Design and synthesis of diosgenin derivatives as apoptosis inducers through mitochondria-related pathways.

Abstract: Diosgenin (DSG) has attracted attention recently as a potential anticancer therapeutic agent due to its profound antitumor activity. To better utilize DSG as an antitumor compound, two series of DSG-amino acid ester derivatives (3a-3g and 7a-7g) were designed and synthesized, and their cytotoxic activities against six human cancer cell lines (K562, T24, MNK45, HepG2, A549, and MCF-7) were evaluated. The results obtained showed that a majority of derivatives exhibited cytotoxic activities against these six human tumor cells. Structure-activity relationship analysis revealed that the introduction of l-tryptophan to the C-3 position of DSG and the C-26 position of derivative 5 was the preferred option for these compounds to display significant cytotoxic activities. Among them, compound 7g exhibited significant cytotoxicity against the K562 cell line (IC50 = 4.41 μM) and was 6.8-fold more potent than diosgenin (IC50 = 30.04 μM). Further cellular mechanism studies in K562 cells elucidated that compound 7g triggered mitochondrial-related apoptosis by increasing the generation of intracellular reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), which was associated with upregulation of the gene and protein expression levels of Bax, downregulation of the gene and protein expression levels of Bcl-2 and activation of the caspase cascade. The above results suggested that compound 7g might be considered a promising scaffold for further modification of more potent anticancer agents.

Ma|Liwei|L| Zhang|Jinling|J| Wang|Xuemei|X| Yang|Jifang|J| Guo|Lina|L| Wang|Xiaoli|X| Song|Bo|B| Dong|Wei|W| Wang|Wenbao|W|

D004354:Drug Screening Assays, Antitumor

Diosgenin
Apoptosis
Antitumor
Amino acid ester


Candida parapsilosis keratitis treated successfully with topical and oral fluconazole.

Abstract: A 73-year-old male patient presented with ocular pain, redness, and blurred vision in the left eye, which had been ongoing for more than 2 months. An oval-shaped paracentral corneal ulcer with stromal infiltration and a mild anterior chamber reaction were found. Despite treatment with empiric antibiotics, the lesion progressed and corneal thinning in the middle area was noted. The culture yielded Candida parapsilosis. We therefore prescribed topical 0.2% fluconazole (FCZ) in combination with oral FCZ as an antifungal treatment, following which the stromal infiltration gradually subsided. Complete epithelial-ization was noted on the 8th day after initiating FCZ therapy. There was no recurrent disease in the subsequent 2 years. Our case demonstrates that topical FCZ 0.2% in combination with oral FCZ can successfully treat C. parapsilosis keratitis and result in a good visual outcome.

Candida parapsilosis
fluconazole
fungal keratitis


Lower limb flexion posture relates to energy absorption during drop landings with soldier-relevant body borne loads.

Abstract: Fifteen military personnel performed 30-cm drop landings to quantify how body borne load (light, ∼6 kg, medium, ∼20 kg, and heavy, ∼40 kg) impacts lower limb kinematics and knee joint energy absorption during landing, and determine whether greater lower limb flexion increases energy absorption while landing with load. Participants decreased peak hip (P = 0.002), and knee flexion (P = 0.007) posture, but did not increase hip (P = 0.796), knee (P = 0.427) or ankle (P = 0.161) energy absorption, despite exhibiting greater peak hip (P = 0.003) and knee (P = 0.001) flexion, and ankle (P = 0.003) dorsiflexion angular impulse when landing with additional load. Yet, when landing with the light and medium loads, greater hip (R(2) = 0.500, P = 0.003 and R(2) = 0.314, P = 0.030) and knee (R(2) = 0.431, P = 0.008 and R(2) = 0.342, P = 0.022) flexion posture predicted larger knee joint energy absorption. Thus, military training that promotes hip and knee flexion, and subsequently greater energy absorption during landing, may potentially reduce risk of musculoskeletal injury and optimize soldier performance.

Brown|T N|TN|
O'Donovan|M|M|
Hasselquist|L|L|
Corner|B|B|
Schiffman|J M|JM|

Energy absorption
Kinematics
Impact force
Kinetics


Osmotic stress in colony and planktonic cells of Pseudomonas putida mt-2 revealed significant differences in adaptive response mechanisms.

Abstract: Planktonic cells and those grown on surfaces (or as colony biofilm) are known to show significant differences regarding growth behavior, cell physiology, gene expression and stress tolerance. In order to compare stress behavior of different growth forms, shake cultures for planktonic growth and agar plate cultivation for colony growth, were carried out with the well investigated model organism, Pseudomonas putida mt-2. Cells were exposed to sodium chloride to cause osmotic stress as one main environmental stressor bacteria have to cope with when growing in soil. Planktonic cells were more tolerant with a complete inhibition of growth at 0.7 M NaCl, compared to 0.5 M for agar-grown cells. Cell surface hydrophobicity, measured as water contact angles, was significantly higher for agar-grown cells (92°) than for planktonic cells (40°), and increased in the presence of NaCl. Agar-grown cells also showed a significantly higher degree of saturation of membrane fatty acids that increased in the presence of NaCl. These results demonstrate that planktonic and colony grown bacteria show different responses when confronted with osmotic stress suggesting that the tolerance and adaptive mechanisms are dependent on the environmental conditions as well as the initial physiological state.

Hachicho|Nancy|N|
Birnbaum|Astrid|A|
Heipieper|Hermann J|HJ|

Osmotic stress
Planktonic cells
Pseudomonas putida
Cell surface hydrophobicity
Membrane fatty acids
Agar grown cells
Stress response


Computing disease incidence, prevalence and comorbidity from electronic medical records.

Abstract: Electronic medical records (EMR) represent a convenient source of coded medical data, but disease patterns found in EMRs may be biased when compared to surveys based on sampling. In this communication we draw attention to complications that arise when using EMR data to calculate disease prevalence, incidence, age of onset, and disease comorbidity. We review known solutions to these problems and identify challenges for future work.

Incidence
Prevalence
Comorbidity
Electronic medical records
Bias


Biomineralization as a Paradigm of Directional Solidification: A Physical Model for Molluscan Shell Ultrastructural Morphogenesis.

Abstract: Molluscan shells are a model system to understand the fundamental principles of mineral formation by living organisms. The diversity of unconventional mineral morphologies and 3D mineral-organic architectures that comprise these tissues, in combination with their exceptional mechanical efficiency, offers a unique platform to study the formation-structure-function relationship in a biomineralized system. However, so far, morphogenesis of these ultrastructures is poorly understood. Here, a comprehensive physical model, based on the concept of directional solidification, is developed to describe molluscan shell biomineralization. The capacity of the model to define the forces and thermodynamic constraints that guide the morphogenesis of the entire shell construct-the prismatic and nacreous ultrastructures and their transitions-and govern the evolution of the constituent mineralized assemblies on the ultrastructural and nanostructural levels is demonstrated using the shell of the bivalve Unio pictorum. Thereby, explicit tools for novel bioinspired and biomimetic bottom-up materials design are provided.

biomineralization
solidification
crystal growth
mollusc shells
phase-field modeling


Oxygenation by ruthenium monosubstituted polyoxotungstates in aqueous solution: experimental and computational dissection of a Ru(III)-Ru(V) catalytic cycle.

Abstract: Molecular polyoxometalates with one embedded ruthenium center, with general formula [Ru(II/III)(DMSO)XW11O39](n-) (X = P, Si; n = 4-6), are readily synthesized in gram scale under microwave irradiation by a flash hydrothermal protocol. These nanodimensional and polyanionic complexes enable aerobic oxygenation in water. Catalytic oxygen transfer to dimethylsulfoxide (DMSO) yielding the corresponding sulfone (DMSO2 ) has been investigated with a combined kinetic, spectroscopic and computational approach addressing: (i ) the Ru(III) catalyst resting state; (ii ) the bimolecular event dictating its transformation in the rate-determining step; (iii ) its aerobic evolution to a high-valent ruthenium oxene species; (iv ) the terminal fate to diamagnetic dimers. This pathway is reminiscent of natural heme systems and of bioinspired artificial porphyrins. The in silico characterization of a key bis-Ru(IV)-μ-peroxo-POM dimeric intermediate has been accessed by density functional theory. This observation indicates a new landmark for tracing POM-based manifolds for multiredox oxygen reduction/activation, where metal-centered oxygenated species play a pivotal role.

Sartorel|Andrea|A| Miró|Pere|P| Carraro|Mauro|M| Berardi|Serena|S| Bortolini|Olga|O| Bagno|Alessandro|A| Bo|Carles|C| Bonchio|Marcella|M|

polyoxometalate
density functional theory
catalysis
oxygen activation


Effects of early pregnancy on uterine lymphocytes and endometrial expression of immune-regulatory molecules in dairy heifers.

Abstract: Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested. The proportions of lymphoid lineage cells and expression of inhibitory signaling molecules in the endometrium during early pregnancy in dairy heifers were determined using flow cytometry, immunofluorescence, and real-time PCR on days 17 and 20 of pregnancy and day 17 of the estrous cycle. Results revealed an increased percentage of NKp46+ and CD8+ cells in the uterus of pregnant heifers. Furthermore, a large percentage of uterine immune cells coexpressed these proteins. Compared to cyclic heifers, CD45+ uterine cells from pregnant heifers exhibited greater degranulation. Endometrium from pregnant heifers had greater mRNA abundance for the inhibitory molecules, CD274 and lymphocyte activating gene 3 (LAG3), and greater cytotoxic T lymphocyte-associated protein 4 (CTLA4), molecules that can interact with receptors on antigen-presenting cells and induce lymphocyte tolerance. This study demonstrates a dynamic regulation of both cytotoxic immune cells and tolerogenic molecules during the peri-implantation period that may be required to support establishment of pregnancy and placentation.

Vasudevan|Sreelakshmi|S|
Kamat|Manasi M|MM|
Walusimbi|Sadhat S|SS|
Pate|Joy L|JL|
Ott|Troy L|TL|

pregnancy
cytotoxic T cells
cattle
endometrium
natural killer cells


Longitudinal pulsatility in arterial occlusion.

Abstract: This pictorial essay aims to generate attention and inform sonographers and clinicians by remembering the "longitudinal pulsatility" as an evocative B-mode echographic sign of arterial occlusion, when the artery exhibits a systolic axial motion instead of its normal radial pulsatility.

longitudinal pulsatility
arterial occlusion
B-mode ultrasonography


Therapy with siRNA for Vegf-c but not for Vegf-d suppresses wide-spectrum organ metastasis in an immunocompetent xenograft model of metastatic mammary cancer.

Abstract: Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. Vascular endothelial growth factors-C and D (VEGF-C and VEGF-D) are heavily involved in lymphangiogenesis. Using small interfering RNA (siRNA) against mouse Vegf-c, and Vegf-d, we sought to inhibit metastasis in a model of metastatic murine mammary cancer. BJMC3879Luc2 cell-induced mammary carcinomas received direct intratumoral injections in vivo of either plasmid VEGF-C/D siRNA (psiVEGF-C, psiVEGF-D) or a vector control followed by in vivo gene electrotransfer weekly for seven weeks. Treatment with psiVEGF-C and with psiVEGF-D resulted in lower tumor volumes as compared to the controls. Treatment with psiVEGF-C suppressed wide-spectrum organ metastasis involving lung and lymph nodes. Treatment with psiVEGF-C further reduced the number of dilated lymphatic vessels with invading cancer cells and inhibited tumor blood microvessel density. In contrast, although treatment with psiVEGF-D was not effective and gave equivocal results, it did induce some insignificant reduction in tumor volume increment, average numbers of lymph node metastases and average number of intratumoral dilated lymphatic vessels. In conclusion, specific silencing of the Vegf-c gene suppresses wide-spectrum organ metastasis, including the lung and lymph nodes. However, therapy with siRNA for Vegf-d was not adequately effective in this murine system.

Shibata|Masa-Aki|MA| Shibata|Eiko|E| Morimoto|Junji|J| Harada-Shiba|Mariko|M|

D042582:Vascular Endothelial Growth Factor C

D042643:Vascular Endothelial Growth Factor D

siRNA
VEGF-C
VEGF-D
metastasis
mammary cancer


A case of peripheral ameloblastoma of retromolar trigone: Histopathological and immunohistochemical profile.

Abstract: Peripheral ameloblastoma (PA) is a rare and unusual entity with histological characteristics similar to those of the common intraosseous ameloblastoma. In this paper, we present a case of PA in a 44-year-old male affecting the right retromolar trigone area along with its immunohistochemical profile using CK19 and Ber-EP4 markers.

Surya|Varun|V| Verma|Priyanka|P| Amale|Kavita|K| Siwach|Pooja|P|

peripheral
Ameloblastoma
retromolar trigone
immunohistochemistry


Reaching the End-Game for GWAS: Machine Learning Approaches for the Prioritization of Complex Disease Loci.

Abstract: Genome-wide association studies (GWAS) have revealed thousands of genetic loci that underpin the complex biology of many human traits. However, the strength of GWAS - the ability to detect genetic association by linkage disequilibrium (LD) - is also its limitation. Whilst the ever-increasing study size and improved design have augmented the power of GWAS to detect effects, differentiation of causal variants or genes from other highly correlated genes associated by LD remains the real challenge. This has severely hindered the biological insights and clinical translation of GWAS findings. Although thousands of disease susceptibility loci have been reported, causal genes at these loci remain elusive. Machine learning (ML) techniques offer an opportunity to dissect the heterogeneity of variant and gene signals in the post-GWAS analysis phase. ML models for GWAS prioritization vary greatly in their complexity, ranging from relatively simple logistic regression approaches to more complex ensemble models such as random forests and gradient boosting, as well as deep learning models, i.e., neural networks. Paired with functional validation, these methods show important promise for clinical translation, providing a strong evidence-based approach to direct post-GWAS research. However, as ML approaches continue to evolve to meet the challenge of causal gene identification, a critical assessment of the underlying methodologies and their applicability to the GWAS prioritization problem is needed. This review investigates the landscape of ML applications in three parts: selected models, input features, and output model performance, with a focus on prioritizations of complex disease associated loci. Overall, we explore the contributions ML has made towards reaching the GWAS end-game with consequent wide-ranging translational impact.

Nicholls|Hannah L|HL|
John|Christopher R|CR|
Watson|David S|DS|
Munroe|Patricia B|PB|
Barnes|Michael R|MR|
Cabrera|Claudia P|CP|

machine learning
genome-wide association study
clinical translation
deep learning
artificial intelligence
candidate gene
data science
genomics


Effectiveness of the "What's Up!" Intervention to Reduce Stigma and Psychometric Properties of the Youth Program Questionnaire (YPQ): Results from a Cluster Non-randomized Controlled Trial Conducted in Catalan High Schools.

Abstract: Mental disorders are highly prevalent in the general population, and people who experience them are frequently stigmatized. Stigma has a very negative impact on social, academic/professional, and personal life. Considering the high rates of mental disorders among children and adolescents (13.4%) and how critical this age is in the formation of nuclear beliefs, many campaigns to combat stigma have been developed in the last decade, with mixed results. The OBERTAMENT initiative has produced various anti-stigma campaigns in Catalonia (Spain). In the present study, the main objective was to report on the effectiveness of the OBERTAMENT "What's up!" intervention, a curricular intervention including education and social contact conducted by the teachers in the classroom with teenagers aged between 14 and 18. Prior to this, we examined the psychometric properties of the Youth Program Questionnaire (YPQ), our main outcome measure, in terms of dimensionality, reliability, and validity. A cluster non-randomized controlled trial was conducted to assess this intervention, which was tested in nine high schools situated in the Barcelona region. A convenience sample of 261 students formed the intervention group and 132 the control group (52% women, mean age = 14, SD = 0.47). The assignment to study conditions was conducted by Departament d'Ensenyament (Department of Education), Generalitat de Catalunya (Catalan Government). Participants were evaluated at baseline, post-intervention, and 9-month follow-up. The main outcome measure of this study was the YPQ. The Reported and Intended Behavior Scale (RIBS) was used as secondary outcome measure. The statistical analysis indicated that the YPQ possesses a two-factor structure (stereotypical attitudes and intended behavior) and sound psychometric properties. The multilevel mixed-effects models revealed statistically significant interactions for both study measures and post hoc intragroup analyses revealed a significant but small improvement in the YPQ and RIBS scores in the intervention group. Overall, our results indicate that "What's up!" produced statistically significant, albeit small improvements in stereotypical attributions and intended behavior toward people with mental disorders. Some methodological limitations and the relatively low levels of stigma observed in our sample may undermine our results. The implications of our results are discussed in relation to stigma research.

Andrés-Rodríguez|Laura|L|
Pérez-Aranda|Adrián|A|
Feliu-Soler|Albert|A|
Rubio-Valera|María|M|
Aznar-Lou|Ignacio|I|
Serrano-Blanco|Antoni|A|
Juncosa|Miquel|M|
Tosas|Anaïs|A|
Bernadàs|Albert|A|
Luciano|Juan V|JV|

stigma
Youth Program Questionnaire
non-randomized controlled trial
mental disorders
Reported and Intended Behavior Scale


Dose-dependent emergence of acute and recurrent corneal lesions in sulfur mustard-exposed rabbit eyes.

Abstract: Sulfur mustard (SM) is a lipid soluble alkylating agent that causes genotoxic injury. The eye is highly sensitive to SM toxicity and exposures exceeding 400 mg min/m3 can elicit irreversible corneal pathophysiologies. Development of medical countermeasures for ocular SM exposure has been hindered by a limited understanding of dose-dependent effects of SM on corneal injury. Here, clinical, histological and ultrastructural analyses were used to characterize the effects of SM dose on corneal injury progression. Corneas were evaluated for up to 20 wk following exposure to saturated SM vapor for 30-150 s, which corresponds to 300-1,500 mg min/m3. In acute studies, a ceiling effect on corneal edema developed at doses associated with full-thickness corneal lesions, implicating endothelial toxicity in corneal swelling. Recurrent edematous lesions (RELs) transiently emerged after 2 wk in a dose-dependent fashion, followed by the development of secondary corneal pathophysiologies such as neovascularization, stromal scarring and endothelial abnormalities. RELs appeared in 96 % of corneas exposed for ≥ 90 s, 52 % of corneas exposed for 60 s and 0 % of corneas exposed for 30 s. While REL latency was variable in corneas exposed for 60 s, REL emergence was synchronized at exposures ≥ 90 s. Corneas did not exhibit more than one REL, suggesting RELs are part of a programmed pathophysiological response to severe alkylating lesions. In post-mortem studies at 12 wk, corneal edema was positively correlated to severity of endothelial pathologies, consistent with previous findings that endothelial toxicity influences long-term outcomes. These results provide novel insight into long-term corneal pathophysiological responses to acute toxicity and identify exposure conditions suitable for therapeutic testing.

McNutt|Patrick M|PM|
Kelly|Kyle E M|KEM|
Altvater|Amber C|AC|
Nelson|Marian R|MR|
Lyman|Megan E|ME|
O'Brien|Sean|S|
Conroy|Matthieu T|MT|
Ondeck|Celinia A|CA|
Bodt|Skylar M L|SML|
Wolfe|Sarah E|SE|
Schulz|Susan M|SM|
Kniffin|Denise M|DM|
Hall|Nicole B|NB|
Hamilton|Tracey A|TA|

Sulfur mustard
Alkylating agents
Cornea
Mustard gas keratopathy


Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis.

Abstract:
INTRODUCTION
As in other viral infections, anti-nuclear antibodies (ANAs) are observed in SARS-CoV-2 infection. We investigated the presence of autoantibodies in acute COVID-19 and the association with early laboratory findings.

MATERIALS AND METHODS
We examined 50 sera (>18 years, 25 Female) from patients with acute COVID-19. ANAs (HEp-20-10 liver biochip), anti-neutrophil cytoplasmic antibody (ANCA, Europlus Granulocyte Mosaic 32) and anti-double stranded DNA were investigated with product of Euroimmune AG (Luebeck, Germany) by indirect immunofluorescence (IIF) method. Also, antibody against cyclic citrullinated peptide (anti-CCP) was examined by a chemiluminisens assay (Euroimmun AG, Luebeck, Germany). Samples from 50 blood bank donors collected before the COVID-19 pandemic were used as controls.

RESULTS
The IIF-ANA test was positive in 18% (N = 9/50) of the patients. The median time of sample collection was 7 days (range: 1-28 days) after diagnosis. ANA was positive in only one (2%) control sample. Five (55.5%) patients were ANA positive with a strong titer (3+). There was no relationship between antibody titration and time of sample collection (p = 0,55). Anti-CCP was detected in a nucleolar (3+) positive patient (2%). ANA was detected in 14.28% (N = 1/7, rods-rings (±), p = 0,78) of patients in the intensive care unit(ICU). Patients treated in the clinic have more and higher titers of ANA, mostly in nucleolar patterns, than ICU patients.

CONCLUSIONS
The variety of antibodies detected in acute COVID-19 and the uncertainty of how long they persist can lead to confusion, especially in the diagnosis of systemic autoimmune rheumatic diseases for IIF-ANA testing in immunology laboratories. Improvements in cell lines and methods will facilitate the diagnostic process.

Peker|Bilal Olcay|BO|
Şener|Aslı Gamze|AG|
Kaptan Aydoğmuş|Figen|F|

D019084:Fluorescent Antibody Technique, Indirect

Laboratory diagnosis
Anti-nuclear antibody
Anti-neutrophil cytoplasmic antibodies
Coronavirus disease 2019
Indirect immunofluorescence test


Rural and urban disparities in selective attention in Chinese young adults: An event-related potential study.

Abstract: Previous studies showed that attention system and its underlying neural mechanisms were profound affected by social inequalities. However, previous studies on social inequalities were mainly focused on family-based factors, such as parental education, parental occupation, and household income. In the present study, we investigated the neural mechanisms underlying more broader social context (e.g., rural verse urban) disparities in selective attention among young adults in China. Event-related potentials (ERPs) were recorded from 22 college students who had born and grown up in rural areas and 22 students who had born and grown up in urban areas during an auditory selective attention task. Although behavioral performance was not significantly different between groups, attentional differences in the negativity difference (Nd) were significantly larger in the urban group than the rural group. Whole sample analysis with hierarchical regression showed that rural/urban status still made a significant contribution to the prediction of Nd amplitudes even after the effects of age, sex, and various family SES measures (include parents' educational levels and annual household income) were controlled for. These findings represent a first step toward understanding the ways in which broad social environmental factors shape the neural basis of selective attention.

Li|Shifeng|S| Yang|Zhen|Z| Wang|Cuicui|C| Xu|Qiongying|Q|

event-related potential (ERP)
Auditory selective attention
negativity difference (Nd)
rural and urban differences
socioeconomic status (SES)


Rapid genomic DNA variation in newly hybridized carp lineages derived from Cyprinus carpio (♀) × Megalobrama amblycephala (♂).

Abstract:
BACKGROUND
Distant hybridization can generate changes in phenotypes and genotypes that lead to the formation of new hybrid lineages with genetic variation. In this study, the establishment of two bisexual fertile carp lineages, including the improved diploid common carp (IDC) lineage and the improved diploid scattered mirror carp (IDMC) lineage, from the interspecific hybridization of common carp (Cyprinus carpio, 2n = 100) (♀) × blunt snout bream (Megalobrama amblycephala, 2n = 48) (♂), provided a good platform to investigate the genetic relationship between the parents and their hybrid progenies.

RESULT
In this study, we investigated the genetic variation of 12 Hox genes in the two types of improved carp lineages derived from common carp (♀) × blunt snout bream (♂). Hox gene clusters were abundant in the first generation of IDC, but most were not stably inherited in the second generation. In contrast, we did not find obvious mutations in Hox genes in the first generation of IDMC, and almost all the Hox gene clusters were stably inherited from the first generation to the second generation of IDMC. Interestingly, we found obvious recombinant clusters of Hox genes in both improved carp lineages, and partially recombinant clusters of Hox genes were stably inherited from the first generation to the second generation in both types of improved carp lineages. On the other hand, some Hox genes were gradually becoming pseudogenes, and some genes were completely pseudogenised in IDC or IDMC.

CONCLUSIONS
Our results provided important evidence that distant hybridization produces rapid genomic DNA changes that may or may not be stably inherited, providing novel insights into the function of hybridization in the establishment of improved lineages used as new fish resources for aquaculture.

Luo|Kaikun|K| Wang|Shi|S| Fu|Yeqing|Y| Zhou|Pei|P| Huang|Xuexue|X| Gu|Qianhong|Q| Li|Wuhui|W| Wang|Yude|Y| Hu|Fangzhou|F| Liu|Shaojun|S|0000-0001-5761-8571

Lineage
Distant hybridization
Hox gene
Recombinant cluster
Pseudogene


Diversity of the vaginal microbiome correlates with preterm birth.

Abstract: Reproductive tract infection is a major initiator of preterm birth (PTB). The objective of this prospective cohort study of 88 participants was to determine whether PTB correlates with the vaginal microbiome during pregnancy. Total DNA was purified from posterior vaginal fornix swabs during gestation. The 16S ribosomal RNA gene was amplified using polymerase chain reaction primers, followed by chain-termination sequencing. Bacteria were identified by comparing contig consensus sequences with the Ribosomal Database Project. Dichotomous responses were summarized via proportions and continuous variables via means ± standard deviation. Mean Shannon Diversity index differed by Welch t test (P = .00016) between caucasians with PTB and term gestation. Species diversity was greatest among African Americans (P = .0045). Change in microbiome/Lactobacillus content and presence of putative novel/noxious bacteria did not correlate with PTB. We conclude that uncultured vaginal bacteria play an important role in PTB and race/ethnicity and sampling location are important determinants of the vaginal microbiome.

Hyman|Richard W|RW|
Fukushima|Marilyn|M|
Jiang|Hui|H|
Fung|Eula|E|
Rand|Larry|L|
Johnson|Brittni|B|
Vo|Kim Chi|KC|
Caughey|Aaron B|AB|
Hilton|Joan F|JF|
Davis|Ronald W|RW|
Giudice|Linda C|LC|


Drying methods affect physicochemical and functional properties of quinoa protein isolate.

Abstract: Quinoa protein possesses great amino acid profiles and can be a potential food ingredient with broad applications. The objective of this study was to investigate the effect of different drying methods, namely freeze drying, spray drying, and vacuum drying on the functional and physicochemical properties of quinoa protein isolate, e.g., morphology, amino acid composition, SDS-PAGE profile, sulfhydryl/disulfide content, secondary structure, surface hydrophobicity, and thermal stability. The freeze-dried protein exhibited the highest emulsification capacity and stability and oil binding capacity, which was contributed to its higher surface hydrophobicity, while the spray-dried sample had the highest solubility and water absorption capacity at pH 7. Gels (8%) prepared with the freeze-dried protein had higher elastic and viscous modulus than that from others. The freeze-dried protein had the highest maximal denaturation temperature but lowest enthalpy, which may be attributed to its higher amount of random coil but lower percent of regular α-helix and β-sheet structures. Overall, quinoa protein isolate from different processing methods demonstrated distinct functional properties. This information will be useful to optimize quinoa protein production and benefit its applications.

D057927:Hydrophobic and Hydrophilic Interactions

Drying methods
Functional properties
Quinoa protein isolate
Physicochemical properties
Plant protein


Designing and developing a high-resolution melting technique for accurate identification of Leishmania species by targeting amino acid permease 3 and cytochrome oxidase II genes using real-time PCR and in silico genetic evaluation.

Abstract: Discrimination, accurate identification, and reliable techniques are required for accurate identification of Leishmania parasites. High-resolution melting (HRM) is recognized as an authentic and exact method. The main objective of this research was optimizing HRM analysis for detecting and screening Leishmania major, Leishmania tropica and mix infections. Thirty-six DNA samples of Leishmania parasite were prepared and analyzed. Two gene regions of amino acid permease 3 (AAP3) and cytochrome oxidase II (COII) were targeted and six pairs of specific new primers were designed. Bioinformatics analysis was employed to predict DNA temperature resolution for each species and compared with in-vitro results. The genetic diversity of the selected gene regions was analyzed using PCR-sequencing method and DnaSP 5.10.01 software. They were submitted in GenBank (KU680818- KU680821 and KY041643- KY041649). The haplotype diversity for both AAP3 and COII genes was 96% and 87%, respectively. Tajima's D index was 0.65 for AAP3 and 0.36 for COII. CLC Genomics Workbench 11 software predictions were significant and close to these findings. The designed primers could be able to identify at least two Leishmania species. Temperature variations in HRM technique separated Iranian Leishmania parasites of L. major, L. tropica and mix infections. The target genes and our modified HRM method proved this technique could be useful in both clinical and experimental settings. Also, it can be effective for detecting Leishmania parasites in different hosts such as humans, reservoir hosts and vectors. Indeed, HRM can be used as a technique in Leishmania identification as well as for ecological and epidemiological research.

Ghafari|Seyedeh Maryam|SM|
Fotouhi-Ardakani|Reza|R|
Parvizi|Parviz|P|

D060888:Real-Time Polymerase Chain Reaction

Leishmania
In silico
Genetic evaluation
Mix infection
qPCR-HRM


Non-Destructive Current Sensing for Energy Efficiency Monitoring in Buildings with Environmental Certification.

Abstract: Nowadays, buildings environmental certifications encourage the implementation of initiatives aiming to increase energy efficiency in buildings. In these certification systems, increased energy efficiency arising from such initiatives must be demonstrated. Thus, a challenge to be faced is how to check the increase in energy efficiency related to each of the employed initiatives without a considerable building retrofit. In this context, this work presents a non-destructive method for electric current sensing to assess implemented initiatives to increase energy efficiency in buildings with environmental certification. This method proposes the use of a sensor that can be installed directly in the low voltage electrical circuit conductors that are powering the initiative under evaluation, without the need for reforms that result in significant costs, repair, and maintenance. The proposed sensor consists of three elements: an air-core transformer current sensor, an amplifying/filtering stage, and a microprocessor. A prototype of the proposed sensor was developed and tests were performed to validate this sensor. Based on laboratory tests, it was possible to characterize the proposed current sensor with respect to the number of turns and cross-sectional area of the primary and secondary coils. Furthermore, using the Least Squares Method, it was possible to determine the efficiency of the air core transformer current sensor (the best efficiency found, considering different test conditions, was 2%), which leads to a linear output response.

Mota|Lia Toledo Moreira|LT|
Mota|Alexandre de Assis|Ade A|
Coiado|Lorenzo Campos|LC|

energy efficiency
non-destructive method
air-core transformer
current sensor
building certification
energy consumption


Acute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity.

Abstract:
RATIONALE
Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity.

OBJECTIVES
The current study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN).

METHODS
In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBDlow]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each).

RESULTS
Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users.

CONCLUSIONS
The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.

Mismatch negativity (MMN)
Cannabis
Δ9-Tetrahydrocannabinol (THC)
Cannabidiol (CBD)
Brain electrophysiology


Identification and molecular characterization of Wolbachia strains in natural populations of Aedes albopictus in China.

Abstract:
BACKGROUND
Aedes albopictus is naturally infected with Wolbachia spp., maternally transmitted bacteria that influence the reproduction of hosts. However, little is known regarding the prevalence of infection, multiple infection status, and the relationship between Wolbachia density and dengue outbreaks in different regions. Here, we assessed Wolbachia infection in natural populations of Ae. albopictus in China and compared Wolbachia density between regions with similar climates, without dengue and with either imported or local dengue.

RESULTS
To explore the prevalence of Wolbachia infection, Wolbachia DNA was detected in mosquito samples via PCR amplification of the 16S rRNA gene and the surface protein gene wsp. We found that 93.36% of Ae. albopictus in China were positive for Wolbachia. After sequencing gatB, coxA, hcpA, ftsZ, fbpA and wsp genes of Wolbachia strains, we identified a new sequence type (ST) of wAlbB (464/465). Phylogenetic analysis indicated that wAlbA and wAlbB strains formed a cluster with strains from other mosquitoes in a wsp-based maximum likelihood (ML) tree. However, in a ML tree based on multilocus sequence typing (MLST), wAlbB STs (464/465) did not form a cluster with Wolbachia strains from other mosquitoes. To better understand the association between Wolbachia spp. and dengue infection, the prevalence of Wolbachia in Ae. albopictus from different regions (containing local dengue cases, imported dengue cases and no dengue cases) was determined. We found that the prevalence of Wolbachia was lower in regions with only imported dengue cases.

CONCLUSIONS
The natural prevalence of Wolbachia infections in China was much lower than in other countries or regions. The phylogenetic relationships among Wolbachia spp. isolated from field-collected Ae. albopictus reflected the presence of dominant and stable strains. However, wAlbB (464/465) and Wolbachia strains did not form a clade with Wolbachia strains from other mosquitoes. Moreover, lower densities of Wolbachia in regions with only imported dengue cases suggest a relationship between fluctuations in Wolbachia density in field-collected Ae. albopictus and the potential for dengue invasion into these regions.

Hu|Yaping|Y| Xi|Zhiyong|Z| Liu|Xiaobo|X| Wang|Jun|J| Guo|Yuhong|Y| Ren|Dongsheng|D| Wu|Haixia|H| Wang|Xiaohua|X| Chen|Bin|B| Liu|Qiyong|Q|

D001425:Bacterial Outer Membrane Proteins

Wolbachia
Aedes albopictus
Infection
Phylogenetic analysis
Dengue virus
MLST genes


The CBL-CIPK Pathway in Plant Response to Stress Signals.

Abstract: Plants need to cope with multitudes of stimuli throughout their lifecycles in their complex environments. Calcium acts as a ubiquitous secondary messenger in response to numerous stresses and developmental processes in plants. The major Ca2+ sensors, calcineurin B-like proteins (CBLs), interact with CBL-interacting protein kinases (CIPKs) to form a CBL-CIPK signaling network, which functions as a key component in the regulation of multiple stimuli or signals in plants. In this review, we describe the conserved structure of CBLs and CIPKs, characterize the features of classification and localization, draw conclusions about the currently known mechanisms, with a focus on novel findings in response to multiple stresses, and summarize the physiological functions of the CBL-CIPK network. Moreover, based on the gradually clarified mechanisms of the CBL-CIPK complex, we discuss the present limitations and potential prospects for future research. These aspects may provide a deeper understanding and functional characterization of the CBL-CIPK pathway and other signaling pathways under different stresses, which could promote crop yield improvement via biotechnological intervention.

Ma|Xiao|X|
Li|Quan-Hui|QH|
Yu|Ya-Nan|YN|
Qiao|Yi-Ming|YM|
Haq|Saeed Ul|SU|
Gong|Zhen-Hui|ZH|0000-0001-6112-7943

D000595:Amino Acid Sequence
D008954:Models, Biological
D010802:Phylogeny
D010940:Plant Proteins
D010944:Plants
D015398:Signal Transduction
D013312:Stress, Physiological

signaling
CBL
CIPK
abiotic stress
biotic stress


Babesia vogeli in dogs in Chile.

Abstract: We report the presence of Babesia vogeli in dogs in Chile. During two surveillance campaigns separated by a year, sixty-three blood samples from free-ranging rural dogs in Coquimbo, Chile, were analysed through conventional PCR screening of the 18S rRNA for Babesia species. Sequencing confirmed the presence of Babesia vogeli in 6.3% of the tested animals, with positive cases in both years. All the sequences showed 100% nucleotide sequence identity among them and 99.8% with other previously published sequences from dogs. No clinical signs or haematological abnormalities other than thrombocytopenia were found in the parasitized individuals. This is the first report of a canine piroplasmid in Chile.


Effect of Synthetic High Density Lipoproteins Modification with Polyethylene Glycol on Pharmacokinetics and Pharmacodynamics.

Abstract: Synthetic high density lipoprotein nanoparticles (sHDLs) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5, and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane. Incorporating PEG did not reduce the ability of sHDL to facilitate cholesterol efflux, nor did it inhibit cholesterol uptake by the liver cells. By either adding more PEG or using PEG of longer chain lengths, the circulation half-life was extended. Addition of PEG also increased the area under the curve for the phospholipid component of sHDL (p < 0.05), but not for the apolipoprotein A-I peptide component of sHDL, suggesting sHDL is remodeled by endogenous lipoproteins in vivo. The extended phospholipid circulation led to a higher mobilization of plasma free cholesterol, a biomarker for facilitation of reverse cholesterol transport. The area under the cholesterol mobilization increased about 2-4-fold (p < 0.05), with greater increases observed for longer PEG chains and higher molar percentages of incorporated PEGylated lipids. Mobilized cholesterol was associated primarily with the HDL fraction, led to a transient increase in VLDL cholesterol, and returned to baseline 24 h postdose. Overall, PEGylation of sHDL led to beneficial changes in sHDL particle pharmacokinetic and pharmacodynamic behaviors.

Li|Dan|D|
Fawaz|Maria V|MV|
Morin|Emily E|EE|
Ming|Ran|R|
Sviridov|Denis|D|
Tang|Jie|J|
Ackermann|Rose|R|
Olsen|Karl|K|
Remaley|Alan T|AT|
Schwendeman|Anna|A|0000-0002-8023-8080

pharmacokinetics
cholesterol
HDL
apolipoproteins
PK−PD modeling
apolipoprotein A-I mimetic peptides
lipoprotein remodeling
lipoproteins/metabolism


Working-memory training: effects on delay discounting in male Long Evans rats.

Abstract: Delay discounting describes the devaluation of a reward as the delay to the receipt of the reward increases. Because steep delay discounting is robustly correlated with a number of behavioral problems (e.g., substance dependence, gambling) and some evidence suggests steep discounting precedes and predicts drug-taking in humans and rats, this study sought to experimentally reduce rats' delay discounting. Human stimulant-dependent participants given working-memory training reportedly decreased their rates of discounting relative to a sham-training group (Bickel, Yi, Landes, Hill, & Baxter, 2011). To evaluate the cross-species generality of this effect, 38 male Long-Evans rats, matched on pretraining delay-discounting rates, were randomly assigned to receive 140 sessions of working-memory training or sham training (which required no memory of the sample stimulus). Large between-group differences in working memory were observed after training; however, posttraining delay-discounting rates were undifferentiated across groups. Potential explanations for these findings are discussed.

Renda|C Renee|CR|
Stein|Jeffrey S|JS|
Madden|Gregory J|GJ|

competing neurobehavioral decisions systems theory


Incorporation of GM-CSF or CD40L Enhances the Immunogenicity of Hantaan Virus-Like Particles.

Abstract: A safe and effective Hantaan virus (HTNV) vaccine is highly desirable because HTNV causes an acute and often fatal disease (hemorrhagic fever with renal syndrome, HFRS). Since the immunity of the inactivated vaccine is weak and the safety is poor, HTNV virus-like particles (VLPs) offer an attractive and safe alternative. These particles lack the viral genome but are perceived by the immune system as virus particles. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this enhancement, we generated chimeric HTNV VLPs containing glycosylphosphatidylinositol (GPI)-anchored granulocyte macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity in vitro. The immunization of mice with chimeric HTNV VLPs containing GM-CSF or CD40L induced stronger humoral immune responses and cellular immune responses compared to the HTNV VLPs and Chinese commercial inactivated hantavirus vaccine. Chimeric HTNV VLPs containing GM-CSF or CD40L also protected mice from an HTNV challenge. Altogether, our results suggest that anchoring immunostimulatory molecules into HTNV VLPs can be a potential approach for the control and prevention of HFRS.

Cheng|Lin-Feng|LF| Wang|Fang|F| Zhang|Liang|L| Yu|Lan|L| Ye|Wei|W| Liu|Zi-Yu|ZY| Ying|Qi-Kang|QK| Wu|Xing-An|XA| Xu|Zhi-Kai|ZK| Zhang|Fang-Lin|FL|

D006480:Hemorrhagic Fever with Renal Syndrome

GM-CSF
CD40L
virus-like particles
Hantaan virus
baculovirus expression system


Early implementation evaluation of a multi-site housing first intervention for homeless people with mental illness: a mixed methods approach.

Abstract: This research sought to determine whether the implementation of Housing First in a large-scale, multi-site Canadian project for homeless participants with mental illness shows high fidelity to the Pathways Housing First model, and what factors help or hinder implementation. Fidelity ratings for 10 Housing First programs in five cities were made by an external quality assurance team along five key dimensions of Housing First based on 84 key informant interviews, 10 consumer focus groups, and 100 chart reviews. An additional 72 key informant interviews and 35 focus groups yielded qualitative data on factors that helped or hindered implementation. Overall, the findings show a high degree of fidelity to the model with more than 71% of the fidelity items being scored higher than 3 on a 4-point scale. The qualitative research found that both delivery system factors, including community and organizational capacity, and support system factors, training and technical assistance, facilitated implementation. Fidelity challenges include the availability of housing, consumer representation in program operations, and limitations to the array of services offered. Factors that accounted for these challenges include low vacancy rates, challenges of involving recently homeless people in program operations, and a lack of services in some of the communities. The study demonstrates how the combined use of fidelity assessment and qualitative methods can be used in implementation evaluation to develop and improve a program.

Nelson|Geoffrey|G| Stefancic|Ana|A| Rae|Jennifer|J| Townley|Greg|G| Tsemberis|Sam|S| Macnaughton|Eric|E| Aubry|Tim|T| Distasio|Jino|J| Hurtubise|Roch|R| Patterson|Michelle|M| Stergiopoulos|Vicky|V| Piat|Myra|M| Goering|Paula|P|

D016032:Randomized Controlled Trials as Topic

Implementation
Housing First
Homelessness
Mixed methods
Fidelity
Mental health


Safe Path Planning Algorithms for Mobile Robots Based on Probabilistic Foam.

Abstract: The planning of safe paths is an important issue for autonomous robot systems. The Probabilistic Foam method (PFM) is a planner that guarantees safe paths bounded by a sequence of structures called bubbles that provides safe regions. This method performs the planning by covering the free configuration space with bubbles, an approach analogous to a breadth-first search. To improve the propagation process and keep the safety, we present three algorithms based on Probabilistic Foam: Goal-biased Probabilistic Foam (GBPF), Radius-biased Probabilistic Foam (RBPF), and Heuristic-guided Probabilistic Foam (HPF); the last two are proposed in this work. The variant GBPF is fast, HPF finds short paths, and RBPF finds high-clearance paths. Some simulations were performed using four different maps to analyze the behavior and performance of the methods. Besides, the safety was analyzed considering the new propagation strategies.

path planning
mobile robot
probabilistic foam
bubbles
safety
A* algorithm


Large eccentric strength increase using the Copenhagen Adduction exercise in football: A randomized controlled trial.

Abstract: Hip adductor injuries are frequent in football, and players with low adductor strength appear to be at increased risk of injury. High adductor muscle activity has been shown in the Copenhagen Adduction exercise (CA); however, an associated strength gain has not been investigated. This study aims to examine the eccentric hip adduction strength (EHAD) gain using the CA in-season. Two U-19 sub-elite football teams, including 24 football players, were randomized to either an 8-week supervised progressive training program in addition to the usual training (intervention) or to continue training as usual (control). EHAD, eccentric hip abduction strength (EHAB), and side-bridge endurance were measured using reliable test procedures at baseline and follow-up by a blinded tester. There was a significant interaction between group and time on EHAD, EHAB, and EHAD/EHAB ratio (P < 0.025). The intervention group demonstrated a 35.7% increase in EHAD (P < 0.001); a 20.3% increase in EHAB (P = 0.003), and 12.3% increase in EHAD/EHAB ratio (P = 0.019). No significant within-group differences were found in the control group (P > 0.335). Compliance was 91.25%, and median muscle soreness ranged from 0 to 2. The CA implemented in-season with an 8-week progressive training program elicited a large significant increase in EHAD, EHAB, and EHAD/EHAB ratio.

Ishøi|L|L|
Sørensen|C N|CN|
Kaae|N M|NM|
Jørgensen|L B|LB|
Hölmich|P|P|
Serner|A|A|

hip adductors
Resistance training
groin injuries
prevention


Characteristics, length of stay, and hospital bills associated with severe odontogenic infections in Houston, TX.

Abstract:
BACKGROUND
There were 2 main purposes of this retrospective chart review study. The first was to describe the demographic, social, and financial characteristics of patients with severe odontogenic infections. The second was to assess the relationships among several demographic, social, and treatment variables and length of stay (LOS) in the hospital and hospital bill (charges).

METHODS
The authors conducted a retrospective chart review for patients admitted to the hospital and taken to the operating room for treatment of severe odontogenic infections at 3 hospitals in Houston, TX (Ben Taub, Memorial Hermann Hospital, and Lyndon B. Johnson) from January 2010 through January 2015.

RESULTS
The authors included data from severe odontogenic infections in 298 patients (55% male; mean age, 38.9 years) in this study. In this population, 45% required admission to the intensive care unit, and the mean LOS was 5.5 days. Most patients (66.6%) were uninsured. The average cost of hospitalization for this patient population was $13,058, and the average hospital bill was $48,351. At multivariable analysis, age (P = .011), preadmission antibiotic use (P = .012), diabetes mellitus (P = .004), and higher odontogenic infection severity score (P < .001) were associated with increased LOS. Higher odontogenic infection severity score, diabetes mellitus, and an American Society of Anesthesiologists score of 3 or more were associated with an increased charge of hospitalization.

CONCLUSIONS
Severe odontogenic infections were associated with substantial morbidity and cost in this largely unsponsored patient population. The authors identified variables associated with increased LOS and charge of hospitalization.

PRACTICAL IMPLICATIONS
Clinicians should consider these findings in their decision-making processes and prioritize early treatment of odontogenic infections potentially to decrease the number of patients admitted to the hospital, LOS, and overall costs of treatment for these infections.

Gams|Kevin|K| Shewale|Jitesh|J| Demian|Nagi|N| Khalil|Kamal|K| Banki|Farzaneh|F|

Infection
dental care use
hospital dentistry
oral health
public health and community dentistry


Discovery of 3(S)-thiomethyl pyrrolidine ERK inhibitors for oncology.

Abstract: Compound 5 (SCH772984) was identified as a potent inhibitor of ERK1/2 with excellent selectivity against a panel of kinases (0/231 kinases tested @ 100 nM) and good cell proliferation activity, but suffered from poor PK (rat AUC PK @10 mpk = 0 μM h; F% = 0) which precluded further development. In an effort to identify novel ERK inhibitors with improved PK properties with respect to 5, a systematic exploration of sterics and composition at the 3-position of the pyrrolidine led to the discovery of a novel 3(S)-thiomethyl pyrrolidine analog 28 with vastly improved PK (rat AUC PK @10 mpk = 26 μM h; F% = 70).

Boga|Sobhana Babu|SB|
Alhassan|Abdul-Basit|AB|
Cooper|Alan B|AB|
Doll|Ronald|R|
Shih|Neng-Yang|NY|
Shipps|Gerald|G|
Deng|Yongqi|Y|
Zhu|Hugh|H|
Nan|Yang|Y|
Sun|Robert|R|
Zhu|Liang|L|
Desai|Jagdish|J|
Patel|Mehul|M|
Muppalla|Kiran|K|
Gao|Xiaolei|X|
Wang|James|J|
Yao|Xin|X|
Kelly|Joseph|J|
Gudipati|Subrahmanyam|S|
Paliwal|Sunil|S|
Tsui|Hon-Chung|HC|
Wang|Tong|T|
Sherborne|Bradley|B|
Xiao|Li|L|
Hruza|Alan|A|
Buevich|Alexei|A|
Zhang|Li-Kang|LK|
Hesk|David|D|
Samatar|Ahmed A|AA|
Carr|Donna|D|
Long|Brian|B|
Black|Stuart|S|
Dayananth|Priya|P|
Windsor|William|W|
Kirschmeier|Paul|P|
Bishop|Robert|R|

D019950:Mitogen-Activated Protein Kinase 1

D048052:Mitogen-Activated Protein Kinase 3

ERK inhibitor
Oncology
ATP competitive
Kinase selectivity
MAP kinases


Proteome-minimized outer membrane vesicles from Escherichia coli as a generalized vaccine platform.

Abstract: Because of their potent adjuvanticity, ease of manipulation and simplicity of production Gram-negative Outer Membrane Vesicles OMVs have the potential to become a highly effective vaccine platform. However, some optimization is required, including the reduction of the number of endogenous proteins, the increase of the loading capacity with respect to heterologous antigens, the enhancement of productivity in terms of number of vesicles per culture volume. In this work we describe the use of Synthetic Biology to create Escherichia coli BL21(DE3)Δ60, a strain releasing OMVs (OMVsΔ60) deprived of 59 endogenous proteins. The strain produces large quantities of vesicles (> 40 mg/L under laboratory conditions), which can accommodate recombinant proteins to a level ranging from 5% to 30% of total OMV proteins. Moreover, also thanks to the absence of immune responses toward the inactivated endogenous proteins, OMVsΔ60 decorated with heterologous antigens/epitopes elicit elevated antigens/epitopes-specific antibody titers and high frequencies of epitope-specific IFN-γ-producing CD8+ T cells. Altogether, we believe that E. coli BL21(DE3)Δ60 have the potential to become a workhorse factory for novel OMV-based vaccines.

Zanella|Ilaria|I|
König|Enrico|E|0000-0002-1560-5948
Tomasi|Michele|M|
Gagliardi|Assunta|A|
Frattini|Luca|L|
Fantappiè|Laura|L|
Irene|Carmela|C|
Zerbini|Francesca|F|
Caproni|Elena|E|
Isaac|Samine J|SJ|
Grigolato|Martina|M|
Corbellari|Riccardo|R|
Valensin|Silvia|S|
Ferlenghi|Ilaria|I|
Giusti|Fabiola|F|
Bini|Luca|L|
Ashhab|Yaqoub|Y|
Grandi|Alberto|A|
Grandi|Guido|G|

vaccines
synthetic biology
cancer
infectious diseases
outer membrane vesicles (OMVs)


Better management of wheat allergy using a very low-dose food challenge: A retrospective study.

Abstract:
BACKGROUND
Low-dose reactive wheat-allergic children are at a high risk of a positive oral food challenge (OFC). The present study aimed to evaluate whether the results of a very low-dose (VL) OFC would contribute to better wheat allergy management in this population.

METHODS
We retrospectively reviewed wheat-allergic subjects who underwent a VL OFC with 2 g of udon noodles (equivalent to 53 mg of wheat protein) and had a previous allergic reaction to <15 g of udon noodles (equivalent to 400 mg of wheat protein) within 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant; those who failed were considered VL reactive. In VL tolerant subjects, the dose was increased to 15 g of udon noodles either during an OFC in our hospital or gradually at home.

RESULTS
Of the 57 included subjects (median age, 2.9 years; range, 1.0-11.8 years), 32 (56%) were VL tolerant and 25 (44%) were VL reactive. Most reactions during the OFC could be treated with an antihistamine and/or a nebulized β2 agonist. VL tolerant subjects consumed 2 g of udon noodles or a seasoning containing wheat. Within a year after the OFC, 18 VL tolerant subjects (56%), but no VL reactive subjects, were able to consume 15 g of udon noodles (p < 0.001).

CONCLUSIONS
A VL OFC can shift the management of some low-dose reactive wheat-allergic children from complete avoidance to partial wheat intake.

Okada|Yu|Y| Yanagida|Noriyuki|N| Sato|Sakura|S| Ebisawa|Motohiro|M|

Disease management
Food allergy
Food hypersensitivity
Specific IgE
Wheat hypersensitivity


Feeding low-quality date leaves as a substitute to conventional forages in dairy cows diet: effects on digestibility, feeding behavior, milk yield, and feed efficiency.

Abstract: This study investigated the possibility of integrating date leaves (DL) as a partial or complete substitute for conventional forage fibre sources into the diet of dairy cows. Nine Holstein cows were assigned to a replicated 3×3 Latin square design, and offered 1 of the 3 diets containing no DL (DL-0), or finely chopped DL partially (50%, DL-50) or completely (100%, DL-100) substituted for lucerne hay and maize silage. The replacement of the forages by DL was established such that the forage NDF (24.5%) was similar across diet despite the decreased forage: concentrate ratio from 0.45:0.55 to 0.33:0.67. Diets were similar in concentration of crude protein and starch, while the indigestible forage NDF (iNDF) increased from 7.2 to 15.4% of DM. Results showed that increasing DL inclusion linearly decreased nutrient intake and digestibility. Moreover, a trend toward a linear decrease in milk yield and percentage of milk protein and lactose were observed with increasing DL proportion in the diet. However, ruminal volatile fatty acids concentration, milk fat content, and feed efficiency were similar across the treatments. A quadratic trend was observed for eating and ruminating time by feeding DL, with the highest values found for cows fed DL-50. Replacing forages with finely chopped DL was effective to meet the fibre requirement, but reduced feed intake and milk yield possibly because of increased forage iNDF. However, conventional forages can be partially replaced with DL in the diet, particularly under forage shortage, because of maintained gross milk yield efficiency and reduced feed cost.

Date leaves
Dairy cows
Fiber digestibility
Forage source


Catastrophizing misinterpretations predict somatoform-related symptoms and new onsets of somatoform disorders.

Abstract:
BACKGROUND
Somatoform disorders are characterized by multiple recurring symptoms that resemble physical illnesses but defy medical explanation. Psychological models suggest that catastrophizing misinterpretations of harmless physical symptoms play a key role. However, the question of whether such biases predict somatoform-related symptoms and the onset of somatoform disorders has not been adressed. Hence, the aim of the present study was to further advance our understanding of the role of catastrophizing misinterpretations in somatoform disorders.

METHODS
In the present study, we used data from the Dresden Predictor Study (N=1538), in which an epidemiologic sample of young German women was tested at two time points approximately 17 months apart. Each participant completed a diagnostic interview, an interpretation questionnaire for somatoform and hypochondriacal symptoms, and three measures of such symptomatology: somatization subscale of the Symptom Checklist-90-Revised (SCL-90-R), Whiteley Index (WI), Body Sensations Questionnaire (BSQ).

RESULTS
At follow-up, 33 women were diagnosed with new onsets of lifetime somatoform disorder. Results showed that catastrophizing misinterpretations assessed at baseline were predictive of somatoform-related symptoms at follow-up, i.e., symptoms assessed with the WI and BSQ. Moreover, catastrophizing misinterpretations were predictive of new onsets of somatoform disorders, even after controlling for general threat-related misinterpretations and indices of somatoform symptoms (i.e., SCL-90-R and BSQ).

CONCLUSIONS
This is the first prospective, longitudinal study to demonstrate that catastrophizing misinterpretations have incremental validity as predictors of future somatoform-related symptomatology and somatoform disorders.

Woud|Marcella L|ML|
Zhang|Xiao Chi|XC|
Becker|Eni S|ES|
Zlomuzica|Armin|A|
Margraf|Jürgen|J|

Catastrophizing misinterpretations
Somatoform disorder
Whiteley index
Body sensation questionnaire
Prospective
Risk factor
SCL-90-R somatization scale


Experience of Primary Care Services Among Early Adolescents in England and Association With Health Outcomes.

Abstract:
PURPOSE
The aim of this study was to investigate adolescents' (11-15 years) experience of their general practitioner (GP), whether poor reported GP experience was associated with worse physical and mental health measures and whether poor previous GP experience was linked to lower utilization of these services.

METHODS
We used logistic regression to analyze data from the 2014 Health Behaviour in School-aged Children study. Four aspects of recent care experience were studied: feeling at ease, feeling treated with respect, satisfaction with doctor's explanation, and feeling able to discuss personal matters. Five dichotomized measures of health status were used: ever self-harmed; fair or poor self-reported health; frequent (at least weekly) low mood; sleeping problems; or headaches.

RESULTS
Of 5,335 students, 4,149 reported having visiting their GP within the past year. Of these, 91.8% felt treated with respect, 78.7% felt at ease, 85.7% were satisfied with explanation, and 53.9% felt able to discuss personal matters. After adjusting for ethnicity, age, gender, and family affluence score, poor experience on any indicator was strongly associated with increased risk of self-harm (adjusted odds ratio range, 2.01-2.70; all p < .001); feeling low (AOR range, 1.53-2.11; all p < .001); and sleeping problems (AOR range, 1.49-1.91; all p ≤ .001). Poor experience on all indicators, except discussing personal matters, was associated with worse self-reported health.

CONCLUSIONS
Nearly half of this large, national study of adolescents did not feel able to discuss personal matters with their doctor. There was a consistent, strong association between reported lack of good GP experience and poor health measures.

Yassaee|Arrash A|AA|
Hargreaves|Dougal S|DS|
Chester|Kayleigh|K|
Lamb|Stephanie|S|
Hagell|Ann|A|
Brooks|Fiona M|FM|

D000293:Adolescent
D000294:Adolescent Behavior
D017677:Age Distribution
D001294:Attitude to Health
D002648:Child
D004739:England
D005260:Female
D015438:Health Behavior
D006304:Health Status
D006306:Health Surveys
D054625:Healthcare Disparities
D006801:Humans
D016015:Logistic Models
D008297:Male
D010817:Physician-Patient Relations
D011320:Primary Health Care
D017678:Sex Distribution
D013222:State Medicine
D014944:World Health Organization

Primary care
Adolescent
GP
Health measures
Student
Patient experience


Cultivation of Head and Neck Squamous Cell Carcinoma Cells with Wound Fluid Leads to Cisplatin Resistance via Epithelial-Mesenchymal Transition Induction.

Abstract: Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.

D000077195:Squamous Cell Carcinoma of Head and Neck

head and neck squamous cell carcinoma
wound fluid
cisplatin resistance
epithelial-mesenchymal transition
Interleukin
cell proliferation


Development of first generation in-situ pathogen detection system (Gen1-IPDS) based on NanoGene assay for near real time E. coli O157:H7 detection.

Abstract: We developed the first generation in-situ pathogen detection system (Gen1-IPDS) based on the NanoGene assay for detecting and quantifying Escherichia coli O157:H7 specific eaeA gene. The NanoGene assay employs the hybridization of target DNA with quantum dot labeled magnetic beads and probe DNAs to detect and quantify the target bacterial gene. The Gen1-IPDS is currently capable of executing four key steps required in the NanoGene assay: sample and reagents introduction, DNA hybridization, magnetic separation of complexes, and sample collection. Operational parameters such as magnet position, hybridization buffer composition, hybridization flow rate, and hybridization temperature were investigated. Using the experimentally determined operational parameters, the target gene was successfully quantified (R(2)=0.97) over a range of six orders of magnitude (10(-12) to 10(-6) mol L(-1)). The limit of detection (LOD) was determined to be 49×10(-15) mol L(-1). The specificity was also demonstrated by the differential discrimination of mismatched target DNAs. The NanoGene assay quantification results via Gen1-IPDS were validated by correlation with its laboratory version (R(2)=0.97).

Mitchell|Kristi A|KA|
Chua|Beelee|B|
Son|Ahjeong|A|

D018829:Adhesins, Bacterial
D015374:Biosensing Techniques
D004269:DNA, Bacterial
D004867:Equipment Design
D004927:Escherichia coli Infections
D019453:Escherichia coli O157
D029968:Escherichia coli Proteins
D006801:Humans
D057230:Limit of Detection
D009693:Nucleic Acid Hybridization
D045663:Quantum Dots

NanoGene assay
Magnetic beads
DNA hybridization
Gene quantification
IPDS
Quantum dot nanoparticles


Symptomatic trochanteric non-union following total hip replacement treated with reattachment combined with two-stage revision surgery of the femoral stem.

Abstract: We present a case of symptomatic trochanteric non-union following total hip replacement treated initially with a Dall-Miles grip plate. After failure of this treatment, the patient had a two-stage revision. Trochanteric non-union is one of the well-described complications after total hip replacement. It is frequently difficult to treat, while potentially causing weakness, altered gait and instability of the artificial joint. We believe that reattachment of the trochanter combined with a staged revision of the femoral stem using a posterior approach for the second stage could be a valuable technique to be added to the orthopaedic armamentarium for recurrent and symptomatic trochanteric non-unions after primary total hip replacement, particularly after failure to treat with all the other techniques described in literature.

Drampalos|E|E| Bayam|L|L| Oakley|J|J| Hemmady|M|M| Hodgkinson|J|J|


Using Wet Electrospun PCL/Gelatin/CNT Yarns to Fabricate Textile-Based Scaffolds for Vascular Tissue Engineering.

Abstract: Incorporating conductive materials in scaffolds has shown advantages in regulating adhesion, mitigation, and proliferation of electroactive cells for tissue engineering applications. Among various conductive materials, carbon nanotubes (CNTs) have shown great promises in tissue engineering because of their good mechanical properties. However, the broad application of CNTs in tissue engineering is limited by current methods to incorporate CNTs in polymers that require miscible solvents to dissolve CNTs and polymers or CNT surface modification. These methods either limit polymer selections or adversely affect the properties of polymer/CNT composites. Here, we report a novel method to fabricate polymer/CNT composite yarns by electrospinning polycaprolactone/gelatin into a bath of CNT dispersion and extracting electrospun fibers out of the bath. The concentration of CNTs in the bath affects the thermal and mechanical properties and the yarns' degradation behavior. In vitro biological test results show that within a limited range of CNT concentrations in the bath, the yarns exhibit good biocompatibility and the ability to guide cell elongation and alignment. We also report the design and fabrication of a vascular scaffold by knitting the yarns into a textile fabric and combining the textile fabric with gelatin. The scaffold has similar mechanical properties to native vessels and supports cell proliferation. This work demonstrates that the wet electrospun polymer/CNT yarns are good candidates for constructing vascular scaffolds and provides a novel method to incorporate CNTs or other functional materials into biopolymers for tissue engineering applications.

textile-based scaffold
vascular tissue engineering
carbon nanotube
polymer/CNT composite
wet electrospinning


Natural succession on abandoned cropland effectively decreases the soil erodibility and improves the fungal diversity.

Abstract: Changes in plants and soils during natural succession have been evaluated, but little is known about the effects of succession on the activities of soil microbes and their interactions with soil erodibility. We conducted a field study on the Chinese Loess Plateau, typical of this semiarid area, to determine the effect of secondary succession on the stability of soil structure against erosion and on the composition of soil fungal communities. Characteristics of plant, soil, and fungal communities were assessed across a 30-yr chronosequence of grassland developed from abandoned cropland. The diversity and composition of the fungal communities were determined using high-throughput sequencing of the internal transcribed spacer. Six grasslands were selected to represent different successional age classes: 0 (cropland), 5, 10, 15, 20, and 30 yr. Short-term decreases (initial 5 yr) in the amounts of soil organic carbon, total nitrogen, available phosphorus, and fungal biomass and in fungal diversity had returned to original levels (i.e., cropland) within 15 yr and were much higher after continued succession. Abandoning cropland for succession caused the soil erodibility (K) decrease and the aboveground coverage, soil nutrient levels, content of larger (>5 mm) water-stable aggregate, mean aggregate weight diameter, and diversity of the fungal communities improvement including arbuscular mycorrhizas (AMF), ectomycorrhizas (EMF), and saprotrophs. The fungal communities were dominated by Ascomycota, Zygomycota, Basidiomycota, and Glomeromycota during the succession. The successional patterns of the plant and fungal communities were similar, although distinct fungal communities were not observed in the two initial stages, suggesting that fungal succession may develop more slowly than plant succession. Plant root biomass, EMF, and soil organic carbon content accounted for most of the variation of soil erodibility (28.6%, 19.5%, and 11.8%, respectively), indicating their importance in shaping soil structure to prevent erosion. Our results demonstrated that abandoning cropland for natural succession could decrease soil erodibility and increase fungal diversity. EMF plays an important role in soil stability against erosion in the Loess Plateau. Abandoning cropland for natural succession should be recommended for alleviating soil erosion and improving the degraded soils in this area.

Zhang|Chao|C| Liu|Guobin|G| Song|Zilin|Z| Qu|Dong|D| Fang|Linchuan|L| Deng|Lei|L|

succession
abandoned cropland
soil erodibility
chronosequence
grassland
fungal diversity and composition
internal transcribed spacer sequencing


Appointment utilization as a trigger for palliative care introduction: A retrospective cohort study.

Abstract:
BACKGROUND
Chronic kidney disease palliative care guidelines would benefit from more diverse and objectively defined health status measures.

AIM
The aim is to identify high-risk patients from administrative data and facilitate timely and uniform palliative care involvement.

DESIGN
It is a retrospective cohort study.

SETTING/PARTICIPANTS
In total, 45,368 Veterans, with chronic kidney disease Stage 3, 4, or 5, were monitored for up to 6 years and categorized into three groups, based on whether they died, started dialysis, or avoided both outcomes.

RESULTS
Patient's appointment utilization was a significant predictor for both outcomes. It separated individuals into low, medium, and high appointment utilizers. Among the low appointment utilizers, the risk of death did not change significantly, while the risk of dialysis increased. Medium appointment utilizers had a stable risk of death and a decreasing risk of dialysis. Significant appointment utilization (above 31 visits during the baseline year) helped high-risk patients avoid both outcomes of interest-death and dialysis.

CONCLUSION
Our model could justify the creation of a novel palliative care introduction trigger, as patients with medium demand for care may benefit from additional palliative care evaluation. The trigger could facilitate the uniformization of conservative treatment preparations. It could prompt messages to a managing physician when a patient crosses the threshold between low and medium appointment utilization. It may also aid in system-level policy development. Furthermore, our results highlight the benefit of significant appointment utilization among high-risk patients.

D000368:Aged
D000369:Aged, 80 and over
D001071:Appointments and Schedules
D005260:Female
D006801:Humans
D007676:Kidney Failure, Chronic
D008297:Male
D008875:Middle Aged
D010166:Palliative Care
D006435:Renal Dialysis
D012189:Retrospective Studies
D014481:United States

palliative care
Kidney diseases
dialysis
survival analysis


Optical measures of changes in cerebral vascular tone during voluntary breath holding and a Sternberg memory task.

Abstract: The human cerebral vasculature responds to changes in blood pressure and demands for oxygenation via cerebral autoregulation. Changes in cerebrovascular tone (vasoconstriction and vasodilation) also mediate the changes in blood flow measured by the BOLD fMRI signal. This cerebrovascular reactivity is known to vary with age. In two experiments, we demonstrate that cerebral pulse parameters measured using optical imaging can quantify changes in cerebral vascular tone, both globally and locally. In experiment 1, 51 older adults (age range=55-87) performed a voluntary breath-holding task while cerebral pulse amplitude measures were taken. We found significant pulse amplitude variations across breath-holding periods, indicating vasodilation during, and vasoconstriction after breath holding. The breath-holding index (BHI), a measure of cerebrovascular reactivity (CVR) was derived and found to correlate with age. BHI was also correlated with performance in the Modified Mini-Mental Status Examination, even after controlling for age and education. In experiment 2, the same participants performed a Sternberg task, and changes in regional pulse amplitude between high (set-size 6) and low (set-size 2) task loads were compared. Only task-related areas in the fronto-parietal network (FPN) showed significant reduction in pulse amplitude, indicating vasodilation. Non-task-related areas such as the somatosensory and auditory cortices did not show such reductions. Taken together, these experiments suggest that optical pulse parameters can index changes in brain vascular tone both globally and locally, using both physiological and cognitive load manipulations.

Tan|Chin Hong|CH|
Low|Kathy A|KA|
Schneider-Garces|Nils|N|
Zimmerman|Benjamin|B|
Fletcher|Mark A|MA|
Maclin|Edward L|EL|
Chiarelli|Antonio M|AM|
Gratton|Gabriele|G|
Fabiani|Monica|M|

Aging
Breath-holding task
Cerebrovascular reactivity (CVR)
Sternberg task
Diffuse optical imaging


The Clinical Efficacy of ReCell® Autologous Cell Regeneration Techniques Combined with Dermabrasion Treatment in Acne Scars.

Abstract:
OBJECTIVE
To evaluate the efficacy of ReCell® autologous cell regeneration techniques combined with dermabrasion treatment on the therapy of acne scars.

METHODS
We analyzed retrospectively 78 patients with acne scars who presented to the Department of Plastic Surgery at Peking Union Medical College Hospital from May 2015 to May 2017; 30 patients were treated with dermabrasion (Group 1), and the other 48 patients were treated with ReCell® autologous regeneration techniques combined with dermabrasion (Group 2). Efficacy was evaluated through self-evaluation of the patient, third-party evaluation and photographs taken before and after treatment. The wound healing time and postoperative complication rate were also recorded.

RESULTS
The study revealed a significant difference in healing time (P < 0.001) between patients treated with dermabrasion (Group 1) and patients treated with ReCell® autologous regeneration techniques combined with dermabrasion (Group 2). The average healing time of Group 1 was 12.30 ± 1.725 days, while the average healing time of Group 2 was 5.27 ± 1.086 days. In Group 2, patient self-evaluation and third-party evaluation were more satisfactory than those of Group 1 (P < 0.001). Moreover, there were no postoperative complications in Group 2 such as pigmentation and scar hyperplasia.

CONCLUSION
The ReCell® technique is simple, minimally invasive, biocompatible and effective in the treatment of acne scars. It can shorten healing time and reduce the occurrence of postoperative complications, thereby providing a safe and effective treatment approach for patients with facial acne scars.

LEVEL OF EVIDENCE IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Chen|Qiao|Q| Yu|Nanze|N| Liu|Zhifei|Z| Zhang|Wenchao|W| Long|Fei|F| Zeng|Ang|A| Zhu|Lin|L| Wang|Xiaojun|X|


Alkaline phosphatase: Structure, expression and its function in bone mineralization.

Abstract: Alkaline phosphatase (ALP) is highly expressed in the cells of mineralized tissue and plays a critical function in the formation of hard tissue. The existing status of this critical enzyme should be reviewed periodically. ALP increases inorganic phosphate local rates and facilitates mineralization as well as reduces the extracellular pyrophosphate concentration, an inhibitor of mineral formation. Mineralization is the production, inside matrix vesicles, of hydroxyapatite crystals that bud from the outermembrane of hypertrophic osteoblasts and chondrocytes. The expansion of hydroxyapatite formsinto the extracellular matrix and its accumulation between collagen fibrils is observed. Among various isoforms, the tissue-nonspecific isozyme of ALP (TNAP) is strongly expressed in bone, liver and kidney and plays a key function in the calcification of bones. TNAP hydrolyzes pyrophosphate and supplies inorganic phosphate to enhance mineralization. The biochemical substrates of TNAP are believed to be inorganic pyrophosphate and pyridoxal phosphate. These substrates concentrate in TNAP deficient condition which results in hypophosphatasia. The increased level of ALP expression and development in this environment would undoubtedly provide new and essential information about the fundamental molecular mechanisms of bone formation, offer therapeutic possibilities for the management of bone-related diseases.

Bone mineralization
ALP
Hydroxyapatite
TNAP
Hypophosphatasia


Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

Abstract:
OBJECTIVES
HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV.

METHODS
The study was a retrospective cohort study (study period 2004-2018). Cases of HIV + and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV + controls without SCD (HIV+/SCD-).

RESULTS
Thirty-five HIV+/SCD + subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6 years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD + had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P = 0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD + and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD + cohort (P = 0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD + cohort showed a more rapid rise and higher total CD4 count (P = 0.012, regression analysis).

CONCLUSION
The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD + achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

Ssenyondwa|Joseph|J|
George|Paul E|PE|
Carlos Bazo-Alvarez|Juan|J|
Mercedes|Rebecca|R|
Kanywa|Jacqueline B|JB|
Naturinda|Ernest|E|
Wasswa|Peter L M|PLM|
Lubega|Joseph|J|

sickle cell disease
paediatric
HIV
Africa
Uganda
CD4
Afrique
Ouganda
VIH
drépanocytose
pédiatrie


Taking stock of the availability and functions of National Ethics Committees worldwide.

Abstract:
BACKGROUND
National Ethics Committees (NECs) offer important oversight and guidance functions and facilitate public debate on bioethical issues. In an increasingly globalized world where technological advances, multi-national research collaborations, and pandemics are creating ethical dilemmas that transcend national borders, coordination and the joining of efforts among NECs are key. The purpose of this study is to take stock of the current NEC landscape, their varying roles and missions, and the range of bioethical topics on which they deliberated since their inception.

METHODS
Data on the availability, functions, and ethical deliberations (publications) of NECs globally were gathered through a systematic search of NEC websites and through contacts known to the authors. The search was conducted in English, French, and Spanish. The data abstraction was done in Excel and included the NEC's country, region, functions, and deliberations on bioethical issues. Deliberation topics were classified into thematic categories through an iterative process of regrouping to arrive at the main set of themes.

RESULTS
124 NECs in 100 countries were identified. 44% of the NECs are in Europe and 47% are in high-income countries. Out of the 1108 retrieved publications, 40% were on bioethics in the context of research, followed by the clinic (28%) and public health issues (22%). The top five topics of these publications were: research ethics (124; 9%), genetics and genomics (62; 6%), organ transplantation (58; 5%), assisted reproductive technology (49; 4%), and end of life (36; 3%).

CONCLUSION
Our study makes an important contribution to understanding the current interests and functions of NECs and the range of their bioethics deliberations. By making the data publicly available through this publication, it allows users to conduct tailored analyses and queries based on their interests, and to seek and strengthen collaboration and exchange. It also makes the case for the fruitfulness of developing and maintaining a global repository of current and new deliberations to more effectively advance this field for the greater good of humanity, research, and public health.

Hummel|Patrik|P|0000-0001-9668-0810 Adam|Taghreed|T| Reis|Andreas|A| Littler|Katherine|K|

National Ethics Committees
Deliberation
Research ethics
Global bioethics
Health policy
Medical ethics
Public health ethics


Evaluating Enhancer Function and Transcription.

Abstract: Cell-type- and condition-specific profiles of gene expression require coordination between protein-coding gene promoters and cis-regulatory sequences called enhancers. Enhancers can stimulate gene activity at great genomic distances from their targets, raising questions about how enhancers communicate with specific gene promoters and what molecular mechanisms underlie enhancer function. Characterization of enhancer loci has identified the molecular features of active enhancers that accompany the binding of transcription factors and local opening of chromatin. These characteristics include coactivator recruitment, histone modifications, and noncoding RNA transcription. However, it remains unclear which of these features functionally contribute to enhancer activity. Here, we discuss what is known about how enhancers regulate their target genes and how enhancers and promoters communicate. Further, we describe recent data demonstrating many similarities between enhancers and the gene promoters they control, and we highlight unanswered questions in the field, such as the potential roles of transcription at enhancers.

enhancers
promoters
histone modifications
gene regulation
noncoding transcription


Determination of irinotecan and SN38 in human plasma by TurboFlow™ liquid chromatography-tandem mass spectrometry.

Abstract: Irinotecan is a cytotoxic agent used in the treatment of metastatic colorectal cancer. Irinotecan is a prodrug when is converted in vivo to an active metabolite SN38, which has potent pharmacological activity. SN38 is then inactivated and excreted as SN38-glucuronide. High-performance liquid chromatography-mass spectrometry is a widely used bioanalysis technique that can be coupled to the turbulent-flow extraction line to shorten preparation time. A technique was developed to quantify irinotecan and its metabolite by liquid chromatography-tandem mass spectrometry coupled with a turbulent-flow online extraction method. Assays were performed on 100 μL of plasma after protein precipitation. The supernatant is injected directly into the extraction column, transferred to the chromatographic column, and analyzed by tandem mass spectrometry. Linearity, reproducibility and repeatability of the method were validated on a concentration range of 25-2500 ng/mL for irinotecan and 5-500 ng/mL for SN38. For the low limit of quantification of irinotecan and SN38, precision is 6.31% and 8.73%, and accuracy is 84.0% and 91.8%, respectively. The SN38-glucuronide determination protocol included a hydrolyzation step. This method was successfully used to quantify irinotecan, SN38 and SN38-G in human plasma in a clinical trial.

Herviou|P|P| Richard|D|D| Roche|L|L| Pinguet|J|J| Libert|F|F| Eschalier|A|A| Durando|X|X| Authier|N|N|

Irinotecan
Human plasma
High-turbulence liquid chromatography
LC–MS/MS


Activation of a T-box-Otx2-Gsc gene network independent of TBP and TBP-related factors.

Abstract: Embryonic development relies on activating and repressing regulatory influences that are faithfully integrated at the core promoter of individual genes. In vertebrates, the basal machinery recognizing the core promoter includes TATA-binding protein (TBP) and two TBP-related factors. In Xenopus embryos, the three TBP family factors are all essential for development and are required for expression of distinct subsets of genes. Here, we report on a non-canonical TBP family-insensitive (TFI) mechanism of transcription initiation that involves mesoderm and organizer gene expression. Using TBP family single- and triple-knockdown experiments, α-amanitin treatment, transcriptome profiling and chromatin immunoprecipitation, we found that TFI gene expression cannot be explained by functional redundancy, is supported by active transcription and shows normal recruitment of the initiating form of RNA polymerase II to the promoter. Strikingly, recruitment of Gcn5 (also known as Kat2a), a co-activator that has been implicated in transcription initiation, to TFI gene promoters is increased upon depletion of TBP family factors. TFI genes are part of a densely connected TBP family-insensitive T-box-Otx2-Gsc interaction network. The results indicate that this network of genes bound by Vegt, Eomes, Otx2 and Gsc utilizes a novel, flexible and non-canonical mechanism of transcription that does not require TBP or TBP-related factors.

D018507:Gene Expression Regulation, Developmental

D035182:TATA Box Binding Protein-Like Proteins

TATA-binding protein
Xenopus
Mesoderm
Organizer
Gene regulation


Varied Pathways of Infant Gut-Associated Bifidobacterium to Assimilate Human Milk Oligosaccharides: Prevalence of the Gene Set and Its Correlation with Bifidobacteria-Rich Microbiota Formation.

Abstract: The infant's gut microbiome is generally rich in the Bifidobacterium genus. The mother's milk contains natural prebiotics, called human milk oligosaccharides (HMOs), as the third most abundant solid component after lactose and lipids, and of the different gut microbes, infant gut-associated bifidobacteria are the most efficient in assimilating HMOs. Indeed, the fecal concentration of HMOs was found to be negatively correlated with the fecal abundance of Bifidobacterium in infants. Given these results, two HMO molecules, 2'-fucosyllactose and lacto-N-neotetraose, have recently been industrialized to fortify formula milk. As of now, however, our knowledge about the HMO consumption pathways in infant gut-associated bifidobacteria is still incomplete. The recent studies indicate that HMO assimilation abilities significantly vary among different Bifidobacterium species and strains. Therefore, to truly maximize the effects of prebiotic and probiotic supplementation in commercialized formula, we need to understand HMO consumption behaviors of bifidobacteria in more detail. In this review, we summarized how different Bifidobacterium species/strains are equipped with varied gene sets required for HMO assimilation. We then examined the correlation between the abundance of the HMO-related genes and bifidobacteria-rich microbiota formation in the infant gut through data mining analysis of a deposited fecal microbiome shotgun sequencing dataset. Finally, we shortly described future perspectives on HMO-related studies.

infant
Bifidobacterium
human milk oligosaccharides
microbiota
breast-feeding


Dental Students' Awareness, Preparedness and Barriers towards Managing Tobacco-Using Patients-A Cross-Sectional Study.

Abstract: Aims: To evaluate Hong Kong dental students' perceived awareness, preparedness and barriers towards managing tobacco-using patients. Methods: A validated questionnaire was administered to dental students who were in their clinical years (the third, fourth, fifth and sixth year of study) in 2017 at the University of Hong Kong. The questionnaire consisted of three sections: (1) awareness towards practicing tobacco cessation counselling (TCC), (2) preparedness in terms of confidence, knowledge and clinical practices when managing tobacco-using patients, and (3) perceived barriers to counselling. Results: All 206 invited students had participated this study. Most (93%) agreed that dentists should deliver TCC. However, only around a quarter (26%) of students were well-prepared to help patients in tobacco cessation. While 60% of students agreed nicotine replacement therapy (NRT) was helpful for patients to quit tobacco use, only 28% understood its mechanism of action, and merely 16% were knowledgeable enough to introduce NRT to their patients. Two-thirds (62%) of students felt they did not have sufficient skills at this stage of their training. Conclusions: Most Hong Kong dental students had good awareness that dental professionals had an important role to promote tobacco cessation in their patient pools. However, not many of them were well-prepared to manage tobacco-using patients. Common barriers were found to be patients' apathy and students' inadequate familiarity with NRT.

tobacco cessation counselling
nicotine replacement therapy
dental education
public health
smoking


Nonomuraea insulae sp. nov., isolated from forest soil.

Abstract: Strain H2R21T, a novel actinobacterium, isolated from a forest soil sample collected from Heybeliada, Istanbul, Turkey, and a polyphasic approach was used for characterisation of the strain. Chemotaxonomic and morphological characterisation of strain H2R21T indicated that it belongs to the genus Nonomuraea. 16S rRNA gene sequence similarity showed that the strain is closely related to Nonomuraea purpurea 1SM4-01T (99.1%) and Nonomuraea solani CGMCC 4.7037T (98.4%). DNA-DNA relatedness values were found to be lower than 70% between the isolate and its phylogenetic neighbours N. purpurea 1SM4-01T, N. solani CGMCC 4.7037T and Nonomuraea rhizophila YIM 67092T. The whole cell hydrolysates of strain H2R21T were found to contain meso-diaminopimelic acid as the diagnostic diamino acid and glucose, madurose, mannose and ribose as the cell sugars. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, dihydroxy-phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, two glycophospholipids and two unidentified lipids. The predominant menaquinones were identified as MK-9(H4) and MK-9(H6). The major fatty acids were found to be iso-C16:0, iso-C16:0 2OH and C17:0 10-methyl. On the basis of DNA-DNA relatedness data and some phenotypic characteristics, it is evident that strain H2R21T can be distinguished from the closely related species in the genus Nonomuraea. Thus, it is concluded that strain H2R21T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea insulae sp. nov. is proposed. The type strain is H2R21T (= DSM 102915T = CGMCC 4.7338T = KCTC 39769T).

Nonomuraea insulae sp. nov.
16S rRNA gene
Actinobacteria
Polyphasic taxonomy


Histatin 5 Metallopeptides and Their Potential against Candida albicans Pathogenicity and Drug Resistance.

Abstract: Usually caused by Candida albicans, buccal candidiasis begins with the morphological transition between yeast and hyphal cells. Over time and without the correct treatment, it can be disseminated through the bloodstream becoming a systemic infection with high mortality rates. C. albicans already shows resistance against antifungals commonly used in treatments. Therefore, the search for new drugs capable of overcoming antifungal resistance is essential. Histatin 5 (Hst5) is an antimicrobial peptide of the Histatin family, that can be found naturally in human saliva. This peptide presents high antifungal activity against C. albicans. However, Hst5 action can be decreased for interaction with enzymes and metal ions present in the oral cavity. The current work aims to bring a brief review of relevant aspects of the pathogenesis and resistance mechanisms already reported for C. albicans. In addition, are also reported here the main immune responses of the human body and the most common antifungal drugs. Finally, the most important aspects regarding Histatin 5 and the benefits of its interaction with metals are highlighted. The intention of this review is to show the promising use of Hst5 metallopeptides in the development of effective drugs.

Histatin 5
metallopeptides
Candida albicans
antifungal peptides