustic and optical waves in a two-dimensional phoxonic crystal hetero-structure cavity.
Phoxonic crystal is a promising material for manipulating sound and light simultaneously. In this paper, we theoretically demonstrate the propagation of acoustic and optical waves along the truncated surface of a two-dimensional square-latticed phoxonic crystal. Further, a phoxonic crystal hetero-structure cavity is proposed, which can simultaneously confine surface acoustic and optical waves. The interface motion and photoelastic effects are taken into account in the acousto-optical coupling. The results show obvious shifts in eigenfrequencies of the photonic cavity modes induced by different phononic cavity modes. The symmetry of the phononic cavity modes plays a more important role in the single-phonon exchange process than in the case of the multi-phonon exchange. Under the same deformation, the frequency shift of the photonic transverse electric mode is larger than that of the transverse magnetic mode.


Formation and evolution of bubbly screens in confined oscillating bubbly liquids.
We consider the dynamics of dilute monodisperse bubbly liquid confined by two plane solid walls and subject to small-amplitude high-frequency oscillations normal to the walls. The initial state corresponds to the uniform distribution of bubbles and motionless liquid. The period of external driving is assumed much smaller than typical relaxation times for a single bubble but larger than the period of volume eigenoscillations. The time-averaged description accounting for the two-way coupling between the liquid and the bubbles is applied. We show that the model predicts accumulation of bubbles in thin sheets parallel to the walls. These singular structures, which are formally characterized by infinitely thin width and infinitely high concentration, are referred to as bubbly screens. The formation of a bubbly screen is described analytically in terms of a self-similar solution, which is in agreement with numerical simulations. We study the evolution of bubbly screens and detect a one-dimensional stationary state, which is shown to be unconditionally unstable.


A practical review of alternatives to the steady pressurisation method for determining building airtightness.
As an important indicator of construction quality and envelope integrity of buildings, airtightness is responsible for a considerable amount of energy losses associated with infiltration. It is crucial to understand building airtightness during construction and retrofitting to achieve a suitable envelope airtightness which is essential for obtaining a desirable building energy efficiency, durability and indoor environment. As a convenient means of measurement, the current steady pressurisation method has long been accepted as a standard testing method for measuring building airtightness. It offers an intuitive and robust approach for measuring building airtightness and performing building diagnostics. However, it also has some shortcomings that are mainly related to its high pressure measurement, requirement for skilful operation, long test duration and change to the building envelope. Efforts have been made by manufacturers and researchers to further improve its accuracy and practicality with much progress achieved. Work has also been done to develop alternative methods that can overcome some of the issues. This paper provides a practical review on the incumbent methodology and efforts that have been made over the past decades in research and development of other methods to achieve a similar purpose. It compares them in relation to aspects that are considered important in achieving an accurate, quick and practical measurement of building airtightness and the finding shows other methods such as acoustic and unsteady technique have their own advantages over the steady pressurisation method but also add some of their own restrictions, which therefore makes them suited for different applications.


Meeting Report: A Poly-Pharmacy Approach to Mitigate Acute Radiation Syndrome.
The National Institute of Allergy and Infectious Diseases, Radiation and Nuclear Countermeasures Program, was tasked by the United States Congress and the U.S. Department of Health and Human Services to identify and fund early-to-mid-stage development of medical countermeasures (MCMs) to treat radiation-induced injuries. In developing MCMs to treat various sub-syndromes (e.g., hematopoietic, gastrointestinal, lung), it is important to investigate whether a poly-pharmacy approach (i.e., drug cocktails) can provide additive benefits to mitigate injuries arising from the acute radiation syndrome (ARS). In addition, potential drug-drug interactions must be examined. For this reason, a workshop was held, which centered on understanding the current state of research investigating poly-pharmacy approaches to treat radiation injuries. The first session set the stage with an introduction to the concept of operations or support available for the response to a nuclear incident, as this is the key to any emergency response, including MCM availability and distribution. The second session followed the natural history of ARS in both humans and animal models to underscore the complexity of ARS and why a poly-pharmacy approach may be necessary. The third session featured talks from investigators conducting current MCM poly-pharmacy research. The meeting closed with a focus on regulatory considerations for the development of poly-pharmacy approaches or combination treatments for ARS.


Topical cilostazol inhibits neointimal hyperplasia in a rat interposition vein graft model.
Neointimal hyperplasia is a common cause of vein graft failure resulting from luminal narrowing and occlusion. Cilostazol is a U.S. Food and Drug Administration-approved phosphodiesterase III and platelet aggregation inhibitor commonly used in peripheral vascular disease. The authors studied whether topical cilostazol treatment at the time of vein grafting helps limit the development of neointimal hyperplasia in a rat model. Six experimental rats and six control rats underwent interposition vein grafting into the femoral artery, followed by a single topical dose of cilostazol applied around the vein graft in the experimental animals. After 4 weeks, grafts were harvested and underwent histologic staining of axial sections to visualize intima thickness and elastin/myocyte content. Quantification was performed to assess total intima area. The intima-to-media and the intima-to-sum of intima and media ratios were determined to control for discrepancies in overall graft size. Cilostazol-treated grafts had a thinner intima layer with less myocyte content compared with control grafts, amounting to an 82 percent decrease in total intima area compared with controls. A similar trend was seen even after controlling for overall graft size, with 85 and 76 percent reductions seen in intima-to-media and intima-to-sum of intima and media ratios, respectively. A single intraoperative dose of cilostazol applied locally significantly reduced intima size and smooth muscle content in rat interposition vein grafts examined 4 weeks postoperatively. A topical dose of cilostazol at surgery may therefore be helpful in controlling neointimal hyperplasia and reducing the need for systemic medications to prolong vein graft patency.


Inhibition of MMP-2 Expression Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinoma by Suppressing the PI3K/AKT/mTOR Pathway.
Sorafenib has been globally approved as the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited because of tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the antitumor efficiency. Here we demonstrated that expression of MMP-2 is positively correlated with the migration ability of HCC cells. Cells with a higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells). Cotreatment of cells with SB-3CT and sorafenib more strongly inhibited migration ability than with sorafenib treatment alone in both HCC cells with high and low expression of MMP-2. In vivo cell metastasis experiments confirmed the synergistic effects of sorafenib and SB-3CT in reducing lung metastasis of SK-HEP-1 cells. Mechanistically, we showed that the synergistic antitumor effect may be attributed to inhibition of the PI3K/AKT/mTOR signaling pathway, but not the RAF/MEK/ERK signaling pathway. With these results taken together, the current study demonstrates that inhibiting MMP-2 expression can enhance the antitumor effect of sorafenib in HCC cells with a high MMP-2 expression, which may provide a novel strategy to improve therapeutic efficiency in HCC.


[Spontaneous pneumomediastinum].
Spontaneous pneumomediastinum (defined by the presence of free air in the mediastinum) is an infrequent entity that is presented in the absence of diseases or precipitating factors. It generally affects young and healthy males. Thoracic pain, dyspnea, or both, are the most frequent symptoms. Other signs and symptoms are subcutaneous emphysema and Hamman's sign. Simple radiography of the thorax allows for the diagnosis in a high percentage of patients. Conservative treatment is indicated in these patients and has a favourable prognosis. Relapses are infrequent.


Social inequalities in young children's sports participation and outdoor play.
Research on social inequalities in sports participation and unstructured physical activity among young children is scarce. This study aimed to assess the associations of family socioeconomic position (SEP) and ethnic background with children's sports participation and outdoor play. We analyzed data from 4726 ethnically diverse 6-year-old children participating in the Generation R Study. Variables were assessed by parent-reported questionnaires when the child was 6 years old. Low level of outdoor play was defined as outdoor play <1 hour per day. Series of multiple logistic regression analyses were performed to assess associations of family SEP and ethnic background with children's sports participation and outdoor play. Socioeconomic inequalities in children's sports participation were found when using maternal educational level (p < 0.05), paternal educational level (p < 0.05), maternal employment status (p < 0.05), and household income (p < 0.05) as family SEP indicator (less sports participation among low SEP children). Socioeconomic inequalities in children's outdoor play were found when using household income only (p < 0.05) (more often outdoor play <1 hour per day among children from low income household). All ethnic minority children were significantly more likely to not to participate in sports and play outdoor <1 hour per day compared with native Dutch children. Adjustment for family SEP attenuated associations considerably, especially with respect to sports participation. Low SEP children and ethnic minority children are more likely not to participate in sports and more likely to display low levels of outdoor play compared with high SEP children and native Dutch children, respectively. In order to design effective interventions, further research, including qualitative studies, is needed to explore more in detail the pathways relating family SEP and ethnic background to children's sports participation and outdoor play.


Kinetics of DNA Strand Displacement Systems with Locked Nucleic Acids.
Locked nucleic acids (LNAs) are conformationally restricted RNA nucleotides. Their increased thermal stability and selectivity toward their complements make them well-suited for diagnostic and therapeutic applications. Although the structural and thermodynamic properties of LNA-LNA, LNA-RNA, and LNA-DNA hybridizations are known, the kinetic effects of incorporating LNA nucleotides into DNA strand displacement systems are not. Here, we thoroughly studied the strand displacement kinetics as a function of the number and position of LNA nucleotides in DNA oligonucleotides. When compared to that of an all-DNA control, with an identical sequence, the leakage rate constant was reduced more than 50-fold, to an undetectable level, and the invasion rate was preserved for a hybrid DNA/LNA system. The total performance enhancement ratio also increased more than 70-fold when calculating the ratio of the invading rate to the leakage rate constants for a hybrid system. The rational substitution of LNA nucleotides for DNA nucleotides preserves sequence space while improving the signal-to-noise ratio of strand displacement systems. Hybrid DNA/LNA systems offer great potential for high-performance chemical reaction networks that include catalyzed hairpin assemblies, hairpin chain reactions, motors, walkers, and seesaw gates.


Diversity and abundance of Bacteria and Archaea in the Bor Khlueng Hot Spring in Thailand.
The prokaryotic diversity in the Bor Khlueng hot spring in Ratchaburi province, Thailand was investigated by a culture-independent molecular approach. This hydrothermal pool is located in the central part of Thailand and contains sulfide-rich mineral water that is believed to relieve muscle ache and pain. The water flow year-round with temperature ranging between 50-57 degrees C. Community DNA was extracted directly from sediment samples by coring to depth of approximately 20-30 cm. Small-subunit rRNA genes (16S rDNA) were amplified by PCR using primers specific for the domains Archaea and Bacteria. The PCR products were cloned and sequenced. For the bacterial rDNA clone library, 200 clones were randomly selected for further analyses. After restriction fragment length polymorphism (RFLP) analysis of rDNA clones and exclusion of chimeric sequences 36 phylotypes were obtained. The Bor Khlueng phylotypes spanned a wide range within the domain Bacteria, occupying eleven major lineages (phyla). Almost a quarter (23%) of the clones were classified as Acidobacteria. The other clones were grouped into the Bacteriodetes (19%), Nitrospirae (13%), Proteobacteria (12%), Deinococcus-Thermus lineage (11%), planctomycetes (6%), and Verrucomicrobia (5%). The four remaining phyla, 5% each, were assigned to Actinobacteria, Chloroflexi, Cyanobacteria, and the candidate division "OP10". For the archaeal 16S rRNA gene sequence library, 25 distinct phylotypes were obtained, 17 clones were found to be associated with Crenarahaeota and 8 clones were associated with Euryarachaeota. The findings of the molecular survey of this so far not investigated site showed that Bor Khlueng hot spring is a potential rich source of unique bacterial and archaeal species. The great majority ( approximately 80%) of the prokaryotic sequences detected in Bor Khlueng were unknown.


Model-based engineering for medical-device software.
This paper demonstrates the benefits of adopting model-based design techniques for engineering medical device software. By using a patient-controlled analgesic (PCA) infusion pump as a candidate medical device, the authors show how using models to capture design information allows for i) fast and efficient construction of executable device prototypes ii) creation of a standard, reusable baseline software architecture for a particular device family, iii) formal verification of the design against safety requirements, and iv) creation of a safety framework that reduces verification costs for future versions of the device software. 1.


Gires-Tournois resonators as ultra-narrowband perfect absorbers for infrared spectroscopic devices.
Ultra-narrowband perfect absorbers and emitters are proposed and realized by engineering multiple-beam interference in Gires-Tournois etalon with the presence of low metallic loss. The absorption mechanism and spectral characteristics of the Gires-Tournois resonators are numerically and experimentally investigated for three configurations: dielectric cavity on metal, metal-dielectric-metal resonator, and distributed Bragg reflector (DBR)-dielectric-metal resonator. Narrowband thermal emitters based on the metal-dielectric-metal cavity and (DBR)-dielectric-metal cavity are experimentally demonstrated with an emissivity of 0.8 and 0.82, and a quality factor of 21 and 85, respectively. A DBR-dielectric-metal resonator-based absorber is directly loaded onto a LiTaO 3 film for the first time to constitute an on-chip ultra-narrowband pyroelectric detector with an excellent quality factor of 151 at the absorption band of methane.


Acid/base-controlled AuI/Au0 reductive transformations of the monogold [(μ14-Au)Pd22(CO)20(PEt3)8]+ monocation into three different neutral digold nanoclusters: Au2Pd21(CO)20(PEt3)10, Au2Pd28(CO)26(PEt3)10, and new five-layer hexagonal close-packed (μ12-Au)2Pd42(CO)30(PEt3)12 with a trigonal-bipyramidal AuPd3Au kernel.
The monogold [(μ(14)-Au)Pd(22)(CO)(20)(PEt(3))(8)](+) nanocation (2, with a [(CF(3)CO(2))(2)H](-) counterion) is shown to be a versatile precursor for the generation of three different neutral Au-Pd nanoclusters with double gold content in their distinctly dissimilar bimetallic architectures. These carbon monoxide (CO)-induced conversions are based on the reduction of Au(I) to Au(0) that is controlled by the reaction medium. Under basic and acidic conditions, the known Au(2)Pd(21)(CO)(20)(PEt(3))(10) (3; >90% yield) and Au(2)Pd(28)(CO)(26)(PEt(3))(10) (4; ∼40% yield), respectively, were obtained, whereas neutral conditions gave rise to the new (μ(12)-Au)(2)Pd(42)(CO)(30)(PEt(3))(12) (1; ∼10-20% yield; all yields based on gold). The molecular structure of 1, established from a 100 K CCD X-ray diffraction study, consists of a five-layer hexoganol close-packed (hcp) Au(2)Pd(42) framework of pseudo-D(3)h symmetry (crystallographic D(3) site symmetry) of the Pd(6)/AuPd(9)/Pd(12)/AuPd(9)/Pd(6) layer sequence, with the Au atoms centering two identical hcp (μ(12)-Au)Pd(12) face-fused anti-cuboctahedral fragments. The 12 Et(3)-attached P atoms are coordinated to the triangular vertex Pd atoms in the four outer layers (except the middle Pd(12)); all five layers are stapled by interlayer bridging COs. The radial Au(cent)-Pd mean distance of 2.79 Å within the two symmetry-equivalent (μ(12)-Au)Pd(12) anti-cuboctahedral fragments of 1 is identical with the radial Pd(cent)-Pd mean distances within hcp (μ(12)-Pd)Pd(12) anti-cuboctahedral fragments of the two geometrically related nondistorted layered structures of Pd(52)(CO)(36)(PEt(3))(14) and [Ni(9)Pd(33)(CO)(41)(PPh(3))(6)](4-) ([PPh(4)](+) counterion), indicating a strain-free structural effect upon the substitution of Au for Pd in their analogous hcp layer-stacked arrangements. It provides prime evidence for an extension to 1 of our previous self-consistent experimental/theoretical-based hypothesis for delocalization of the 6s valence Au electrons in Au(2)Pd(21) (3) and Au(2)Pd(28) (4) toward a formal closed-shell Au(+) configuration that is electronically equivalent to that of zerovalent Pd.


Identification of Bradyrhizobium elkanii USDA61 Type III Effectors Determining Symbiosis with Vigna mungo.
Bradyrhizobium elkanii USDA61 possesses a functional type III secretion system (T3SS) that controls host-specific symbioses with legumes. Here, we demonstrated that B. elkanii T3SS is essential for the nodulation of several southern Asiatic Vigna mungo cultivars. Strikingly, inactivation of either Nod factor synthesis or T3SS in B. elkanii abolished nodulation of the V. mungo plants. Among the effectors, NopL was identified as a key determinant for T3SS-dependent symbiosis. Mutations of other effector genes, such as innB, nopP2, and bel2-5, also impacted symbiotic effectiveness, depending on host genotypes. The nopL deletion mutant formed no nodules on V. mungo, but infection thread formation was still maintained, thereby suggesting its pivotal role in nodule organogenesis. Phylogenetic analyses revealed that NopL was exclusively conserved among Bradyrhizobium and Sinorhizobium (Ensifer) species and showed a different phylogenetic lineage from T3SS. These findings suggest that V. mungo evolved a unique symbiotic signaling cascade that requires both NFs and T3Es (NopL).


Detection of electrically neutral and nonpolar molecules in ionic solutions using silicon nanowires.
We report on a technique that can extend the use of nanowire sensors to the detection of interactions involving nonpolar and neutral molecules in an ionic solution environment. This technique makes use of the fact that molecular interactions result in a change in the permittivity of the molecules involved. For the interactions taking place at the surface of nanowires, this permittivity change can be determined from the analysis of the measured complex impedance of the nanowire. To demonstrate this technique, histidine was detected using different charge polarities controlled by the pH value of the solution. This included the detection of electrically neutral histidine at a sensitivity of 1 pM. Furthermore, it is shown that nonpolar molecules, such as hexane, can also be detected. The technique is applicable to the use of nanowires with and without a surface-insulating oxide. We show that information about the changes in amplitude and the phase of the complex impedance reveals the fundamental characteristics of the molecular interactions, including the molecular field and the permittivity.


Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice.
Fragile X syndrome (FXS) is a major developmental disorder and the most frequent monogenic cause of autism. Surprisingly, most existing studies on the Fmr1-KO mouse model for FXS have focused on males, although FX women, who are mostly heterozygous for the Fmr1 mutation, are known to exhibit several behavioral deficits, including autistic-like features. Furthermore, most animal research has been carried out on adults only; so that little is known about the age progression of the behavioral phenotype of Fmr1 mutants, which is a crucial issue to optimize the impact of therapeutic interventions. Here, we performed an extensive analysis of autistic-like social behaviors in heterozygous (HET) Fmr1-KO females and their WT littermates at different ages. No behavioral difference between HET and WT mice was observed at infancy, but some abnormalities in social interaction and communication were first detected at juvenile age. At adulthood some of these alterations disappeared, but avoidance of social novelty appeared, together with other FXS-relevant behavioral deficits, such as hyperactivity and reduced contextual fear response. Our data provide for the first time evidence for the presence of autistic-relevant behavioral abnormalities in Fmr1-HET female mice, demonstrating the utility of this mouse line to model autistic-like behaviors in both sexes. These results also highlight the importance of taking into account age differences when using the Fmr1-KO mouse model, suggesting that the early post-natal phases are the most promising target for preventive interventions and the adult age is the most appropriate to investigate the behavioral impact of potential therapies. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1067-1078. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Transfer and Decontamination of S. aureus in Transmission Routes Regarding Hands and Contact Surfaces.
Hand hygiene, cleaning and disinfection are pre-requirements for hygiene management in hospital settings and the food industry. In order to facilitate risk management, different contamination scenarios and interventions need to be evaluated. In the present study data on transfer rates and reductions of Staphylococcus aureus were provided in an experimental set-up using artificial skin. Using this methodology, test persons were not exposed with pathogenic bacteria. An exposure assessment model was developed and applied to evaluate different contamination routes and hygiene interventions. The transfer rates of S. aureus from inoculated VITRO-SKIN® to fomites were calculated from blotting series. The VITRO-SKIN® was more prone to spread bacteria than fomites. When different surfaces were cleaned, the reduction of S. aureus varied between <1 and 7 log CFU. It could not be concluded that a certain coupon material, cleaning agent, cleaning wipe, soiling or humidity consistently resulted in a high or low reduction of S. aureus. The reduction of S. aureus and E. coli during hand washing was evaluated on artificial skin, VITRO-SKIN®. The reduction of E. coli on VITRO-SKIN® was similar to the log reduction obtained when washing human hands. The S. aureus count on a human hand was both calculated in different scenarios describing different contamination routes starting from a contaminated hand using the exposure assessment model, and measured on an experimental setup using VITRO-SKIN® for validation. A linear relationship was obtained between the analysed level of S. aureus and the calculated level. However, the calculated levels of S. aureus on the VITRO-SKIN® in the scenarios were 1-1.5 log lower than the analysed level. One of the scenarios was used to study the effect of interventions like hand washing and cleaning of surfaces.


Determination of plasmakinin & kininogen levels in man.
1. A method for the estimation of free plasma kinin and kininogen is described, which is suitable for samples of blood taken in hospital.2. The method permits the assay of very low levels of kinin and substantially eliminates errors due to the presence of amines and other interfering substances.3. In normal subjects the mean value of free kinin is 2.8 ng (bradykinin equivalent)/ml. plasma, and 6.1 mug kininogen/ml.4. In vasovagal fainting, carcinoid flush, and dumping syndrome, during the phase of peripheral vasodilatation, the free kinin exceeds 10 ng/ml., and is often in excess of 30 ng/ml.5. Sudden release of free kinin is accompanied by a fall in kininogen level.


Challenging the "Culture" of the Tracheal Aspirate.
The tracheal aspirate (TA) culture is commonly ordered in the NICU, but it has low sensitivity and specificity, limited by contamination. Interpretation of a TA culture out of context can lead to antibiotic overuse, which should be avoided. Clinicians should practice caution in the diagnosis of congenital pneumonia and use newer, published approaches to the diagnosis of ventilator-associated pneumonia in neonates. A subset of neonatal patients with risk factors of maternal fever or chorioamnionitis requiring intubation may benefit from TA culture performed within 12 hours after birth, to help identify an organism when blood culture may be negative, and tailor antimicrobial therapies. The more invasive, but more sensitive, technique of nonbronchoscopic bronchoalveolar lavage should be considered in older infants when bacterial isolation from the lower respiratory tract is necessary, because TA culture cannot distinguish between colonization and infection in that population.


Numerical research on the lateral global buckling characteristics of a high temperature and pressure pipeline with two initial imperfections.
With the exploitation of offshore oil and gas gradually moving to deep water, higher temperature differences and pressure differences are applied to the pipeline system, making the global buckling of the pipeline more serious. For unburied deep-water pipelines, the lateral buckling is the major buckling form. The initial imperfections widely exist in the pipeline system due to manufacture defects or the influence of uneven seabed, and the distribution and geometry features of initial imperfections are random. They can be divided into two kinds based on shape: single-arch imperfections and double-arch imperfections. This paper analyzed the global buckling process of a pipeline with 2 initial imperfections by using a numerical simulation method and revealed how the ratio of the initial imperfection's space length to the imperfection's wavelength and the combination of imperfections affects the buckling process. The results show that a pipeline with 2 initial imperfections may suffer the superposition of global buckling. The growth ratios of buckling displacement, axial force and bending moment in the superposition zone are several times larger than no buckling superposition pipeline. The ratio of the initial imperfection's space length to the imperfection's wavelength decides whether a pipeline suffers buckling superposition. The potential failure point of pipeline exhibiting buckling superposition is as same as the no buckling superposition pipeline, but the failure risk of pipeline exhibiting buckling superposition is much higher. The shape and direction of two nearby imperfections also affects the failure risk of pipeline exhibiting global buckling superposition. The failure risk of pipeline with two double-arch imperfections is higher than pipeline with two single-arch imperfections.


Disability Attitudes of Nursing Students: A Curriculum Intervention.
People with disabilities (PWD) have reported that health care workers' negative attitudes are among the most significant barriers to accessing health care services. PWD constitute one quarter of the population, yet the curriculum for PWD is inconsistent. This study describes a curriculum intervention allowing student interaction with a panel of PWD to change nursing student attitudes. Surveys were administered before and after the intervention. Our pilot study did not reveal a significant change in attitudes, which suggests that more exposure to PWD and education may be needed.


Background Stress Inventory: Developing a Measure of Understudied Stress.
Background stress is an understudied source of stress that involves both ambient stress and daily hassles upon which new stressors are superimposed. To date, an accurate measure of the background stress construct has not been available. We developed the Background Stress Inventory, a 25-item self-report measure that asks respondents to indicate how distressed they have felt over the past month and the majority of the past year across five domains: financial, occupation, environment, health and social. Seven hundred seventy-two participants completed the paper-and-pencil measure; the sample was randomly split into two separate subsamples for analyses. Exploratory factor analysis suggested five factors corresponding to these domains, and confirmatory factor analysis showed acceptable global fit (X(2)(255) = 456.47, comparative fit index = 0.94, root mean square error of approximation = 0.045). Cronbach's alpha (0.89) indicated good internal reliability. Construct validity analyses showed significant positive relationships with measures of perceived stressfulness (r = 0.62) and daily hassles (0.41), p's < 0.01. Depressive symptoms (0.62) and basal blood pressure (0.21) were both significantly associated with background stress, p's < 0.01. The importance of the proposed measure is reflected in the limited research base on the impact of background stress. Systematic investigation of this measure will provide insight into this understudied form of chronic stress and its potential influence on both psychological and physical endpoints.


Electronic structure and optical properties of 1T-TiS2 and lithium intercalated 1T-TiS2 for lithium batteries.
We report results of first-principles calculations of electronic and optical properties of pristine 1T-TiS(2) and 1T-TiS(2) intercalated with lithium. Calculations have been performed using the full-potential linearized augmented plane wave method based on density functional theory together with the local density approximation for the exchange correlation energy functional. We have calculated the band structure, density of states, and the linear optical properties. We compare our results of the intercalated 1T-LiTiS(2) with the host 1T-TiS(2) to ascertain the effect of Li intercalation on the electronic and optical properties. The Li-s and Li-p bands are very broad and do not contribute much to the density of states. Our calculations show that the electronic and optical properties are influenced significantly when TiS(2) is intercalated with lithium.


Antibacterial properties of phosphine gold(I) complexes with 5-fluorouracil.
New gold(I) complexes with coordination to 5-fluorouracil (5-FU), an anticancer drug with antibacterial properties, have been synthesised and characterised, and are the first reported examples of 5-FU-Au compounds. These new complexes show high solution stability, even in the presence of a cysteine derivative, and so were evaluated as antibacterial compounds against model Gram-positive and Gram-negative bacteria. All the complexes show excellent antibacterial activity against Gram-positive B. subtilis, most of them improving the activity of 5-FU alone. Furthermore, these new complexes are also active against Gram-negative E. coli, where [Au(5-FU)(PTA)], the complex with the smallest phosphane, is the most bactericidal, 32 times more active than 5-FU on its own.


Frequency of eating occasions reported by young New Zealand Polynesian and European women.
The frequency of eating occasions reported by young New Zealand Polynesian and European women was examined. The timing and content of meals and snacks were analysed from 80 self-reported seven-day food diaries from a previous study of 80 young women (39 New Zealand Polynesian and 41 European) aged between 18 and 27 years. Nineteen Polynesian and 20 European women had a body mass index (BMI) greater than 30 kg.m-2 and were classified as obese. Breakfast was eaten more often by the European women than the Polynesian (median 4 versus 3 times.week-1, P = 0.012). Eleven (28%) of the Polynesian women skipped breakfast every day of the study week compared to only three (7%) of the Europeans (P = 0.019). Dinner was eaten more frequently by the European women (P = 0.020) who also ate significantly more meals during the week than the Polynesian (P = 0.039). Non-obese Europeans ate breakfast more frequently than their obese counterparts (P = 0.002) while no significant difference was observed between non-obese and obese Polynesians. The obese European and Polynesian groups reported similar patterns of breakfast consumption which differed significantly from the non-obese Europeans (P = 0.008). The young women in this study did not eat breakfast every day with the young Polynesian women eating fewer meals than the Europeans. There was an association between ethnic origin, body size and eating patterns in the women. These findings in comparison with previous studies in other countries indicate that the frequency of eating breakfast may be declining with time.


Determination of heavy metals in honey in Kahramanmaraş City, Turkey.
Heavy metals in honey are of interest not only for quality control, but also for determination environmental contamination. The objective of this work was to determine distribution of the levels of selected heavy metals. Levels of copper (Cu), cadmium (Cd), manganese (Mn), Iron (Fe), magnesium (Mg) and nickel (Ni) in honey samples (21) in Kahramanmaraş region were determined by atomic absorption spectrometer (AAS). The mean values for Cu, Cd, Mn, Fe, and Mg were 0.01, 0.32, 0.03, 0.36 and 10.45 ppm, respectively. Nickel was not detected in honey samples. Kahramanmaraş honey samples were not free of heavy metals but the levels of them were found well below the permitted levels. The results suggested that honey may be useful for assessing the presence of environmental contaminants.


Breastfeeding and mental health in adulthood: A birth cohort study in Brazil.
Breastfeeding is negatively associate with behavioral and internalization problems, psychological stress, and depressive/anxiety symptoms. However, studies evaluating specific mental health disorders are scarce. We aimed to assess the association between breastfeeding and mental health outcomes in young adults. In 1982, hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n=5914). Information on breastfeeding was collected in early childhood. In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for the diagnosis of major depression (MD), generalized anxiety disorder (GAD) and social anxiety disorder (SAD). In addition, we used the Beck Depression Inventory (BDI-II) and the Self-reported Questionnaire (SRQ-20), to evaluate depressive symptoms severity and common mental disorders (CMD), respectively. We used multivariable regression models to evaluate the association between breastfeeding and mental health outcomes. We evaluated 3657 individuals. Prevalence of CMD, MD, GAD and SAD was 24.3%, 7.9%, 12.7% and 3.6%, respectively. In multivariable models the odds of having a more severe case of depression (BDI-II) was smaller among those breastfed for 6 or more months (OR=0.69 95%CI [0.53-0.89]). We observed a similar pattern for MD and CMD, however, confidence intervals included the reference. We had no information on home environment characteristics during childhood. Lack of power and a small effect size could explain why we did not detect an association between breastfeeding and MD. Breastfeeding reduced the odds of having more severe depressive symptoms.


[Brooke-Spiegler syndrome: an heterogeneous entity].
The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a predisposition to develop different adnexal tumors. Clinically it is characterized by the presence of multiple cylindromas, trichoepitheliomas, and occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial cylindromatosis and multiple familial trichoepithelioma were initially described as separate entities, the recently identified identical mutations in the gene of cylindromatosis suggest that they represent fenotypic variations of the same entity. In this article we present the case of a woman and her daughter, both affected by this rare genodermatosis.


S-1 vs. paclitaxel plus carboplatin as adjuvant chemotherapy for completely resected stage II/IIIA non-small-cell lung cancer.
The majority of patients with completely resected stage II or IIIA non-small-cell lung cancer (NSCLC) require adjuvant chemotherapy to improve survival following surgery. In the present trial, the 2-year disease-free survival (DFS), and the feasibility and safety of S-1 as an adjuvant chemotherapy for advanced lung cancer were evaluated. A total of 40 patients with completely resected stage II or IIIA NSCLC were enrolled and randomized to receive postoperative chemotherapy with either up to 4 cycles of paclitaxel plus carboplatin (arm A) or with up to 1 year of S-1 (arm B). The primary endpoint was 2-year DFS. The secondary endpoints were feasibility and toxicity. A total of 40 patients were enrolled, but 3 were excluded in accordance with the exclusion criteria. The remaining 37 patients were analyzed. The 2-year DFS rate was 54.2% in arm A and 84.2% in arm B. Overall, 15/18 (83.3%) patients completed 4 cycles of paclitaxel plus carboplatin and 13/19 (68.4%) completed 1-year of S-1adjuvant chemotherapy. Of the 18 (16.7%) patients in arm A, 3 experienced grade 3 or 4 adverse events, while none in arm B experienced such events. Therefore, S-1 chemotherapy for patients with completely resected stage II or IIIA NSCLC was a feasible and safe regimen, and it may therefore be considered as a potential adjuvant chemotherapy option for advanced NSCLC.


Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition.
Collateral fattening refers to the process whereby excess fat is deposited as a result of the body's attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity.


Evidence for nucleolus organizer regions as the units of regulation in nucleolar dominance in Arabidopsis thaliana interecotype hybrids.
Nucleolar dominance describes the silencing of one parent's ribosomal RNA (rRNA) genes in a genetic hybrid. In Arabidopsis thaliana, rRNA genes are clustered in two nucleolus organizer regions, NOR2 and NOR4. In F(8) recombinant inbreds (RI) of the A. thaliana ecotypes Ler and Cvi, lines that display strong nucleolar dominance inherited a specific combination of NORs, Cvi NOR4 and Ler NOR2. These lines express almost all rRNA from Cvi NOR4. The reciprocal NOR genotype, Ler NOR4/Cvi NOR2, allowed for expression of rRNA genes from both NORs. Collectively, these data reveal that neither Cvi rRNA genes nor NOR4 are always dominant. Furthermore, strong nucleolar dominance does not occur in every RI line inheriting Cvi NOR4 and Ler NOR2, indicating stochastic effects or the involvement of other genes segregating in the RI mapping population. A partial explanation is provided by an unlinked locus, identified by QTL analysis, that displays an epistatic interaction with the NORs and affects the relative expression of NOR4 vs. NOR2. Collectively, the data indicate that nucleolar dominance is a complex trait in which NORs, rather than individual rRNA genes, are the likely units of regulation.


A gaze bias with coarse spatial indexing during a gambling task.
Researchers have used eye-tracking methods to infer cognitive processes during decision making in choice tasks involving visual materials. Gaze likelihood analysis has shown a cascading effect, suggestive of a causal role for the gaze in preference formation during evaluative decision making. According to the gaze bias hypothesis, the gaze serves to build commitment gradually towards a choice. Here, we applied gaze likelihood analysis in a two-choice version of the well-known Iowa Gambling Task. This task requires active learning of the value of different choice options. As such, it does not involve visual preference formation, but choice optimization through learning. In Experiment 1 we asked subjects to choose between two decks with different payoff structures, and to give their responses using mouse clicks. Two groups of subjects were exposed to stable versus varying outcome contingencies. The analysis revealed a pronounced gaze bias towards the chosen stimuli in both groups of subjects, plateauing at more than 400 ms before the choice. The early plateauing suggested that the gaze effect partially reflected eye-hand coordination. In Experiment 2 we asked subjects to give responses using a key press. The results again showed a clear gaze bias towards the chosen deck, this time without any influence from eye-hand coordination. In both experiments, there was a clear gaze bias towards the choice even though the gaze fixations did not narrowly focus on the spatial positions of choice options. Taken together, the data suggested a role for gaze in coarse spatial indexing during non-perceptual decision making.


Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO.
The characteristics of arteriolar myogenic responses of female rats have not been investigated. Thus experiments were conducted on isolated gracilis muscle arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats: male rats, female rats, ovariectomized female rats with no estrogen replacement (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50 microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter changes in response to increases in perfusion pressure from 20 to 140 mmHg and to various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO synthase. Arteriolar diameters of male and OV female rats were significantly less at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at 80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA elicited a significantly greater downward shift of pressure-diameter curves in arterioles of normal female and OV + E2 female rats than in arterioles of male and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/- 2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP were significantly greater (by 50-60%) than those from male and OV female rats (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L-NNA did not affect dilations to SNP but significantly reduced the dilation of arterioles in all groups to SP, more so in arterioles of male and OV female rats than in arterioles of the other two groups. We conclude that pressure-induced myogenic constriction of arterioles of female rats is less pronounced than that of male rats; this is, most likely, due to the enhanced release and/or activity of NO related to the presence of estrogen.


Quality improvement opportunities in caring for patients with nonepileptic seizures.
Background. Patients with nonepileptic seizures (NES) are challenging to treat for myriad reasons. Often patients may be misdiagnosed with having epilepsy and then may suffer unintended consequences of treatment side effects with antiepileptic medication. In addition, patients may be maligned by health care providers due to a lack of ownership by both psychiatrists and neurologists and a dearth of dedicated professionals who are able to effectively treat and reduce severity and frequency of symptoms. Aims of Case Report. Many psychiatrists and neurologists are unaware of the extent of the barriers to care faced by patients with NES (PWNES) and the degree of perception of maltreatment or lack of therapeutic alliance at various stages of their care, including medical workup, video-EEG monitoring, and follow-up plans. We present the case of a patient with NES who experienced numerous barriers as well as incoordination to her care despite being offered a breadth of resources and discuss the quality improvement opportunities that may exist to improve care of patients with NES. Conclusion. No known literature has documented the extensive barriers to care of PWNES in parallel to quality improvement opportunities for improving their care. We endeavor to contribute to the overall formulation and development of a clinical care pathway for PWNES.


RN to BSN Transition: A Concept Analysis.
Over 670,000 ADN- and diploma-prepared nurses will need to complete their BSN degrees to meet the Institute of Medicine's recommendation that at least 80% of registered nurses (RNs) be BSN-prepared by year 2020. Understanding motivators, barriers, and the transition experience for RNs to advance their degree will help educators and nurse leaders understand the importance of a partnership to educate and mentor RNs to pursue a BSN degree.


Symptomatic Pneumocephalus after Lumbar Disc Surgery: a Case Report.
Symptomatic pneumocephalus is frequently seen after traumatic fracture of the skull base bone. However, it has rarely been reported after spinal surgery and its mechanism has not been fully explained. In this paper, we present a 30 year old male patient who had lumbar discectomy due to a symptomatic midline lumbar disc herniation. He had developed symptomatic pneumocephalus after the lumbar disc surgery associated with application of a vacuum suction device. We present and discuss our patient in the light of the literatures.


Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions.
Tryptophan metabolites are known to participate in the regulation of many cells of the immune system and are involved in various immune-mediated diseases and disorders. Kynurenic acid (KYNA) is a product of one branch of the kynurenine pathway of tryptophan metabolism. The influence of KYNA on important neurophysiological and neuropathological processes has been comprehensively documented. In recent years, the link of KYNA to the immune system, inflammation, and cancer has become more apparent. Given this connection, the anti-inflammatory and immunosuppressive functions of KYNA are of particular interest. These characteristics might allow KYNA to act as a "double-edged sword." The metabolite contributes to both the resolution of inflammation and the establishment of an immunosuppressive environment, which, for instance, allows for tumor immune escape. Our review provides a comprehensive update of the significant biological functions of KYNA and focuses on its immunomodulatory properties by signaling via G-protein-coupled receptor 35 (GPR35)- and aryl hydrocarbon receptor-mediated pathways. Furthermore, we discuss the role of KYNA-GPR35 interaction and microbiota associated KYNA metabolism for gut homeostasis.


Epidemiologic and clinical characteristics of pelvic inflammatory disease associated with Mycoplasma hominis, Chlamydia trachomatis, and Neisseria gonorrhoeae.
We studied selected epidemiologic, clinical, serologic, and microbiologic findings and their interrelationships among 57 women with acute pelvic inflammatory disease (PID). Cervical cultures positive for Neisseria gonorrhoeae alone and for both N. gonorrhoeae and Chlamydia trachomatis were associated with young age, nulliparity, and use of birth-control pills. Positive serologic findings for C. trachomatis were associated with the isolation of C. trachomatis and/or N. gonorrhoeae from the cervix and predicted the presence of a pelvic mass. High levels of antibody to Mycoplasma hominis were associated with increasing age and parity, and predicted a low concentration of C-reactive protein (CRP), a long hospital stay, and a high convalescent-phase erythrocyte sedimentation rate (ESR). Women with recurrent PID had higher titers of antibody to C. trachomatis than those with primary PID. The use of an intrauterine contraceptive device predicted high CRP, high acute-phase ESR, long hospital stay, and was frequently associated with positive serologic tests for M. hominis. These results demonstrate that the clinical picture of PID depends not only on the microorganisms involved but also on many epidemiologic factors such as age, contraceptive method, and parity.


Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.
Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold). In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.


Escherichia coli isolated from calves with diarrhea: mannose-resistant haemagglutination and colonisation factor.
A study was carried out for detection of the adhesive antigen K99 on 84 Escherichia coli strains isolated from calves with diarrhea. The methods utilized were the Brush-Border and the slide agglutination tests; the strains were also tested in their ability to evoke mannose-resistant haemagglutination. The positive results obtained with the slide agglutination test were higher with comparison to the positive results obtained with other tests. The bacteria had the other piliated structures, besides the K99 antigen, that require further studies.


Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis.
Risedronate has been shown to be effective in the treatment of postmenopausal osteoporosis when given orally in daily or weekly doses or on 2 consecutive days per month. This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen. Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650) in a double-blind fashion for 2 years. Study drug was taken on an empty stomach at least 30 min before breakfast. Bone mineral density, bone turnover markers, fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine bone mineral density after 1 year. 538 patients in the daily group (83.8%) and 556 patients in the once-a-month group (85.5%) completed 1 year. The mean percent change in lumbar spine bone mineral density was 3.4% (95% confidence interval, 3.03% to 3.82%) in the daily group and 3.5% (95% confidence interval, 3.15% to 3.93%) in the once-a-month group. The difference between groups was -0.1% (95% confidence interval, -0.51% to 0.27%). The once-a-month regimen was determined to be non-inferior to the daily regimen based on prospectively defined criteria. The mean percent changes in bone mineral density at sites in the hip (total proximal femur, femoral neck, femoral trochanter) were also similar in both dose groups, as were the changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the 2 treatment groups. Both regimens were well tolerated; the percent of patients who withdrew from treatment as a result of an adverse event was 9.5% in the daily group and 8.6% in the once-a-month group. Risedronate 150 mg once a month is similar in efficacy and safety to daily dosing and may provide an alternative for patients who prefer once-a-month oral dosing.


Heart and bladder detection and segmentation on FDG PET/CT by deep learning.
Positron emission tomography (PET)/ computed tomography (CT) has been extensively used to quantify metabolically active tumors in various oncology indications. However, FDG-PET/CT often encounters false positives in tumor detection due to 18fluorodeoxyglucose (FDG) accumulation from the heart and bladder that often exhibit similar FDG uptake as tumors. Thus, it is necessary to eliminate this source of physiological noise. Major challenges for this task include: (1) large inter-patient variability in the appearance for the heart and bladder. (2) The size and shape of bladder or heart may appear different on PET and CT. (3) Tumors can be very close or connected to the heart or bladder. A deep learning based approach is proposed to segment the heart and bladder on whole body PET/CT automatically. Two 3D U-Nets were developed separately to segment the heart and bladder, where each network receives the PET and CT as a multi-modal input. Data sets were obtained from retrospective clinical trials and include 575 PET/CT for heart segmentation and 538 for bladder segmentation. The models were evaluated on a test set from an independent trial and achieved a Dice Similarity Coefficient (DSC) of 0.96 for heart segmentation and 0.95 for bladder segmentation, Average Surface Distance (ASD) of 0.44 mm on heart and 0.90 mm on bladder. This methodology could be a valuable component to the FDG-PET/CT data processing chain by removing FDG physiological noise associated with heart and/or bladder accumulation prior to image analysis by manual, semi- or automated tumor analysis methods.


Membrane proteases in the bacterial protein secretion and quality control pathway.
Proteolytic cleavage of proteins that are permanently or transiently associated with the cytoplasmic membrane is crucially important for a wide range of essential processes in bacteria. This applies in particular to the secretion of proteins and to membrane protein quality control. Major progress has been made in elucidating the structure-function relationships of many of the responsible membrane proteases, including signal peptidases, signal peptide hydrolases, FtsH, the rhomboid protease GlpG, and the site 1 protease DegS. These enzymes employ very different mechanisms to cleave substrates at the cytoplasmic and extracytoplasmic membrane surfaces or within the plane of the membrane. This review highlights the different ways that bacterial membrane proteases degrade their substrates, with special emphasis on catalytic mechanisms and substrate delivery to the respective active sites.


Practice patterns in complex ventral hernia repair and place of biological grafts: a national survey among French digestive academic surgeons.
Despite the prevalence of complex ventral hernias, there is little agreement on the most appropriate technique or prosthetic to repair these defects, especially in contaminated fields. Our objective was to determine French surgical practice patterns among academic surgeons in complex ventral hernia repair (CVHR) with regard to indications, most appropriate techniques, choice of prosthesis, and experience with complications. A survey consisting of 21 questions and 6 case-scenarios was e-mailed to French practicing academic surgeons performing CVHR, representing all French University Hospitals. Forty over 54 surgeons (74%) responded to the survey, representing 29 French University Hospitals. Regarding the techniques used for CVHR, primary closure without reinforcement was provided in 31.6% of cases, primary closure using the component separation technique without mesh use in 43.7% of cases, mesh positioned as a bridge in 16.5% of cases, size reduction of the defect by using aponeurotomy incisions without mesh use in 8.2% of cases. Among the 40 respondents, 36 had experience with biologic mesh. There was a strong consensus among surveyed surgeons for not using synthetic mesh in contaminated or dirty fields (100%), but for using it in clean settings (100%). There was also a strong consensus between respondents for using biologic mesh in contaminated (82.5%) or infected (77.5%) fields and for not using it in clean setting (95%). In clean-contaminated surgery, there was no consensus for defining the optimal therapeutic strategy in CVHR. Infection was the most common complication reported after biologic mesh used (58%). The most commonly reported influences for the use of biologic grafts included literature, conferences and discussion with colleagues (85.0%), personal experience (45.0%) and cost (40.0%). Despite a lack of level I evidence, biologic meshes are being used by 90% of surveyed surgeons for CVHR. Importantly, there was a strong consensus for using them in contaminated or infected fields and for not using them in clean setting. To better guide surgeons, prospective, randomized trials should be undertaken to evaluate the short- and long-term outcomes associated with these materials in various surgical wound classifications.