Two-Dimensional Metal Organic Framework Nanosheets as Bifunctional Catalyst for Electrochemical and Photoelectrochemical Water Oxidation.

Abstract: Electrochemical (EC) and photoelectrochemical (PEC) water splitting represent promising strategies for renewable energy conversion and fuel production and require design of efficient catalysts for the oxygen evolution reaction (OER). Herein, we report the synthesis of two-dimensional (2D) Co-based metal organic framework (Co-MOF) nanosheets and their bifunctional catalytic properties for both EC and PEC OER. Benefiting from the large surface area and abundant isolated metal active sites, the Co-MOF nanosheets exhibited excellent OER activity and stability. The efficient electron-hole generation and separation of the nanosheets, owing to dimensional confinement, contributed to an improved visible light response in PEC OER. This study presents a new strategy to design EC/PEC bifunctional catalyst utilizing unique structural and electronic features of 2D MOF.

Liu|Chang|C| Shen|Xiaochen|X| Johnson|Grayson|G| Zhang|Yulu|Y| Zhang|Changlin|C| Chen|Jiafu|J| Li|Lingyan|L| Sheehan|Colton|C| Peng|Zhenmeng|Z| Zhang|Sen|S|

metal organic framework
nanosheet
bifunctional catalyst
photoelectrochemical water oxidation
oxygen evolution reaction


Regulation of epigenetic homeostasis in uveal melanoma and retinoblastoma.

Abstract: Uveal melanoma (UM) and retinoblastoma (RB), which cause blindness and even death, are the most frequently observed primary intraocular malignancies in adults and children, respectively. Epigenetic studies have shown that changes in the epigenome contribute to the rapid progression of both UM and RB following classic genetic changes. The loss of epigenetic homeostasis plays an important role in oncogenesis by disrupting the normal patterns of gene expression. The targetable nature of epigenetic modifications provides a unique opportunity to optimize treatment paradigms and establish new therapeutic options for both UM and RB with these aberrant epigenetic modifications. We aimed to review the research findings regarding relevant epigenetic changes in UM and RB. Herein, we 1) summarize the literature, with an emphasis on epigenetic alterations, including DNA methylation, histone modifications, RNA modifications, noncoding RNAs and an abnormal chromosomal architecture; 2) elaborate on the regulatory role of epigenetic modifications in biological processes during tumorigenesis; and 3) propose promising therapeutic candidates for epigenetic targets and update the list of epigenetic drugs for the treatment of UM and RB. In summary, we endeavour to depict the epigenetic landscape of primary intraocular malignancy tumorigenesis and provide potential epigenetic targets in the treatment of these tumours.

Chai|Peiwei|P| Jia|Ruobing|R| Li|Yongyun|Y| Zhou|Chuandi|C| Gu|Xiang|X| Yang|Ludi|L| Shi|Hanhan|H| Tian|Hao|H| Lin|Huimin|H| Yu|Jie|J| Zhuang|Ai|A| Ge|Shengfang|S| Jia|Renbing|R| Fan|Xianqun|X|

Epigenetics
Uveal melanoma
Retinoblastoma
RNA Modifications
Noncoding RNA
Chromosome conformation


Development and validation of an MRI-based radiomic signature for the preoperative prediction of treatment response in patients with invasive functional pituitary adenoma.

Abstract:
PURPOSE
The preoperative prediction of treatment response is important for determining individual treatment strategies for invasive functional pituitary adenoma (IFPA). This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomic signature for preoperative prediction of treatment response in IFPA.

METHOD
One hundred and sixty-three patients with IFPA were enrolled and divided into primary (n = 108) and validation cohorts (n = 55) according to time point. IFPA patients were divided into remission and non-remission according to postoperative hormone levels. Radiomic features were extracted from their MR images and a radiomic signature was built using a support vector machine. Subsequently, multivariable logistic regression analysis was used to select the most informative clinical features, and a radiomic model incorporating the radiomic signature and selected clinical features was constructed and used as the final predictive model.

RESULTS
Seven radiomic features were selected to construct the radiomic signature, which achieved an area under the curve (AUC) of 0.834 and 0.808 on the primary and validation cohorts respectively. The radiomic model incorporating the radiomic signature and Knosp grade showed good discrimination abilities and calibration, with AUCs of 0.832 and 0.811 for the primary and validation cohorts respectively. The radiomic signature and radiomic model better estimated the treatment responses of patients with IFPA than our clinical features model. Decision curve analysis showed the radiomic model was clinically useful.

CONCLUSIONS
This radiomic model may help neurosurgeons predict the treatment responses of patients with IFPA before surgery and determine individual treatment strategies.

Fan|Yanghua|Y| Liu|Zhenyu|Z| Hou|Bo|B| Li|Longfei|L| Liu|Xiaohai|X| Liu|Zehua|Z| Wang|Renzhi|R| Lin|Yusong|Y| Feng|Feng|F| Tian|Jie|J| Feng|Ming|M|

D000236:Adenoma
D000328:Adult
D019540:Area Under Curve
D005260:Female
D006801:Humans
D008279:Magnetic Resonance Imaging
D008297:Male
D010902:Pituitary Gland
D010911:Pituitary Neoplasms
D011237:Predictive Value of Tests
D011300:Preoperative Care
D015203:Reproducibility of Results
D012189:Retrospective Studies
D060388:Support Vector Machine
D016896:Treatment Outcome

Radiomics
Treatment response
Invasive functional pituitary adenoma
Magnetic resonance imaging


Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors.

Abstract: Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for embryonic blood vessel development and tumor angiogenesis. Several compounds that showed potent activity toward this attractive anticancer drug target in the assay have been reported. In order to investigate the structure-activity correlation of indolocarbazole series compounds and modify them to improve their selectivity and activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular docking was used to check the results. Based on the common sketch align, two good QSAR models with high predictabilities (CoMFA model: q(2) = 0.823, r(2) = 0.979; CoMSIA model: q(2) = 0.804, r(2) = 0.967) were obtained and the contour maps obtained from both models were applied to identify the influence on the biological activity. Molecular docking was then used to confirm the results. Combined with the molecular docking results, the detail binding mode between the ligands and Tie-2 was elucidated, which enabled us to interpret the structure-activity relationship. These satisf actory results not only offered help to comprehend the action mechanism of indolocarbazole series compounds, but also provide new information for the design of new potent inhibitors.

Tian|Yuanxin|Y| Xu|Jian|J| Li|Zhonghuang|Z| Zhu|Zhengguang|Z| Zhang|Jiajie|J| Wu|Shuguang|S|

D057927:Hydrophobic and Hydrophilic Interactions

docking
CoMSIA
3D-QSAR, CoMFA
Tie-2 kinase inhibitor


MRI assessment of cardiac tumours: part 1, multiparametric imaging protocols and spectrum of appearances of histologically benign lesions.

Abstract: Cardiac magnetic resonance imaging (MRI) is the reference standard technique for assessment and characterization of a suspected cardiac tumour. It provides an unrestricted field of view, high temporal resolution and non-invasive tissue characterization based on multi-parametric assessment of the chemical micro-environment. MRI exploits differences in hydrogen proton density in conjunction with T1 and T2 relaxation properties of different tissues to help differentiation normal from abnormal and benign from malignant lesions. In this article we review specific cardiac MRI techniques, tumour protocol design and the appearance of the spectrum of histologically benign tumours.

Hoey|Edward T D|ET|
Shahid|Muhammad|M|
Ganeshan|Arul|A|
Baijal|Shobhit|S|
Simpson|Helen|H|
Watkin|Richard W|RW|

cardiac tumour
Magnetic resonance imaging (MRI)
myxoma


Anterior skull base duplication requiring delivery via EXIT procedure: A case report.

Abstract: Duplication of the anterior skull base structures is an extremely rare malformation of failed midline blastogenesis. We present the case of a child with an obstructive oral cavity mass diagnosed on prenatal imaging. The child was successfully delivered by EXIT procedure, a tracheotomy was performed, and postnatal imaging demonstrated an array of craniofacial malformations, including complete duplication of the maxilla, pituitary glands, aqueducts of Sylvius, and basilar arteries. The child underwent excision of the duplicate maxilla, resulting in a wide cleft palate that will be repaired at a future date.

Shires|Courtney B|CB|
Giurintano|Jonathan P|JP|
McLevy-Bazzanella|Jennifer|J|
Thompson|Jerome|J|


Suppression of the inflammatory response by disease-inducible interleukin-10 gene therapy in a three-dimensional micromass model of the human synovial membrane.

Abstract:
BACKGROUND
Gene therapy has the potential to provide long-term production of therapeutic proteins in the joints of osteoarthritis (OA) patients. The objective of this study was to analyse the therapeutic potential of disease-inducible expression of anti-inflammatory interleukin-10 (IL-10) in the three-dimensional micromass model of the human synovial membrane.

METHODS
Synovial tissue samples from OA patients were digested and the cells were mixed with Matrigel to obtain 3D micromasses. The CXCL10 promoter combined with the firefly luciferase reporter in a lentiviral vector was used to determine the response of the CXCL10 promoter to tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and lipopolysaccharide (LPS). The effects of recombinant IL-10 on gene expression were determined by quantitative PCR. The production of IL-10 from the CXCL10p-IL10 vector and the effects on pro-inflammatory cytokine production were assessed by multiplex ELISA.

RESULTS
Micromasses made from whole synovial membrane cell suspensions form a distinct surface composition containing macrophage and fibroblast-like synoviocytes thus mimicking the synovial lining. This lining can be transduced by lentiviruses and allow CXCL-10 promoter-regulated transgene expression. Adequate amounts of IL-10 transgene were produced after stimulation with pro-inflammatory factors able to reduce the production of synovial IL-1β and IL-6.

CONCLUSIONS
Synovial micromasses are a suitable model to test disease-regulated gene therapy approaches and the CXCL10p-IL10 vector might be a good candidate to decrease the inflammatory response implicated in the pathogenesis of OA.

Broeren|Mathijs G A|MG|
de Vries|Marieke|M|
Bennink|Miranda B|MB|
Arntz|Onno J|OJ|
van Lent|Peter L E M|PL|
van der Kraan|Peter M|PM|
van den Berg|Wim B|WB|
van den Hoogen|Frank H J|FH|
Koenders|Marije I|MI|
van de Loo|Fons A J|FA|

D060888:Real-Time Polymerase Chain Reaction

Gene therapy
Micromasses
Osteoarthritis
Cytokines
Inflammation
Synovium


Patterns of tobacco use, quit attempts, readiness to quit and self-efficacy among smokers with anxiety or depression: Findings among six countries of the EUREST-PLUS ITC Europe Surveys.

Abstract:
INTRODUCTION
We compared smoking behaviors, past quit attempts, readiness to quit and beliefs about quitting among current cigarette smokers with probable anxiety or depression (PAD) to those without PAD, from six European Union (EU) Member States (MS).

METHODS
A nationally representative cross-sectional sample of 6011 adult cigarette smokers from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) was randomly selected through a multistage cluster sampling design in 2016. Respondents were classified as having PAD based on self-reported current diagnosis or treatment for anxiety or depression, or a positive screen for major depression, according to a validated two-item instrument. Sociodemographic characteristics, patterns of tobacco use, past quitting, readiness to quit, self-efficacy and beliefs about quitting were assessed for patients with and without PAD. Logistic regression was used to examine predictors of PAD. All analyses were conducted using the complex samples package of SPSS.

RESULTS
Among smokers sampled, 21.0% (95% CI: 19.3-22.9) were identified as having PAD. Logistic regression analyses controlling for socioeconomic variables and cigarettes smoked per day found smokers with PAD were more likely to have made an attempt to quit smoking in the past (AOR=1.48; 95% CI: 1.25-1.74), made a quit attempt in the last 12 months (AOR=1.75; 95% CI: 1.45-2.11), and report lower self-efficacy with quitting (AOR=1.83; 95% CI: 1.44-2.32) compared to smokers without PAD. Additionally, it was found that individuals with PAD were more likely to report having received advice to quit from a doctor or health professional and having used quitline support as part of their last quit attempt.

CONCLUSIONS
Smokers with PAD report a greater interest in quitting in the future and more frequent failed quit attempts than smokers without PAD; however, the high rates of untreated anxiety or depression, nicotine dependence, low confidence in the ability to quit, infrequent use of cessation methods, as well as socioeconomic factors may make quitting difficult.

Petroulia|Ioanna|I|
Kyriakos|Christina N|CN|
Papadakis|Sophia|S|
Tzavara|Chara|C|
Filippidis|Filippos T|FT|
Girvalaki|Charis|C|
Peleki|Theodosia|T|
Katsaounou|Paraskevi|P|
McNeill|Ann|A|
Mons|Ute|U|
Fernández|Esteve|E|
Demjén|Tibor|T|
Trofor|Antigona C|AC|
Herbeć|Aleksandra|A|
Zatoński|Witold A|WA|
Tountas|Yannis|Y|
Fong|Geoffrey T|GT|
Vardavas|Constantine I|CI|
|||

anxiety
depression
Europe
mental health
smoking cessation


Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents.

Abstract: Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance,we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity.We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport,without affecting Cl- transport or Na+,K+-pump activity. Rt was unaffected. Na+ transport recovered 18 h after exposure. Concentrations (100-360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro.

Zaccone|Eric J|EJ|
Goldsmith|W Travis|WT|
Shimko|Michael J|MJ|
Wells|J R|JR|
Schwegler-Berry|Diane|D|
Willard|Patsy A|PA|
Case|Shannon L|SL|
Thompson|Janet A|JA|
Fedan|Jeffrey S|JS|

Diacetyl
2,3-Pentanedione
Ion transport
Dicarbonyl/l-xylulose reductase
Human airway epithelial cells
Vapor exposure


An atypical presentation of pulmonary sequestration.

Abstract: Pulmonary sequestration (PS) is a rare congenital malformation of the lower respiratory tract and is commonly complicated by recurrent infections and presents with respiratory failure. We report an atypical clinical presentation of postprandial abdominal pain and cramps in a patient with intralobar PS.

pulmonary sequestration
Abdominal angina
steal syndrome


Transporting Subgroup Analyses of Randomized Controlled Trials for Planning Implementation of New Interventions.

Abstract: Subgroup analyses of randomized controlled trials guide resource allocation and implementation of new interventions by identifying groups of individuals who are likely to benefit most from the intervention. Unfortunately, trial populations are rarely representative of the target populations of public health or clinical interest. Unless the relevant differences between trial and target populations are accounted for, subgroup results from trials might not reflect which groups in the target population will benefit most from the intervention. Transportability provides a rigorous framework for applying results derived in potentially highly selected study populations to external target populations. The method requires that researchers measure and adjust for all variables that 1) modify the effect of interest and 2) differ between the target and trial populations. To date, applications of transportability have focused on the external validity of overall study results and understanding within-trial heterogeneity; however, this approach has not yet been used for subgroup analyses of trials. Through an example from the Iniciativa Profilaxis Pre-Exposición (iPrEx) study (multiple countries, 2007-2010) of preexposure prophylaxis for human immunodeficiency virus, we illustrate how transporting subgroup analyses can produce target-specific subgroup effect estimates and numbers needed to treat. This approach could lead to more tailored and accurate guidance for resource allocation and cost-effectiveness analyses.

Mehrotra|Megha L|ML|
Westreich|Daniel|D|
Glymour|M Maria|MM|
Geng|Elvin|E|
Glidden|David V|DV|

D016032:Randomized Controlled Trials as Topic

transportability
subgroup analyses
implementation
external validity
number needed to treat
target-specific subgroup analyses


Key genes and drug delivery systems to improve the efficiency of chemotherapy.

Abstract: Cancer cells can develop resistance to anticancer drugs, thereby becoming tolerant to treatment through different mechanisms. The biological mechanisms leading to the generation of anticancer treatment resistance include alterations in transmembrane proteins, DNA damage and repair mechanisms, alterations in target molecules, and genetic responses, among others. The most common anti-cancer drugs reported to develop resistance to cancer cells include cisplatin, doxorubicin, paclitaxel, and fluorouracil. These anticancer drugs have different mechanisms of action, and specific cancer types can be affected by different genes. The development of drug resistance is a cellular response which uses differential gene expression, to enable adaptation and survival of the cell to diverse threatening environmental agents. In this review, we briefly look at the key regulatory genes, their expression, as well as the responses and regulation of cancer cells when exposed to anticancer drugs, along with the incorporation of alternative nanocarriers as treatments to overcome anticancer drug resistance.

Torres-Martinez|Zally|Z|
Delgado|Yamixa|Y|
Ferrer-Acosta|Yancy|Y|
Suarez-Arroyo|Ivette J|IJ|
Joaquín-Ovalle|Freisa M|FM|
Delinois|Louis J|LJ|
Griebenow|Kai|K|

drug delivery systems
Cancer resistance
resistance genes


The transcription factor p53: not a repressor, solely an activator.

Abstract: The predominant function of the tumor suppressor p53 is transcriptional regulation. It is generally accepted that p53-dependent transcriptional activation occurs by binding to a specific recognition site in promoters of target genes. Additionally, several models for p53-dependent transcriptional repression have been postulated. Here, we evaluate these models based on a computational meta-analysis of genome-wide data. Surprisingly, several major models of p53-dependent gene regulation are implausible. Meta-analysis of large-scale data is unable to confirm reports on directly repressed p53 target genes and falsifies models of direct repression. This notion is supported by experimental re-analysis of representative genes reported as directly repressed by p53. Therefore, p53 is not a direct repressor of transcription, but solely activates its target genes. Moreover, models based on interference of p53 with activating transcription factors as well as models based on the function of ncRNAs are also not supported by the meta-analysis. As an alternative to models of direct repression, the meta-analysis leads to the conclusion that p53 represses transcription indirectly by activation of the p53-p21-DREAM/RB pathway.

D050759:Cyclin-Dependent Kinase Inhibitor p21

DREAM, DP, RB-like, E2F4, and MuvB complex


Chronic Overexpression of Bradykinin in Kidney Causes Polyuria and Cardiac Hypertrophy.

Abstract: Acute intra-renal infusion of bradykinin increases diuresis and natriuresis via inhibition of vasopressin activity. However, the consequences of chronically increased bradykinin in the kidneys have not yet been studied. A new transgenic animal model producing an excess of bradykinin by proximal tubular cells (KapBK rats) was generated and submitted to different salt containing diets to analyze changes in blood pressure and other cardiovascular parameters, urine excretion, and composition, as well as levels and expression of renin-angiotensin system components. Despite that KapBK rats excrete more urine and sodium, they have similar blood pressure as controls with the exception of a small increase in systolic blood pressure (SBP). However, they present decreased renal artery blood flow, increased intrarenal expression of angiotensinogen, and decreased mRNA expression of vasopressin V1A receptor (AVPR1A), suggesting a mechanism for the previously described reduction of renal vasopressin sensitivity by bradykinin. Additionally, reduced heart rate variability (HRV), increased cardiac output and frequency, and the development of cardiac hypertrophy are the main chronic effects observed in the cardiovascular system. In conclusion: (1) the transgenic KapBK rat is a useful model for studying chronic effects of bradykinin in kidney; (2) increased renal bradykinin causes changes in renin angiotensin system regulation; (3) decreased renal vasopressin sensitivity in KapBK rats is related to decreased V1A receptor expression; (4) although increased renal levels of bradykinin causes no changes in mean arterial pressure (MAP), it causes reduction in HRV, augmentation in cardiac frequency and output and consequently cardiac hypertrophy in rats after 6 months of age.

Barros|Carlos C|CC|
Schadock|Ines|I|
Sihn|Gabin|G|
Rother|Franziska|F|
Xu|Ping|P|
Popova|Elena|E|
Lapidus|Irina|I|
Plehm|Ralph|R|
Heuser|Arnd|A|
Todiras|Mihail|M|
Bachmann|Sebastian|S|
Alenina|Natalia|N|
Araujo|Ronaldo C|RC|
Pesquero|Joao B|JB|
Bader|Michael|M|

polyuria
rats
blood pressure
kallikrein-kinin system
kinin


Convergent validity of the Integrated Visual and Auditory Continuous Performance Test (IVA+Plus): associations with working memory, processing speed, and behavioral ratings.

Abstract: Though the Integrated Visual and Auditory Continuous Performance Test (IVA + Plus) is commonly used by researchers and clinicians, few investigations have assessed its convergent and discriminant validity, especially with regard to its use with children. The present study details correlates of the IVA + Plus using measures of cognitive ability and ratings of child behavior (parent and teacher), drawing upon a sample of 90 psychoeducational evaluations. Scores from the IVA + Plus correlated significantly with the Working Memory and Processing Speed Indexes from the Fourth Edition of the Wechsler Intelligence Scales for Children (WISC-IV), though fewer and weaker significant correlations were seen with behavior ratings scales, and significant associations also occurred with WISC-IV Verbal Comprehension and Perceptual Reasoning. The overall pattern of relations is supportive of the validity of the IVA + Plus; however, general cognitive ability was associated with better performance on most of the primary scores of the IVA + Plus, suggesting that interpretation should take intelligence into account.

IVA
WISC-IV
ADHD
CPT
Psychoeducational assessment


A New Method for Prediction of Dental Arch Perimeter.

Abstract:
Purpose
Dental arch length, width, and perimeter are considered to be important for the diagnosis and treatment of orthodontic cases. This study aimed to utilize dental arch width and length to create an equation for predicting dental arch perimeter.

Materials and methods
Sixty-seven pairs of study models for patients with normal occlusion who received dental treatment were included in this study. Dental arch width at the level of the canines, first premolars, and first molars, in addition to dental arch length and perimeter, were measured using a digital vernier with 0.01mm accuracy. Data were subjected to step-wise regression analysis to determine the major predictors of arch perimeters and develop regression equations for both arches. The predicted arch perimeters were compared with the actual measured values using paired sample t-test.

Results
For both arches, the perimeter showed a direct, moderate to strong, highly significant correlation with the length and width measurements. Findings from step-wise regression analysis indicated that there was a strong correlation between arch perimeter and the inter-canine width and arch length, which explained 67.7% of the variation in arch perimeter in the maxillary arch. In the mandibular arch, inter-molar width, inter-canine width, and arch length explained 55.1% of the variation in the dental arch perimeter. The arch perimeter values predicted from the developed equations were not significantly different from the actual values that were measured.

Conclusion
New regression equations based on dental arch width and length at the level of the premolars, molars, and canines were developed to predict dental arch perimeters for both the mandibular and maxillary arches.

dental arch perimeter
arch length
arch widths
regression


In vitro selection of antibiotic-binding aptamers.

Abstract: Despite its wide applicability the selection of small molecule-binding RNA aptamers with high affinity binding and specificity is still challenging. We will present here a protocol which allows the in vitro selection of antibiotic-binding aptamers which turned out to be important building blocks for the design process of synthetic riboswitches. The presented methods will be compared with alternative in vitro selection protocols. A detailed note section will point out useful tips and pitfalls.

D000900:Anti-Bacterial Agents
D052157:Aptamers, Nucleotide
D058928:Riboswitch
D052156:SELEX Aptamer Technique

In vitro selection
RNA aptamer
Biotechnology
Combinatorial chemistry
SELEX


Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element.

Abstract:
OBJECTIVE
Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes.

METHODS
After the identification of a deletion upstream of SLC20A2, we assessed its consequences on gene function by reverse transcriptase droplet digital polymerase chain reaction (RT-ddPCR), an ex vivo inorganic phosphate uptake assay, and introduced the deletion of a putative SLC20A2 enhancer mapping to this region in human embryonic kidney 293 (HEK293) cells by clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9).

RESULTS
The 8p11.21 deletion, segregating with PFBC in a family, mapped 35 kb upstream of SLC20A2. The deletion carriers/normal controls ratio of relative SLC20A2 mRNA levels was 60.2% (P < 0.001). This was comparable with that of patients carrying an SLC20A2 premature stop codon (63.4%; P < 0.001). The proband exhibited a 39.3% decrease of inorganic phosphate uptake in blood (P = 0.015). In HEK293 cells, we observed a 39.8% decrease in relative SLC20A2 mRNA levels after normalization on DNA copy number (P < 0.001).

DISCUSSION
We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-of-function alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. © 2020 International Parkinson and Movement Disorder Society.

Cassinari|Kévin|K|0000-0003-2683-4073 Rovelet-Lecrux|Anne|A| Tury|Sandrine|S| Quenez|Olivier|O| Richard|Anne-Claire|AC| Charbonnier|Camille|C| Olaso|Robert|R| Boland|Anne|A| Deleuze|Jean-François|JF| Besancenot|Jean-François|JF| Delpont|Benoit|B| Pouliquen|Dorothée|D| Lecoquierre|François|F| Chambon|Pascal|P| Thauvin-Robinet|Christel|C| Campion|Dominique|D| Frebourg|Thierry|T| Battini|Jean-Luc|JL| Nicolas|Gaël|G|0000-0001-9391-7800

D050611:Sodium-Phosphate Cotransporter Proteins, Type III

primary familial brain calcification
SLC20A2
enhancer
CNV
regulation


Drosophila ezoana uses an hour-glass or highly damped circadian clock for measuring night length and inducing diapause.

Abstract: Insects inhabiting the temperate zones measure seasonal changes in day or night length to enter the overwintering diapause. Diapause induction occurs after the duration of the night exceeds a critical night length (CNL). Our understanding of the time measurement mechanisms is continuously evolving subsequent to Bünning's proposal that circadian systems play the clock role in photoperiodic time measurement (Bünning, 1936). Initially, the photoperiodic clocks were considered to be either based on circadian oscillators or on simple hour-glasses, depending on 'positive' or 'negative' responses in Nanda-Hamner and Bünsow experiments (Nanda & Hammer, 1958; Bünsow, 1960). However, there are also species whose responses can be regarded as neither 'positive', nor as 'negative', such as the Northern Drosophila species Drosophila ezoana, which is investigated in the present study. In addition, modelling efforts show that the 'positive' and 'negative' Nanda-Hamner responses can also be provoked by circadian oscillators that are damped to different degrees: animals with highly sustained circadian clocks will respond 'positive' and those with heavily damped circadian clocks will respond 'negative'. In the present study, an experimental assay is proposed that characterizes the photoperiodic oscillators by determining the effects of non-24-h light/dark cycles (T-cycles) on critical night length. It is predicted that there is (i) a change in the critical night length as a function of T-cycle period in sustained-oscillator-based clocks and (ii) a fixed night-length measurement (i.e. no change in critical night length) in damped-oscillator-based clocks. Drosophila ezoana flies show a critical night length of approximately 7 h irrespective of T-cycle period, suggesting a damped-oscillator-based photoperiodic clock. The conclusion is strengthened by activity recordings revealing that the activity rhythm of D. ezoana flies also dampens in constant darkness.

damped‐oscillator‐model of photoperiodic clock


A chemoenzymatic approach to protein immobilization onto crystalline cellulose nanoscaffolds.

Abstract: The immobilization of bioactive molecules onto nanocellulose leads to constructs that combine the properties of the grafted compounds with the biocompatibility and low cytotoxicity of cellulose carriers and the advantages given by their nanometer dimensions. However, the methods commonly used for protein grafting suffer from lack of selectivity, long reaction times, nonphysiological pH ranges and solvents, and the necessity to develop a tailor-made reaction strategy for each individual case. To overcome these restrictions, a generic two-step procedure was developed that takes advantage of the highly efficient oxime ligation combined with enzyme-mediated protein coupling onto the surface of peptide-modified crystalline nanocellulose. The described method is based on efficient and orthogonal transformations, requires no organic solvents, and takes place under physiological conditions. Being site-directed and regiospecific, it could be applied to a vast number of functional proteins.

Uth|Christina|C| Zielonka|Stefan|S| Hörner|Sebastian|S| Rasche|Nicolas|N| Plog|Andreas|A| Orelma|Hannes|H| Avrutina|Olga|O| Zhang|Kai|K| Kolmar|Harald|H|

immobilization
ligation
bioorthogonal protein immobilization
cellulose nanocrystals
enzyme catalysis


Highly active promoters and native secretion signals for protein production during extremely low growth rates in Aspergillus niger.

Abstract:
BACKGROUND
The filamentous ascomycete Aspergillus niger is used in many industrial processes for the production of enzymes and organic acids by batch and fed-batch cultivation. An alternative technique is continuous cultivation, which promises improved yield and optimized pipeline efficiency.

RESULTS
In this work, we have used perfusion (retentostat) cultivation to validate two promoters that are suitable for A. niger continuous cultivation of industrially relevant products. Firstly, promoters of genes encoding either an antifungal protein (Panafp) or putative hydrophobin (PhfbD) were confirmed as active throughout retentostat culture by assessing mRNA and protein levels using a luciferase (mluc) reporter system. This demonstrated the anafp promoter mediates a high but temporally variable expression profile, whereas the hfbD promoter mediates a semi-constant, moderate-to-high protein expression during retentostat culture. In order to assess whether these promoters were suitable to produce heterologous proteins during retentostat cultivation, the secreted antifungal protein (AFP) from Aspergillus giganteus, which has many potential biotechnological applications, was expressed in A. niger during retentostat cultivation. Additionally, this assay was used to concomitantly validate that native secretion signals encoded in anafp and hfbD genes can be harnessed for secretion of heterologous proteins. Afp mRNA and protein abundance were comparable to luciferase measurements throughout retentostat cultivation, validating the use of Panafp and PhfbD for perfusion cultivation. Finally, a gene encoding the highly commercially relevant thermal hysteresis protein (THP) was expressed in this system, which did not yield detectable protein.

CONCLUSION
Both hfbD and anafp promoters are suitable for production of useful products in A. niger during perfusion cultivation. These findings provide a platform for further optimisations for high production of heterologous proteins with industrial relevance.

Wanka|Franziska|F|
Arentshorst|Mark|M|
Cairns|Timothy C|TC|
Jørgensen|Thomas|T|
Ram|Arthur F J|AF|
Meyer|Vera|V|

D015966:Gene Expression Regulation, Fungal

Promoter
Aspergillus niger
Antifungal protein
Hydrophobin
Perfusion cultivation
Zero growth rate


A Dual Zinc plus Arginine formulation attenuates the pathogenic properties of Porphyromonas gingivalis and protects gingival keratinocyte barrier function in an in vitro model.

Abstract:
Background and objectives
Porphyromonas gingivalis, a late colonizer of the periodontal biofilm, has been strongly associated with the chronic form of periodontitis. The aim of this study was to investigate the effects of a Dual Zinc plus Arginine formulation (aqueous solution and dentifrice) on the pathogenic properties of P. gingivalis and the barrier function of an in vitro gingival epithelium model.

Results
The Dual Zinc plus Arginine aqueous solution and dentifrice inhibited the hemolytic and proteolytic activities of P. gingivalis. The Dual Zinc plus Arginine aqueous solution and dentifrice enhanced the barrier function of an in vitro gingival epithelium model as determined by a time-dependent increase in transepithelial electrical resistance and decrease in paracellular permeability. This was associated with an increased immunolabeling of two important tight junction proteins: zonula occludens-1 and occludin. The deleterious effects of P. gingivalis on keratinocyte barrier function as well as the ability of the bacterium to translocate through a gingival epithelium model were attenuated in the presence of either Dual Zinc plus Arginine aqueous solution or dentifrice.

Conclusions
The Dual Zinc plus Arginine formulation may offer benefits for patients affected by periodontal disease through its ability to attenuate the pathogenic properties of P. gingivalis and promote keratinocyte barrier function.

Ben Lagha|Amel|A|
Yang|Ying|Y|
Trivedi|Harsh M|HM|
Masters|James G|JG|
Grenier|Daniel|D|

zinc
Arginine
Porphyromonas gingivalis
periodontitis
dentifrice
periodontal disease
epithelial barrier
gingipain
toothpaste


Navigated macular laser decreases retreatment rate for diabetic macular edema: a comparison with conventional macular laser.

Abstract:
BACKGROUND
The purpose of this study was to evaluate and compare clinical outcomes and retreatment rates using navigated macular laser versus conventional laser for the treatment of diabetic macular edema (DME).

METHODS
In this prospective, interventional pilot study, 46 eyes from 46 consecutive patients with DME were allocated to receive macular laser photocoagulation using navigated laser. Best corrected visual acuity and retreatment rate were evaluated for up to 12 months after treatment. The control group was drawn based on chart review of 119 patients treated by conventional laser at the same institutions during the same time period. Propensity score matching was performed with Stata, based on the nearest-neighbor method.

RESULTS
Propensity score matching for age, gender, baseline visual acuity, and number of laser spots yielded 28 matched patients for the control group. Visual acuity after navigated macular laser improved from a mean 0.48 ± 0.37 logMAR by a mean +2.9 letters after 3 months, while the control group showed a mean -4.0 letters (P = 0.03). After 6 months, navigated laser maintained a mean visual gain of +3.3 letters, and the conventional laser group showed a slower mean increase to +1.9 letters versus baseline. Using Kaplan-Meier analysis, the laser retreatment rate showed separation of the survival curves after 2 months, with fewer retreatments in the navigated group than in the conventional laser group during the first 8 months (18% versus 31%, respectively, P = 0.02).

CONCLUSION
The short-term results of this pilot study suggest that navigated macular photocoagulation is an effective technique and could be considered as a valid alternative to conventional slit-lamp laser for DME when focal laser photocoagulation is indicated. The observed lower retreatment rates with navigated retinal laser therapy in the first 8 months suggest a more durable treatment effect.

Neubauer|Aljoscha S|AS|
Langer|Julian|J|
Liegl|Raffael|R|
Haritoglou|Christos|C|
Wolf|Armin|A|
Kozak|Igor|I|
Seidensticker|Florian|F|
Ulbig|Michael|M|
Freeman|William R|WR|
Kampik|Anselm|A|
Kernt|Marcus|M|

macular laser
diabetic macular edema
Navilas®
diabetes mellitus
diabetic retinopathy
navigated focal laser


A three-step test of phosphate sorption efficiency of potential agricultural drainage filter materials.

Abstract: Phosphorus (P) eutrophication of lakes and streams, coming from drained farmlands, is a serious problem in areas with intensive agriculture. Installation of P sorbing filters at drain outlets may be a solution. Efficient sorbents to be used for such filters must possess high P bonding affinity to retain ortho-phosphate (Pi) at low concentrations. In addition high P sorption capacity, fast bonding and low desorption is necessary. In this study five potential filter materials (Filtralite-P(®), limestone, calcinated diatomaceous earth, shell-sand and iron-oxide based CFH) in four particle size intervals were investigated under field relevant P concentrations (0-161 μM) and retentions times of 0-24 min. Of the five materials examined, the results from P sorption and desorption studies clearly demonstrate that the iron based CFH is superior as a filter material compared to calcium based materials when tested against criteria for sorption affinity, capacity and stability. The finest CFH and Filtralite-P(®) fractions (0.05-0.5 mm) were best with P retention of ≥90% of Pi from an initial concentration of 161 μM corresponding to 14.5 mmol/kg sorbed within 24 min. They were further capable to retain ≥90% of Pi from an initially 16 μM solution within 1½ min. However, only the finest CFH fraction was also able to retain ≥90% of Pi sorbed from the 16 μM solution against 4 times desorption sequences with 6 mM KNO3. Among the materials investigated, the finest CFH fraction is therefore the only suitable filter material, when very fast and strong bonding of high Pi concentrations is needed, e.g. in drains under P rich soils during extreme weather conditions.

Lyngsie|G|G|
Borggaard|O K|OK|
Hansen|H C B|HC|

Eutrophication
Carbonates
Farmland drainage
Iron oxides
Water quality


Efficient Hole Trapping in Carbon Dot/Oxygen-Modified Carbon Nitride Heterojunction Photocatalysts for Enhanced Methanol Production from CO2 under Neutral Conditions.

Abstract: Artificial photosynthesis of alcohols from CO2 is still unsatisfactory owing to the rapid charge relaxation compared to the sluggish photoreactions and the oxidation of alcohol products. Here, we demonstrate that CO2 is reduced to methanol with 100 % selectivity using water as the only electron donor on a carbon nitride-like polymer (FAT) decorated with carbon dots. The quantum efficiency of 5.9 % (λ=420 nm) is 300 % higher than the previously reported carbon nitride junction. Using transient absorption spectroscopy, we observed that holes in FAT could be extracted by the carbon dots with nearly 75 % efficiency before they become unreactive by trapping. Extraction of holes resulted in a greater density of photoelectrons, indicative of reduced recombination of shorter-lived reactive electrons. This work offers a strategy to promote photocatalysis by increasing the amount of reactive photogenerated charges via structure engineering and extraction before energy losses by deep trapping.

carbon dots
photocatalysis
carbon dioxide fixation
charge trapping
time-resolved spectroscopy


Fabrication of Aptamer-Modified Paper Electrochemical Devices for On-Site Biosensing.

Abstract: Electrochemical aptamer-based (E-AB) sensors offer a powerful and general means for analyte detection in complex samples for various applications. Paper-based E-AB sensors could enable portable, low-cost, and rapid detection of a broad range of targets, but it has proven challenging to fabricate suitable three-electrode systems on paper. Here, we demonstrate a simple, economic, and environmentally friendly strategy for fabricating aptamer-modified paper electrochemical devices (PEDs) via ambient vacuum filtration. The material, shape, size, and thickness of the three-electrode PED system can be fully customized. We developed aptamer-modified PEDs that enable sensitive and specific detection of small molecules in minimally processed biosamples. The sensitivity and stability of the PEDs are comparable to E-AB sensors based on commercial gold electrodes. We believe our strategy can lead to the development of high performance PEDs for the on-site detection of a variety of analytes.

Yu|Haixiang|H| Chen|Zhimin|Z| Liu|Yingzhu|Y| Alkhamis|Obtin|O| Song|Zhiping|Z| Xiao|Yi|Y|0000-0001-7278-9811

paper electrochemical devices
small molecules
aptamers
biosensors
nanomaterials


Spastic paraparesis associated with advanced liver cirrhosis: a condition obscure in terms of treatment and prognosis.

Abstract: Hepatic myelopathy or spastic paraparesis of liver disease is an insidious onset condition with pure motor spastic paraparesis without sensory, bladder or bowel involvement in patients with chronic liver disease, in which the neurological dysfunction cannot be explained by other causes. It is a rare, relentlessly progressive and mostly irreversible neurological complication resulting from portosystemic shunts occurring spontaneously, created surgically or due to 'functional shunting'. In some cases, no evidence of shunting is elicitable due to difficulty in locating the hidden collaterals. We report this rare case of a 33-year-old man with chronic liver disease presenting with spastic paraparesis after 11 months of resolution of an episode of hepatic encephalopathy.

cirrhosis
alcoholic liver disease
spinal cord


Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy.

Abstract: The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.

drug resistance
immunotherapy
bacterial infection
cancer therapy
dual stimulus responsiveness


Control of in vivo mineral bone cement degradation.

Abstract: The current study aimed to prevent the formation of hydroxyapatite reprecipitates in brushite-forming biocements by minimizing the availability of free Ca(2+) ions in the cement matrix. This was achieved by both maximizing the degree of cement setting to avoid unreacted, calcium-rich cement raw materials which can deliver Ca(2+) directly to the cement matrix after dissolution, and by a reduction in porosity to reduce Ca(2+) diffusion into the set cement matrix. In addition, a biocement based on the formation of the magnesium phosphate mineral struvite (MgNH4PO4·6H2O) was tested, which should prevent the formation of low-solubility hydroxyapatite reprecipitates due to the high magnesium content. Different porosity levels were fabricated by altering the powder-to-liquid ratio at which the cements were mixed and the materials were implanted into mechanically unloaded femoral defects in sheep for up to 10 months. While the higher-porosity brushite cement quantitatively transformed into crystalline octacalcium phosphate after 10 months, slowing down cement resorption, a lower-porosity brushite cement modification was found to be chemically stable with the absence of reprecipitate formation and minor cement resorption from the implant surface. In contrast, struvite-forming cements were much more degradable due to the absence of mineral reprecipitates and a nearly quantitative cement degradation was found after 10 months of implantation.

Kanter|Britta|B| Geffers|Martha|M| Ignatius|Anita|A| Gbureck|Uwe|U|

Hydroxyapatite
Struvite
Brushite
Bone replacement material
Calcium magnesium phosphate cement


High yield production of four-carbon dicarboxylic acids by metabolically engineered Escherichia coli.

Abstract: Several metabolic engineered Escherichia coli strains were constructed and evaluated for four-carbon dicarboxylic acid production. Fumarase A, fumarase B and fumarase C single, double and triple mutants were constructed in a ldhA adhE mutant background overexpressing the pyruvate carboxylase from Lactococcus lactis. All the mutants produced succinate as the main four-carbon (C4) dicarboxylic acid product when glucose was used as carbon source with the exception of the fumAC and the triple fumB fumAC deletion strains, where malate was the main C4-product with a yield of 0.61-0.67 mol (mole glucose)-1. Additionally, a mdh mutant strain and a previously engineered high-succinate-producing strain (SBS550MG-Cms pHL413-Km) were investigated for aerobic malate production from succinate. These strains produced 40.38 mM (5.41 g/L) and 50.34 mM (6.75 g/L) malate with a molar yield of 0.53 and 0.55 mol (mole succinate)-1, respectively. Finally, by exploiting the high-succinate production capability, the strain SBS550MG-Cms243 pHL413-Km showed significant malate production in a two-stage process from glucose. This strain produced 133 mM (17.83 g/L) malate in 47 h, with a high yield of 1.3 mol (mole glucose)-1 and productivity of 0.38 g L-1 h-1.

Martinez|Irene|I|
Gao|Haijun|H|
Bennett|George N|GN|
San|Ka-Yiu|KY|0000-0002-1449-4406

D000426:Alcohol Dehydrogenase
D002244:Carbon
D003998:Dicarboxylic Acids
D004926:Escherichia coli
D005649:Fumarate Hydratase
D005947:Glucose
D007770:L-Lactate Dehydrogenase
D013294:Lactococcus lactis
D008293:Malates
D060847:Metabolic Engineering
D009154:Mutation
D019802:Succinic Acid

Dicarboxylic acids
Metabolic engineering
Escherichia coli
Succinate
Malate


Olfactory flow in the sea catfish, Ariopsis felis (L.): Origin, regulation, and resampling.

Abstract: The olfactory epithelium of the sea catfish, Ariopsis felis, is found on a pinnate array of lamellae (the olfactory rosette) housed within a nasal chamber. The nasal anatomy of A. felis suggests an ability to capture external water currents. We prepared models from X-ray micro-computed tomography scans of two preserved specimens of A. felis. We then used dye visualisation and computational fluid dynamics to show that an external current induced a flow of water through a) the nasal chamber and b) the sensory channels of the olfactory rosette. The factors responsible for inducing flow through the nasal chamber are common to fishes from two other orders. The dye visualisation experiments, together with observations of sea catfishes in vivo, indicate that flow through the nasal chamber is regulated by a mobile nasal flap. The position of the nasal flap - elevated (significant flow) or depressed (reduced flow) - is controlled by the sea catfish's movements. Flow in the sensory channels of the olfactory rosette can pass through either a single channel or, via multiple pathways, up to four consecutive channels. Flow through consecutive sensory channels (olfactory resampling) is more extensive at lower Reynolds numbers (200 and 300, equivalent to swimming speeds of 0.5-1.0 total lengths s-1), coinciding with the mean swimming speed of the sea catfishes observed in vivo (0.6 total lengths s-1). Olfactory resampling may also occur, via a vortex, within single sensory channels. In conclusion, olfactory flow in the sea catfish is regulated and thoroughly sampled by novel mechanisms.

Cox|Matthew A L|MAL|
Garwood|Russell J|RJ|
Behnsen|Julia|J|
Hunt|Jeremy N|JN|
Dalby|Luke J|LJ|
Martin|Graham S|GS|
Maclaine|James S|JS|
Wang|Zhijin|Z|
Cox|Jonathan P L|JPL|

Anguilla
Esox
Microfluidic chemical sensor
Polypteridae
Sturgeon


Online information discrepancies regarding safety of medicine use during pregnancy and lactation: an IMI ConcePTION study.

Abstract: Background: Inconsistencies in information on safety of medicine use during pregnancy and lactation can result in sub-optimal treatment for pregnant and lactating women, risks to the fetus or child and unnecessary weaning off breastfeeding. The objective of this study was to analyze information discrepancies regarding medicine use during pregnancy and lactation between on-line sources for patients and health care professionals (HCPs) in four European languages.Research design and methods: The medicines analyzed were ibuprofen, ondansetron, olanzapine, fingolimod, methylphenidate and adalimumab. Recommendations were classified into different data source categories, for patients and for HCPs, and compared between the data source categories for each medicine and language.Results: For patients, 11/24 (46%) and 4/24 (17%) comparisons of the pregnancy and lactation recommendations, respectively, were consistent between all sources. The corresponding figures for HCP-sources were 13/24 (54%) and 5/24 (21%). Regulatory sources had generally more restrictive recommendations. Teratology Information Services (TIS) centers' recommendations for medicine use during pregnancy and lactation were consistent in 25/27 (93%) and 15/22 (68%) of cases respectively.Conclusion: Discrepancies between online information sources regarding medicine use during pregnancy and lactation are common, especially for lactation. TIS centers recommendations were more aligned. Additional work is needed to harmonize information within and between countries to avoid conflicting messages.

Nörby|Ulrika|U| Noël-Cuppers|Benedikte|B| Hristoskova|Sashka|S| Desai|Monali|M| Härmark|Linda|L| Steel|Michael|M| El-Haddad|Chantal|C| Douarin|Ludivine|L|

D064420:Drug-Related Side Effects and Adverse Reactions

Information discrepancies
medicines
pregnancy
lactation


XLSearch: a Probabilistic Database Search Algorithm for Identifying Cross-Linked Peptides.

Abstract: Chemical cross-linking combined with mass spectrometric analysis has become an important technique for probing protein three-dimensional structure and protein-protein interactions. A key step in this process is the accurate identification and validation of cross-linked peptides from tandem mass spectra. The identification of cross-linked peptides, however, presents challenges related to the expanded nature of the search space (all pairs of peptides in a sequence database) and the fact that some peptide-spectrum matches (PSMs) contain one correct and one incorrect peptide but often receive scores that are comparable to those in which both peptides are correctly identified. To address these problems and improve detection of cross-linked peptides, we propose a new database search algorithm, XLSearch, for identifying cross-linked peptides. Our approach is based on a data-driven scoring scheme that independently estimates the probability of correctly identifying each individual peptide in the cross-link given knowledge of the correct or incorrect identification of the other peptide. These conditional probabilities are subsequently used to estimate the joint posterior probability that both peptides are correctly identified. Using the data from two previous cross-link studies, we show the effectiveness of this scoring scheme, particularly in distinguishing between true identifications and those containing one incorrect peptide. We also provide evidence that XLSearch achieves more identifications than two alternative methods at the same false discovery rate (availability: https://github.com/COL-IU/XLSearch ).

Ji|Chao|C|
Li|Sujun|S|
Reilly|James P|JP|
Radivojac|Predrag|P|
Tang|Haixu|H|

chemical cross-linking
machine learning
mass spectrometry
ribosome
structural biology


The Value of Neutrophil:Lymphocyte Ratio and Platelet:Lymphocyte Ratio in Predicting Clinical Severity in Children with Carbon Monoxide Poisoning.

Abstract:
OBJECTIVE
To compare the values of neutrophil:lymphocyte ratio (NLR), platelet:lymphocyte ratio (PLR), and mean platelet volume (MPV) with carboxyhemoglobin (COHb) and lactate levels in children with acute CO intoxication.

METHODS
In this retrospective study, the patients were divided into two groups: mild-to-moderate carbon monoxide poisoning (COP) (COHb 10%-20%) and severe COP (COHb > 20%) according to the COHb levels in the application. All patients were compared in terms of NLR, PLR, and MPV parameters according to the severity of poisoning and the high lactate levels (≥ 2.2 mmol/L).

RESULTS
A total of 261 children with COP were included in the study. The number of patients with mild-to-moderate COP was 183 (70.1%), and the number of patients with severe COP was 78 (29.9%). NLR [2.57 (3.27), 1.65 (1.93), (p = 0.001)] and PLR [123.0 (88.24), 92.8 (54.1), (p = 0.001)] values of mild-to-moderate COP were statistically significantly lower than the severe COP group. In the group with high lactate level, PLR values were significantly lower [120.1 (71.9), 100.2 (85.4), (p = 0.017)]. NLR and PLR values were found to be predictive of severe COP.

CONCLUSION
NLR and PLR can be used for detection of clinical severity in patients with COP. PLR can be used in conjunction with lactate levels to detect tissue-level exposure in patients with COP.

Neutrophil:Lymphocyte ratio
Platelet:Lymphocyte ratio
Carbon monoxide poisoning
Lactate


Historical Oppression, Resilience, and Transcendence: Can a Holistic Framework Help Explain Violence Experienced by Indigenous People?

Abstract: Although all minorities experience inequalities, indigenous peoples in the United States tend to experience the most severe violent victimization. Until now, an organizing framework to explain or address the disproportionate rates of violent victimization was absent. Thus, the purpose of this conceptual article is to (a) introduce the concept of historical oppression, expanding the concept of historical trauma to make it inclusive of contemporary oppression; (b) describe the framework of historical oppression, resilience, and transcendence, which draws from distinct but related theoretical frameworks (that is, critical theory and resilience theory); and (c) apply the framework of historical oppression, resilience, and transcendence to the problem of violence against indigenous women. The proposed framework of historical oppression, resilience, and transcendence prioritizes social justice and strengths; it provides a culturally relevant framework, which can be used to explain, predict, and prevent violence. The article concludes with recommendations for future research, implications for practice, and recommended applications to other problems and populations.

Burnette|Catherine Elizabeth|CE|
Figley|Charles R|CR|

historical oppression
resilience
historical trauma
American Indians
Native Americans


Malondialdehyde levels in oral sub mucous fibrosis: a clinicopathological and biochemical study.

Abstract:
BACKGROUND
Oral submucous fibrosis is one of the most commonly occurring potentially malignant disorders in the South-East Asia. Levels of lipid peroxidation product malondialdehyde have been recently correlated with clinical grades of oral Submucous fibrosis.

AIMS
The aims of this study were to estimate the levels of malondialdehyde in serum, saliva and tissue in patients with oral submucous fibrosis, to correlate change in levels of malodialdehyde with the histopathological grading.

MATERIALS AND METHODS
The study group comprised of 65 clinically diagnosed and histopathologically confirmed cases of oral submucous fibrosis, 21 age and sex matched controls were also enrolled into the study. The serum saliva and tissue samples in the study groups were evaluated by the thiobarbutric acid reactive substances.

RESULTS
There was a significant difference between the serum and salivary malondialdehyde among the histopathological grades of oral submucous fibrosis. Tissue malonaldehyde levels were significantly higher as the grading progressed but tissue levels in grade 3 oral submucous fibrosis were lower than the controls.

CONCLUSION
This decrease in tissue malonaldehyde could possibly be associated to collagen cross linking occurring during the advanced stages of oral submucous fibrosis.

Shetty|Shishir Ram|SR|
Babu|Subhas G|SG|
Kumari|Suchetha|S|
Rao|Vaman|V|
Vijay|R|R|
Karikal|Arvind|A|

Lipid peroxidation
Serum
Saliva
Tissue
Collagen
Cross-linking


Rapid dynamic quantification of sulfide generation flux in spatially heterogeneous sediments of gravity sewers.

Abstract: Compared with anaerobic pressure sewers, gravity sewers have much more complex operational conditions, such as anaerobic/aerobic spatial variations along variable structures of the pipe network. This greatly complicates the prediction of sulfide generation from spatially heterogeneous sewer sediments. This study proposes a novel quantitative approach for rapidly estimating the sulfide generation flux by understanding the sulfidogenic conversion under complex sewer conditions. Significant anaerobic/aerobic spatial variations were the most critical factor affecting the sulfide production in residential gravity sewers. The dynamic aeration-related process stimulated the growth of sulfide-oxidizing bacteria (SOB) in the surface zone, while the sulfidogenic and methanogenic zone moved into deeper layers. A detailed mechanism model incorporating dynamic alternative anaerobic/aerobic transformation was developed to predict apparent sulfide production, as well as the microscale spatial profiles of chemicals and microbial communities in sediments. The model was evaluated to establish a rapid quantitative approach that only depended on a few key parameters (e.g., flow velocity, pipe diameter, slope, mean hydraulic depth and sulfate concentration), which can provide an important basis for estimating different sulfide generation fluxes under various sewer factors. The identification of sulfide generation hotspots will greatly help determine how to economically control sulfide generation by chemical dosing or pipe structural modification.

Zuo|Zhiqiang|Z| Ren|Daheng|D| Qiao|Longkai|L| Li|He|H| Huang|Xia|X| Liu|Yanchen|Y|

Quantification
Sediment
Gravity sewer
Dynamic sulfide flux
Model prediction


Adverse Perioperative Events in Children with Complex Congenital Heart Disease Undergoing Operative Scoliosis Repair in the Contemporary Era.

Abstract: Scoliosis is common in children with congenital heart disease (CHD) and may have deleterious effects on quality of life and hemodynamics. Relatively little is known about the outcomes of spinal fusion for scoliosis repair in children with complex CHD. We reviewed all cases of children with CHD undergoing first time spinal fusion excluding those with minor CHD between 1995 and 2015. Seventy-eight patients were identified and included in the study. 97.4% of patients included had undergone prior cardiac surgery and sixteen patients had single ventricle circulations. 17.9% of patients experienced a significant perioperative event defined as an aggregate of the presence of any of the following: need for early unanticipated reoperation, neurologic deficit, postoperative bleeding requiring intervention, end organ dysfunction, or death. There were no deaths in our cohort. 38.5% of patients experienced any adverse event, the majority of which were related to perioperative fluid shifts. Larger preoperative Cobb angle and longer length of spinal fusion were associated with increased risk of significant perioperative event while larger preoperative Cobb angle and longer length of spinal fusion, older age at time of surgery, single ventricle circulation, cyanosis and patients taking cardiac medications at the time of surgery were more likely to experience any adverse event. Operative repair of scoliosis in children with complex CHD has been performed without mortality over a 20-year period in a single institution, albeit with a higher rate of perioperative complication than is seen in the general pediatric population. Patients with large preoperative Cobb angles and cyanotic single ventricle circulations appear to be at the highest risk for perioperative complications.

Congenital heart disease
Scoliosis
Spinal fusion


Severe Babesia microti infection in an American immunocompetent patient diagnosed in Spain.

Abstract: We report a severe Babesia microti infection in an immunocompetent patient diagnosed in Spain. A 66-year-old woman coming from USA presented with fever, thrombocytopenia, and multiorgan failure. Intraerythrocytic parasites were observed in Giemsa-stained peripheral blood smears and B. microti was first suspected by optical microscopy and afterward confirmed by specific polymerase chain reaction (PCR). Patient received antibiotic therapy, vital support measures and one red blood cell (RBC) exchange procedure. After 15 days, patient recovered and she was transferred to her reference hospital. This case report highlights the importance of clinical suspicion by physicians in non-endemic areas to diagnose this entity, the differential diagnosis with malaria infection, and the indication of RBC exchange as a therapeutic apheresis modality in the management of severe forms.

de Ramón|Cristina|C|
Cid|Joan|J|
Rodríguez-Tajes|Sergio|S|
Álvarez-Martínez|Míriam J|MJ|
Valls|Ma Eugenia|ME|
Fernández|Javier|J|
Lozano|Miguel|M|

Immunocompetent
Therapeutic apheresis
Babesiosis


Occurrence and removal of polycyclic aromatic hydrocarbons and their derivatives in an ecological wastewater treatment plant in South China and effluent impact to the receiving river.

Abstract: Ecological wastewater treatment plant (EWWTP), a kind of emerging wastewater treatment plant (WWTP) in recent years, combined microbiology with botany which is efficient for the removal of nitrogen and organic matter, as well as deodorization. The occurrence and removal of micro-organic pollutants in EWWTPs were still not well known. Polycyclic aromatic hydrocarbons (PAHs) and their typical derivatives (SPAHs) including the oxygenated PAHs (OPAHs), chlorinated PAHs (ClPAHs), and methyl PAHs (MPAHs) were investigated in an EWWTP in Guangdong Province, China. The concentrations of the Σ6 OPAHs (114-384 ng/L) were higher than the Σ16 PAHs (92-250 ng/L), and much higher than the Σ4 MPAHs (13-64 ng/L) and Σ9 ClPAHs (2-3 ng/L) in the EWWTP and the effluent receiving river. The total removal efficiencies of the PAHs, OPAHs, MPAHs, and ClPAHs in the EWWTP (43 ± 14%, 41 ± 7%, 55 ± 16%, and 18 ± 4%) were lower than the traditional WWTPs, probably due to the lower concentration of the sludge in the ecological treatment. The advanced treatment process (microfiltration and UV disinfection treatment) contributed much less (0-20%) to the whole removal efficiency than the ecological treatment (80-100%). The effluent from the EWWTP slightly reduced the PAHs and SPAHs concentrations in the receiving river. The high concentrations of the PAHs and SPAHs in the receiving river were similar to the influent of the EWWTP, indicating that some untreated wastewater was directly discharged to the river, especially in the upstream.

Qiao|Meng|M| Fu|Lujing|L| Cao|Wei|W| Bai|Yaohui|Y| Huang|Qiuxin|Q| Zhao|Xu|X|

Polycyclic aromatic hydrocarbon derivatives


The circular RNA of peripheral blood mononuclear cells: Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis.

Abstract: It has been reported that circular RNA (circRNA) is associated with human cancer. However, few studies have been reported in active pulmonary tuberculosis (APTB). The global circRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) of APTB patients (n=5) and health controls (HC) (n=5) by using high-throughput sequencing. According to the systematical bioinformatics analysis, the basic content of circRNAs and their fold changes in the two groups were calculated. We selected 6 significant differentially expressed circRNAs, hsa_circ_0005836, hsa_circ_0009128, hsa_circ_0003519, hsa_circ_0023956, hsa_circ_0078768, and hsa_circ_0088452 and validated the expression in PBMCs from APTB (n=10) and HC (n=10) by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Further, the verification of these specific circRNAs (hsa_circ_0005836 and hsa_circ_0009128) between APTB (n=34) and HC (n=30) in PBMCs was also conducted by qRT-PCRs. The RNA-seq data showed the significant differential expression of the 523 circRNAs between the APTB and HC groups (199 circRNAs were significantly up-regulated and 324 circRNAs were down-regulated). Hsa_circ_0005836 and hsa_circ_0009128 expression was significantly down-regulated in the PBMCs of APTB (P<0.05) in the samples of APTB compared to HC in our study. The gene ontology based enrichment analysis of the circRNA-miRNA-mRNAs network showed that cellular catabolic process (P=7.10E-08), regulation of metabolic process (P=2.10E-06), catalytic activity (P=3.67E-08), protein binding (P=1.71E-07), cell part (P=3.46E-06), intracellular part (P=1.71E-07), and intracellular (P=3.67E-08) were recognized in the comparisons between APTB and HC. Based on KEGG analysis, HTLV-I infection, regulation of actin cytoskeleton, neurotrophin signaling pathway and mTOR signaling pathway were relevant during tuberculosis bacillus infection. We found for the first time that hsa_circ_0005836 and hsa_circ_0009128 were significantly down-regulated in the PBMCs of APTB compared with HC. Our findings indicate hsa_circ_0005836 might serve as a novel potential biomarker for TB infection.

Zhuang|Ze-Gang|ZG|
Zhang|Jun-Ai|JA|
Luo|Hou-Long|HL|
Liu|Gan-Bin|GB|
Lu|Yuan-Bin|YB|
Ge|Nan-Hai|NH|
Zheng|Bi-Ying|BY|
Li|Rui Xi|RX|
Chen|Chen|C|
Wang|Xin|X|
Liu|Yu-Qing|YQ|
Liu|Feng-Hui|FH|
Zhou|Yong|Y|
Cai|Xiao-Zhen|XZ|
Chen|Zheng W|ZW|
Xu|Jun-Fa|JF|

Circular RNA
Biomarker
Active pulmonary tuberculosis
RNA sequence


Investigating owner use of dietary supplements in dogs with idiopathic epilepsy.

Abstract: Epilepsy is the most common chronic neurological disorder in dogs. Some diets have been shown to have a positive impact upon the seizure activity in dogs with idiopathic epilepsy (IE), while other diets and dietary supplements (DS), although marketed as providing health benefits, lack conclusive scientific evidence on their actual beneficial effects. A web-based owner questionnaire was designed to assess how and why owners of dogs with IE use different dietary regimes and DS. The study cohort, with 297 valid responses, consisted mainly of pure-breed (82.5%) male neutered (52.9%) dogs. Over two-thirds of owners (67.7%) changed their dog's diet after their dog received a diagnosis of IE. Nearly half of the owners (45.8%) reported giving DS, the most common being coconut oil or derived medium-chain triglyceride oil (71.3%). Some owner justifications of DS use included improvement of seizure frequency (88.2%), seizure severity (61.8%) and protection from potential drug side effects (62.5%). Many owners give DS to their dog with IE. The pharmacokinetic properties of anti-epileptic drugs, such as efficacy, absorption and clearance can be influenced by other medications, diets and possibly by DS. We propose that use of DS should be considered and monitored by veterinary surgeons in epilepsy management.

Berk|Benjamin Andreas|BA|
Packer|Rowena Mary Anne|RMA|
Law|Tsz Hong|TH|
Volk|Holger Andreas|HA|

Dietary supplement
Epilepsy
Diet
Seizure
Neurodietetics
Veterinary neurology


Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix.

Abstract: The success of tissue regenerative therapies is contingent on functional and multicellular vasculature within the redeveloping tissue. Although endothelial cells (ECs), which compose the vasculature's inner lining, are intrinsically able to form nascent networks, these structures regress without the recruitment of pericytes, supporting cells that surround microvessel endothelium. Reconstruction of typical in vivo microvascular architecture traditionally has been done using distinct cell sources of ECs and pericytes within naturally occurring matrices; however, the limited sources of clinically relevant human cells and the inherent chemical and physical properties of natural materials hamper the translational potential of these approaches. Here we derived a bicellular vascular population from human pluripotent stem cells (hPSCs) that undergoes morphogenesis and assembly in a synthetic matrix. We found that hPSCs can be induced to codifferentiate into early vascular cells (EVCs) in a clinically relevant strategy amenable to multiple hPSC lines. These EVCs can mature into ECs and pericytes, and can self-organize to form microvascular networks in an engineered matrix. These engineered human vascular networks survive implantation, integrate with the host vasculature, and establish blood flow. This integrated approach, in which a derived bicellular population is exploited for its intrinsic self-assembly capability to create microvasculature in a deliverable matrix, has vast ramifications for vascular construction and regenerative medicine.

Kusuma|Sravanti|S| Shen|Yu-I|YI| Hanjaya-Putra|Donny|D| Mali|Prashant|P| Cheng|Linzhao|L| Gerecht|Sharon|S|

D002460:Cell Line
D042783:Endothelial Cells
D004730:Endothelium, Vascular
D005109:Extracellular Matrix
D006801:Humans
D018919:Neovascularization, Physiologic
D039904:Pluripotent Stem Cells
D044968:Regenerative Medicine
D023822:Tissue Engineering


Climbing Fiber-Mediated Spillover Transmission to Interneurons Is Regulated by EAAT4.

Abstract: Neurotransmitter spillover is a form of communication not readily predicted by anatomic structure. In the cerebellum, glutamate spillover from climbing fibers recruits molecular layer interneurons in the absence of conventional synaptic connections. Spillover-mediated signaling is typically limited by transporters that bind and reuptake glutamate. Here, we show that patterned expression of the excitatory amino acid transporter 4 (EAAT4) in Purkinje cells regulates glutamate spillover to molecular layer interneurons. Using male and female Aldolase C-Venus knock-in mice to visualize zebrin microzones, we find larger climbing fiber-evoked spillover EPSCs in regions with low levels of EAAT4 compared with regions with high EAAT4. This difference is not explained by presynaptic glutamate release properties or postsynaptic receptor density but rather by differences in the glutamate concentration reaching receptors on interneurons. Inhibiting glutamate transport normalizes the differences between microzones, suggesting that heterogeneity in EAAT4 expression is a primary determinant of differential spillover. These results show that neuronal glutamate transporters limit extrasynaptic transmission in a non-cell-autonomous manner and provide new insight into the functional specialization of cerebellar microzones.SIGNIFICANCE STATEMENT Excitatory amino acid transporters (EAATs) help maintain the fidelity and independence of point-to-point synaptic transmission. Whereas glial transporters are critical to maintain low ambient levels of extracellular glutamate to prevent excitotoxicity, neuronal transporters have more subtle roles in shaping excitatory synaptic transmission. Here we show that the patterned expression of neuronal EAAT4 in cerebellar microzones controls glutamate spillover from cerebellar climbing fibers to nearby interneurons. These results contribute to fundamental understanding of neuronal transporter functions and specialization of cerebellar microzones.

Malhotra|Shreya|S|
Banumurthy|Gokulakrishna|G|
Pennock|Reagan L|RL|
Vaden|Jada H|JH|
Sugihara|Izumi|I|0000-0002-4598-9882
Overstreet-Wadiche|Linda|L|
Wadiche|Jacques I|JI|

D050581:Excitatory Amino Acid Transporter 4

spillover
cerebellum
glutamate
EAAT
synaptic transmission


COVID-19 pandemic: ten research questions Africa must answer for itself.

Abstract:
The COVID-19 pandemic is spreading through Africa and governments are making frantic efforts to control spread, hospitalizations and deaths. While control measures are being taken, research into the biomedical and socio-cultural aspects of the pandemic, relevant to the African population, should not be ignored. It should not be assumed that research performed in Asian, American and European populations will always be applicable to Africa. Rather, research should be done in Africa to answer questions peculiar to the epidemic on the continent and help inform international guidelines. National guidelines for treatment and prevention, patient recoveries and discharge, and public health control measures should be based on research performed in the appropriate context for them to be effective and robust. Urgent research is needed in viral immunology and shedding, treatment and prevention trials, protection of healthcare personnel, and antimicrobial use among others. In this article, we propose ten research questions that when answered in a timely manner by scientists in Africa, will enhance Africa's response to the pandemic.

Funding
GBK is supported by a fellowship from the European Developing Countries Clinical Trials Fellowship as part of the EDCTP (2) program. The funder had no role in the preparation of this manuscript.

Bonney|Evelyn Y|EY|
Lamptey|Helena|H|
Puplampu|Peter|P|
Kyei|George B|GB|


Knowledge and factors influencing long acting reversible contraceptive use among women of reproductive age in Nigeria.

Abstract: Background: Approximately 48% of unintended pregnancies occur as a result of contraceptive failure around the world, which is largely due to incorrect use, poor adherence and/or technology failure. Long-acting reversible contraceptive (LARC) methods have been developed to close this gap because it's not dependent on compliance with a pill-taking regimen; remembering to change patch or ring; or fixing an appointment with physicians. The main aim of this study is to identify the factors influencing the women associated with use of LARC and to examine the relationship between knowledge of LARC and its current use. Methods: This study assessed the PMA2020 methodology and secondary dataset using female datasets from PMA 2016 (Round 3) exercise. PMA 2016 was a survey carried out in seven states of Nigeria. The target population for this study was women of reproductive age (15-49 years) currently using contraception prior to the survey. The sample size of women meeting inclusion criteria in this study was 1927. The data were analyzed using frequency distribution, chi-square and logistic regression at 5% level of significant. Results: The results showed that 21.0% of women were using traditional methods. Concerning LARC methods, the table showed that 14.8% of the sampled women were using LARC methods. Findings further showed that at both levels of analyses there is a significant relationship (P<0.05 and P=0.00 for binary and multivariable logistic regression, respectively) between knowledge of LARCs and uses in this study. This means that knowledge of LARC & other socio-demographic variables among women of reproductive age in Nigeria can influence the use of it. Conclusions: From the result of the study we concluded that 14.8% of women using contraception were using LARC. Additionally, level of education, age of women, household wealth and number of living children were significantly associated with using LARC.

Knowledge
Factors
Influencing
Contraceptive use
Women
Reproductive age
LARC
Nigeria.


A Spontaneous Membrane-Adsorption Approach to Enhancing Second Near-Infrared Deep-Imaging-Guided Intracranial Tumor Therapy.

Abstract: Herein, a functional class of microenvironment-associated nanomaterials is reported for improving the second near-infrared (NIR-II) imaging and photothermal therapeutic effect on intracranial tumors via a spontaneous membrane-adsorption approach. Specific peptides, photothermal agents, and biological alkylating agents were designed to endow the nanogels with high targeting specificity, photothermal properties, and pharmacological effects. Importantly, the frozen scanning electron microscopy technology (cryo-SEM) was utilized to observe the self-association of nanomaterials on tumor cells. Interestingly, the spontaneous membrane-adsorption behavior of nanomaterials was captured through direct imaging evidence. Histological analysis showed that the cross-linking adhesion in intracranial tumor and monodispersity in normal tissues of the nanogels not only enhanced the retention time but also ensured excellent biocompatibility. Impressively, in vivo data confirmed that the microenvironment-associated nanogels could significantly enhance brain tumor clearance rate within a short treatment timeframe (only two weeks). In short, utilizing the spontaneous membrane-adsorption strategy can significantly improve NIR-II diagnosis and phototherapy in brain diseases while avoiding high-risk complications.

Li|Luoyuan|L| Zhang|Bei|B| Liu|Yuxin|Y| Gao|Rongyao|R| Zhou|Jing|J|0000-0002-5348-1966 Fu|Li-Min|LM| Wang|Jian|J|0000-0002-3298-6367

membrane-adsorption
intracranial tumors
NIR-II imaging
microenvironment association
multistimulus response


Brucellar epididymo-orchitis: a retrospective multicenter study of 28 cases and review of the literature.

Abstract:
OBJECTIVE
To review retrospectively the clinical symptoms, laboratory findings and treatment outcomes of patients with Brucellar epididymo-orchitis.

MATERIAL AND METHOD
Retrospective data of 28 patients with Brucellar epididymo-orchitis who admitted to four medical centers between 2005 and 2013 were retrospectively reviewed. Positive blood culture, positive Rose Bengal test results or high agglutination titres of ≥ 1/160 with the positive clinical and ultrasonographic findings of orchitis were accepted as the main criteria for Brucellar epididymo-orchitis.

RESULTS
The mean patient age was 31 ± 16.9 years. Testicular involvement was on the left side in 16 patients and on the right side in 11 patients, one had bilateral disease. Testicular pain and swelling were the most common symptoms and elevation of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leucocytosis were the most common laboratory findings. Initial treatment was orchidectomy in six patients due to malignancy suspicion. All but three patients were successfully treated with antibiotic combinations of rifampicin, doxycycline and streptomycin. Two of three treatment resistant patients underwent orchidectomy.

CONCLUSION
Brucellosis is a common cause of epididymo-orchitis in endemic regions. Early diagnosis and treatment is crucial in the management and thus it must be kept in mind in endemic and non-endemic regions.

Savasci|Umit|U|
Zor|Murat|M|
Karakas|Ahmet|A|
Aydin|Emsal|E|
Kocaaslan|Ramazan|R|
Oren|N Cem|NC|
Coskun|Omer|O|
Turhan|Vedat|V|
Gul|H Cem|HC|
Cicek|A Fuat|AF|
Aydur|Emin|E|
Eyigun|Can Polat|CP|

Orchitis Brucella Epididymis Granulomatous Testis


Structural Engineering of Hollow Microflower-like CuS@C Hybrids as Versatile Electrochemical Sensing Platform for Highly Sensitive Hydrogen Peroxide and Hydrazine Detection.

Abstract: Designing metal sulfides with unique configurations and exploring their electrochemical activities for hydrogen peroxide (H2O2) and hydrazine (N2H4) is challenging and desirable for various fields. Herein, hollow microflower-like CuS@C hybrids were successfully assembled and further exploited as a versatile electrochemical sensing platform for H2O2 reduction and N2H4 oxidation, of which the elaborate strategies make the perfect formation of hollow architecture, providing considerable electrocatalytic sites and fast charge transfer rate, while the appropriate introduction polydopamine-derived carbon skeleton facilitates the electronic conductivity and boosts structural robustness, thus generating wide linear range (0.05-14 and 0.01-10 mM), low detection limit (0.22 μM and 0.07 μM), and a rather low overpotential (-0.15 and -0.05 V) toward H2O2 and N2H4, as well as good selectivity, excellent reproducibility, and admirable long-term stability. It should be highlighted that the operating potentials can compare favorably with those of some reported H2O2 and N2H4 sensors based on noble metals. In addition, good recoveries and acceptable relative standard deviations (RSDs) attained in serum and water samples fully verify the accuracy and anti-interference capability of our proposed sensor systems. These results not only elucidate an effective structural nanoengineering strategy for electroanalytical science but also advance the rational utilization of H2O2 and N2H4 in practicability.

Ma|Xiaoqing|X| Tang|Kang-Lai|KL| Lu|Kang|K| Zhang|Chenke|C| Shi|Wenbing|W| Zhao|Wenxi|W|

hollow microflower-like CuS@C hybrids
hydrogen peroxide
hydrazine
electrochemical sensor
ion-exchange strategy


High antibody titres induced by protein subunit vaccines using Mycobacterium ulcerans antigens Hsp18 and MUL_3720 with a TLR-2 agonist fail to protect against Buruli ulcer in mice.

Abstract:
Background
Mycobacterium ulcerans is the causative agent of a debilitating skin and soft tissue infection known as Buruli ulcer (BU). There is no vaccine against BU. The purpose of this study was to investigate the vaccine potential of two previously described immunogenic M. ulcerans proteins, MUL_3720 and Hsp18, using a mouse tail infection model of BU.

Methods
Recombinant versions of the two proteins were each electrostatically coupled with a previously described lipopeptide adjuvant. Seven C57BL/6 and seven BALB/c mice were vaccinated and boosted with each of the formulations. Vaccinated mice were then challenged with M. ulcerans via subcutaneous tail inoculation. Vaccine performance was assessed by time-to-ulceration compared to unvaccinated mice.

Results
The MUL_3720 and Hsp18 vaccines induced high titres of antigen-specific antibodies that were predominately subtype IgG1. However, all mice developed ulcers by day-40 post-M. ulcerans challenge. No significant difference was observed in the time-to-onset of ulceration between the experimental vaccine groups and unvaccinated animals.

Conclusions
These data align with previous vaccine experiments using Hsp18 and MUL_3720 that indicated these proteins may not be appropriate vaccine antigens. This work highlights the need to explore alternative vaccine targets and different approaches to understand the role antibodies might play in controlling BU.

Mangas|Kirstie M|KM|
Tobias|Nicholas J|NJ|
Marion|Estelle|E|
Babonneau|Jérémie|J|
Marsollier|Laurent|L|
Porter|Jessica L|JL|
Pidot|Sacha J|SJ|
Wong|Chinn Yi|CY|
Jackson|David C|DC|
Chua|Brendon Y|BY|
Stinear|Timothy P|TP|

Antibody
Subunit vaccine
Vaccination
Mycobacterium
Mycobacterium ulcerans
Buruli ulcer
ELISA


Hybrid proximal linearized algorithm for the split DC program in infinite-dimensional real Hilbert spaces.

Abstract: To be the best of our knowledge, the convergence theorem for the DC program and split DC program are proposed in finite-dimensional real Hilbert spaces or Euclidean spaces. In this paper, to study the split DC program, we give a hybrid proximal linearized algorithm and propose related convergence theorems in the settings of finite- and infinite-dimensional real Hilbert spaces, respectively.

Critical point
DC function
Strongly monotonicity
Subdifferential


Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease.

Abstract:
BACKGROUND
Omega-3 polyunsaturated fatty acids (PUFAs) have a highly anti-angiogenic effect in animal models. However, the clinical relevance of omega-3PUFAs in human retinal pathologies remains unclear. The ARED 2 study found no effect of omega-3 PUFA supplementation on progression of age related macular degeneration (AMD). The aim of this study was to compare serum levels of omega-3- and omega-6 PUFAs between patients with diabetic retinopathy (DR), AMD and retinal vein occlusion (RVO), and to identify potential confounders of serum level measurements.

METHODS
Venous blood samples were collected from 44 patients with DR, 25 with AMD, 12 with RVO and 27 controls. The lipid phase was extracted and analyzed using mass spectrometry. Retinal disease staging was done by indirect funduscopy and FAG where appropriate. Patient demographics and medical history including current medication and fasting state were acquired. Tukey contrasts for multiple comparisons of the mean and linear regression analysis were used for statistical analysis.

RESULTS
Our data revealed no significant differences in omega-6 PUFA serum levels between patients with AMD, DR, RVO and controls (p > 0.858). Uncorrected omega-3 PUFA levels were significantly higher in patients with AMD compared to DR but not compared to controls (p = 0.004). However, after correcting for possible confounders such as body mass index (BMI), age, sex, fasting and use of statins, no statistically significant difference remained for serum omega-3 PUFA levels. Fasting was identified as an independent confounder of total omega-6 PUFAs, three individual omega-6 PUFAs and one omega-3 PUFA(p < 0.0427). Statin use was identified as an independent confounder of α-linolenic acid (an omega-3PUFA; p = 0.0210).

CONCLUSION
In this pilot study with relatively low patient numbers, we report significant differences in serum levels of omega-3PUFAs among patients with different types of retinal diseases. However, these differences were not robust for disease specificity after correction for possible confounders in our cohort. Our results demonstrate that serum lipid profiles need to be interpreted with caution since they are significantly altered by variables like fasting and medication use independent from the underlying disease. Correcting for respective confounders is thus necessary to compare serum lipid profiles in clinical studies.

Bühler|Anima D|AD|
Bucher|Felicitas|F|
Augustynik|Michael|M|
Wöhrl|Jan|J|
Martin|Gottfried|G|
Schlunck|Günther|G|
Agostini|Hansjürgen|H|
Böhringer|Daniel|D|
Pütz|Gerhard|G|
Stahl|Andreas|A|

D016022:Case-Control Studies
D003930:Diabetic Retinopathy
D015525:Fatty Acids, Omega-3
D043371:Fatty Acids, Omega-6
D005260:Female
D006801:Humans
D008268:Macular Degeneration
D008297:Male
D013058:Mass Spectrometry
D010865:Pilot Projects
D012044:Regression Analysis
D012170:Retinal Vein Occlusion


Lymphoma of the female genital tract: a clinicopatholngical analysis of 25 cases.

Abstract: Occurrence of lymphoma of the female genital tract (FGT) is extremely rare, and cohort studies on survival rates of affected patients are sparse. The aim of this study was to retrospectively evaluate the clinicopathological characteristics of patients diagnosed with non-Hodgkin lymphoma of the FGT. This study included 25 women diagnosed with lymphoma of the FGT. Their data on presenting pathological subtype, International Federation of Gynecology and Obstetrics (FIGO) and Ann Arbor staging, International Prognostic Index (IPI) score, treatment, and survival time were collected. Among the 25 patients, the most prevalent histological subtype was diffuse large B-cell lymphoma (23/25). Tumors were most commonly located in the ovary (15/25), with the remainder located in the cervix (7/25) and uterine corpus (3/25). 76% of cases by Ann Arbor were stage III or IV, and 70% of cases by FIGO were stage III or IV. The overall median survival from diagnosis of lymphoma was estimated to be 71 months, with 3-year and 5-year survival rates of 92% and 80%, respectively. The FIGO and Ann Arbor staging and IPI score were significantly correlated with overall survival time.

Wang|Jingping|J|
Zeng|Linggong|L|
Chen|Shoukang|S|
Wu|Qiong|Q|
Ma|Li|L|
Wu|Shiwu|S|
Wang|Z Peter|ZP|
Tao|Yisheng|Y|
Chai|Damin|D|

Lymphoma
FGT
FIGO
ann arbor stage
survival time


Development of an Automated, Non-Enzymatic Nucleic Acid Amplification Test.

Abstract: Among nucleic acid diagnostic strategies, non-enzymatic tests are the most promising for application at the point of care in low-resource settings. They remain relatively under-utilized, however, due to inadequate sensitivity. Inspired by a recent demonstration of a highly-sensitive dumbbell DNA amplification strategy, we developed an automated, self-contained assay for detection of target DNA. In this new diagnostic platform, called the automated Pi-powered looping oligonucleotide transporter, magnetic beads capture the target DNA and are then loaded into a microfluidic reaction cassette along with the other reaction solutions. A stepper motor controls the motion of the cassette relative to an external magnetic field, which moves the magnetic beads through the reaction solutions automatically. Real-time fluorescence is used to measure the accumulation of dumbbells on the magnetic bead surface. Left-handed DNA dumbbells produce a distinct signal which reflects the level of non-specific amplification, acting as an internal control. The autoPiLOT assay detected as little as 5 fM target DNA, and was also successfully applied to the detection of S. mansoni DNA. The autoPiLOT design is a novel step forward in the development of a sensitive, user-friendly, low-resource, non-enzymatic diagnostic test.

automation
non-enzymatic
DNA amplification
microfluidic
fluorescence
L-DNA


Endothelin-1 as a master regulator of whole-body Na+ homeostasis.

Abstract: The current study was designed to determine whether vascular endothelial-derived endothelin-1 (ET-1) is important for skin Na(+) buffering. In control mice (C57BL/6J), plasma Na(+) and osmolarity were significantly elevated in animals on high- vs. low-salt (HS and LS, respectively) intake. The increased plasma Na(+) and osmolarity were associated with increased ET-1 mRNA in vascular tissue. There was no detectable difference in skin Na(+):H2O in HS fed mice (0.119 ± 0.005 mM vs. 0.127 ± 0.007 mM; LS vs. HS); however, skin Na(+):H2O was significantly increased by blockade of the endothelin type A receptor with ABT-627 (0.116 ± 0.006 mM vs. 0.137 ± 0.007 mM; LS vs. HS; half-maximal inhibitory concentration, 0.055 nM). ET-1 peptide content in skin tissue was increased in floxed control animals on HS (85.9 ± 0.9 pg/mg vs. 106.4 ± 6.8 pg/mg; P < 0.05), but not in vascular endothelial cell endothelin-1 knockout (VEET KO) mice (76.4 ± 5.7 pg/mg vs. 65.7 ± 7.9 pg/mg; LS vs. HS). VEET KO mice also had a significantly elevated skin Na(+):H2O (0.113 ± 0.007 mM vs. 0.137 ± 0.005 mM; LS vs. HS; P < 0.05). Finally, ET-1 production was elevated in response to increasing extracellular osmolarity in cultured human endothelial cells. These data support the hypothesis that increased extrarenal vascular ET-1 production in response to HS intake is mediated by increased extracellular osmolarity and plays a critical role in regulating skin storage of Na(+).

Speed|Joshua S|JS|
Heimlich|J Brett|JB|
Hyndman|Kelly A|KA|
Fox|Brandon M|BM|
Patel|Vivek|V|
Yanagisawa|Masashi|M|
Pollock|Jennifer S|JS|
Titze|Jens M|JM|
Pollock|David M|DM|


Inhibitory effect of chlorogenic acid on digestion of potato starch.

Abstract: The effect of the chlorogenic acid isomer 5-O-caffeoylquinic acid (5-CQA) on digestion of potato starch by porcine pancreatic alpha amylase (PPAA) was investigated using isolated starch and cooked potato tuber as substrates. In vitro digestion was performed on five varieties of potato with varying phenolic content. Co- and pre-incubation of PPAA with 5-CQA significantly reduced PPAA activity in a dose dependent manner with an IC50 value of about 2mgmL(-1). Lineweaver-Burk plots indicated that 5-CQA exerts a mixed type inhibition as km increased and Vmax decreased. The total polyphenol content (TPC) of peeled tuber tissue ranged from 320.59 to 528.94mg 100g(-1)dry weight (DW) in raw tubers and 282.03-543.96mg 100g(-1)DW in cooked tubers. With the exception of Désirée, TPC and 5-CQA levels decreased after cooking. Principle component analysis indicated that digestibility is affected by multiple factors including phenolic, dry matter and starch content.

Chlorogenic acid
Digestion
Potato
Starch
Alpha amylase
Polyphenol
Enzyme kinetics
Solanum tuberosum


Relative contributions of task-relevant and task-irrelevant dimensions in priming of pop-out.

Abstract: Intertrial effects such as priming of pop-out (PoP) often occur for task-irrelevant dimensions as well as task-relevant dimensions, though to a weaker extent. Here we test the hypothesis that increased priming for task-relevant dimensions is due to greater passive build-up of priming for the task-relevant dimension rather than to an active filtering of task-irrelevant dimensions; if this is the case, then we should observe a positive correlation between the magnitude of task-relevant and task-irrelevant priming. We tested this hypothesis using a pop-out search task in which the task-relevant dimension was orientation and the task-irrelevant dimension was color. We found a strong, positive association between task-relevant and task-irrelevant priming across a large group of participants (N = 100); additionally, we observed increased priming over consecutive repetitions for the task-relevant dimension, whereas task-irrelevant priming was constant across multiple repetitions. As further evidence against an active filtering account, task-irrelevant priming showed no systematic relationship with visual short-term memory capacity, which has been shown to correlate with filtering ability. Together, our results suggest that task-irrelevant dimensions are co-selected rather than filtered out during target search. Further, increased task-relevant priming may reflect an enhanced representation of the task-relevant dimension that is reinforced over consecutive repetitions.

Michal|Audrey L|AL|
Lleras|Alejandro|A|
Beck|Diane M|DM|

task-relevance
priming of pop-out
visual short term memory