Determination of the utility of the Intubation Difficulty Scale for use with indirect laryngoscopes.
The purpose of this study was to determine whether the Intubation Difficulty Scale is meaningful when used with indirect laryngoscopes. Data were analysed from previously published clinical trials from our group that compared the indirect laryngoscopes with the Macintosh laryngoscope. For each laryngoscope type, the Intubation Difficulty Scale score obtained for each tracheal intubation was correlated with data for duration of the intubation attempt and with the user rated difficulty of the intubation attempt. The strengths of the correlations between these indices were then compared for tracheas intubated with the Macintosh vs the indirect laryngoscopes. The Intubation Difficulty Scale performed well when compared with data for duration and user rated difficulty of the intubation attempts for the both direct and indirect laryngoscopy. However, the correlation between the Intubation Difficulty Scale score and both user rated difficulty (p = 0.001) and the duration of tracheal intubation (p = 0.003) were significantly stronger for the Macintosh laryngoscope compared with the indirect laryngoscopes. In contrast, the correlation between user rated difficulty scores and the data for duration of tracheal intubation was not different between the device types. The Intubation Difficulty Scale performs less well with indirect laryngoscopes than with the Macintosh laryngoscope. These findings suggest the need for caution with the use of this score with indirect laryngoscopes.


Temporal trends and spatial distribution of PCDD, PCDF, and PCB in pine and spruce shoots.
In Germany, there is a lack of consistent and comparable data for the time dependent behaviour and spatial distribution of dioxin-like and indicator PCB in ambient air, deposition and plants. The aim of this study was to improve the data on PCDD/PCDF, dioxin-like PCB and non dioxin-like PCB in spruce and pine shoots from different locations and years by retrospective monitoring. The survey was conducted with archived samples of one-year old spruce shoots (Picea abies) and pine shoots (Pinus sylvestris) from the German environmental specimen bank. Two sets of samples from locations in urbanized areas in western and eastern Germany (Warndt and Duebener Heide Mitte, respectively) were investigated as time series. Additionally, spruce shoots from seven different rural locations sampled in the years 2000-2004 were analyzed in order to get an overview about the spatial distribution of PCB and PCDD/PCDF. The analytical results of the samples from the two urbanized areas clearly show that the atmospheric contamination with PCDD and PCDF has declined by about 75% between 1985 and 1997 at Warndt and about 40% between 1991 and 1997 at Duebener Heide. However, concentrations stayed virtually constant at both locations from 1997 to 2004 at a level of about 1 ng WHO-TEQ/kg dry matter (d.m.). Similarly, the investigation of spruce shoots from rural locations from 2000 to 2004 did not reveal a temporal trend at any site. PCDD/PCDF levels were between 0.1 and 1.0 ng WHO-TEQ/kg d.m. At the urbanized location Warndt the six indicator PCB as well as the 12 dioxin-like PCB according to WHO revealed a significant decline by more than 75% between 1985 and 1999. Thereafter, PCB levels stayed virtually constant. At the location Duebener Heide an overall decrease of PCB concentrations in pine shoots of about 60% was detected between 1991 and 2004. Spruce shoots from all locations showed a relevant contribution of dioxin-like PCB to the total WHO toxicity equivalent (PCDD/PCDF+PCB). In most samples, the contribution of dioxin-like PCB was between 21% and 41%. The TEQ contribution of PCB in the samples from three rural sites was higher and similar to the TEQ value of PCDD/PCDF. The investigated pine shoots from the urbanized site Duebener Heide showed a 15-28% contribution of dioxin-like PCB to total TEQ and thus lower than in spruce shoots from different locations. In all samples except one PCB 126 contributed to more than 80% to the PCB-TEQ.


First Report of Diplodia corticola Causing Branch Cankers on Live Oak (Quercus virginiana) in Florida.
Numerous cankers on small branches showing dieback were observed on live oak (Quercus virginiana) trees in September 2010 in Marion County, FL. Approximately 24 12-year-old landscape trees planted on a farm displayed symptoms. Samples were collected from six of the symptomatic trees and returned to the laboratory for processing. Isolations were made from canker margins after surface sterilization of samples in 2.5% sodium hypochlorite and by plating on potato dextrose agar (PDA). A suspect Botryosphaeriaceae sp. (based on colony morphology) was consistently isolated from the symptomatic branches from all six trees sampled. Fungal colonies consisted of plentiful, white, aerial mycelium that turned dark olive after 5 to 7 days at 23°C with the underside of the cultures turning black (1). Total genomic DNA from three representative Botryosphaeriaceae sp. isolates was extracted and the internal transcribed spacer (ITS1-5.8s-ITS2) region of the rDNA (GenBank Accessions Nos. JF798638, JF798639, and JF798640) using the primers ITS1 and ITS4 (3) and a portion of the β-tubulin gene (Bt), (GenBank Accession Nos. JF798641, JF798642, and JF798641) using the primers Bt2a and Bt2b (2) were amplified, sequenced, and deposited in GenBank. BLASTn searches of the ITS-rDNA sequences resulted in 100% homology (467 of 467, 467 of 467, and 540 of 540, respectively) with Diplodia corticola isolate CBS 112074 (GenBank Accession No. AY268421). BLASTn searches of the Bt sequences resulted in 99, 98, and 99% (391 of 393, 396 of 400, and 392 of 394, respectively) matches with D. corticola strain UCD2397TX, GenBank Accession No. GU294724. To complete Koch's postulates, nine seedlings of Q. virginiana, 0.6 to 0.9 cm in diameter at ground line maintained in a greenhouse, were inoculated with isolate PL949 (GenBank Accession Nos. JF798638 and JF798641) by making a 1.5-cm incision with a single-edge razor blade into the xylem 10 cm above ground line. Inoculations were done by placing mycelial plugs (1 × 0.25 cm) from cultures on PDA in the incision with the mycelium facing the center of the stem. Wounds were sealed by wrapping them with Parafilm. Three negative controls were mock inoculated as previously described except sterile PDA plugs were used. Eight weeks postinoculation, the lengths of the necrotic lesions were measured. Mean lesion length of the inoculated seedlings was 41.2 cm ± SE 4.5 and ranged between 27 and 63 cm. The negative control inoculations showed no necrotic lesions. Three of the inoculated seedlings were plated on PDA in an effort to reisolate the inoculated fungus. D. corticola was reisolated from each and all had the same ITS sequence as D. corticola strain CBS 112074. To our knowledge, this is the first report of D. corticola causing cankers on Q. virginiana and the first report of the disease occurring in Florida. D. corticola has been reported to cause cankers and dieback in several Quercus spp. in Greece, Hungary, Italy, Morocco, Portugal, and Spain and has recently been reported to cause cankers on Q. chrysolepis and Q. agrifolia in California. References: (1) A. Alves et al. Mycologia. 96:598, 2004. (2) N. L. Glass and G. C. Donaldson. Appl. Environ. Microbiol. 61:1323, 1995. (3) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.


Positive Feedback Defines the Timing, Magnitude, and Robustness of Angiogenesis.
Angiogenesis is driven by the coordinated collective branching of specialized leading "tip" and trailing "stalk" endothelial cells (ECs). While Notch-regulated negative feedback suppresses excessive tip selection, roles for positive feedback in EC identity decisions remain unexplored. Here, by integrating computational modeling with in vivo experimentation, we reveal that positive feedback critically modulates the magnitude, timing, and robustness of angiogenic responses. In silico modeling predicts that positive-feedback-mediated amplification of VEGF signaling generates an ultrasensitive bistable switch that underpins quick and robust tip-stalk decisions. In agreement, we define a positive-feedback loop exhibiting these properties in vivo, whereby Vegf-induced expression of the atypical tetraspanin, tm4sf18, amplifies Vegf signaling to dictate the speed and robustness of EC selection for angiogenesis. Consequently, tm4sf18 mutant zebrafish select fewer motile ECs and exhibit stunted hypocellular vessels with unstable tip identity that is severely perturbed by even subtle Vegfr attenuation. Hence, positive feedback spatiotemporally shapes the angiogenic switch to ultimately modulate vascular network topology.


Cavitary pulmonary lesion wall thickness, presence of additional nodules, and intralesional contrast enhancement are associated with malignancy in dogs and cats.
To investigate the CT features of cavitary pulmonary lesions and determine their utility to differentiate malignant from benign lesions. This retrospective study included cases from 5 veterinary medical centers between January 1 2010, and December 31, 2020. Inclusion criteria included having a gas-filled cavitary pulmonary lesion on thoracic CT and definitive diagnosis by either cytology or histopathology. Forty-two animals (27 dogs and 15 cats) were included in this study. Medical records systems/imaging databases were searched, and cases meeting inclusion criteria were selected. The CT studies were interpreted by a third-year radiology resident, and findings were reviewed by a board-certified veterinary radiologist. 7 of the 13 lesion characteristics investigated were not statistically associated with the final diagnosis of the lesion, whereas 6 were statistically associated. Those that were associated included the presence of intralesional contrast enhancement, type of intralesional contrast enhancement (heterogenous and homogenous analyzed separately), presence of additional nodules, wall thickness of the lesion at its thickest point, and wall thickness at the thinnest point. Results from the present study showed that thoracic CT imaging of cavitary pulmonary lesions can be used to further refine the list of differential diagnoses. Based on this data set, in lesions that have heterogenous contrast enhancement, additional pulmonary nodules, and wall thickness > 40 mm at their thickest point, it would be reasonable to consider malignant neoplastic disease higher on the list of differentials than other causes.


Highly efficient oxygen evolution from CoS2/CNT nanocomposites via a one-step electrochemical deposition and dissolution method.
The oxygen evolution reaction (OER) has been viewed as a critical step in electrochemical energy conversion and storage devices. However, searching for cheap and efficient OER electrocatalysts still remains an urgent task. Herein, we develop a new strategy involving a one-step electrochemical deposition and dissolution method to fabricate hydrophilic porous CoS2/carbon nanotube (CNT) composites (CNT-CoS2). X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy measurements confirm the formation of hydrophilic groups on the surface of the porous CoS2 during electrochemical oxidation. Our design holds several advantages. The electricity conductivity of CoS2 is increased by introducing CNTs as a conductive substrate. The porous nanostructures of CoS2 increase its surface area, and provide paths to promote charge and reactant transfer. The active edge sites modified with hydrophilic groups can increase the content of electrolyte-electrode contact points, increasing the intrinsic catalytic performance of CoS2. These factors allow CNT-CoS2 to achieve a low onset potential of 1.33 V vs. RHE, a stable current density (j) of 10 mA cm-2 at an overpotential of 290 mV, and excellent stability under alkaline conditions compared to that of IrO2. The comprehensive performance of the CNT-CoS2 electrocatalyst is comparable to or better than that of any reported noble metal-free OER catalyst, even RuO2 and IrO2. This facile synthesis strategy involving synchronous electrochemical deposition and dissolution should be easily adapted for large-scale water electrolysis.


The form of response of body protein accretion to dietary amino acid supply.
The mean response of body protein accretion in growing animals to their amino acid intake is sometimes described by a rectilinear ("broken-line") model and sometimes by a curvilinear model. The response of a population may be curvilinear as a result of averaging individual rectilinear responses or because individual responses are themselves curvilinear. This experiment was undertaken to distinguish these possibilities by examining the responses of individual animals. Eighteen pigs with a mean initial weight of 35 kg and a mean final weight of 73 kg were each fed, in a different sequence, six diets providing a daily nitrogen intake of 0.5, 1.5, 1.83, 2.17, 2.5 or 3.5 g/kg body wt0.75. Each diet was given for 10 d, with complete collections of feces over the last 6 d and of urine over the last 4 d. Rates of nitrogen retention (expressed per kg0.75 per day) were related to rates of nitrogen intake (in the same units) using a rectilinear (broken line), an exponential or a saturation kinetics model. Mean square errors were significantly larger for the rectilinear model than for either of the curvilinear models and were slightly but not significantly less for the saturation kinetics model than for the exponential model.


Major and trace elements and cosmic-ray produced radioisotopes in lunar samples.
Analytical data for 42 major and trace elements were mostly obtained by a combination of instrumental and radiochemical neutron activation analyses using both thermal and 14-million-electronvolt neutrons. Excesses of nitrogen and chlorine in the fines, compared with the rocks, are attributed to the solar wind. A striking similarity for contents of seven elements in lunar metal and metal from the calcium-rich achondrite Juvinas was noted. Fractional dissolution was used to separate five radionuclides produced by cosmic-ray bombardment in the fines and rock 57-40. Results for argon-39 from the reaction potassium-39 (n,p), and for argon-37, from the reaction calcium-40 (n,a), seem to require a neutron spectrum conitaining more neutrons below 2 million electronvolts than the evaporation spectrum or that given by Arnold, Honda, and Lal (1) or a strong time dependence for the neutron flux.


The role of the Wilms tumour gene (WT1) in normal and malignant haematopoiesis.
In addition to its loss playing a pivotal role in the development of a childhood kidney malignancy, the Wilms tumour 1 gene (WT1) has emerged as an important factor in normal and malignant haematopoiesis. Preferentially expressed in CD34+ haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation. Putative target genes, such as BCL2, MYC, A1 and cyclin E, may cooperate with WT1 to modulate cell growth. However, the effects of WT1 on target gene expression appear to be isoform-specific. Certain WT1 isoforms are over-represented in leukaemia, but the exact mechanisms underlying the role of WT1 in transformation remain unclear. The ubiquity of WT1 in haematological malignancies has led to efforts to exploit it as a marker for minimal residual disease and as a prognostic factor, with conflicting results. In vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours. Alternative methods employing WT1-specific immunotherapy are being investigated and might ultimately be used to optimise multimodal therapy of haematological malignancies.


Structural and kinetic properties of Rhodobacter sphaeroides photosynthetic reaction centers containing exclusively Zn-coordinated bacteriochlorophyll as bacteriochlorin cofactors.
The Zn-BChl-containing reaction center (RC) produced in a bchD (magnesium chelatase) mutant of Rhodobacter sphaeroides assembles with six Zn-bacteriochlorophylls (Zn-BChls) in place of four Mg-containing bacteriochlorophylls (BChls) and two bacteriopheophytins (BPhes). This protein presents unique opportunities for studying biological electron transfer, as Zn-containing chlorins can exist in 4-, 5-, and (theoretically) 6-coordinate states within the RC. In this paper, the electron transfer perturbations attributed exclusively to coordination state effects are separated from those attributed to the presence, absence, or type of metal in the bacteriochlorin at the HA pocket of the RC. The presence of a 4-coordinate Zn(2+) ion in the HA bacteriochlorin instead of BPhe results in a small decrease in the rates of the P*→P(+)HA(-)→P(+)QA(-) electron transfer, and the charge separation yield is not greatly perturbed; however coordination of the Zn(2+) by a fifth ligand provided by a histidine residue results in a larger rate decrease and yield loss. We also report the first crystal structure of a Zn-BChl-containing RC, confirming that the HA Zn-BChl was either 4- or 5-coordinate in the two types of Zn-BChl-containing RCs studied here. Interestingly, a large degree of disorder, in combination with a relatively weak anomalous difference electron density was found in the HB pocket. These data, in combination with spectroscopic results, indicate partial occupancy of this binding pocket. These findings provide insights into the use of BPhe as the bacteriochlorin pigment of choice at HA in both BChl- and Zn-BChl-containing RCs found in nature.


Efficacy assessments in randomized controlled studies of acute therapy for hereditary angioedema.
Hereditary angioedema (HAE) is a rare disorder caused by a deficiency of C1 esterase inhibitor, characterized by recurrent, highly variable attacks of subcutaneous or submucosal edema that may affect multiple body sites. Clinical studies of acute HAE therapies have required the use of assessment tools to evaluate both pretreatment attack severity (baseline severity) and changes in symptom severity following treatment (treatment response). This article reviews the range of assessment tools used for efficacy determination of acute HAE therapies, based on a review of relevant clinical studies. Because the goal is relief of symptoms (rather than cure), patient-reported outcomes (PROs) form the basis of these tools. Tools used to evaluate baseline severity typically employ location-specific assessment of symptom severity, using either categorical descriptions (which may be converted into numerical variables) or a visual analog scale (VAS). Some studies define the initial or most symptomatic site as an "index" site for purposes of efficacy determination, while others (such as the Mean Symptom Complex Severity score used in clinical studies of ecallantide) use a composite score that reflects all sites. Assessment of treatment response typically employs the same tool(s) to evaluate baseline severity, and may be either time-based (e.g., time to achievement of minimal or no symptoms) or symptom-based (e.g., degree of symptom relief at predetermined time points). Although it is unlikely that therapies will be compared using identical assessment tools, prospective or retrospective validation ensures the adequacy and relevance of such tools, which should be taken into consideration when therapies are compared.


First Report of Sweet potato leaf curl Georgia virus on Sweet Potato in China.
Begomoviruses infecting sweet potato (Ipomoea batatas) are phylogenetically distinct from other members of the genus Begomovirus, and have been named "sweepoviruses" (1). Sweepoviruses cause sweet potato yield losses and cultivar decline, and have been found in China (1,3). In 2011, a survey was conducted to determine the incidence, genetic diversity, and distribution of sweepoviruses in China. Thirty sweet potato cuttings showing upward leaf curl, leaf roll, chlorosis, and stunting were collected from fields in Jiangsu, Guangxi, Guizhou, Shanxi, Henan, and Hebei Provinces. Five-leaf growth stage I. setosa plants were inoculated by side-grafting with scions from these samples, and grown in an insect-proof greenhouse in 20-cm-diameter clay pots. Each sample was grafted onto three replicate plants. Healthy, non-grafted I. setosa plants were used as the negative control treatment. Total nucleic acids were extracted from 100 mg fresh leaves harvested 30 days post-inoculation (dpi) from symptomatic and negative control plants using the Universal Genomic DNA Extraction Kit (TaKaRa, Dalian, China). Universal primers for amplification of Geminiviruses (BM-V [5'-KSGGGTCGACGTCATCAATGACGTTRTAC-3'] and BM-C [5'-AARGAATTCATKGGGGCCCARARRGACTGGC-3']) (2) were used to amplify the begomovirus A component by PCR assay. A DNA fragment of the expected size (2.8 kb) was obtained from grafted leaf samples of the Hebei Province plant, and was cloned into the pMD-19T vector (TaKaRa). The recombinant plasmid was transformed into competent cells of Escherichia coli strain JM109, and the inserted fragment sequenced. The nucleotide sequence obtained (GenBank Accession No. JX448368) was 2,785 nt long, and contained two open reading frames (ORFs) in the virion sense, and four ORFs in the complementary sense, similar to other monopartite begomoviruses (1). The sequence was compared with sequences in GenBank using BLAST. The results revealed the greatest nucleotide sequence identity, 90.8%, with that of the Sweet potato leaf curl Georgia virus (SPLCGV) from Georgia, United States (AF326775). The sequence also shared identities of <89% with other sweepoviruses, and was therefore designated SPLCGV-China: Hebei: 2011. Comparison of the complete genome sequence of SPLCGV-China: Hebei: 2011 with SPLCGV revealed an 18 nucleotide insertion between AV-1 and AC-3. The results confirmed that the sweet potato sample from which SPLCGV-China: Hebei: 2011 was obtained was infected with SPLCGV. To our knowledge, this is the first report of the natural occurrence of SPLCGV in China. This study will assist with understanding the presence of this virus and genetic diversity of sweepoviruses in China. References: (1) H. P. Bi and P. Zhang. Arch. Virol. 157:441, 2012. (2) R. W. Briddon and P. G. Markham. Mol. Biotechnol. 1:202, 1994. (3) Y. S. Luan et al. Virus Genes 35:379, 2007.


Sexual function in women with advanced multiple sclerosis.
Changes in sexual function in 47 women with advanced multiple sclerosis are described. Twenty eight (59.6%) of the women reported decreased sexual desire. Seventeen (36.2%) reported decreased lubrication. Five (10.6%) others did not know if they lubricated or not. Eighteen women (38.3%) reported diminished orgasmic capacity and six (12.8%) others had never had an orgasm. Sensory dysfunction in the genital area was experienced by 61.7% of the women and 76.6% had weakness of the pelvic muscles. Sixty six per cent had bowel problems and 89.4% had bladder dysfunction. The changes in sexual function correlated both with neurological symptoms from the sacral segments, such as weakness of the pelvic floor and bladder and bowel dysfunction, and to other symptoms such as ataxia and vertigo as well as with age and the occurrence of amenorrhoea. A significant correlation was found between expanded disability status scale (EDSS) score and cohabitation. Problems with sexual function were reported significantly more often by women with lower EDSS scores. Most women (83%) found the interview a positive experience.


The identification of human semen by a chemiluminescent assay of choline.
A method for proving the presence of semen has been established by utilizing chemiluminescence for an assay of choline, a nonprotein constituent of semen, and medicolegal testings were carried out to evaluate its effectiveness. The sensitivity of this method to choline was 3 nmol/ml, and as a result of assays of the choline content in semen and in several other human body fluids and secreta, the choline level in semen was found to be 10.88-26.78 mumol/ml (mean = 16.69 +/- 4.01 mumol/ml), which was markedly higher. The choline content in semen specimens from subjects with oligospermia or azoospermia was similarly as high. Although choline was also detected in samples of certain dairy products, vegetable juice, and fruit juice, whose stains are almost indistinguishable from semen to the naked eye, the choline content in these specimens was much lower than in semen. Further, even when human semen specimens were heated to 100 degrees C for 30 min and seminal stains were heated to 200 degrees C for 30 min, the choline content still retained 71.6% and 66.9% of the pre-heating value, respectively. As for specimens of semen and seminal stains that were stored at room temperature for 12 months, about 1/3 and 1/2 of the original choline level were detected, respectively. Also, the presence of intravaginal drugs was shown to have no large influence on the detection of choline. Choline even could be detected in aged seminal stains stored for 11 years, so that the presence of semen was demonstrated. Finally, the presence of semen in the vaginal contents, collected on medicolegal autopsy, could also be demonstrated by the detection of choline. Thus utilizing chemiluminescence for detecting choline is considered useful for establishing medicolegal proof of the presence of semen.


Mechanisms that regulate morphogenesis of a highly branched neuron in C. elegans.
The shape of an individual neuron is linked to its function with axons sending signals to other cells and dendrites receiving them. Although much is known of the mechanisms for axonal outgrowth, the striking complexity of dendritic architecture has hindered efforts to uncover pathways that direct dendritic branching. Here we review the results of an experimental strategy that exploits the power of genetic analysis and live cell imaging of the PVD sensory neuron in C. elegans to reveal key molecular drivers of dendrite morphogenesis.


Methodological and Ethical Considerations in Research With Immigrant and Refugee Survivors of Intimate Partner Violence.
To promote safe and positive health outcomes by utilizing culturally relevant evidence-based interventions for immigrant and refugee women survivors of intimate partner violence, their active participation in research is critical. With 43.6 million immigrants and refugees living in the United States, there is a need for research studies to eliminate health disparities in these populations. However, barriers to recruiting and retaining these populations in research prevent the provision of quality and culturally informed services to meet their needs. The aim of this article is to discuss the recruitment and retention strategies employed and analyze the methodological and ethical challenges in the context of the weWomen Study. The use of a multifaceted approach informed by best practices maximized recruitment efforts and active participation that generated high numbers of immigrant and refugee women participants. The study also substantiated the need for more community-based participatory approaches to engage community members in the development of culturally appropriate approaches that instill a sense of ownership over the research process. Active research participation of immigrant and refugee survivors will help investigators understand their unique needs and facilitate the implementation of targeted evidence-based interventions.


Effect of environmental contaminants on Beta cell function.
There is an increasing concern that chemicals in the environment are contributing to the global rise in the prevalence of type 2 diabetes (T2D). However, there is limited evidence for direct effects of these chemicals on beta cell function. Therefore, the goals of this study were (1) to test the hypothesis that environmental contaminants can directly affect beta cell function and (2) examine mechanistic pathways by which these contaminants could affect beta cell function. Using mouse beta TC-6 cells, we examined the acute effects of 6 substances (benzo[a]pyrene, bisphenol A [BPA], propylparaben, methylparaben, perfluorooctanoic acid, and perfluorooctyl sulfone) on insulin secretion. Only BPA treatment directly affected insulin secretion. Furthermore, chronic exposure to BPA altered the expression of key proteins in the cellular and endoplasmic reticulum stress response. These data suggest that long-term BPA exposure may be detrimental to beta cell function and ultimately be an important contributor to the etiology of T2D.


A kinematic examination of hand perception.
Previous research has found that the perception of our hands is inaccurate. This distorted representation has several constant characteristics including an overestimation of hand width and an underestimation of finger length. In this study, we further investigate this phenomenon by exploring the boundaries of hand representation. Participants placed one hand underneath a table top so it was occluded from view. Using their free hand, participants were instructed to point to the location where they believed the tips and bases of each of their fingers were. These ten landmarks were recorded using a motion capture system. One group of participants pointed to the landmarks in a random order (as done in previous studies) while another group pointed to them in a systematic fashion (from the tip of the thumb sequentially through to the pinky). Furthermore, to explore if having a frame of reference facilitates hand perception, some participants initiated each of their estimations directly from the previous landmark while others initiated them from a home spot located outside the span of the hand. Results showed that the participants who pointed in the systematic order made numerous accurate judgments of hand size and were overall more precise than participants who pointed in a random order. Including a frame of reference however, had no effect on the judgments. The results also showed asymmetries in hand perception. These findings are discussed in relation to different possible internal body representations and hemispheric asymmetries in body perception.


Connectedness, sense of community, and academic satisfaction in a novel community campus medical education model.
Developing a sense of community and establishing connectivity are important in enhancing learners' success and preventing their sense of isolation. The A.T. Still University School of Osteopathic Medicine in Arizona (SOMA) has implemented a novel approach to medical education in which, beginning in the second year, students are geographically dispersed to 11 community campuses associated with community health centers around the United States, at both inner-city and rural locations. This study assessed students' sense of community, academic satisfaction, and level of connectedness in their first through fourth years of medical school at SOMA. The Rovai Classroom Community Scale and open-ended questions were administered via an online survey instrument to 412 students enrolled at SOMA for the 2011-2012 academic year. Participation was voluntary, and all results were anonymous. Data were analyzed using one-way ANOVA to compare results between classes. Comparisons revealed an increasing degree of isolation and a decreasing sense of community and academic satisfaction progressing from the first through fourth years of medical school. Students suggested possible solutions that may be applied to medical schools and other graduate schools to improve the level of connectedness for students who are learning at a distance. Connectivity, sense of community, and academic satisfaction may decrease for students in undergraduate medical education participating in a combination of distance learning and intermittent in-person activities. Interventions have the potential to improve these parameters. Long-term follow-up of students' satisfaction is suggested.


Effect of rapid maxillary expansion on monosymptomatic primary nocturnal enuresis.
To evaluate the effects of rapid maxillary expansion (RME) on nocturnal enuresis (NE) related to the nasal airway, nasal breathing, and plasma osmolality (as an indicator for antidiuretic hormone). Nineteen patients with monosymptomatic primary NE, aged 6-15 years, were treated with RME for 10-15 days. To exclude a placebo effect of the RME appliance, seven patients were first treated with a passive appliance. Computed tomography of nasal cavity, rhinomanometric, and plasma osmolality measurements were made 2-3 days before and 2-3 months after the RME period. RME effects on NE were followed for three more years. Two to three months after the expansion there were significant improvements in the breathing function and a decrease in the plasma osmolality. NE decreased significantly in all patients after the RME period, and all patients showed full dryness after 3 years. This study demonstrates that RME causes complete dryness in all patients, with significant effects on pathophysiological mechanisms related to NE.


Abnormal P600 word repetition effect in elderly persons with preclinical Alzheimer's disease.
We sought cognitive event-related potential (ERP) biomarkers of "Preclinical Alzheimer's disease" (Pre-AD) using an incidental verbal learning paradigm with high sensitivity to prodromal AD. Seven elderly persons, with normal cognition at the time of ERP recordings, but who showed subsequent cognitive decline or AD pathology at autopsy (n = 5, mean Braak stage = 2.8), were compared to 12 "robust" normal elderly (RNE) persons who remained cognitively normal (Mfollow-up = 9.0 years). EEG was recorded during a word repetition paradigm (semantically congruous (50%) and incongruous target words repeat ~10-140 seconds later). The RNE P600 congruous word repetition ERP effects (New minus Old congruous words) were significantly larger than in Pre-AD (mean amplitudes = 3.28 vs. 0.10 μV, p = .04). High group discrimination (84%) was achieved (by a P600 amplitude cutoff of ~1.5 μV). Abnormal P600 word repetition effects in cognitively normal elderly persons may be an important sign of synaptic dysfunction and Preclinical AD.


Spiny keratoderma--a demonstration of hair keratin and hair type keratinization.
Six cases of spiny keratoderma were analyzed with hair specific antikeratin antibodies (AE13, AE14) and by electron microscopy. The keratotic column exhibited a different keratin birefringence and the underlying viable epidermis was less eosinophilic than the surrounding epidermis. AE13, which is specific for hair cortex, was positive in the lower column and variably positive in the viable epidermis, often beyond the columnar lesion. AE14 was negative in the lesion. Electron microscopy demonstrated features of keratinization of normal hair cortex, i.e. by the accretion of keratin filaments without production of keratohyalin or trichohyalin granules. Cementsomes (lamellar granules) and marginal bands were not produced as they are not formed in normal cortical keratinization. It was suggested that spiny keratoderma represents an ectopic hair formation of palms and soles.


Proximal versus distal influences on underrepresented minority students pursuing health professional careers.
The Health Careers Opportunities Program (HCOP) at Creighton University provides an important illustration of the short- and long-term successes of pipeline programming. The Pipeline to Success program at Creighton University provides exposure and enrichment activities to participants beginning in middle school and continuing through a one-year postbaccalaureate component in order to ensure that they are knowledgeable about health professional careers and competitive in applying for these training programs. This study hypothesized that the enrichment activities experienced by participants would have the additional benefit of providing indirect or distal influences to motivate participants to meet their career goals. In partial support of this hypothesis, a MANOVA demonstrated that the middle-school participants demonstrated a different pattern of influence from the other program components. Results indicate that as participants progressed through the Pipeline to Success HCOP at Creighton University, the program resources impacted their desire to pursue health professional careers in addition to positively preparing them for health professional training programs. We conclude that these findings have particular importance for planning and implementing student education programs.


Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial.
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans. This dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial was done at the Centre for Clinical Vaccinology and Tropical Medicine (Oxford, UK) and included healthy people aged 18-50 years with negative pre-vaccination tests for HIV antibodies, hepatitis B surface antigen, and hepatitis C antibodies (and a negative urinary pregnancy test for women). Participants received a single intramuscular injection of ChAdOx1 MERS at three different doses: the low-dose group received 5 × 109 viral particles, the intermediate-dose group received 2·5 × 1010 viral particles, and the high-dose group received 5 × 1010 viral particles. The primary objective was to assess safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited, unsolicited, and serious adverse events after vaccination. The secondary objective was to assess the cellular and humoral immunogenicity of ChAdOx1 MERS, measured by interferon-γ-linked enzyme-linked immunospot, ELISA, and virus neutralising assays after vaccination. Participants were followed up for up to 12 months. This study is registered with ClinicalTrials.gov, NCT03399578. Between March 14 and Aug 15, 2018, 24 participants were enrolled: six were assigned to the low-dose group, nine to the intermediate-dose group, and nine to the high-dose group. All participants were available for follow-up at 6 months, but five (one in the low-dose group, one in the intermediate-dose group, and three in the high-dose group) were lost to follow-up at 12 months. A single dose of ChAdOx1 MERS was safe at doses up to 5 × 1010 viral particles with no vaccine-related serious adverse events reported by 12 months. One serious adverse event reported was deemed to be not related to ChAdOx1 MERS. 92 (74% [95% CI 66-81]) of 124 solicited adverse events were mild, 31 (25% [18-33]) were moderate, and all were self-limiting. Unsolicited adverse events in the 28 days following vaccination considered to be possibly, probably, or definitely related to ChAdOx1 MERS were predominantly mild in nature and resolved within the follow-up period of 12 months. The proportion of moderate and severe adverse events was significantly higher in the high-dose group than in the intermediate-dose group (relative risk 5·83 [95% CI 2·11-17·42], p<0·0001) Laboratory adverse events considered to be at least possibly related to the study intervention were self-limiting and predominantly mild in severity. A significant increase from baseline in T-cell (p<0·003) and IgG (p<0·0001) responses to the MERS-CoV spike antigen was observed at all doses. Neutralising antibodies against live MERS-CoV were observed in four (44% [95% CI 19-73]) of nine participants in the high-dose group 28 days after vaccination, and 19 (79% [58-93]) of 24 participants had antibodies capable of neutralisation in a pseudotyped virus neutralisation assay. ChAdOx1 MERS was safe and well tolerated at all tested doses. A single dose was able to elicit both humoral and cellular responses against MERS-CoV. The results of this first-in-human clinical trial support clinical development progression into field phase 1b and 2 trials. UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research.


Multiple network-constrained regressions expand insights into influenza vaccination responses.
Systems immunology leverages recent technological advancements that enable broad profiling of the immune system to better understand the response to infection and vaccination, as well as the dysregulation that occurs in disease. An increasingly common approach to gain insights from these large-scale profiling experiments involves the application of statistical learning methods to predict disease states or the immune response to perturbations. However, the goal of many systems studies is not to maximize accuracy, but rather to gain biological insights. The predictors identified using current approaches can be biologically uninterpretable or present only one of many equally predictive models, leading to a narrow understanding of the underlying biology. Here we show that incorporating prior biological knowledge within a logistic modeling framework by using network-level constraints on transcriptional profiling data significantly improves interpretability. Moreover, incorporating different types of biological knowledge produces models that highlight distinct aspects of the underlying biology, while maintaining predictive accuracy. We propose a new framework, Logistic Multiple Network-constrained Regression (LogMiNeR), and apply it to understand the mechanisms underlying differential responses to influenza vaccination. Although standard logistic regression approaches were predictive, they were minimally interpretable. Incorporating prior knowledge using LogMiNeR led to models that were equally predictive yet highly interpretable. In this context, B cell-specific genes and mTOR signaling were associated with an effective vaccination response in young adults. Overall, our results demonstrate a new paradigm for analyzing high-dimensional immune profiling data in which multiple networks encoding prior knowledge are incorporated to improve model interpretability. The R source code described in this article is publicly available at https://bitbucket.org/kleinstein/logminer . firstname.lastname@example.com or firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Correlates of Strengthening Lessons from HIV/AIDS Treatment and Care Services in Ethiopia Perceived Access and Implications for Health System.
Access to healthcare is an important public health concept and has been traditionally measured by using population level parameters, such as availability, distribution and proximity of the health facilities in relation to the population. However, client based factors such as their expectations, experiences and perceptions which impact their evaluations of health care access were not well studied and integrated into health policy frameworks and implementation programs. This study aimed to investigate factors associated with perceived access to HIV/AIDS Treatment and care services in Wolaita Zone, Ethiopia. A cross-sectional survey was conducted on 492 people living with HIV, with 411 using ART and 81 using pre-ART services accessed at six public sector health facilities from November 2014 to March 2015. Data were analyzed using the ologit function of STATA. The variables explored consisted of socio-demographic and health characteristics, type of health facility, type of care, distance, waiting time, healthcare responsiveness, transportation convenience, satisfaction with service, quality of care, financial fairness, out of pocket expenses and HIV disclosure. Of the 492 participants, 294 (59.8%) were females and 198 (40.2%) were males, with a mean age of 38.8 years. 23.0% and 12.2% believed they had 'good' or 'very good' access respectively, and 64.8% indicated lower ratings. In the multivariate analysis, distance from the health facility, type of care, HIV clinical stage, out of pocket expenses, employment status, type of care, HIV disclosure and perceived transportation score were not associated with the perceived access (PA). With a unit increment in satisfaction, perceived quality of care, health system responsiveness, transportation convenience and perceived financial fairness scores, the odds of providing higher rating of PA increased by 29.0% (p<0.001), 6.0%(p<0.01), 100.0% (p<0.001), 9.0% (p<0.05) and 6.0% (p<0.05) respectively. Perceived quality of care, health system responsiveness, perceived financial fairness, transportation convenience and satisfaction with services were correlates of perceived access and affected healthcare performance. Interventions targeted at improving access to HIV/AIDS treatment and care services should address these factors. Further studies may be needed to confirm the findings.


Textual query of personal photos facilitated by large-scale web data.
The rapid popularization of digital cameras and mobile phone cameras has led to an explosive growth of personal photo collections by consumers. In this paper, we present a real-time textual query-based personal photo retrieval system by leveraging millions of Web images and their associated rich textual descriptions (captions, categories, etc.). After a user provides a textual query (e.g., "water"), our system exploits the inverted file to automatically find the positive Web images that are related to the textual query "water" as well as the negative Web images that are irrelevant to the textual query. Based on these automatically retrieved relevant and irrelevant Web images, we employ three simple but effective classification methods, k-Nearest Neighbor (kNN), decision stumps, and linear SVM, to rank personal photos. To further improve the photo retrieval performance, we propose two relevance feedback methods via cross-domain learning, which effectively utilize both the Web images and personal images. In particular, our proposed crossdomain learning methods can learn robust classifiers with only a very limited amount of labeled personal photos from the user by leveraging the prelearned linear SVM classifiers in real time. We further propose an incremental cross-domain learning method in order to significantly accelerate the relevance feedback process on large consumer photo databases. Extensive experiments on two consumer photo data sets demonstrate the effectiveness and efficiency of our system, which is also inherently not limited by any predefined lexicon.


Synergistic activation of the androgen receptor by bombesin and low-dose androgen.
Neuropeptide growth factors such as bombesinare implicated in progression to androgen-independent prostate cancer (PC). We examined the impact of bombesin on androgen receptor (AR)-mediated gene expression. The AR together with the AR-responsive probasin ARR(3)tk-luc or PSA-pPUE-ELB-luc promoter was cotransfected into Swiss 3T3 and PC-3 cells, both of which express high-affinity bombesin receptors; the cells were incubated with bombesin (0-50 nM) and dihydrotestosterone (DHT; 0-10 nM), and luciferase activities were measured. DHT increased transcription approximately 40-fold at doses of 1 and 10 nM but had no effect at 10 pM. Bombesin alone, or with 1 or 10 nM DHT, did not further increase transcription. However, 5 nM bombesin and 10 pM DHT, doses that by themselves had no effect, resulted in a approximately 20 fold increase in transcription (P < 0.005). This synergistic effect was blocked by bombesin receptor antagonists and recombinant neutral endopeptidase, which hydrolyzes bombesin. Bombesin and DHT together also increased binding of nuclear extracts from PC-3 cells transfected with AR to a consensus androgen response element in mobility shift assays and increased the level of secreted prostate-specific antigen in LNCaP cell supernatant compared with DHT or bombesin alone. Immunoprecipitation of AR from (32)P-labeled LNCaP cells revealed that 5 nM bombesin + 10 pM DHT induced AR phosphorylation comparable with 1 nM DHT, whereas bombesin or 10 pM DHT alone did not. These data indicate that bombesin can synergize with low (castrate) levels of DHT to induce AR-mediated transcription and suggest that neuropeptides promote AR-mediated signaling in androgen-independent prostate cancer.


Defects in bilayer silica and graphene: common trends in diverse hexagonal two-dimensional systems.
By combining first-principles and classical force field calculations with aberration-corrected high-resolution transmission electron microscopy experiments, we study the morphology and energetics of point and extended defects in hexagonal bilayer silica and make comparison to graphene, another two-dimensional (2D) system with hexagonal symmetry. We show that the motifs of isolated point defects in these 2D structures with otherwise very different properties are similar, and include Stone-Wales-type defects formed by structural unit rotations, flower defects and reconstructed double vacancies. The morphology and energetics of extended defects, such as grain boundaries have much in common as well. As both sp(2)-hybridised carbon and bilayer silica can also form amorphous structures, our results indicate that the morphology of imperfect 2D honeycomb lattices is largely governed by the underlying symmetry of the lattice.


The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity.
Latrepirdine (Dimebon) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-β (Aβ) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Aβ:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Aβ42 aggregates was assessed by thioflavin-T fluorescence, western immunoblotting and atomic force microscopy (AFM). Despite showing a reduction in thioflavin-T fluorescence with latrepirdine treatment, indicating a decrease in aggregation, immunoblotting and AFM showed a modest increase in both the formation and size of Aβ aggregates. The discrepancies between thioflavin-T and the other assays are consistent with previous evidence that cyclic molecules can interfere with thioflavin-T binding of amyloid protein preparations. The ability of latrepirdine to modulate Aβ aggregation appears to be independent of its neuroprotective effects, and is unlikely to be a mechanism by which latrepirdine offers protection. This study investigates the effect of latrepirdine on Aβ aggregation, and presents evidence suggesting that caution should be applied in the use of thioflavin-T fluorescence based assays as a method for screening compounds for protein aggregation altering properties.


The mitochondrial electron transport chain is dispensable for proliferation and differentiation of epidermal progenitor cells.
Tissue stem cells and germ line or embryonic stem cells were shown to have reduced oxidative metabolism, which was proposed to be an adaptive mechanism to reduce damage accumulation caused by reactive oxygen species. However, an alternate explanation is that stem cells are less dependent on specialized cytoplasmic functions compared with differentiated cells, therefore, having a high nuclear-to-cytoplasmic volume ratio and consequently a low mitochondrial content. To determine whether stem cells rely or not on mitochondrial respiration, we selectively ablated the electron transport chain in the basal layer of the epidermis, which includes the epidermal progenitor/stem cells (EPSCs). This was achieved using a loxP-flanked mitochondrial transcription factor A (Tfam) allele in conjunction with a keratin 14 Cre transgene. The epidermis of these animals (Tfam(EKO)) showed a profound depletion of mitochondrial DNA and complete absence of respiratory chain complexes. However, despite a short lifespan due to malnutrition, epidermal development and skin barrier function were not impaired. Differentiation of epidermal layers was normal and no proliferation defect or major increase of apoptosis could be observed. In contrast, mice with an epidermal ablation of prohibitin-2, a scaffold protein in the inner mitochondrial membrane, displayed a dramatic phenotype observable already in utero, with severely impaired skin architecture and barrier function, ultimately causing death from dehydration shortly after birth. In conclusion, we here provide unequivocal evidence that EPSCs, and probably tissue stem cells in general, are independent of the mitochondrial respiratory chain, but still require a functional dynamic mitochondrial compartment.


Intake rates and the functional response in shorebirds (Charadriiformes) eating macro-invertebrates.
As field determinations take much effort, it would be useful to be able to predict easily the coefficients describing the functional response of free-living predators, the function relating food intake rate to the abundance of food organisms in the environment. As a means easily to parameterise an individual-based model of shorebird Charadriiformes populations, we attempted this for shorebirds eating macro-invertebrates. Intake rate is measured as the ash-free dry mass (AFDM) per second of active foraging; i.e. excluding time spent on digestive pauses and other activities, such as preening. The present and previous studies show that the general shape of the functional response in shorebirds eating approximately the same size of prey across the full range of prey density is a decelerating rise to a plateau, thus approximating the Holling type II ('disc equation') formulation. But field studies confirmed that the asymptote was not set by handling time, as assumed by the disc equation, because only about half the foraging time was spent in successfully or unsuccessfully attacking and handling prey, the rest being devoted to searching.A review of 30 functional responses showed that intake rate in free-living shorebirds varied independently of prey density over a wide range, with the asymptote being reached at very low prey densities (<150/m-2). Accordingly, most of the many studies of shorebird intake rate have probably been conducted at or near the asymptote of the functional response, suggesting that equations that predict intake rate should also predict the asymptote.A multivariate analysis of 468 'spot' estimates of intake rates from 26 shorebirds identified ten variables, representing prey and shorebird characteristics, that accounted for 81% of the variance in logarithm-transformed intake rate. But four-variables accounted for almost as much (77.3%), these being bird size, prey size, whether the bird was an oystercatcher Haematopus ostralegus eating mussels Mytilus edulis, or breeding. The four variable equation under-predicted, on average, the observed 30 estimates of the asymptote by 11.6%, but this discrepancy was reduced to 0.2% when two suspect estimates from one early study in the 1960s were removed. The equation therefore predicted the observed asymptote very successfully in 93% of cases. We conclude that the asymptote can be reliably predicted from just four easily measured variables. Indeed, if the birds are not breeding and are not oystercatchers eating mussels, reliable predictions can be obtained using just two variables, bird and prey sizes. A multivariate analysis of 23 estimates of the half-asymptote constant suggested they were smaller when prey were small but greater when the birds were large, especially in oystercatchers. The resulting equation could be used to predict the half-asymptote constant, but its predictive power has yet to be tested. As well as predicting the asymptote of the functional response, the equations will enable research workers engaged in many areas of shorebird ecology and behaviour to estimate intake rate without the need for conventional time-consuming field studies, including species for which it has not yet proved possible to measure intake rate in the field.


Vitamin D-related changes in intracranial volume in older adults: a quantitative neuroimaging study.
Vitamin D is involved in skeletal and brain health. Recently, serum 25-hydroxyvitamin D (25OHD) concentration was found to be inversely correlated with intracranial volume in younger adults. Since hypovitaminosis D is most common in older adults, our objective was to determine whether this inverse correlation between 25OHD concentration and intracranial volume also occurred in older adults. Cross-sectional study. One hundred and ten Caucasian older community-dwellers (mean, 71.7±5.7 years; 45.5% female) received a blood test and an MRI of the brain at the same period. The intracranial volume and the subvolumes of cerebrospinal fluid, total brain, infratentorial brain, supratentorial brain, total white matter, total gray matter, cortical gray matter and subcortical gray matter were measured using FreeSurfer volumetry on T1-weighted images. Vitamin D insufficiency was defined as serum 25OHD<50nmol/L. Age, gender, body mass index, education level, use of vitamin D supplements, season of evaluation, serum concentrations of calcium and thyroid stimulating hormone were used as covariables in the analysis. We found that participants with vitamin D insufficiency (n=41) had greater intracranial volume than those without (1555.0±1379.2cm(3) versus 1488.0±167.4cm(3), P=0.033). Serum 25OHD concentration was cross-sectionally associated with decreased intracranial volume in mm(3) (unadjusted β=-1194.4, P=0.028), even after adjustment for covariables (adjusted β=-994.3, P=0.048). We found an inverse correlation of serum 25OHD with intracranial volume (r=-0.21, P=0.028) and the volume of white matter (r=-0.20, P=0.033). The other subvolumes did not correlate with serum 25OHD concentration. Serum 25OHD concentration was independently and inversely associated with intracranial volume in older adults.


A machine learning-based method to improve docking scoring functions and its application to drug repurposing.
Docking scoring functions are notoriously weak predictors of binding affinity. They typically assign a common set of weights to the individual energy terms that contribute to the overall energy score; however, these weights should be gene family dependent. In addition, they incorrectly assume that individual interactions contribute toward the total binding affinity in an additive manner. In reality, noncovalent interactions often depend on one another in a nonlinear manner. In this paper, we show how the use of support vector machines (SVMs), trained by associating sets of individual energy terms retrieved from molecular docking with the known binding affinity of each compound from high-throughput screening experiments, can be used to improve the correlation between known binding affinities and those predicted by the docking program eHiTS. We construct two prediction models: a regression model trained using IC(50) values from BindingDB, and a classification model trained using active and decoy compounds from the Directory of Useful Decoys (DUD). Moreover, to address the issue of overrepresentation of negative data in high-throughput screening data sets, we have designed a multiple-planar SVM training procedure for the classification model. The increased performance that both SVMs give when compared with the original eHiTS scoring function highlights the potential for using nonlinear methods when deriving overall energy scores from their individual components. We apply the above methodology to train a new scoring function for direct inhibitors of Mycobacterium tuberculosis (M.tb) InhA. By combining ligand binding site comparison with the new scoring function, we propose that phosphodiesterase inhibitors can potentially be repurposed to target M.tb InhA. Our methodology may be applied to other gene families for which target structures and activity data are available, as demonstrated in the work presented here.


Parks as Social and Cultural Spaces Among U.S.- and Foreign-Born Latinas.
Parks provide opportunities for people to engage in activities that can promote physical and emotional well-being. Using focus groups and personal interviews conducted in select neighborhoods of a Northeastern city with a high rate of obesity, we examined perceptions of barriers and facilitators regarding the use of parks and park features that would promote physical activity among Latina women ( N = 39). Foreign-born Latinas emphasized the environmental characteristics of parks and the types of amenities that can support preferred cultural and social activities, while U.S.-born Latinas emphasized the use of parks for physical activity and weight management. Most striking were the different ways in which foreign-born participants conceptualized parks as sociocultural family centers, extending more common conceptualizations centered on exercise or individual health gain. These findings suggest the need for new policies that incorporate culturally specific park programming to promote national goals of increasing levels of physical activity for health.


The moving target: a qualitative study of elderly patients' decision-making regarding total joint replacement surgery.
Total joint replacement is an accepted, cost-effective, and underutilized treatment for moderate-to-severe hip and knee arthritis. Yet, research has suggested that many patients with arthritis are unwilling to consider total joint replacement surgery. We sought to understand these patients' unwillingness by exploring the nature of their decision-making processes. In-depth interviews were conducted with seventeen individuals with moderate-to-severe arthritis who were appropriate candidates for, but unwilling to consider, total joint replacement. The interviews were analyzed with use of qualitative methods and content analysis techniques. Symptoms and information sources were the two main factors influencing patient decision-making. Participants engaged in individualized processes of trading off perceived costs and benefits. Accommodation to pain and disability and minimization of the quality-of-life benefit, in view of decreasing life span, led to a process whereby the threshold at which the benefits compared with the risks would tilt in favor of total joint replacement was constantly shifting, a phenomenon we called "the moving target." The moving-target characterization sheds light on patients' conceptions of their arthritis and on their unwillingness to consider total joint replacement. This process needs to be considered when developing ways to aid decision-making.


Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.
Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P < .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Further study of soma, dendrite, and axon excitation in single neurons.
The present investigation continues a previous study in which the soma-dendrite system of sensory neurons was excited by stretch deformation of the peripheral dendrite portions. Recording was done with intracellular leads which were inserted into the cell soma while the neuron was activated orthodromically or antidromically. The analysis was also extended to axon conduction. Crayfish, Procambarus alleni (Faxon) and Orconectes virilis (Hagen), were used. 1. The size and time course of action potentials recorded from the soma-dendrite complex vary greatly with the level of the cell's membrane potential. The latter can be changed over a wide range by stretch deformation which sets up a "generator potential" in the distal portions of the dendrites. If a cell is at its resting unstretched equilibrium potential, antidromic stimulation through the axon causes an impulse which normally overshoots the resting potential and decays into an afternegativity of 15 to 20 msec. duration. The postspike negativity is not followed by an appreciable hyperpolarization (positive) phase. If the membrane potential is reduced to a new steady level a postspike positivity appears and increases linearly over a depolarization range of 12 to 20 mv. in various cells. At those levels the firing threshold of the cell for orthodromic discharges is generally reached. 2. The safety factor for conduction between axon and cell soma is reduced under three unrelated conditions, (a) During the recovery period (2 to 3 msec.) immediately following an impulse which has conducted fully over the cell soma, a second impulse may be delayed, may invade the soma partially, or may be blocked completely. (b) If progressive depolarization is produced by stretch, it leads to a reduction of impulse height and eventually to complete block of antidromic soma invasion, resembling cathodal block, (c) In some cells, when the normal membrane potential is within several millivolts of the relaxed resting state, an antidromic impulse may be blocked and may set up within the soma a local potential only. The local potential can sum with a second one or it may sum with potential changes set up in the dendrites, leading to complete invasion of the soma. Such antidromic invasion block can always be relieved by appropriate stretch which shifts the membrane potential out of the "blocking range" nearer to the soma firing level. During the afterpositivity of an impulse in a stretched cell the membrane potential may fall below or near the blocking range. During that period another impulse may be delayed or blocked. 3. Information regarding activity and conduction in dendrites has been obtained indirectly, mainly by analyzing the generator action under various conditions of stretch. The following conclusions have been reached: The large dendrite branches have similar properties to the cell body from which they arise and carry the same kind of impulses. In the finer distal filaments of even lightly depolarized dendrites, however, no axon type all-or-none conduction occurs since the generator potential persists to a varying degree during antidromic invasion of the cell. With the membrane potential at its resting level the dendrite terminals contribute to the prolonged impulse afternegativity of the soma. 4. Action potentials in impaled axons and in cell bodies have been compared. It is thought that normally the over-all duration of axon impulses is shorter. Local activity during reduction of the safety margin for conduction was studied. 5. An analysis was made of high frequency grouped discharges which occasionally arise in cells. They differ in many essential aspects from the regular discharges set up by the generator action. It is proposed that grouped discharges occur only when invasion of dendrites is not synchronous, due to a delay in excitation spread between soma and dendrites. Each impulse in a group is assumed to be caused by an impulse in at least one of the large dendrite branches. Depolarization of dendrites abolishes the grouped activity by facilitating invasion of the large dendrite branches.


The quality of the DSM-IV obsessive-compulsive personality disorder construct as a prototype category.
The study evaluated the quality of the DSM-IV obsessive-compulsive personality disorder (OCPD) construct as a prototype category. A sample of 2237 patients from the Norwegian Network of Psychotherapeutic Day Hospitals was examined by a variety of psychometric analyses. A high number of OCPD patients (77%) had co-occurrent PDs, but only the co-occurrence with paranoid was significantly higher than expected. Exploratory factor analysis of the PD criteria indicated that OCPD consists of 2 dimensions. The first dimension, perfectionism, was constituted by OCPD criteria only and was significantly related to obsessive-compulsive disorder. The second dimension, aggressiveness, included 2 OCPD criteria, reluctance to delegate and stubbornness, but was also defined by criteria from paranoid, antisocial, and borderline PD. Confirmatory factor analysis of the OCPD criteria indicated a poor fit of both a unitary model and a 3-dimensional model. Overall, the OCPD criteria had poor psychometric properties. Although it seems that the quality of the DSM-IV OCPD as a prototype construct is insufficient, it may be improved by deleting the criteria hoarding behavior and miserliness. Alternative criteria could be related to problems in close relationships involving the need for predictability. Such revisions may add a third dimension to the 2 dimensions of perfectionism and aggressiveness.


Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol.
Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine-CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N(8),N(8)-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3'-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3'-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself.


Gauging a quantum heat bath with dissipative Landau-Zener transitions.
We calculate the exact Landau-Zener transition probabilities for a qubit with an arbitrary linear coupling to a bath at zero temperature. The final quantum state exhibits a peculiar entanglement between the qubit and the bath. In the special case of diagonal coupling, the bath does not influence the transition probability, whatever the speed of the Landau-Zener sweep. It is proposed to use Landau-Zener transitions to determine both the reorganization energy and the integrated spectral density of the bath. Possible applications include circuit QED and molecular nanomagnets.


A method for fine mapping quantitative trait loci in outbred animal stocks.
High-resolution mapping of quantitative trait loci (QTL) in animals has proved to be difficult because the large effect sizes detected in crosses between inbred strains are often caused by numerous linked QTLs, each of small effect. In a study of fearfulness in mice, we have shown it is possible to fine map small-effect QTLs in a genetically heterogeneous stock (HS). This strategy is a powerful general method of fine mapping QTLs, provided QTLs detected in crosses between inbred strains that formed the HS can be reliably detected in the HS. We show here that single-marker association analysis identifies only two of five QTLs expected to be segregating in the HS and apparently limits the strategy's usefulness for fine mapping. We solve this problem with a multipoint analysis that assigns the probability that an allele descends from each progenitor in the HS. The analysis does not use pedigrees but instead requires information about the HS founder haplotypes. With this method we mapped all three previously undetected loci [chromosome (Chr.) 1 logP 4.9, Chr. 10 logP 6.0, Chr. 15 logP 4.0]. We show that the reason for the failure of single-marker association to detect QTLs is its inability to distinguish opposing phenotypic effects when they occur on the same marker allele. We have developed a robust method of fine mapping QTLs in genetically heterogeneous animals and suggest it is now cost effective to undertake genomewide high-resolution analysis of complex traits in parallel on the same set of mice.


Critical reflection about socioeconomic inequalities among White young men from poor and working-class backgrounds.
An intersectional approach to human development emphasizes the multiple social categories individuals occupy, some of which confer privilege (e.g., being White) and some of which confer marginalization (e.g., being poor). This approach is needed especially in critical consciousness scholarship, and particularly in regard to understanding whether and how it may manifest among youth who simultaneously experience privileges due to some aspects of their identities and marginalization due to other aspects of their identities. We explored critical reflection (CR) about socioeconomic inequalities through interviews with 31 White young men from low-income and working-class backgrounds who were attending trade colleges in Pennsylvania. Participants were asked about their understandings of the causes of poverty in the United States and potential solutions. Multiple rounds of qualitative analysis were conducted to understand the potential manifestation of CR in responses. Inductive across-case thematic analysis yielded 11 themes describing participants' understandings of poverty. We then conducted case-based analyses to identify the specific attributions about poverty that each participant made (structural, fatalistic, and/or individual), the ways in which these attributions arose in responses, and how the pattern identified related to CR. Eight participants were identified as having some CR or the potential to develop CR, and their responses were explored for references to experiences that may have been related to CR as well as their membership in a privileged racial and gender group, and more marginalized socioeconomic group. Implications for examining and promoting CR in different groups of youth are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Molecular characterization of the first leptospires isolated from goats in Brazil.
Two Leptospira sp. isolates were obtained by the first time from goats in Brazil and characterized by sequencing rrs, rpoB and secY genes, PFGE and typing with monoclonal antibodies. Both isolates are identical and belong to Leptospira santarosai. Analysis of the rrs and the rpoB genes sequences revealed 100% identity between the goat isolates and the Bananal reference strain. When secY sequences of the two isolates were compared to each other, it was observed that they had identical sequences. However, when compared to that of the Bananal reference strain, there were 15 mismatches along the 549 bp secY sequence. In conclusion, molecular methods are increasingly useful for the characterization of leptospires and allowed to identify those isolates of caprine origin as closely related but not identical to serovar Bananal, and constitute a new type named Carioca.


Effects of rosa mosqueta oil supplementation in lipogenic markers associated with prevention of liver steatosis.
Rosa mosqueta (RM) oil is rich in α-linolenic acid (ALA) - a precursor of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), and it has a high antioxidant activity due to its abundant content of tocopherols. Additionally, it has been observed that RM oil administration prevents hepatic steatosis. Thus, the aim of this study was to demonstrate the antilipogenic mechanism related to RM oil administration in a high-fat diet (HFD) fed mice model by evaluating markers associated with the regulation of lipid droplet metabolism (PLIN2, PLIN5 and PPAR-γ), and proteins associated with lipogenesis (FAS and SREBP-1c). C57BL/6J mice were fed either a control diet or a HFD, with and without RM oil supplementation for 12 weeks. The results showed that RM oil supplementation decreases hepatic PLIN2 and PPAR-γ mRNA expression and SREBP-1c, FAS and PLIN2 protein levels, whereas we did not find changes in the level of PLIN5 among the groups. These results suggest that modulation of lipogenic markers could be one of the mechanisms, through which RM oil supplementation prevents the hepatic steatosis induced by HFD consumption in a mice model.


Cortical blood flow during rest and Wisconsin Card Sorting Test performance in schizophrenia.
The aim of this study is to examine if patients with schizophrenia differ in prefrontal, orbitofrontal, temporal, parietal and occipital blood flow from healthy controls during performance of the Wisconsin Card Sorting Test (WCST). We conducted a 99mTc-hexamethylpropylene amine oxime-SPECT study in patients with schizophrenia (n = 21) and in healthy controls (n = 18). The assessment of relative regional cerebral blood flow (relCBF) was achieved by comparing blood flow of well-defined cortical regions to whole brain blood flow. relCBF at rest and during WCST was compared between the groups and in the groups. Significant bilateral prefrontal and right-sided parietal increases of relCBF were found in patients (p < 0.05) during resting conditions, while prefrontal and parietal interhemispheric asymetry were higher in patients (p < 0.005). However, patients failed to increase right prefrontal and frontobasal relCBF as well as orbitofrontal interhemispheric asymetry during WCST performance in contrast to the control group (p < 0.05). The right occipital relCBF increased significantly in patients only (p < 0.05). In our study we could confirm the common hypothesis of schizophrenic hypofrontality at rest and during WCST performance. Moreover, due to our method, we identified significant frontal and parietal interhemispheric asymmetries in schizophrenia at rest as well as right occipital hyperperfusion during WCST.


A person-centred and thriving-promoting intervention in nursing homes - study protocol for the U-Age nursing home multi-centre, non-equivalent controlled group before-after trial.
The literature suggests that person-centred care can contribute to quality of life and wellbeing of nursing home residents, relatives and staff. However, there is sparse research evidence on how person-centred care can be operationalised and implemented in practice, and the extent to which it may promote wellbeing and satisfaction. Therefore, the U-Age nursing home study was initiated to deepen the understanding of how to integrate person-centred care into daily practice and to explore the effects and meanings of this. The study aims to evaluate effects and meanings of a person-centred and thriving-promoting intervention in nursing homes through a multi-centre, non-equivalent controlled group before-after trial design. Three nursing homes across three international sites have been allocated to a person-centred and thriving-promoting intervention group, and three nursing homes have been allocated to an inert control group. Staff at intervention sites will participate in a 12-month interactive educational programme that operationalises thriving-promoting and person-centred care three dimensions: 1) Doing a little extra, 2) Developing a caring environment, and 3) Assessing and meeting highly prioritised psychosocial needs. A pedagogical framework will guide the intervention. The primary study endpoints are; residents' thriving, relatives' satisfaction with care and staff job satisfaction. Secondary endpoints are; resident, relative and staff experiences of the caring environment, relatives' experience of visiting their relative and the nursing home, as well as staff stress of conscience and perceived person-centredness of care. Data on study endpoints will be collected pre-intervention, post-intervention, and at a six-month follow up. Interviews will be conducted with relatives and staff to explore experiences and meanings of the intervention. The study is expected to provide evidence that can inform further research, policy and practice development on if and how person-centred care may improve wellbeing, thriving and satisfaction for people who reside in, visit or work in nursing homes. The combination of quantitative and qualitative data will illuminate the operationalisation, effects and meaning of person-centred and thriving-promoting care. The trial was registered at ClinicalTrials.gov March 19, 2016, identifier NCT02714452 .


Evaluation of the results of external choledochoduodenostomy for retained, recurrent, or primary common duct stones.
Twenty-five patients were treated for retained, recurrent, or primary common duct stones by permanent drainage of the biliary tract with external choledochoduodenostomy. Twenty-one patients had common duct stones which became evident two to fifty years after the initial biliary tract procedure and which may represent stones formed in the common duct. Three recent patients had a clinical history of primary common duct stones, had stones which were soluble in chloroform-methanol solution, and had hepatic bile which was lithogenic as determined by evaluating the molar percentage of cholesterol, phospholipid, and bile salt in bile samples obtained at the time of choledochoduodenostomy. These data suggest that further stone formation is possible and that permanent bypass of the sphincter of Oddi is indicated to prevent recurrent bile duct obstruction. Long-term evaluation of the results of external choledochoduodenostomy indicates that the procedure is safe and effective in the prevention of recurrent biliary tract calculi.


A scoping review to improve conceptual clarity of interprofessional interventions.
Interprofessional education (IPE) and interprofessional collaboration (IPC) have been identified in health education and health care as playing an important role in improving health care services and patient outcomes. Despite a growth in the amount of research in these areas, poor conceptualizations of these interprofessional activities have persisted. Given the conceptual challenges, a scoping review of the interprofessional field was undertaken to map the literature available in order to identify key concepts, theories and sources of evidence. The objective of this review was to develop a theoretically based and empirically tested understanding of IPE and IPC. A total of 104 studies met the criteria and were included for analysis. Studies were examined for their approach to conceptualization, implementation, and assessment of their interprofessional interventions. Half of the studies were used for interprofessional framework development and half for framework testing and refinement. The final framework contains three main types of interprofessional interventions: IPE; interprofessional practice; and interprofessional organization; and describes the nature of each type of intervention by stage, participants, intervention type, interprofessional objectives, and outcomes. The outcomes are delineated as intermediate, patient, and system outcomes. There was very limited use of theory in the studies, and thus theoretical aspects could not be incorporated into the framework. This study offers an initial step in mapping out the interprofessional field and outlines possible ways forward for future research and practice.


Regional Differences in Efficacy, Safety, and Biomarkers for Second-Line Axitinib in Patients with Advanced Hepatocellular Carcinoma: From a Randomized Phase II Study.
An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial (ClinicalTrial.gov No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors. The data from this phase II study were analyzed for the efficacy and safety of axitinib/BSC in patients from Asia versus non-Asia versus Asian subgroups (Japan, Korea, or mainland China/Hong Kong/Taiwan) and predictive/prognostic values of baseline microRNAs and serum soluble proteins, using the Cox proportional hazards model. Of 202 patients, 78 were from non-Asia and 124 from Asia (37 Japanese, 36 Korean, and 51 Chinese). No significant differences in OS were found between axitinib/BSC and placebo/BSC in non-Asians, Asians, or Asian subgroups. However, in an exploratory analysis, axitinib/BSC showed favorable OS in Asians, especially Japanese, when patients intolerant to prior antiangiogenic therapy were excluded from the data set. Axitinib/BSC was well tolerated by non-Asians and Asians alike. The presence of 4 circulating microRNAs, including miR-5684 and miR-1224-5p, or a level lower than or equal to the median protein level of stromal cell-derived factor 1 at baseline was significantly associated with longer OS in axitinib/BSC-treated Asians or non-Asians. Axitinib/BSC did not prolong survival over placebo/BSC in non-Asians, Asians, or Asian subgroups, but favorable OS with axitinib/BSC was observed in a subset of Japanese patients. A patient population that excludes sorafenib-intolerant patients might potentially be more suitable for clinical trials of new agents in advanced HCC. Since these results are very preliminary, further investigation is warranted. The potential predictive/prognostic value of several baseline microRNAs and soluble proteins identified in this study would require validation in prospective studies on a large cohort of patients.


TRKing signals through the Golgi.
The subcellular localization of transmembrane receptors and other signaling proteins has emerged as a key component in the regulation of the intensity and specificity of their activity. Recent research indicates that immature TrkA neurotrophin receptors are transactivated in the Golgi apparatus after stimulation of neuropeptide pituitary adenylate cyclase-activating polypeptide PAC1 receptors or adenosine A(2A) receptors. Transactivation occurs independently of the TrkA extracellular ligand, nerve growth factor (NGF), through a signaling pathway that is distinct from that used in the transactivation of other receptor tyrosine kinases and has consequences distinct from those elicited by NGF at the plasma membrane.


Evidence for the ventral origin of oligodendrocyte precursors in the rat spinal cord.
The neuroepithelial cells of the mammalian neural tube are thought to give rise to all classes of differentiated neurons and macroglial cells in the adult CNS. In most cases, the regulation and timing of commitment of neuroepithelial cells to specific differentiative pathways are unknown. It has been proposed that in developing spinal cord, the macroglial cells--astrocytes and oligodendrocytes--arise either by the direct transformation of radial glial cells in the developing cord or, alternatively, by the differentiation of distinct precursor cells which migrate to presumptive white matter from the region of the central canal during development. In this study, the timing of oligodendrocyte differentiation in different levels of the spinal cord and the capacity of specific regions of the spinal cord to give rise to oligodendrocytes at various ages was tested in vitro. At embryonic day 14, all complete segments, as well as all ventral regions along the rostral-caudal axis of the spinal cord, have the capacity for oligodendrogenesis. By contrast, dorsal regions of the thoracic and lumbar spinal cord do not develop the capacity for oligodendrogenesis until later in development. The capacity of dorsal rat spinal cord to give rise to oligodendrocytes appears to be associated with the ventral-to-dorsal migration of oligodendrocyte precursors. These observations suggest that commitment to an oligodendrocyte differentiative pathway appears to occur in a distinct population of ventrally located glial precursors in the embryonic rat spinal cord.


Exploring the Genomic Diversity and Antimicrobial Susceptibility of Bifidobacterium pseudocatenulatum in a Vietnamese Population.
Bifidobacterium pseudocatenulatum is a member of the human gut microbiota, and specific variants of B. pseudocatenulatum have been associated with health benefits such as improving gut integrity and reducing inflammatory responses. Here, we aimed to assess the genomic diversity and predicted metabolic profiles of B. pseudocatenulatum cells found colonizing the gut of healthy Vietnamese adults and children. We found that the population of B. pseudocatenulatum from each individual was distinct and highly diverse, with intraclonal variation attributed largely to a gain or loss of carbohydrate-utilizing enzymes. The B. pseudocatenulatum genomes were enriched with glycosyl hydrolases predicted to target plant-based nondigestible carbohydrates (GH13, GH43) but not host-derived glycans. Notably, the exopolysaccharide biosynthesis region from organisms isolated from healthy children showed extensive genetic diversity and was subject to a high degree of genetic modification. Antimicrobial susceptibility profiling revealed that the Vietnamese B. pseudocatenulatum cells were uniformly susceptible to beta-lactams but exhibited variable resistance to azithromycin, tetracycline, ciprofloxacin, and metronidazole. The genomic presence of ermX and tet variants conferred resistance against azithromycin and tetracycline, respectively; ciprofloxacin resistance was associated with a mutation(s) in the quinolone resistance-determining region (GyrA, S115, and/or D119). Our work provides the first detailed genomic and antimicrobial resistance characterization of B. pseudocatenulatum found in the Vietnamese population, which can be exploited for the rational design of probiotics. IMPORTANCE Bifidobacterium pseudocatenulatum is a beneficial member of the human gut microbiota. The organism can modulate inflammation and has probiotic potential, but its characteristics are largely strain dependent and associated with distinct genomic and biochemical features. Population-specific beneficial microbes represent a promising avenue for the development of potential probiotics, as they may exhibit a more suitable profile in the target population. This study investigates the underexplored diversity of B. pseudocatenulatum in Vietnam and provides more understanding of its genomic diversity, metabolic potential, and antimicrobial susceptibility. Such data from indigenous populations are essential for selecting probiotic candidates that can be accelerated into further preclinical and clinical investigations.


Antibody-mediated modulation of cytokinins in tobacco: organ-specific changes in cytokinin homeostasis.
Cytokinins comprise a group of phytohormones with an organ-specific mode of action. Although the mechanisms controlling the complex networks of cytokinin metabolism are partially known, the role of individual cytokinin types in the maintenance of cytokinin homeostasis remains unclear. Utilizing the overproduction of single-chain Fv antibodies selected for their ability to bind trans-zeatin riboside and targeted to the endoplasmic reticulum, we post-synthetically modulated cytokinin ribosides, the proposed transport forms of cytokinins. We observed asymmetric activity of cytokinin biosynthetic genes and cytokinin distribution in wild-type tobacco seedlings with higher cytokinin abundance in the root than in the shoot. Antibody-mediated modulation of cytokinin ribosides further enhanced the relative cytokinin abundance in the roots and induced cytokinin-related phenotypes in an organ-specific manner. The activity of cytokinin oxidase/dehydrogenase in the roots was strongly up-regulated in response to antibody-mediated formation of the cytokinin pool in the endoplasmic reticulum. However, we only detected a slight decrease in the root cytokinin levels. In contrast, a significant decrease of cytokinins occurred in the shoot. We suggest the roots as the main site of cytokinin biosynthesis in tobacco seedlings. Conversely, cytokinin levels in the shoot seem to depend largely on long-range transport of cytokinin ribosides from the root and their subsequent metabolic activation.


Physiological Role of Chlorinated Aryl Alcohols Biosynthesized De Novo by the White Rot Fungus Bjerkandera sp. Strain BOS55.
The white rot fungus Bjerkandera sp. strain BOS55 produces veratryl, anisyl, 3-chloroanisyl, and 3,5-dichloroanisyl alcohol and the corresponding aldehydes de novo from glucose. All metabolites are produced simultaneously with the extracellular ligninolytic enzymes and have an important physiological function in the fungal ligninolytic system. Both mono- and dichlorinated anisyl alcohols are distinctly better substrates for the extracellular aryl alcohol oxidases than veratryl alcohol. The aldehydes formed are readily recycled by reduction by washed fungal mycelium, thus creating an extracellular H(2)O(2) production system regulated by intracellular enzymes. Lignin peroxidase does not oxidize the chlorinated anisyl alcohols either in the absence or in the presence of veratryl alcohol. It was therefore concluded that the chlorinated anisyl alcohols are well protected against the fungus's own aggressive ligninolytic enzymes. The relative amounts of veratryl alcohol and the chlorinated anisyl alcohols differ significantly according to the growth conditions, indicating that production of veratryl alcohol and the production of the (chlorinated) anisyl metabolites are independently regulated. We conclude that the chlorinated anisyl metabolites biosynthesized by the white rot fungus Bjerkandera sp. strain BOS55 can be purposefully produced for ecologically significant processes such as lignin degradation.


A membrane anchored DNA-based energy/electron transfer assembly.
In this work the trapping and conversion of visible light energy into chemical energy is examined using a supramolecular assembly. This consists of a light absorbing antenna and a porphyrin redox centre both covalently attached to a DNA strand, which in turn is bound to a lipid membrane. The excitation energy is finally trapped as a benzoquinone radical anion that could potentially be used in subsequent chemical reactions.


Normal patellofemoral kinematic patterns during daily activities in dogs.
Patellar abnormalities are a common cause of pain and lameness in dogs; however, in vivo the relative motion between the femur and patella in dogs is not well described. The objective of this study was to define normal in vivo sagittal plane patellofemoral kinematics in three axes of motion using non-invasive methods. We hypothesized patellofemoral alignment in the sagittal plane would tightly correlate with the femorotibial flexion angle. Six healthy dogs without orthopedic disease underwent computed tomography (CT) of their hind limbs to create 3-D models of the patella and femur. Normal stifle joint motion was captured via flat-panel imaging while each dog performed a series of routine activities, including sitting, walking, and trotting. The 3-D models of the patella and femur were digitally superimposed over the radiographic images with shape-matching software and the precise movement of the patella relative to the femur was calculated. As the femorotibial joint flexed, the patellofemoral joint also flexed and the patella moved caudally and distally within the femoral trochlea during each activity. Patellar flexion and distal translation during walk and sit were linearly coupled with the femorotibial flexion angle. Offset was evident while trotting, where patella poses were significantly different between early and late swing phase (p ≤ 0.003). Patellar flexion ranged from 51 to 6° while trotting. The largest flexion angle (92°) occurred during sit. The patella traversed the entire proximodistal length of the femoral trochlea during these daily activities. Using single-plane flat-panel imaging, we demonstrated normal in vivo patellofemoral kinematics is tightly coupled with femorotibial kinematics; however, trot kinematic patterns did not follow the path defined by walking and stand-to-sit motions. Our normal data can be used in future studies to help define patellofemoral joint kinematics in dogs with stifle abnormalities.