Aerosol jet printed p- and n-type electrolyte-gated transistors with a variety of electrode materials: exploring practical routes to printed electronics.

Abstract: Printing electrically functional liquid inks is a promising approach for achieving low-cost, large-area, additive manufacturing of flexible electronic circuits. To print thin-film transistors, a basic building block of thin-film electronics, it is important to have several options for printable electrode materials that exhibit high conductivity, high stability, and low-cost. Here we report completely aerosol jet printed (AJP) p- and n-type electrolyte-gated transistors (EGTs) using a variety of different electrode materials including highly conductive metal nanoparticles (Ag), conducting polymers (polystyrenesulfonate doped poly(3,4-ethylendedioxythiophene, PEDOT:PSS), transparent conducting oxides (indium tin oxide), and carbon-based materials (reduced graphene oxide). Using these source-drain electrode materials and a PEDOT:PSS/ion gel gate stack, we demonstrated all-printed p- and n-type EGTs in combination with poly(3-hexythiophene) and ZnO semiconductors. All transistor components (including electrodes, semiconductors, and gate insulators) were printed by AJP. Both kinds of devices showed typical p- and n-type transistor characteristics, and exhibited both low-threshold voltages (<2 V) and high hole and electron mobilities. Our assessment suggests Ag electrodes may be the best option in terms of overall performance for both types of EGTs.

Hong|Kihyon|K|
Kim|Se Hyun|SH|
Mahajan|Ankit|A|
Frisbie|C Daniel|CD|

aerosol jet printing
electrolyte-gated transistors
electrode materials
ion-gel gate insulator


Identification and Characterization of a Novel Lectin from the Clam Glycymeris yessoensis and Its Functional Characterization under Microbial Stimulation and Environmental Stress.

Abstract: Lectin from the bivalve Glycymeris yessoensis (GYL) was purified by affinity chromatography on porcine stomach mucin-Sepharose. GYL is a dimeric protein with a molecular mass of 36 kDa, as established by SDS-PAGE and MALDI-TOF analysis, consisting of 18 kDa subunits linked by a disulfide bridge. According to circular dichroism data, GYL is a β/α-protein with the predominance of β-structure. GYL preferentially agglutinates enzyme-treated rabbit erythrocytes and recognizes glycoproteins containing O-glycosidically linked glycans, such as porcine stomach mucin (PSM), fetuin, thyroglobulin, and ovalbumin. The amino acid sequences of five segments of GYL were acquired via mass spectrometry. The sequences have no homology with other known lectins. GYL is Ca2+-dependent and stable over a range above a pH of 8 and temperatures up to 20 °C for 30 min. GYL is a pattern recognition receptor, as it binds common pathogen-associated molecular patterns, such as peptidoglycan, LPS, β-1,3-glucan and mannan. GYL possesses a broad microbial-binding spectrum, including Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Vibrio proteolyticus), but not the fungus Candida albicans. Expression levels of GYL in the hemolymph were significantly upregulated after bacterial challenge by V. proteolyticus plus environmental stress (diesel fuel). Results indicate that GYL is probably a new member of the C-type lectin family, and may be involved in the immune response of G. yessoensis to bacterial attack.

pattern recognition receptors
hemolymph
bivalve lectins
microorganism binding


Application of transient elastography in nonalcoholic fatty liver disease.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

Zhang|Xinrong|X|
Wong|Grace Lai-Hung|GL|
Wong|Vincent Wai-Sun|VW|

D065626:Non-alcoholic Fatty Liver Disease

Fatty liver
Obesity
Diagnostic imaging
Liver cirrhosis
Metabolic syndrome


Protective effect of SIRT6 on cholesterol crystal-induced endothelial dysfunction via regulating ACE2 expression.

Abstract: Sirtuins are a family of highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes. Among the sirtuins, SIRT1 and SIRT6 participate in the regulation of endothelial functions and play significant roles in the physiological and pathological processes of cardiovascular diseases (CVD). Recently, our study found that minute cholesterol crystals (CC) can be endocytosed by endothelial cells and further impair endothelial functions. Since previous studies have reported that angiotensin-converting enzyme (ACE2) involves Angiotensin (Ang) II-induced inflammation in endothelial cells, this study was designed to investigate the role of SIRT1 and SIRT6 in CC-induced variation of ACE2 expression and the related mechanism between SIRT6 and ACE2. We found that ACE2 is involved in CC-induced endothelial dysfunction, which inhibits decreases in nitric oxide (NO) level and endothelial nitric oxide synthase (eNOS) activity and increases in inflammatory factors and adhesion molecules. Besides, SIRT1 and SIRT6 regulated the protein expression of ACE2 in CC-stimulated human umbilical vein endothelial cells (HUVECs). Moreover, bioinformatics analysis from the Enrichr database indicated that activating transcription factor 2 (ATF2), is highly correlated with genes that significantly upregulated after infection with the SIRT6 adenovirus vector. In CC-induced HUVECs, ACE2 expression was up-regulated in cells transfected with ATF2 siRNA. However, further mechanism studies revealed that overexpression of SIRT6 decreases the accumulation of p-ATF2 in the nucleus, but did not affect p-ATF2 expression in the cytoplasm. Taken together, these data indicated that SIRT6 regulates ACE2 might via inhibiting the accumulation of nucleus p-ATF2 in CC-induced endothelial dysfunction.

Zheng|Zihan|Z| Wang|Bo|B| Lv|Xiaohan|X| Yao|Feng|F| Gao|Hongqian|H| Jin|Zhen|Z| Liu|Yizhen|Y| Deng|Ying|Y| Chen|Danli|D| Ning|Xuan|X| Wang|Weirong|W| He|Jianyu|J| Lin|Rong|R|

D051698:Activating Transcription Factor 2

D061307:Human Umbilical Vein Endothelial Cells


Well-defined CuC2F5 complexes and pentafluoroethylation of acid chlorides.

Abstract: Four new well-defined Cu(I) complexes bearing a C2 F5 ligand have been prepared and fully characterized: [(Ph3 P)2 CuC2 F5 ] (2), [(bpy)CuC2 F5 ] (3), [(Ph3 P)Cu(phen)C2 F5 ] (4), and [(IPr*)CuC2 F5 ] (5). X-ray structures of all four have been determined, showing that the C2 F5 -ligated Cu atom can be di- (5), tri- (2 and 3), and tetracoordinate (4). The mixed phen-PPh3 complex 4 is a highly efficient fluoroalkylating agent for a broad variety of acid chlorides. This high-yielding transformation represents the first general method for the synthesis of RCOC2 F5 from the corresponding RCOCl.

Panferova|Liubov I|LI|
Miloserdov|Fedor M|FM|
Lishchynskyi|Anton|A|
Martínez Belmonte|Marta|M|
Benet-Buchholz|Jordi|J|
Grushin|Vladimir V|VV|

pentafluoroethylation
copper
fluorine
organometallic synthesis
pentafluoroethyl ketones


MicroRNA-34a promotes iNOS secretion from pulmonary macrophages in septic suckling rats through activating STAT3 pathway.

Abstract: Pediatric sepsis is frequently a fatal condition and a major cause of death globally. The mortality rate of sepsis remains high despite that the advanced therapeutic methods have been carried out. Our research aims to investigate the potentials of miR-34a in the treatment of pediatric sepsis. Results indicated that miR-34a was up-regulated in Lipopolysaccharide (LPS)-induced pulmonary macrophages and U937 cell lines. In addition, miR-34a silence reduced the production of iNOS through inactivating STAT3 pathway in U937 cell lines and cecal ligation and puncture (CLP)-induced lung tissues. Besides, high expression of iNOS and STAT3 in cells transfected with miR-34a mimic further validated it. Furthermore, in vivo experiment demonstrated that miR-34a silence protected CLP-induced suckling rats from lung injury. All in all, our study demonstrated that miR-34a promoted iNOS secretion from pulmonary macrophages in LPS-induced sepsis suckling rats through activating STAT3 pathway. These results provided a possibility to convert miR-34a into clinical application.

Cheng|Dong-Liang|DL| Fang|Hong-Xing|HX| Liang|Yuan|Y| Zhao|Yi|Y| Shi|Chang-Song|CS|

MicroRNA-34a
iNOS
Pulmonary macrophages
STAT3 pathways
Sepsis


Avulsion fracture of the iliac crest in a child.

Abstract: Avulsion fractures of the apophysis of the iliac crest have rare incidence and are little known. In this article, we report the case of an 11-year-old female patient who presented this injury after indirect trauma. From careful radiographic analysis, an avulsion fracture of the iliac crest was identified. It was decided to use nonsurgical treatment comprising analgesia and load restriction. This case report emphasizes the importance of suspecting avulsion fractures in cases of low-energy trauma, and also guides the treatment, so as to prevent functional deficit and deformities.

Mortati|Rafael Borghi|RB|
Borghi Mortati|Lucas|L|
Silva Teixeira|Matheus|M|
Itiro Takano|Marcelo|M|
Armelin Borger|Richard|R|

Cartilage fractures
Epiphysis/lesions
Epiphysis/physiopathology
Ilium


Experiences of mental health professionals providing services to adults with intellectual disabilities and mental health problems: A systematic review and meta-synthesis of qualitative research studies.

Abstract:
BACKGROUND
Mental health professionals play an important role in providing care and treatment for adults with intellectual disabilities. A number of studies use qualitative methods to explore the experiences of these professionals and their perspectives regarding the mental health services for this population. A systematic review using meta-ethnographic approach was undertaken to summarise this research.

METHOD
A systematic search found 14 relevant studies which were critically appraised. Key themes from these studies were extracted and synthesised.

RESULTS
Three main themes were identified: 1) Understanding the person, 2) Relational interaction and 3) Organisational factors.

CONCLUSIONS
The findings of this review identified the issues mental health professionals raised in relation to their work. They described the complex presenting problems as intense yet fulfilling therapeutic relationships with their clients and their wish to improve their knowledge and skills. They identified organisational issues that need to be addressed to improve staff morale and efficiency.

mental health professionals
services
intellectual disabilities
qualitative research
staff experiences


Discovery of scmR as a global regulator of secondary metabolism and virulence in Burkholderia thailandensis E264.

Abstract: Bacteria produce a diverse array of secondary metabolites that have been invaluable in the clinic and in research. These metabolites are synthesized by dedicated biosynthetic gene clusters (BGCs), which assemble architecturally complex molecules from simple building blocks. The majority of BGCs in a given bacterium are not expressed under normal laboratory growth conditions, and our understanding of how they are silenced is in its infancy. Here, we have addressed this question in the Gram-negative model bacterium Burkholderia thailandensis E264 using genetic, transcriptomic, metabolomic, and chemical approaches. We report that a previously unknown, quorum-sensing-controlled LysR-type transcriptional regulator, which we name ScmR (for secondary metabolite regulator), serves as a global gatekeeper of secondary metabolism and a repressor of numerous BGCs. Transcriptionally, we find that 13 of the 20 BGCs in B. thailandensis are significantly (threefold or more) up- or down-regulated in a scmR deletion mutant (ΔscmR) Metabolically, the ΔscmR strain displays a hyperactive phenotype relative to wild type and overproduces a number of compound families by 18- to 210-fold, including the silent virulence factor malleilactone. Accordingly, the ΔscmR mutant is hypervirulent both in vitro and in a Caenorhabditis elegans model in vivo. Aside from secondary metabolism, ScmR also represses biofilm formation and transcriptionally activates ATP synthesis and stress response. Collectively, our data suggest that ScmR is a pleiotropic regulator of secondary metabolism, virulence, biofilm formation, and other stationary phase processes. A model for how the interplay of ScmR with pathway-specific transcriptional regulators coordinately silences virulence factor production is proposed.

Mao|Dainan|D|
Bushin|Leah B|LB|
Moon|Kyuho|K|
Wu|Yihan|Y|
Seyedsayamdost|Mohammad R|MR|

D015964:Gene Expression Regulation, Bacterial

regulation
virulence
Burkholderia thailandensis
biosynthetic gene clusters
natural products


Is It Time to Say Farewell to the ISDS System? Comment on "The Trans-Pacific Partnership: Is It Everything We Feared for Health?"

Abstract: Investor-state dispute settlement (ISDS) continues to plague health-oriented government regulation. This is particularly reflected in recent challenges to tobacco control measures through bilateral investment agreements. There are numerous reform proposals circulating within the public health community. However, I suggest that perhaps it is time for the community to explore a stronger position on ISDS. I draw from mounting evidence on the problematic uses of the ISDS to explore the proposition that ISDS is no longer justified. I tackle the normative question of should the ISDS system persist and point out that the ISDS system is not justifiable from a development perspective and because of its nefarious use, is of no added value to a system that could rely on domestic courts.

D003132:Commerce
D034462:Dissent and Disputes
D006291:Health Policy
D006801:Humans
D007391:International Cooperation
D011634:Public Health

Investor-State Dispute Settlement (ISDS)

Trans-Pacific Partnership (TPP) Agreement


Competitive Coordination of Chloride and Fluoride Anions Towards Trivalent Lanthanide Cations (La3+ and Nd3+ ) in Molten Salts.

Abstract: Molten salt electrolysis is a vital technique to produce high-purity lanthanide metals and alloys. However, the coordination environments of lanthanides in molten salts, which heavily affect the related redox potential and electrochemical properties, have not been well elucidated. Here, the competitive coordination of chloride and fluoride anions towards lanthanide cations (La3+ and Nd3+ ) is explored in molten LiCl-KCl-LiF-LnCl3 salts using electrochemical, spectroscopic, and computational approaches. Electrochemical analyses show that significant negative shifts in the reduction potential of Ln3+ occur when F- concentration increases, indicating that the F- anions interact with Ln3+ via substituting the coordinated Cl- anions, and confirm [LnClx Fy ]3-x-y (ymax =3) complexes are prevailing in molten salts. Spectroscopic and computational results on solution structures further reveal the competition between Cl- and F- anions, which leads to the formation of four distinct Ln(III) species: [LnCl6 ]3- , [LnCl5 F]3- , [LnCl4 F2 ]3- and [LnCl4 F3 ]4- . Among them, the seven-coordinated [LnCl4 F3 ]4- complex possesses a low-symmetry structure evidenced by the pattern change of Raman spectra. After comparing the polarizing power (Z/r) among different metal cations, it was concluded that Ln-F interaction is weaker than that between transition metal and F- ions.

coordination
lanthanides
X-ray absorption spectroscopy
electrochemistry
molecular dynamics simulations


Construction of NaYF4 Library for Morphology-Controlled Multimodality Applications.

Abstract: Morphology and size of the nanoparticles are highly related to the properties; establishing a library to summarize the relationship between the morphology/size and property is very helpful for associated applications. However, the NaYF4 library and thus the correlation between the morphology and property are still absent. Here NaYF4 library is presented and their morphologies and structures are illustrated at atomic scale for the first time. How about the crystal formation affects the morphology is further used to guide the property. Through rational doping, upconversion luminescence, magnetic resonance (MR) and computed tomography are investigated with the nanoprisms, nanoflowers, and nanoplates as models to reveal the effect of the size and morphology. The difference of the properties provides strong evidence on the importance of the library. In particular, the "imperfect structure" of nanoflower is observed on atomic scale and enhances the MR response. The different upconversion intensity ratio for the emissions at 475 and 693 nm is observed from doped NaYF4 with different morphology. Thus, controllable fabrication of NaYF4 with desired morphology is indispensable to achieve the optimal properties as the guidance on how to choose matrix from the library to meet the specific applications.


A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome.

Abstract:
BACKGROUND
Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost-effectiveness is lacking.

OBJECTIVE
We aimed to assess cost-effectiveness of small-intestinal release peppermint oil versus placebo in IBS patients.

METHODS
In a multicenter randomized placebo-controlled trial, cost-effectiveness was evaluated from a societal perspective. The incremental cost-effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight-week treatment period with placebo versus peppermint oil. Cost-utility and uncertainty were estimated using non-parametric bootstrapping. Sensitivity analyses were performed.

RESULTS
The analysis comprised 126 patients (N = 64 placebo, N = 62 small-intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net-benefit acceptability curve showed that peppermint oil has a 56% probability of being cost-effective at a conservative willingness-to-pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost-effective.

CONCLUSIONS
In patients with IBS, small-intestinal release peppermint oil appears to be a cost-effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost-effective. The use of peppermint oil, which is a low-cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long-term data are necessary to confirm the cost-effectiveness of peppermint oil. NCT02716285.

Weerts|Zsa Zsa R M|ZZRM|https://orcid.org/0000-0001-7522-9916

Jonkers|Daisy M A E|DMAE|https://orcid.org/0000-0001-8981-8965

peppermint oil
irritable bowel syndrome
cost-effectiveness
ICER
QALY
Abdominal pain
economic burden


Miniforceps EBUS-guided lymph node biopsy: impact on diagnostic yield.

Abstract:
INTRODUCTION
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard diagnostic method for sampling mediastinal and hilar lymph nodes. Non-diagnostic samples have led some pulmonologists to add a miniforceps biopsy (EBUS-TBFB) in order to increase diagnostic yield. Our study aims to analyze the impact of adding EBUS-TBFB to the EBUS-TBNA in cases where Rapid On-site Evaluation (ROSE) was negative for malignancy or was non-diagnostic.

MATERIAL AND METHODS
This retrospective chart review included 91 patients who were aged 18-90 years old and underwent EBUS with both TBNA and TBFB between January 1, 2013 and July 1, 2018.

RESULTS
There was no significant statistical difference in the diagnostic yield of TBNA vs TBFB with a McNemar value of 0.167, and this conclusion was the same when stratified by race, age and lymph node size. Using TBNA as a gold standard, the sensitivity and specificity of TBFB was 87% and 69%, respectively. Out of the non-diagnostic TBNA samples on ROSE and cell-block, subsequent TBFB resulted in additional pathologic diagnoses in 16% of cases, of which 67% were non-caseating granulomas. Furthermore, two additional malignant cases were identified by TBFB consisting of small cell carcinoma and non-Hodgkin's lymphoma.

CONCLUSION
In conclusion, TBFB is a useful adjunctive tool in the diagnosis of non-malignant conditions (i.e. granulomatous diseases) with the potential to spare the patient from more invasive surgical biopsies. Training of future fellows in performing TBFB in addition to TBNA should be strongly encouraged.

Shiari|Aryan|A|0000-0002-6707-5029 Aljundi|Lamia|L| Boshara|Peter|P| Zein|Rami|R| Zalt|Mohammad|M|

D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration

EBUS-TBNA
EBUS-TBFB
Rapid On-site Evaluation
ROSE
sarcoidosis


Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo.

Abstract:
BACKGROUND
Currently, direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule compounds. Delivery of transcriptional factors may affect genome stability, while small-molecule compounds may require more evaluations when applied in vivo. Thus, a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal trans-differentiation.

RESULTS
Here, we report that a defined medium (5C) consisting of basic fibroblast growth factor (bFGF), N2 supplement, leukemia inhibitory factor, vitamin C (Vc), and β-mercaptoethanol (βMe) induces the direct conversion of somatic cells to cells with neuronal characteristics. Application of 5C medium converted mouse embryonic fibroblasts (MEFs) into TuJ+ neuronal-like cells, which were capable of survival after being transplanted into the mouse brain. The same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics in vitro and facilitated the recovery of brain injury, possibly by inducing similar conversions, when infused into the mouse brain in vivo. Crucially, 5C medium could also induce neuronal characteristics in several human cell types.

CONCLUSIONS
In summary, this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection in vitro but might also be useful to produce neurons in vivo for neurodegenerative disease treatment.

He|Songwei|S| Guo|Yiping|Y| Zhang|Yixin|Y| Li|Yuan|Y| Feng|Chengqian|C| Li|Xiang|X| Lin|Lilong|L| Guo|Lin|L| Wang|Haitao|H| Liu|Chunhua|C| Zheng|Yi|Y| Luo|Chuanming|C| Liu|Qiang|Q| Wang|Fuhui|F| Sun|Hao|H| Liang|Lining|L| Li|Lingyu|L| Su|Huanxing|H| Chen|Jiekai|J| Pei|Duanqing|D| Zheng|Hui|H|

Somatic cells
Neurons
Defined medium
Trans-differentiation
Astrocytes


The elevated transcription of ADAM19 by the oncohistone H2BE76K contributes to oncogenic properties in breast cancer.

Abstract: The recent discovery of the cancer-associated E76K mutation in histone H2B (H2BE76-to-K) in several types of cancers revealed a new class of oncohistone. H2BE76K weakens the stability of histone octamers, alters gene expression, and promotes colony formation. However, the mechanism linking the H2BE76K mutation to cancer development remains largely unknown. In this study, we knock in the H2BE76K mutation in MDA-MB-231 breast cancer cells using CRISPR/Cas9 and show that the E76K mutant histone H2B preferentially localizes to genic regions. Interestingly, genes upregulated in the H2BE76K mutant cells are enriched for the E76K mutant H2B and are involved in cell adhesion and proliferation pathways. We focused on one H2BE76K target gene, ADAM19 (a disintegrin and metalloproteinase-domain-containing protein 19), a gene highly expressed in various human cancers including breast invasive carcinoma, and demonstrate that H2BE76K directly promotes ADAM19 transcription by facilitating efficient transcription along the gene body. ADAM19 depletion reduced the colony formation ability of the H2BE76K mutant cells, whereas wild-type MDA-MB-231 cells overexpressing ADAM19 mimics the colony formation phenotype of the H2BE76K mutant cells. Collectively, our data demonstrate the mechanism by which H2BE76K deregulates the expression of genes that control oncogenic properties through a combined effect of its specific genomic localization and nucleosome destabilization effect.

Kang|Tze Zhen Evangeline|TZE|
Zhu|Lina|L|
Yang|Du|D|
Ding|Dongbo|D|
Zhu|Xiaoxuan|X|
Wan|Yi Ching Esther|YCE|
Liu|Jiaxian|J|
Ramakrishnan|Saravanan|S|
Chan|Landon Long|LL|
Chan|Siu Yuen|SY|
Wang|Xin|X|
Gan|Haiyun|H|
Han|Junhong|J|
Ishibashi|Toyotaka|T|
Li|Qing|Q|
Chan|Kui Ming|KM|

D015972:Gene Expression Regulation, Neoplastic

transcription
oncohistone
breast cancer
ADAM
epigenetics


Gene expression analysis of antimony resistance in Leishmania tropica using quantitative real-time PCR focused on genes involved in trypanothione metabolism and drug transport.

Abstract: Pentavalent antimonials remain the treatment of choice for all the clinical forms of leishmaniasis. The increasing rates of antimony resistance are becoming a serious health problem in treatment of anthroponotic cutaneous leishmaniasis (ACL). Accordingly, unraveling molecular markers is crucial for improving medication strategies and monitoring of drug-resistant parasites. Different studies have suggested the importance of genes involved in trypanothione metabolism and drug transport. In this regard, present study was designed to investigate the RNA expression level of five genes including γ-GCS, ODC, TRYR (involved in trypanothione metabolism), AQP1 (acts in drug uptake) and MRPA (involved in sequestration of drug) in sensitive and resistant Leishmania tropica isolates. Seven antimony-resistant and seven antimony-sensitive L. tropica clinical isolates were collected from ACL patients. Drug sensitivity test was performed on the samples as well as reference strains; afterwards, gene expression analysis was performed on clinical isolates by quantitative real-time PCR. The results revealed that the average expression level of AQP1 gene was decreased (0.47-fold) in resistant isolates compared to sensitive ones whereas MRPA (2.45), γ-GCS (2.1) and TRYR (1.97) was upregulated in resistant isolates. The average expression of ODC (1.24-fold) gene was not different significantly between sensitive and resistant isolates. Our findings suggest that AQP1, MRPA, GSH1 and TRYR can be considered as potential molecular markers for screening of antimony resistance in some L. tropica clinical isolates.

D060888:Real-Time Polymerase Chain Reaction

Gene expression
Leishmania tropica
Quantitative real-time PCR
Potential molecular marker
Natural antimony resistance


Bubble CPAP and oxygen for child pneumonia care in Malawi: a CPAP IMPACT time motion study.

Abstract:
BACKGROUND
In some low-resource settings bubble continuous positive airway pressure (bCPAP) is increasingly used to treat children with pneumonia. However, the time required for healthcare workers (HCWs) to administer bCPAP is unknown and may have implementation implications. This study aims to compare HCW time spent administering bCPAP and low-flow nasal oxygen care at a district hospital in Malawi during CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial).

METHODS
Eligible participants were 1-59 months old with WHO-defined severe pneumonia and HIV-infection, HIV-exposure, severe malnutrition, or hypoxemia and were randomized to either bCPAP or oxygen. We used time motion techniques to observe hospital care in four hour blocks during treatment initiation or follow up (maintenance). HCW mean time per patient at the bedside over the observation period was calculated by study arm.

RESULTS
Overall, bCPAP required an average of 34.71 min per patient more than low-flow nasal oxygen to initiate (bCPAP, 118.18 min (standard deviation (SD) 42.73 min); oxygen, 83.47 min (SD, 20.18 min), p < 0.01). During initiation, HCWs spent, on average, 12.45 min longer per patient setting up bCPAP equipment (p < 0.01) and 11.13 min longer per patient setting up the bCPAP nasal interface (p < 0.01), compared to oxygen equipment and nasal cannula set-up. During maintenance care, HCWs spent longer on average per patient adjusting bCPAP, compared to oxygen equipment (bCPAP 4.57 min (SD, 4.78 min); oxygen, 1.52 min (SD, 2.50 min), p = 0.03).

CONCLUSION
Effective bCPAP implementation in low-resource settings will likely create additional HCW burden relative to usual pneumonia care with oxygen.

TRIAL REGISTRATION
Clinicaltrials.gov NCT02484183 , June 29, 2015.

D045422:Continuous Positive Airway Pressure

Bubble continuous positive airway pressure


Corrosive extracellular polysaccharides of the rock-inhabiting model fungus Knufia petricola.

Abstract: Melanised cell walls and extracellular polymeric matrices protect rock-inhabiting microcolonial fungi from hostile environmental conditions. How extracellular polymeric substances (EPS) perform this protective role was investigated by following development of the model microcolonial black fungus Knufia petricola A95 grown as a sub-aerial biofilm. Extracellular substances were extracted with NaOH/formaldehyde and the structures of two excreted polymers studied by methylation as well as NMR analyses. The main polysaccharide (~ 80%) was pullulan, also known as α-1,4-; α-1,6-glucan, with different degrees of polymerisation. Αlpha-(1,4)-linked-Glcp and α-(1,6)-linked-Glcp were present in the molar ratios of 2:1. A branched galactofuromannan with an α-(1,2)-linked Manp main chain and a β-(1,6)-linked Galf side chain formed a minor fraction (~ 20%). To further understand the roles of EPS in the weathering of minerals and rocks, viscosity along with corrosive properties were studied using atomic force microscopy (AFM). The kinetic viscosity of extracellular K. petricola A95 polysaccharides (≈ 0.97 × 10-6 m2 s-1) ranged from the equivalent of 2% (w/v) to 5% glycerine, and could thus profoundly affect diffusion-dominated processes. The corrosive nature of rock-inhabiting fungal EPS was also demonstrated by its effects on the aluminium coating of the AFM cantilever and the silicon layer below.

Breitenbach|Romy|R|
Silbernagl|Dorothee|D|
Toepel|Jörg|J|
Sturm|Heinz|H|
Broughton|William J|WJ|
Sassaki|Guilherme L|GL|
Gorbushina|Anna A|AA|

Corrosion
EPS
Pullulan
Melanised microcolonial fungi (MCF)
Sub-aerial biofilms (SAB)
α-1,4- and α-1,6-glucans


A rare case of pneumocephalus and pneumorrhachis after epidural anesthesia.

Abstract: Both pneumocephalus and pneumorrhachis are rare but serious complications following epidural anesthesia. We report a rare case of simultaneous pneumocephalus and pneumorrhachis in a patient after undergoing epidural anesthesia. The patient lost consciousness and received emergent external ventricular drainage for pneumocephalus in another medical center. The patient was clear after external ventricular drain placement until 4 days later, when sudden onset of subdural hemorrhage occurred and an emergent craniectomy was performed. The patient passed away 2 days after craniectomy, due to multiorgan failure. Pneumocephalus with or without pneumorrhachis should be kept in mind when there is a sudden change of consciousness or persistent convulsions after epidural anesthesia.

Hsieh|Xhang-Xian|XX| Hsieh|Sun-Wung|SW| Lu|Chueng-He|CH| Wu|Zhi-Fu|ZF| Ju|Da-Tong|DT| Huh|Billy|B| Wang|Jia-Chang|JC| Kuo|Chan-Yang|CY|

pneumocephalus
pneumorrhachis
epidural
anesthesia
subdural hemorrhage


The Combination of Cholecystokinin and Stress Amplifies an Inhibition of Appetite, Gastric Emptying, and an Increase in c-Fos Expression in Neurons of the Hypothalamus and the Medulla Oblongata.

Abstract: Cholecystokinin (CCK) had been the first gastrointestinal hormone known to exert anorexic effects. CCK had been inferred to contribute to the onset of functional dyspepsia (FD) symptoms. To understand the pathophysiology of FD, the roles of stress have to be clarified. In this study, we aimed to clarify the influence of stress on the action of cholecystokinin (CCK) on appetite and gastric emptying. Using rats, stress was simulated by giving restraint stress or intraperitoneal injection of the stress-related peptide hormone urocortin 1 (UCN1). The effects of CCK and restraint stress, alone or in combination, on food intake and gastric motility were examined, and c-Fos expression in the neurons of appetite control network in the central nervous system was assessed by immunohistochemical staining. CCK inhibited food intake and gastric emptying in a dose-dependent manner. Food intake for 1 h was significantly lower with UCN1 (2 nmol/kg) than with the saline control. Restraint stress amplified the suppressive effects of CCK on food intake for 1 h and on gastric emptying. With regard to brain function, the CCK induced c-Fos expression in the neurons of the nucleus tractus solitarius and paraventricular nucleus of the hypothalamus was markedly and significantly amplified by the addition of restraint stress with CCK. The results suggested that stress might amplify the anorexic effects of CCK through activation of the nuclei that comprise the brain neuronal network for satiation; this might play a role in the pathogenesis of the postprandial distress syndromes of functional dyspepsia.

Cholecystokinin
Stress
Gastric emptying
c-Fos
Urocortin 1


General control nonderepressible 2 (GCN2) kinase protects oligodendrocytes and white matter during branched-chain amino acid deficiency in mice.

Abstract: Branched-chain amino acid (BCAA) catabolism is regulated by branched-chain α-keto acid dehydrogenase, an enzyme complex that is inhibited when phosphorylated by its kinase (BDK). Loss of BDK function in mice and humans causes BCAA deficiency and epilepsy with autistic features. In response to amino acid deficiency, phosphorylation of eukaryotic initiation factor 2α (eIF2∼P) by general control nonderepressible 2 (GCN2) activates the amino acid stress response. We hypothesized that GCN2 functions to protect the brain during chronic BCAA deficiency. To test this idea, we generated mice lacking both Gcn2 and Bdk (GBDK) and examined the development of progeny. GBDK mice appeared normal at birth, but they soon stopped growing, developed severe ataxia, tremor, and anorexia, and died by postnatal day 15. BCAA levels in brain were diminished in both Bdk(-/-) and GBDK pups. Brains from Bdk(-/-) pups exhibited robust eIF2∼P and amino acid stress response induction, whereas these responses were absent in GBDK mouse brains. Instead, myelin deficiency and diminished expression of myelin basic protein were noted in GBDK brains. Genetic markers of oligodendrocytes and astrocytes were also reduced in GBDK brains in association with apoptotic cell death in white matter regions of the brain. GBDK brains further demonstrated reduced Sod2 and Cat mRNA and increased Tnfα mRNA expression. The data are consistent with the idea that loss of GCN2 during BCAA deficiency compromises glial cell defenses to oxidative and inflammatory stress. We conclude that GCN2 protects the brain from developing a lethal leukodystrophy in response to amino acid deficiencies.

She|Pengxiang|P|
Bunpo|Piyawan|P|
Cundiff|Judy K|JK|
Wek|Ronald C|RC|
Harris|Robert A|RA|
Anthony|Tracy G|TG|

Amino Acid
Epilepsy
Brain
Myelin
Leukodystrophy
Endoplasmic Reticulum Stress
Gene Knock-out
Glia
Translation Initiation Factors


Multidisciplinary rehabilitation in ventilator-dependent patients: Call for action in specialized inpatient facilities.

Abstract: The numbers of patients needing prolonged mechanical ventilation are growing. The rehabilitation programs to be implemented in specialized inpatient facilities are ill defined. There is a clear need to establish guidelines to define the optimal rehabilitation program in this setting. In this article we review the current evidence and propose some guidance.

Rehabilitation
Ventilator-dependent patients
Weaning facilities


Radiation safety analysis for the A-BNCT facility in Korea.

Abstract: A Proton Accelerator based Boron Neutron Capture Therapy (A-BNCT) facility is under development in Korea. Neutron beams for treatment are produced from a beryllium (Be) target and an 8 mA, 10 MeV proton beam. The purpose of the research is a radiation shielding analysis and an activation analysis for the facility design satisfying the radiation safety requirements as well as obtaining an operating license for the radiation facility according to a domestic nuclear commissioning procedure. The radiation shielding analysis was performed using the MCNPX computational particle transport code. The radiation source terms in the facility were evaluated and utilized in the shielding calculations. The minimum concrete thickness satisfying the designated dose rate of 5 μSv/h for the worker's area and 0.25 μSv/h for the public area were estimated and applied to the design. For an assessment of the radiation safety inside the facility, the dose rates were evaluated at several positions, such as behind the shielding door, around the primary barriers near the radiation sources, and in the penetrations of the ducts. The dose rate distribution was mapped for verification of the radiation safety for the entire facility. An activation analysis was carried out for the concrete walls, air, target assembly, beryllium target, and cooling water using FISPACT-2010 code. Concentrations of the activation products and dose rate induced by the radionuclides after shutdown were evaluated for the purpose of safe operation of the facility. The results were reviewed with the radiation safety regulations in Korea. As a result, it was proved that the final facility design satisfies the safety requirements.

D005160:Facility Design and Construction

Proton accelerator
Boron Neutron Capture Therapy
Radiation shielding analysis
Activation analysis
Monte Carlo simulation


Social Media as a Tool to Promote Health Awareness: Results from an Online Cervical Cancer Prevention Study.

Abstract: Online social media platforms represent a promising opportunity for public health promotion. Research is limited, however, on the effectiveness of social media at improving knowledge and awareness of health topics and motivating healthy behavior change. Therefore, we investigated whether participation in an online social media platform and receipt of brief, tailored messages is effective at increasing knowledge, awareness, and prevention behaviors related to human papillomavirus (HPV) and cervical cancer. We conducted an online study in which 782 recruited participants were consecutively assigned to nine-person groups on a social media platform. Participants were shown a unique random set of 20 tailored messages per day over five days. Participants completed a baseline and post survey to assess their knowledge, awareness, and prevention behaviors related to HPV and cervical cancer. There were no statistically significant changes in knowledge and prevention behaviors from the baseline to the post survey among study participants. There was a modest, statistically significant change in response to whether participants had ever heard of HPV, increasing from 90 to 94% (p = 0.003). Our findings suggest that most study participants had substantial knowledge, awareness, and engagement in positive behaviors related to cervical cancer prevention at the start of the study. Nevertheless, we found that HPV awareness can be increased through brief participation in an online social media platform and receipt of tailored health messages. Further investigation that explores how social media can be used to improve knowledge and adoption of healthy behaviors related to cervical cancer is warranted.

D007722:Health Knowledge, Attitudes, Practice

Social media
Health awareness
Cervical cancer prevention
Health promotion


Apolipoprotein A-1 mimetic peptide 4F promotes endothelial repairing and compromises reendothelialization impaired by oxidized HDL through SR-B1.

Abstract: Disruption of endothelial monolayer integrity is the primary instigating factor for many cardiovascular diseases. High density lipoprotein (HDL) oxidized by heme enzyme myeloperoxidase (MPO) is dysfunctional in promoting endothelial repair. Apolipoprotein A-1 mimetic 4F with its pleiotropic benefits has been proven effective in many in vivo models. In this study we investigated whether 4F promotes endothelial repair and restores the impaired function of oxidized HDL (Cl/NO2-HDL) in promoting re-endothelialization. We demonstrate that 4F and Cl/NO2-HDL act on scavenger receptor type I (SR-B1) using human aorta endothelial cells (HAEC) and SR-B1 (-/-) mouse aortic endothelial cells. Wound healing, transwell migration, lamellipodia formation and single cell migration assay experiments show that 4F treatment is associated with a recovery of endothelial cell migration and associated with significantly increased endothelial nitric oxide synthase (eNOS) activity, Akt phosphorylation and SR-B1 expression. 4F increases NO generation and diminishes oxidative stress. In vivo, 4F can stimulate cell proliferation and re-endothelialization in the carotid artery after treatment with Cl/NO2-HDL in a carotid artery electric injury model but fails to do so in SR-B1(-/-) mice. These findings demonstrate that 4F promotes endothelial cell migration and has a potential therapeutic benefit against early endothelial injury in cardiovascular diseases.

He|Dan|D|
Zhao|Mingming|M|
Wu|Congying|C|
Zhang|Wenjing|W|
Niu|Chenguang|C|
Yu|Baoqi|B|
Jin|Jingru|J|
Ji|Liang|L|
Willard|Belinda|B|
Mathew|Anna V|AV|
Chen|Y Eugene|YE|
Pennathur|Subramaniam|S|
Yin|Huiyong|H|
He|Yuan|Y|
Pan|Bing|B|
Zheng|Lemin|L|


Modeling pharmaceutical emissions and their toxicity-related effects in life cycle assessment (LCA): A review.

Abstract: Over the last few decades, worldwide detection of active pharmaceutical ingredients (APIs) in aquatic environments and the associated toxicological effects on wildlife and human health have become a matter of public and scientific debate. While life cycle assessment (LCA) and life cycle impact assessment (LCIA) models are increasingly used to assess the potential eco- and human-toxicological effects of chemical emissions, few studies have looked into the issue of modeling pharmaceutical emissions specifically and their toxicity-related effects in an LCA context. This paper reviews the state of the art to inventory and characterize API emissions in LCA with the goal to identify relevant gaps and challenges. A search for 208 environmentally relevant APIs in 2 life cycle inventory (LCI) databases revealed a meager representation of this group of chemicals. Similarly, the LCIA model USEtox was found to include characterization factors (CFs) for less than 60 APIs. First approaches to model API emissions in LCA were identified on the basis of an examination of 40 LCA case studies in the pharmaceutical sector and in the field of wastewater treatment. Moreover, CFs for 79 additional APIs, expressing their ecotoxicity and/or human toxicity potential, were gathered from literature. An analysis of the variability of API-CFs in different LCIA models showed a variation of about 2-3 orders of magnitude. Based on the review results, 3 main gaps in the modeling and characterization of API emissions in an LCA context were identified: (1) incomplete modeling of API flows and API emissions along the life cycle of human pharmaceuticals, especially during their use and end-of-life phase, (2) limited API coverage in existing LCIA toxicity models, and (3) missing pharma-specific impact pathways (e.g., endocrine disruption and antibiotic resistance) in existing LCIA models. Recommendations to tackle these gaps are provided, and priority action steps are discussed. Integr Environ Assess Manag 2019;15:6-18. © 2018 SETAC.

Emara|Yasmine|Y| Lehmann|Annekatrin|A| Siegert|Marc-William|MW| Finkbeiner|Matthias|M|

D054750:Ecotoxicology
D004784:Environmental Monitoring
D008956:Models, Chemical
D004364:Pharmaceutical Preparations
D018570:Risk Assessment
D014874:Water Pollutants, Chemical

Pharmaceuticals
Life cycle impact assessment
Life cycle inventory
Ecotoxicity
Human toxicity


Detection of circulating tumor DNA by digital droplet PCR in resectable lung cancer as a predictive tool for recurrence.

Abstract: Lung cancer is the leading cause of cancer-related mortality worldwide due to difficulties in early detection and high postsurgical recurrence rate. Current European Guidelines recommend follow-up via computerized tomography (CT) scans on regular basis within the first 2 years after radical surgical resection. Despite these efforts, recurrence rates remain high with 30-70 %. Therefore, it is imperative to develop predictive markers for metastases and postsurgical recurrence using minimally invasive methods. This prospective study aims at defining the feasibility of detecting circulating tumor DNA (ctDNA) in presurgical plasma samples of patients with lung cancer by digital droplet PCR. Resected tumor tissue and simultaneous blood samples were collected from 24 patients with lung cancer in stage I-IIIA (12 stage I, 8 stage II, 4 stage III). Genomic DNA from the tumor tissue samples were analyzed for hotspot mutations using a 17 gene panel next-generation sequencing (NGS) assay. CtDNA from corresponding plasma samples were analyzed using digital droplet PCR (ddPCR). Additionally, DNA sequencing results were correlated with patients' outcome. At least one somatic mutation was detected by NGS (96 %) in 23 of the tested tissue samples. DdPCR detected mutations in circulating cell-free DNA (ccfDNA) of nine patients' samples (9/23, 39 %). Postsurgical outcome analysis was performed for those patients who had received complete tumor resection (n = 21). Four of them suffered from an early relapse within the first two years after surgery, including two with detectable somatic mutations in ccfDNA during primary staging. Taken together, we showed that the 17 gene panel assay revealed in 23 of 24 patients at least one somatic mutation in the primary tumor by NGS. Tumor-specific mutation was detectable in 39 % from the blood of early stage lung cancer patients by ddPCR.

Gassa|Asmae|A| Fassunke|Jana|J| Schueten|Sarah|S| Kuhlmann|Luca|L| Scherer|Marie|M| Qien|Jie|J| Zhao|Yue|Y| Michel|Max|M| Loeser|Heike|H| Wolf|Juergen|J| Buettner|Reinhard|R| Doerr|Fabian|F| Heldwein|Matthias|M| Hagmeyer|Lars|L| Frank|Konrad|K| Merkelbach-Bruse|Sabine|S| Quaas|Alexander|A| Bruns|Christiane|C| Hekmat|Khosro|K| Weiss|Jonathan|J| Wahlers|Thorsten|T| Alakus|Hakan|H|

Digital droplet PCR
Next-generation sequencing
Cell-free DNA
Early stage lung cancer
Liquid biopsy


Recent advances in polysaccharides stabilized emulsions for encapsulation and delivery of bioactive food ingredients: A review.

Abstract: Many bioactive food ingredients were encapsulated in different forms to improve their stability and bioavailability. Emulsions have showed excellent properties in encapsulation, controlled release, and targeted delivery of bioactives. Polysaccharides are widely available and have different structures with different advantages including non-toxic, easily digested, biocompatible and can keep stable over a wide range of pH and temperatures. In this review, the most common polysaccharides and polysaccharide based complexes as emulsifiers to stabilize emulsions in recent ten years are described. The close relationships between the types and structures of polysaccharides and their emulsifying capacities are discussed. In addition, the absorption and bioavailability of bioactive food components loaded in polysaccharide stabilized emulsions are summarized. The main goal of the review is to emphasize the important roles of polysaccharides in stabilizing emulsions. Moreover, speculations regarded to some issues for the further exploration and possible onward developments of polysaccharides stabilized emulsions are also discussed.

Zhang|Ruyuan|R| Belwal|Tarun|T| Li|Li|L| Lin|Xingyu|X| Xu|Yanqun|Y| Luo|Zisheng|Z|

D001682:Biological Availability
D045703:Emulsifying Agents
D004655:Emulsions
D000074385:Food Ingredients
D010316:Particle Size
D011134:Polysaccharides
D013499:Surface Properties

Polysaccharides
Stability
Emulsions
Bioactive food ingredients
Bioavailability


Synergistic dark and photo-fermentation continuous system for hydrogen production from molasses by Clostridium acetobutylicum ATCC 824 and Rhodobacter capsulatus DSM 1710.

Abstract: This study investigated synergistic dark and photo-fermentation using continuous fermentation system (CFS). The system relies on connecting several fermenters from bottom of one to top culture level of the next in a manner that allows for delaying movement of the substrate and thus for its full consumption. While H2 was collected, CFS allowed for moving liquid byproducts toward the outlet and hence continuous productivity. CFS could be efficiently used for: (1) Continuous dark and photo-fermentation H2 production by Clostridium acetobutylicum and Rhodobacter capsulatus producing 5.65moleH2mole-1 hexose; (2) Continuous dark-fermentation synergistic H2, acetone, butanol and ethanol (ABE) production by C. acetobutylicum which produced per mole hexose, 2.43mol H2 along with 73.08g ABE (3) Continuous H2 and methane production by C. acetobutylicum and bacterial sludge producing, per mole hexose, 1.64mol pure H2 and 2.56mol CH4 mixed with 0.37mol H2·The hydraulic retention time (HRT) for whole system was short where organic acids produced in dark-fermentation in first fermenter were synergistically utilized for H2 production by R. capsulatus in subsequent fermenters. CFS is suitable for fast-digestible sugars but not lignocelluloses or other hard-digestible organics, requiring prolonged HRT, unless such polymeric organics were hydrolyzed prior to fermentation.

Hydrogen Fermentation Acetone Butanol Ethanol Methane


Microemulsion-based synergistic dual-drug codelivery system for enhanced apoptosis of tumor cells.

Abstract: A microemulsion-based synergistic dual-drug codelivery system was developed for enhanced cell apoptosis by transporting coix seed oil and etoposide into A549 (human lung carcinoma) cells simultaneously. Results obtained by dynamic light scattering showed that an etoposide (VP16)-loaded coix seed oil microemulsion (EC-ME) delivery system had a small size around 35 nm, a narrow polydispersity index, and a slightly negative surface charge. The encapsulating efficiency and total drug loading rate were 97.01% and 45.48%, respectively, by high-performance liquid chromatography. The release profiles at various pH values showed an obvious pH-responsive difference, with the accumulated amount of VP16 released at pH 4.5 (and pH 5.5) being 2.7-fold higher relative to that at pH 7.4. Morphologic alteration (particle swelling) associated with a mildly acidic pH environment was found on transmission electron microscopy. In the cell study, the EC-ME system showed a significantly greater antiproliferative effect toward A549 cells in comparison with free VP16 and the mixture of VP16 and coix seed oil. The half-maximal inhibitory concentration of the EC-ME system was 3.9-fold and 10.4-fold lower relative to that of free VP16 and a mixture of VP16 and coix seed oil, respectively. Moreover, fluorescein isothiocyanate and VP16 (the green fluorescent probe and entrapped drug, respectively) were efficiently internalized into the cells by means of coix seed oil microemulsion through intuitive observation and quantitative measurement. Importantly, an EC-ME system containing 20 μg/mL of VP16 showed a 3.3-fold and 3.5-fold improvement in induction of cell apoptosis compared with the VP-16-loaded microemulsion and free VP16, respectively. The EC-ME combination strategy holds promise as an efficient drug delivery system for induction of apoptosis and treatment of lung cancer.

Qu|Ding|D| Ma|Yihua|Y| Sun|Wenjie|W| Chen|Yan|Y| Zhou|Jing|J| Liu|Congyan|C| Huang|Mengmeng|M|

dual-drug codelivery
coix seed oil
microemulsion
apoptosis induction
synergistic effect


Preservation of deep-layer fat of lateral zones prevents postoperative seroma after TRAM-flap harvesting for breast reconstruction: a retrospective study.

Abstract:
OBJECTIVE
The present study elucidates whether or not preserving fat tissues deeper than the Scarpa's fascia in zone 3 and zone 4 reduces postoperative fluid collection after harvesting the transverse rectus-abdominis muscle (TRAM) flap.

METHODS
Thirty-one patients for whom breast reconstruction with free TRAM flaps had been performed were included in the study. Fat tissues deeper than the Scarpa's fascia in zone 3 and zone 4 were addressed in two ways. With 17 patients, these tissues were preserved on the abdominal wall; with 14 patients, these fat tissues were harvested as part of the TRAM flap. The former and latter groups were named the Preservation Group and Non-Preservation Group, respectively. Drainage tubes were placed at the donor site until daily drainage became less than 20 ml, at which time the tubes were removed. The total amount of postoperative fluid drained from the donor site and the days required before tube removal were compared between the two groups.

RESULTS
The total volume of drained fluid was significantly greater for the Non-Preservation Group (444 ± 48.2 ml) than for the Preservation Group (230 ± 21.9 ml); the period before removal of drainage tubes was significantly longer for the Non-Preservation Group (12.4 ± 0.84 days) than for the Preservation Group (7.6 ± 0.55 days).

CONCLUSION
Preservation of deep-fat tissues in zone 3 and zone 4 reduces postoperative fluid exuded from the donor site, and enables earlier removal of drainage tubes. For cases where optimal breast shape can be achieved without these fat tissues, the fat tissues should be preserved.

Nagasao|Tomohisa|T| Tamai|Motoki|M| Moromomi|Tadaaki|T| Miki|Takanori|T| Kogure|Tetsukuni|T| Hamamoto|Yusuke|Y| Kudo|Hiroo|H| Tanaka|Yoshio|Y|

fat
Breast
reconstruction
TRAM flap
drainage
complication


Characterization of thrombin/factor Xa inhibitors in Rhizoma Chuanxiong through UPLC-MS-based multivariate statistical analysis.

Abstract:
Background
The dry root and rhizome of Ligusticum chuanxiong Hort., or Chuanxiong, has been used as a blood-activating and stasis-removing traditional Chinese medicine for 1000 years. Our previous studies have shown the inhibitory activity on platelet and thrombin (THR) of Chuanxiong. THR and factor Xa (FXa) play significant roles in the coagulation cascade and their inhibitors are of valuable in the treatment of thromboembolic diseases. The aim of the present study is to screen THR and FXa inhibitors from Chuanxiong.

Methods
Four extracts [ethyl acetate (EA), butanol (BA) and remained extract (RE) from 75% ethanol extract, and water extract (WE)] of Chuanxiong were prepared, and their THR/FXa inhibitory activities were assessed in vitro. Following silica-gel column chromatography (SC), the active EA extract and BA extract was further partitioned, respectively. Their active fractions (EA-SC1 to EA-SC5; BA-SC1 to BA-SC5) were obtained and analyzed by LC-MS. After modeling by the principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA), the specific marker compounds were predicted and identified. Their enzyme inhibitory was assessed in vitro and interactions with THR/FXa were investigated by molecular docking analysis.

Results
Chuanxiong EA extract showed strong activity against THR and BA extract was more effective in inhibiting FXa activity, and their fractions exhibited obvious difference in enzyme inhibitory activity. Furthermore, marker compounds a-h were predicted by PCA and OPLS-DA, and their chemical structures were identified. Among them, senkyunolide A, Z-ligustilide, ferulic acid and senkyunolide I (IC50 was determined as 0.77 mM) with potential THR inhibitory activity, as well as isochlorogenic acid A with FXa inhibitory activity were screened out. It was found that the four components could interact with the active site of THR, and the binding energy was lower than - 5 kcal/mol. Isochlorogenic acid A were bound to the active site of FXa, and the binding energy was - 9.39 kcal/mol. The IC50 was determined as 0.56 mM.

Conclusions
THR/FXa inhibitory components in different extracts of Chuanxiong were successfully characterized by the method of enzyme inhibition activity assays with ultra performance liquid chromatography-quadrupole time of flight mass spectrometry-based multivariate statistical analysis.

Yang|Yi-Yao|YY| Wu|Zhao-Yu|ZY| Xia|Fang-Bo|FB| Zhang|Hao|H| Wang|Xu|X| Gao|Jian-Li|JL| Yang|Feng-Qing|FQ|0000-0002-9300-5710 Wan|Jian-Bo|JB|

Thrombin
Factor Xa
Chuanxiong
Multivariate statistical analysis
Molecular docking
Enzyme inhibitor


Minerals in thalassaemia major patients: An overview.

Abstract: Thalassaemia major (TM) is a hereditary blood disease characterised by reduced or absent production of beta globin chains. Erythrocyte transfusions are given to raise the haemoglobin level in patients with thalassaemia major. However, transfusions have been related to increased risk of iron overload and tissue damage related to excess iron. Both elevated oxidative stress due to iron overload and increased hemolysis lead to over utilisation of minerals required for antioxidant enzymes activities. Iron chelators have been used to prevent iron overload in thalassaemia major patients, but these chelators have the possibility of removing minerals from the body. Thalassaemia patients are more at risk for mineral deficiency because of increased oxidative stress and iron chelation therapies. Growth and maturational delay, cardiomyopathy, endocrinopathies and osteoporosis are the complications of thalassaemia. Minerals may play a particular role to prevent these complications. In the current review, we provide an overview of minerals including zinc (Zn), copper (Cu), selenium (Se), magnesium (Mg) and calcium (Ca) in thalassaemia major patients. We, also, underline that some complications of thalassaemia can be caused by an increased need for minerals or lack of the minerals.

Ozturk|Zeynep|Z|
Genc|Gizem Esra|GE|
Gumuslu|Saadet|S|

Mineral
Thalassaemia
Iron
Zinc
Selenium
Trace element


Resurrection of the Island Rule: Human-Driven Extinctions Have Obscured a Basic Evolutionary Pattern.

Abstract: Islands are or have been occupied by unusual species, such as dwarf proboscideans and giant rodents. The discussion of the classical but controversial island rule-which states that mammalian body sizes converge on intermediate sizes on islands-has been stimulated by these unusual species. In this study, we use an unprecedented global data set of the distributions and body sizes of late Quaternary mammal species and a novel analytical method to analyze body size evolution on islands. The analyses produced strong support for the island rule. Islands have suffered massive human-driven losses of species, and we found that the support for the island rule was substantially stronger when the many late Quaternary extinct species were also considered (particularly the tendency for dwarfing in large taxa). The decisive support for the island rule in this study confirms that evolution plays out in a markedly different way on islands and that human impact may obscure even fundamental evolutionary patterns.

islands
body size
mammals
evolution
Anthropocene


Scandcleft trial of primary surgery for unilateral cleft lip and palate: Craniofacial cephalometrics at 8 years.

Abstract:
BACKGROUND
The Scandcleft trial is a randomized controlled trial that includes children with unilateral cleft lip and palate where registrations are standardized and therefore provides the opportunity to describe craniofacial characteristics in a very large sample of patients.

OBJECTIVES
The aim of this study was to describe craniofacial growth and morphology in a large study sample of 8-year-old children with unilateral cleft lip and palate (UCLP); before orthodontic treatment and before secondary alveolar bone grafting; and to compare the cephalometric values with age-matched non-cleft children from previous growth studies to identify the differences between untreated cleft- and non-cleft children.

MATERIALS
There are 429 eight-year-old UCLP patients in the Scandcleft study group. A total of 408 lateral cephalograms with a mean age of 8.1 years were analysed. Cephalometric analyses were performed digitally. The results from three previously published growth studies on non-cleft children were used for comparison.

RESULTS
Cephalometric analyses showed a large variation in craniofacial morphology among the UCLP group. In general, they present with significant maxillary retrusion and reduced intermaxillary relationships compared to the age-matched non-cleft children. In addition, the vertical jaw relationship was decreased, mainly due to decreased maxillary inclination. The upper and lower incisors were retroclined. It can be expected that these differences will increase in significance as the children age.

CONCLUSION
Results from this study provide proposed norms for the young UCLP before any orthodontic treatment and can be valuable for the clinician in future treatment planning.

TRIAL REGISTRATION
ISRCTN29932826.

Scandcleft
unilateral cleft lip and palate
randomized controlled trials
craniofacial growth
Lateral cephalograms
cephalometry


Redox-sensitive mPEG-SS-PTX/TPGS mixed micelles: An efficient drug delivery system for overcoming multidrug resistance.

Abstract: The main cause of multidrug resistance (MDR) is overexpression of active efflux transporters, such as P-glycoprotein (P-gp). To reverse MDR and improve the chemotherapy effect of paclitaxel (PTX), we propose a new drug delivery system based on mixed micelles constructed with d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and the mPEG-SS-PTX conjugate with consideration that TPGS is a P-gp inhibitor that can block the cancer cell action of pumping drugs outside of cells and can enhance the anticancer effect. mPEG-SS-PTX is synthesized by conjugating hydrophilic mPEG with a hydrophobic drug, PTX, via a redox-sensitive disulfide bond. The mPEG-SS-PTX conjugate is amphiphilic and can self-assemble in water. Mixed micelles formed by the mPEG-SS-PTX conjugate and TPGS have a low critical micelle concentration (CMC, ∼1.05×10-3mg/mL) and high drug loading content (∼19.6%). The disulfide bond in the mPEG-SS-PTX conjugate can be broken in cancer cells (a reductive environment) and release PTX to kill cancer cells. In vitro cytotoxicity and cell uptake suggest that mixed micelles can effectively improve the accumulation of PTX in multidrug-resistant MCF-7 cells. Therefore, the present as-prepared mixed micelles very effectively reverse the MDR and enhance the therapeutic effect.

Zhao|Dujuan|D| Zhang|Huiyuan|H| Yang|Shengfeng|S| He|Wenxiu|W| Luan|Yuxia|Y|

D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1

Redox-sensitive
TPGS
Multidrug resistance
Polymer-drug conjugate


Spatial Heterogeneity of Vibrio spp. in Sediments of Chinese Marginal Seas.

Abstract: Vibrio spp. are ubiquitous marine bacteria with high metabolism flexibility and genome plasticity. Previous studies have revealed the dynamics of planktonic vibrios in relation to environmental forces, such as temperature and salinity. However, little is known about Vibrio ecology in benthic environments. Here, we elucidate the abundance, diversity, and spatial distribution of Vibrio spp. in sediments of the Chinese marginal seas, with a wide spatial range from north to south covering the Yellow Sea (YS), East China Sea (ECS), and South China Sea (SCS). Quantitative analysis showed that Vibrio spp. were most abundant in the SCS (∼9.04 × 105 copies/g) compared to the YS (∼1.00 × 105 copies/g) and ECS (∼8.86 × 105 copies/g). Vibrio community compositions derived from Illumina sequencing of Vibrio-specific 16S rRNA genes varied significantly between sampling areas, which was reflected by a strong distance-decay pattern. The spatial distribution of Vibrio was governed by a joint effect of spatial and environmental factors (especially temperature, salinity, and SiO3 2-), and their respective pure effects explained only a small fraction of the community variation. Moreover, we identified the most prominent operational taxonomic units (OTUs) that were partitioned in these sea areas. Whereas Vibrionaceae OTU20 and Photobacterium lipolyticum were prevalent in the YS, Vibrio gigantis and Photobacterium piscicola, and P. piscicola, Photobacterium lutimaris, and Photobacterium alginatilyticum were prevalent in the ECS and SCS, respectively. Our study demonstrated clear spatial heterogeneity of Vibrio spp. in sediments of the Chinese marginal seas, laying a foundation for fully understanding the marine Vibrio ecology and the ecological roles of the species.IMPORTANCE Vibrio is an important component of natural marine microbial populations in terms of pathogenicity and roles in carbon cycling. Compared to the marine pelagic environment, our knowledge of the diversity and distribution pattern of Vibrio spp. in sediment is limited. Here, we show higher Vibrio abundance in Chinese marginal seas than in other studied sediments. There was a clear spatial differentiation of Vibrio abundance and community composition in different sea areas. The benthic Vibrio community displayed a strong distance-decay pattern across a wide spatial range, which was formed under the combined effects of spatial and environmental factors. These results provide deep insights into the ecological dynamics of Vibrio and its environmental controls, facilitating a more comprehensive understanding of the marine Vibrio ecology.

Wang|Xiaolei|X| Liu|Jiwen|J| Li|Bei|B| Liang|Jinchang|J| Sun|Hao|H| Zhou|Shun|S| Zhang|Xiao-Hua|XH|

spatial heterogeneity
Vibrio
sediments
Chinese marginal seas


Effect of Group Cognitive Behavioural Therapy on Loneliness in a Community Sample of Older Adults: A Secondary Analysis of a Randomized Controlled Trial.

Abstract:
OBJECTIVES
Research suggests a link between loneliness, depression, and anxiety. Multiple studies have examined treatment programs for loneliness; however, none have examined the efficacy of Cognitive Behavioral Therapy (CBT) for depression and anxiety in reducing loneliness.

METHODS
Change in loneliness in sixty-two older adults (≥60 yrs; 65% female) who took part in a previously reported randomized controlled trial for the treatment of comorbid depression and anxiety was examined. Older adults were randomized to a 12-week group CBT or waitlist control condition. Participants who took part in CBT were followed-up three months later.

RESULTS
Linear Mixed Model analyses indicated that after controlling for baseline cognition, depression, and anxiety, participants who completed CBT experienced a significant decrease in loneliness while the control group did not. This reduction was maintained at follow-up.

CONCLUSIONS
CBT programs for depression and anxiety are likely to be effective at reducing loneliness. This may be due to shared underlying cognitive and behavioral mechanisms between loneliness, depression, and anxiety such as sensitivity to perceived threat and social withdrawal. Further research is needed to understand if specific loneliness interventions are more effective.

CLINICAL IMPLICATIONS
CBT may be effective at reducing loneliness among older adults with depression and anxiety.

Loneliness
older adults
depression
anxiety
Cognitive Behavioral Therapy


Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress.

Abstract:
AIM
To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage.

METHODS
Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay.

RESULTS
CD11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin.

CONCLUSION
Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.

de Souza|Veruska Cintia Alexandrino|VCA|

de Castro|Maria Carolina Accioly Brelaz|MCAB|

Figueiredo|Regina Celia Bressan Queiroz|RCBQ|

Monocytes
Liver fibrosis
Glutathione
Bone marrow mononuclear cells
Cell therapy
Macrophages


Cystic fibrosis prevalence among a group of high-risk children in the main referral children hospital in Iran.

Abstract:
BACKGROUND
Knowledge about cystic fibrosis (CF) in Iran is very limited. The objective of this study was to determine the prevalence of CF among a group of high-risk children with suggestive clinical features in the main referral hospital in Iran.

MATERIALS AND METHODS
This study children consisted of 505 patients who had presented with one or more of the following symptoms: chronic or recurrent respiratory symptoms, gastrointestinal symptoms as rectal prolapse, steatorrhea, hepatobiliary disease as prolonged jaundice, failure to thrive, hyperglycemia and glycosuria, hypochloremic metabolic alkalosis, hypoprothrombinemia, anemia or edema, and positive family history of CF. Patients were screened using pilocarpine iontophoresis to collect sweat and chemical analysis of its chloride content with classic Gibson and Cooke technique.

RESULTS
Of 505 patients, 89 (17.6%) had positive sweat chloride screening test. Five (1%) patients had required cystic fibrosis transmembrane conductive regulator protein mutation analysis to confirm CF.

CONCLUSION
Our findings suggest that in Iran, CF is more common than what previously anticipated. Larger studies are warranted to identify the incidence, molecular basis, and clinical pattern of CF in the Iranian population.

Modaresi|Mohammad Reza|MR|
Faghinia|Jamal|J|
Reisi|Mohsen|M|
Keivanfar|Majid|M|
Navaie|Shiva|S|
Seyyedi|Javad|J|
Baharzade|Faride|F|


Educational outcomes necessary to enter pharmacy residency training.

Abstract: It is the position of the American College of Clinical Pharmacy (ACCP) that formal postgraduate residency training, or equivalent experience, is required to enter direct patient care practice. Therefore, it is important to align professional degree educational outcomes with the knowledge, skills, and attitudes needed to enter residency training. This position statement addresses the outcomes necessary in the professional degree program curriculum to ensure the ability of pharmacy graduates to transition effectively into postgraduate year one residency training. Five key outcome areas are identified: communication, direct patient care, professionalism, research, and practice management. The position statement examines how performance in each of the five outcome areas should be addressed by professional degree programs. The ACCP believes that for the student to achieve the clinical proficiency necessary to enter residency training, the professional degree program should emphasize, assess, and provide adequate opportunities for students to practice: communication with patients, caregivers, and members of the health care team in direct patient care environments; provision of direct patient care in a wide variety of practice settings, especially those involving patient-centered, team-based care; professionalism under the supervision and guidance of faculty and preceptors who model and teach the traits of a health care professional; application of principles of research that engender an appreciation for the role of research and scholarship in one's professional development; and application of practice management, including documentation of direct patient care activities that affect drug-related outcomes.

Hester|Elizabeth Kelly|EK|
McBane|Sarah E|SE|
Bottorff|Michael B|MB|
Carnes|Tristan A|TA|
Dell|Kamila|K|
Gonyeau|Michael J|MJ|
Greco|Angelo J|AJ|
McConnell|Karen J|KJ|
Skaar|Debra J|DJ|
Splinter|Michele Y|MY|
Trujillo|Toby C|TC|

pharmacy residency
educational standards
experiential education
pharmacy curricula


Plastome phylogenomic study of Gentianeae (Gentianaceae): widespread gene tree discordance and its association with evolutionary rate heterogeneity of plastid genes.

Abstract:
BACKGROUND
Plastome-scale data have been prevalent in reconstructing the plant Tree of Life. However, phylogenomic studies currently based on plastomes rely primarily on maximum likelihood inference of concatenated alignments of plastid genes, and thus phylogenetic discordance produced by individual plastid genes has generally been ignored. Moreover, structural and functional characteristics of plastomes indicate that plastid genes may not evolve as a single locus and are experiencing different evolutionary forces, yet the genetic characteristics of plastid genes within a lineage remain poorly studied.

RESULTS
We sequenced and annotated 10 plastome sequences of Gentianeae. Phylogenomic analyses yielded robust relationships among genera within Gentianeae. We detected great variation of gene tree topologies and revealed that more than half of the genes, including one (atpB) of the three widely used plastid markers (rbcL, atpB and matK) in phylogenetic inference of Gentianeae, are likely contributing to phylogenetic ambiguity of Gentianeae. Estimation of nucleotide substitution rates showed extensive rate heterogeneity among different plastid genes and among different functional groups of genes. Comparative analysis suggested that the ribosomal protein (RPL and RPS) genes and the RNA polymerase (RPO) genes have higher substitution rates and genetic variations among plastid genes in Gentianeae. Our study revealed that just one (matK) of the three (matK, ndhB and rbcL) widely used markers show high phylogenetic informativeness (PI) value. Due to the high PI and lowest gene-tree discordance, rpoC2 is advocated as a promising plastid DNA barcode for taxonomic studies of Gentianeae. Furthermore, our analyses revealed a positive correlation of evolutionary rates with genetic variation of plastid genes, but a negative correlation with gene-tree discordance under purifying selection.

CONCLUSIONS
Overall, our results demonstrate the heterogeneity of nucleotide substitution rates and genetic characteristics among plastid genes providing new insights into plastome evolution, while highlighting the necessity of considering gene-tree discordance into phylogenomic studies based on plastome-scale data.

Plastome
Gentianeae
Gene trees
Phylogenetic discordance
Nucleotide substitution rates
Phylogenetic informativeness
Coalescence
Gene characteristics


Hypnic Headache Responds to Topiramate: A Case Report and a Review of Mechanisms of Action of Therapeutic Agents.

Abstract: Hypnic headaches are unique as they are exclusively nocturnal, occurring in rapid-eye movement (REM) and non-REM sleep. Their nocturnal nature suggests a role for cyclic mechanisms involving the hypothalamus despite conflicting imaging results for the role of the posterior hypothalamus. Nevertheless, pharmacological therapeutics acting as highly effective agents, such as caffeine and melatonin, can modulate the sleep-wake cycle. In addition, indole agents such as indomethacin that are anti-nociceptive and affect cerebral blood flow also prove to be efficacious. Gabanoids and topiramate also have reported efficacy. We report the case of a topiramate-responsive hypnic headache patient and outline in detail the potential mechanisms of topiramate and the other therapeutic agents and adumbrate on the neuronal networks of migraine, the trigeminal autonomic cephalgias and suggest a potential neural circuit for hypnic headaches.

headache disorders
medication therapy management


Polymicrobial Staphylococcus aureus bacteremia: Frequency, distinguishing characteristics and outcome.

Abstract: Staphylococcus aureus bacteremia (SAB) is usually monomicrobial (M-SAB). We reviewed SAB in adults (≥18years old) over a 13year-period and compared polymicrobial (P-SAB) and M-SAB. We encountered 93 P-SAB among 1537 SAB cases (6.1%). The source distribution was comparable; however, source-specified differences were apparent. P-SAB was noted in 12/58 (20.7%) necrotizing soft tissue infections/sacral decubiti and foot gangrene vs. 1/122 (0.8%) cellulitis/abscesses (P<0.001), in 7/64 (10.9%) femoral intravascular catheters (IVC) vs.16/376 (4.3%) IVC in other sites (P=0.03) and 15/134 (11.2%) healthcare-associated pneumonia (HAP) vs. 1/33 (3.0%) community-associated cases (P=0.1). Methicillin-resistance frequency was similar but community-associated SCCmec types (IV/V) were infrequent (17.9% vs. 34.2%; P=0.04). P-SAB was associated with higher mortality (50.5% vs. 24.2%; P<0.001) across nearly all sources. In summary, P-SAB is infrequent, usually encountered in necrotizing soft tissue infections/decubiti, femoral IVC and possibly HAP. The actual incidence of S. aureus in these infections should be defined.

Khatib|Riad|R|
Sharma|Mamta|M|
Johnson|Leonard B|LB|
Riederer|Kathleen|K|
Briski|Laurence|L|

Polymicrobial
Staphylococcus aureus
Bacteremia


Jaw tumor in recurrent primary hyperparathyroidism: A case report.

Abstract:
BACKGROUND
Brown tumor may present as uni/multilocular osteolytic lesions with bone expansion, bone pain or pathologic fracture in primary, secondary and tertiary hyperparathyroidism. However, recently, such presentation is rare due to early detection using blood screening techniques before symptomatic bone lesions appear.

CASE REPORT
A 65-year-old woman was admitted to our hospital with generalized bone pain and a progressive painless mass in her jaw appeared since 6 months ago. She had a history of two times parathyroidectomy. In recent hospitalization, she presented with the complaint of weakness, bone pain and a progressive swelling in her jaw. Laboratory analysis showed a hypercalcemia and plasma PTH of 398 pg/ml. Dual energy X-ray (DXA) showed osteoporosis at the neck of hip and lumbar spine. The neck MRI revealed an 11 * 6 mm soft tissue nodule posterior to left thyroid lobe and a 20*18 mm T2 hypersignal, T1hyposignal nodule at right thyroid lobe. The SPECT-CT scintigraphy with 99mTc-MIBI was suggestive of bilateral parathyroid adenomas and/or parathyroid hyperplasia and showed a MIBI- avid lytic lesion in the mandible. Surgical management was performed. After removing the adenoma the PTH marked a decrease from the initial value to 57 pg/ml. The histological examination revealed the thyroid tissue with MNG and a left parathyroid adenoma. Follow-up after surgery revealed normal blood calcium and urine calcium levels with no increase. PTH levels also did not increase. The patient was treated with calcium and vitamin D supplements and the jaw mass decreased gradually.

CONCLUSIONS
Primary or secondary HPT may be recognized by the presence of an osteolytic lesion with giant cells, a condition referred as brown tumor. Consideration should be made that non-specificity of hypercalcemia symptoms can also be a bone tumor including jaw lesion as a manifestation of hyperparathyroidism.

Amini Nezhad|Farzaneh|F|
Payab|Moloud|M|
Nayebandi|Sara|S|
Hasani-Ranjbar|Shirin|S|

Hyperparathyroidism
Brown tumor
Hypercalcemia
Hyperparathyroidism jaw-tumor syndrome


Rapid formation and rupture of an infectious basilar artery aneurysm from meningitis following suprasellar region meningioma removal: a case report.

Abstract:
BACKGROUND
Infectious basilar artery (BA) aneurysm has been occasionally reported to be generated from meningitis following transcranial operation. However, infectious BA aneurysm formed by intracranial infection after endoscopic endonasal operation has never been reported.

CASE PRESENTATION
A 53-year-old man who was diagnosed with suprasellar region meningioma received tumor removal via endoscopic endonasal approach. After operation he developed cerebrospinal fluid (CSF) leak and intracranial infection. The patient ultimately recovered from infection after anti-infective therapy, but a large fusiform BA aneurysm was still formed and ruptured in a short time. Interventional and surgical measures were impossible due to the complicated shape and location of aneurysm and state of his endangerment, therefore, conservative anti-infective therapy was adopted as the only feasible method. Unfortunately, the aneurysm did not disappear and the patient finally died from repeating subarachnoid hemorrhage (SAH).

CONCLUSION
Though extremely rare, it was emphasized that infectious aneurysm can be formed at any stage after transnasal surgery, even when the meningitis is cured. Because of the treatment difficulty and poor prognosis, it was recommended that thorough examination should be timely performed for suspicious patient to make correct diagnosis and avoid fatal SAH.

Wang|Xu|X| Chen|Ge|G| Li|Mingchu|M| Liang|Jiantao|J| Guo|Hongchuan|H| Song|Gang|G| Bao|Yuhai|Y|

D057605:Natural Orifice Endoscopic Surgery

Bacterial meningitis
Endoscopic transnasal operation
Infectious intracranial aneurysms
Septic microemboli


Complete mitochondrial genomes provide current refined phylogenomic hypotheses for relationships among ten Hirundo species.

Abstract: Hirundo is the most species-rich genus of the passerine swallow family (Hirundinidae) and has a cosmopolitan distribution. Here we report the complete, annotated mitochondrial genomes for 25 individuals from 10 of the 14 extant Hirundo species; these include representatives from four subspecies of the barn swallow, H. rustica. Mitogenomes were conserved in size, ranging from 18,500 to 18,700 base pairs. They all contained 13 protein-coding regions, 22 tRNAs, a control region, and large and small ribosomal subunits. Phylogenetic analysis resolved most of the relationships between the studied species and subspecies which were largely consistent with previously published trees. Several new relationships were observed within the phylogeny that could have only been discovered with the increased amount of genetic material. This study represents the largest Hirundo mitochondrial phylogeny to date, and could serve as a vital tool for other studies focusing on the evolution of the Hirundo genus.

phylogenomic Hirundo mitogenome phylogenetic


Supply of and demand for assisted reproductive technologies in the United States: clinic- and population-based data, 1995-2010.

Abstract:
OBJECTIVE
To study national-level trends in assisted reproduction technology (ART) treatments and outcomes as well as the characteristics of women who have sought this form of infertility treatment.

DESIGN
Population-based study.

SETTING
Not applicable.

PATIENT(S)
For CDC: All reporting clinics from 1996-2010. For NSFG: for the logistic analysis, sample comprising 2,325 women aged 22-44 years who have ever used medical help to get pregnant, excluding women who used only miscarriage prevention services.

INTERVENTION(S)
None.

MAIN OUTCOME MEASURE(S)
CDC data (number of cycles, live birth deliveries, live births, patient diagnoses); and NSFG data (individual use of ART procedures).

RESULT(S)
Between 1995 and 2010, use of ART increased. Parity and age are strong predictors of using ART procedures. The other correlates are higher education, having had tubal surgery, and having a current fertility problem.

CONCLUSION(S)
The two complementary data sets highlight the trends of ART use. An increase in the use of ART services over this time period is seen in both data sources. Nulliparous women aged 35-39 years are the most likely to have ever used ART services.

Stephen|Elizabeth Hervey|EH|
Chandra|Anjani|A|
King|Rosalind Berkowitz|RB|

D006301:Health Services Needs and Demand

D010342:Patient Acceptance of Health Care

ever use of medical help to get pregnant


Intravital Imaging Allows Organ-Specific Insights Into Immune Functions.

Abstract: Leukocytes are among the most mobile and versatile cells that have many essential functions in homeostasis and survival. Especially cells from the innate immune system, i.e., neutrophils and macrophages, play an important role as rapid first responders against invading microorganisms. With the advent of novel imaging techniques, new ways of visualizing innate immune cells have become available in recent years, thereby enabling more and more detailed discoveries about their nature, function and interaction partners. Besides intravital spinning-disc and 2-photon microscopy, clearing and 3D-imaging techniques provide new insights into the mechanism of innate immune cell behavior in their natural environment. This mini review focuses on the contributions of novel-imaging techniques to provide insight into the functions of neutrophils and macrophages under homeostasis and in infections. Imaging setups for different organs like the liver, kidney, heart, lung, and the peritoneal cavity are discussed as well as the current limitations of these imaging techniques.

neutrophil
macrophage
liver
kidney
lung
peritoneal cavity
Intravital microscopy


The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses.

Abstract: Current clinical studies showed distinct therapeutic outcomes, in which CRC patients with mismatch repair-deficient (dMMR)/microsatellite instability high (MSI-H) seem to be relatively more "sensitive" in response to anti-programmed death-1 receptor (PD-1)/programmed death-1 receptor ligand 1 (PD-L1) therapy than those with mismatch repair-proficient (pMMR)/microsatellite instability-low (MSI-L). The mechanisms by which the same PD-1/PD-L1 blockades lead to two distinct therapeutic responses in CRC patients with different MSI statuses remain poorly understood and become a topic of great interest in both basic research and clinical practice. In this review of the potential mechanisms for the distinct response to PD-1/PD-L1 blockades between dMMR/MSI-H CRCs and pMMR/MSI-L CRCs, relevant references were electronically searched and collected from databases PubMed, MEDLINE, and Google scholar. Sixty-eight articles with full text and 10 articles by reference-cross search were included for final analysis after eligibility selection according to the guidelines of PRISMA. Analysis revealed that multiple factors e.g. tumor mutation burden, immune cell densities and types in the tumor microenvironment, expression levels of PD-1/PD-L1 and cytokines are potential determinants of such distinct response to PD-1/PD-L1 blockades in CRC patients with different MSI statuses which might help clinicians to select candidates for anti-PD-1/PD-L1 therapy and improve therapeutic response in patients with CRC.

colorectal cancer
therapy
immune checkpoint
inhibitor
metastasis


Ultrastructure of male reproductive system of Eurydema ventrale Kolenati 1846 (Heteroptera: Pentatomidae).

Abstract: The male reproductive system of Eurydema ventrale Kolenati 1846 is studied morphologically and histologically by using light, scanning and transmission electron microscopes. The reproductive system of the male E.ventrale consists of a pair of testis, a pair of vas deferens, a pair of seminal vesicles, accessory glands, a bulbus ejaculatorius, a pair of ectodermal sacs, and a ductus ejaculatorius. The testicular follicles have three different development zones (growth zone, maturation zone, and differentiation zone). The testes are connected to the seminal vesicles by the vas deferens that is a specialized in sperm storage. Sperm have an elongated head and a tail (flagellum) with an axonema and two mitochondrial derivatives. Vas deferens and seminal vesicles are fine, long, and cylindrical. The seminal vesicle is connected with bulbus ejaculatorius, which is balloon shaped and surrounded with accessory glands. The bulbus ejaculatorius is continuous with ductus ejaculatorius which is connected to the aedeagus.

ultrastructure heteroptera morphology histology spermatogenesis


An Efficient Numerical Algorithm for Exact Inference in Meta Analysis.

Abstract: The performance of commonly used asymptotic inference procedures for the random effects model used in meta analysis relies on the number of studies. When the number of studies is moderate or small, the exact inference procedure is more reliable than the asymptotic counterparts. However, the related numerical computation may be demanding and an obstacle of routine use of the exact method. In this paper, we proposed a novel numerical algorithm for constructing the exact 95% confidence interval of the location parameter in the random effects model. The algorithm is much faster than the naive method and may greatly facilitate the use of the more appropriate exact inference procedure in meta analysis. Numerical studies and real data examples are used to illustrate the advantage of the proposed method.

exact inference
Meta analysis
random effects model


Combining repurposed drugs to treat colorectal cancer.

Abstract: The drug development process, especially of antineoplastic agents, has become increasingly costly and ineffective. Drug repurposing and drug combination are alternatives to de novo drug development, being low cost, rapid, and easy to apply. These strategies allow higher efficacy, decreased toxicity, and overcoming of drug resistance. The combination of antineoplastic agents is already being applied in cancer therapy, but the combination of repurposed drugs is still under-explored in pre- and clinical development. In this review, we provide a set of pharmacological concepts focusing on drug repurposing for treating colorectal cancer (CRC) and that are relevant for the application of new drug combinations against this disease.

Drug repurposing
Drug combination
Chemotherapy
Colon cancer


Immunomodulation-A Molecular Solution to Treating Patients with Severe Bladder Pain Syndrome?

Abstract:
Background
Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available.

Objective
Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model. Treatment with an IL-1 receptor antagonist (IL-1RA) restored health in genetically susceptible mice, linking IL-1-dependent inflammation to pain and pathology in the bladder mucosa. The study objective was to investigate whether IL-1RA treatment might be beneficial in patients with bladder pain syndrome.

Design setting and participants
Patients diagnosed with bladder pain syndrome were invited to participate and subjected to daily IL-1RA injections for 1 wk, followed by a treatment break. Patients with other urological disorders accompanied by pain were included as controls.

Outcome measurements and statistical analysis
When symptoms returned, treatment was resumed and responding patients were maintained on treatment long term, with individualized dosing regimens. Symptom scores were recorded and molecular effects were quantified by neuropeptide and gene expression analysis. DNA samples were subjected to exome genotyping.

Results and limitations
IL-1RA treatment reduced bladder pain and the frequency of urination in 13/17 patients (p < 0.001). Substance P levels in urine were lowered, and responders returned to a more normal lifestyle. Neuroinflammatory-dependent and IL-1-dependent gene networks were inhibited, as well as regulators of innate immunity. Genotyping revealed disease-associated IL1R1, NLRP3, and IL1RN DNA sequence variants in the responders. Controls did not benefit from IL-1RA treatment, except for one patent with cystitis cystica.

Conclusions
In this clinical study, IL-1RA treatment is proposed to reduce chronic bladder pain, immediately and in the long term. Despite the limited number of study patients, the potent acute effect and lasting symptom relief indicate that this therapeutic approach may be worth exploring in controlled clinical trials.

Patient summary
Treatment with an interleukin-1 (IL-1) receptor antagonist is proposed for treating bladder pain syndrome, as it can result in symptom relief and increase quality of life. Reduced neuroinflammation and IL-1 signaling provided molecular evidence of the treatment effects.

Wullt|Björn|B|
Butler|Daniel S C|DSC|
Ambite|Ines|I|
Kinsolving|Julia|J|
Krintel|Christian|C|
Svanborg|Catharina|C|

Bladder pain syndrome
Immunotherapy
Interleukin-1 receptor antagonist
Interstitial cystitis


Designing a Clean Label Fish Patty with Olive, Citric, Pomegranate, or Rosemary Extracts.

Abstract: The natural functional ingredients derived from pomegranate (41.4% punicalagin), rosemary (5.8% carnosic acid and carnosol), hydroxytyrosol (7.3%), and citrus (55% hesperidin) fruits were combined separately with acerola (17% vitamin C) and essential oils rich in fatty acids (45% α-linolenic (ALA) and 40% docosahexaenoic (DHA)) provide a natural substitute of synthetic preservatives for fish patties, avoiding E-numbers on labels. Microbiological and physicochemical properties of the formulations were examined, sensory analysis was conducted, and changes in their shelf life due to storage for 14 days under chilled storage, adding these ingredients, were determined. The results obtained showed that the fish patties reported a high level of protein (14%), low fat (<2%), with a high contribution of phosphorus and selenium minerals, and higher levels of ALA up to 40% (in the case of rosemary extract (R)) and DHA by 30% (Ct), compared to the Control sample. The fish patties suffered microbiological, flavor, and odor spoilage and rapid lipid oxidation associated with rancidity. It can be said that the fish preparations have a duration of less than 7 days (between 4-6 days), except for the preparation with pomegranate extract (P) that has a longer life, from 7 to 11 days. Consequently, replacing synthetic additives by natural extracts offers a new clean label product with potential health benefits that resembles the commercial fish patties.

fish patties
hydroxytyrosol
citrus
Punica granatum
Rosmarinus officinalis
antioxidant
natural preservatives


Biomechanical Role of Bone Anisotropy Estimated on Clinical CT Scans by Image Registration.

Abstract: Image-based modeling is a popular approach to perform patient-specific biomechanical simulations. Accurate modeling is critical for orthopedic application to evaluate implant design and surgical planning. It has been shown that bone strength can be estimated from the bone mineral density (BMD) and trabecular bone architecture. However, these findings cannot be directly and fully transferred to patient-specific modeling since only BMD can be derived from clinical CT. Therefore, the objective of this study was to propose a method to predict the trabecular bone structure using a µCT atlas and an image registration technique. The approach has been evaluated on femurs and patellae under physiological loading. The displacement and ultimate force for femurs loaded in stance position were predicted with an error of 2.5% and 3.7%, respectively, while predictions obtained with an isotropic material resulted in errors of 7.3% and 6.9%. Similar results were obtained for the patella, where the strain predicted using the registration approach resulted in an improved mean squared error compared to the isotropic model. We conclude that the registration of anisotropic information from of a single template bone enables more accurate patient-specific simulations from clinical image datasets than isotropic model.

Taghizadeh|Elham|E| Reyes|Mauricio|M| Zysset|Philippe|P| Latypova|Adeliya|A| Terrier|Alexandre|A| Büchler|Philippe|P|

Anisotropy
Trabecular bone
Femur
Patella
Finite element analysis (FEA)