Glucose-Responsiveness of Pancreatic β-Like (GRP β-L) Cells Generated from Human Pluripotent Stem Cells.

Abstract: The International Diabetic Federation estimated that 415 million adults currently have diabetes and 318 million adults had impaired glucose tolerance, putting them at high risk of developing diabetes in the future. In Type 1 Diabetes (T1D), the β cells are lost because of autoimmune reactions. Although islet transplantation has been a promising therapy for T1D, it is greatly limited by pancreatic donors. Here, we describe a protocol to generate glucose- responsive pancreatic β-like (GRPβ-L) cells from human-induced pluripotent stem (iPS) cells. We recapitulate in vivo pancreas development by in vitro induction of differentiating human (iPS) cells with stage-specific signaling molecules and proteins. Inhibition of Tyrosine Kinase receptor AXL, TGF-β, and Notch signaling pathways in the final stage of the five-stage protocol could efficiently generate GRPβ-L from the endocrine progenitor. Differentiation of human iPS cells through the protocol could result in functional GRPβ-L cells, which could be used in pharmaceutical and β cell biology studies. © 2018 by John Wiley & Sons, Inc.

embryonic stem (ES) cell
induced pluripotent stem (iPS) cell
insulin
protocol to generate beta cells
β-like cells


Dorsogluteal intramuscular injection depth needed to reach muscle tissue according to body mass index and gender: A systematic review.

Abstract:
AIMS AND OBJECTIVE(S)
The objective of this systematic review was to determine the needle length required to reach the dorsogluteal muscle based on body mass index and sex. Our aim was to provide evidence-based recommendations to current intramuscular injection guidelines from the result(s) of this review.

BACKGROUND
Studies worldwide are documenting reduced medication effectiveness due to improperly placed dorsogluteal intramuscular injections because of incorrect needle length, wrong site selection and/or obesity. Current intramuscular injection guidelines lack specific instructions according to weight or sex. While there are similar concerns with other injectable sites, this review focuses solely on adult dorsogluteal intramuscular injections.

DESIGN
A systematic review of relevant literature of dorsogluteal intramuscular injections based on body mass index and sex.

METHODS
This systematic review was reported using the PRISMA checklist 2020. The review protocol was registered with Center for Open Science (OSF). We analysed 1,412 articles from nine databases. We compared twelve studies that utilised computerised tomography or ultrasonography using The Johns Hopkins Evidence-Based Practice Model and Guidelines.

RESULTS
A significant number of dorsogluteal intramuscular injections are administered into subcutaneous tissue rather than muscle because needles are too short for populations with body mass indexes over 25, especially women. Poor landmarking often results in improperly placed injections.

CONCLUSIONS
To prevent administering a dorsogluteal intramuscular injection into subcutaneous tissue, women with a BMI of 25 and over require needles longer than 38 mm (1.5 inches). Men have less subcutaneous tissue in the dorsogluteal area and only require longer needles if BMI is 35 and over. If skin-to-muscle depth is questionable in either sex, an ultrasound-guided intramuscular injection is warranted for accurate dorsogluteal placement. Landmarking and needle length are key to appropriately placed IM injections.

RELEVANCE TO CLINICAL PRACTICE
Dorsogluteal injections are often injected into subcutaneous tissue rather than muscle because needles are not long enough to reach muscle, especially in women. Critical elements that determine placement of intramuscular injections into muscle versus subcutaneous tissue are sex, BMI, needle length and landmarking. Medications delivered into subcutaneous tissue may have reduced bioavailability.

dorsogluteal
Intramuscular injections
needle length
sex
obesity
weight
BMI


Lung nodule and functional changes in smokers after smoking cessation short-term treatment.

Abstract:
BACKGROUND
Tobacco smoke causes lung disfunction and inflammation.

METHODS
Twenty-two consecutive smokers with undetermined lung nodules were included. All underwent a baseline imaging, exhaled carbon monoxide level evaluation and spirometry, repeated at three months from smoking cessation therapy.

RESULTS
A significant reduction in size of the lung nodules was reported (p = .037) as a trend in number reduction (p = .11). A significant increase in blood arterial oxygen pressure (p < .0001), heart rate reduction (p < .01), and FEV1 increase (p < .0001) was recorded.

CONCLUSIONS
Smoking cessation reduces number and size of lung nodules and improves in lung functionality.

Maci|Eliana|E|
Comito|Francesca|F|
Frezza|Anna Maria|AM|
Tonini|Giuseppe|G|
Pezzuto|Aldo|A|

Smoking cessation
Tobacco
High resolution tomography
Lung nodule evolution


Graphitic carbon nitride: synthesis, properties, and applications in catalysis.

Abstract: Graphitic carbon nitride, g-C3N4, is a polymeric material consisting of C, N, and some impurity H, connected via tris-triazine-based patterns. Compared with the majority of carbon materials, it has electron-rich properties, basic surface functionalities and H-bonding motifs due to the presence of N and H atoms. It is thus regarded as a potential candidate to complement carbon in material applications. In this review, a brief introduction to g-C3N4 is given, the methods used for synthesizing this material with different textural structures and surface morphologies are described, and its physicochemical properties are referred. In addition, four aspects of the applications of g-C3N4 in catalysis are discussed: (1) as a base metal-free catalyst for NO decomposition, (2) as a reference material in differentiating oxygen activation sites for oxidation reactions over supported catalysts, (3) as a functional material to synthesize nanosized metal particles, and (4) as a metal-free catalyst for photocatalysis. The reasons for the use of g-C3N4 for such applications are also given, and we expect that this paper will inspire readers to search for further new applications for this material in catalysis and in other fields.

Zhu|Junjiang|J|
Xiao|Ping|P|
Li|Hailong|H|
Carabineiro|Sónia A C|SA|

graphitic carbon nitride
synthesis
applications
physicochemical properties
metal-free catalyst
reference material
functional material


Using a Stacked Autoencoder for Mobility and Fall Risk Assessment via Time-Frequency Representations of the Timed Up and Go Test.

Abstract: Fall risk assessment is very important for the graying societies of developed countries. A major contributor to the fall risk of the elderly is mobility impairment. Timely detection of the fall risk can facilitate early intervention to avoid preventable falls. However, continuous fall risk monitoring requires extensive healthcare and clinical resources. Our objective is to develop a method suitable for remote and long-term health monitoring of the elderly for mobility impairment and fall risk without the need for an expert. We employed time-frequency analysis (TFA) and a stacked autoencoder (SAE), which is a deep neural network (DNN)-based learning algorithm, to assess the mobility and fall risk of the elderly according to the criteria of the timed up and go test (TUG). The time series signal of the triaxial accelerometer can be transformed by TFA to obtain richer image information. On the basis of the TUG criteria, the semi-supervised SAE model was able to achieve high predictive accuracies of 89.1, 93.4, and 94.1% for the vertical, mediolateral and anteroposterior axes, respectively. We believe that deep learning can be used to analyze triaxial acceleration data, and our work demonstrates its applicability to assessing the mobility and fall risk of the elderly.

Chen|Shih-Hai|SH|
Lee|Chia-Hsuan|CH|
Jiang|Bernard C|BC|
Sun|Tien-Lung|TL|


Comparison of current practices of cardiopulmonary perfusion technology in Iran with American Society of Extracorporeal Technology's standards.

Abstract:
INTRODUCTION
Standards have a significant role in showing the minimum level of optimal optimum and the expected performance. Since the perfusion technology staffs play an the leading role in providing the quality services to the patients undergoing open heart surgery with cardiopulmonary bypass machine, this study aimed to assess the standards on how Iranian perfusion technology staffs evaluate and manage the patients during the cardiopulmonary bypass process and compare their practice with the recommended standards by American Society of Extracorporeal Technology.

METHODS
In this descriptive study, data was collected from 48 Iranian public hospitals and educational health centers through a researcher-created questionnaire. The data collection questionnaire assessed the standards which are recommended by American Society of Extracorporeal Technology.

RESULTS
Findings showed that appropriate measurements were carried out by the perfusion technology staffs to prevent the hemodilution and avoid the blood transfusion and unnecessary blood products, determine the initial dose of heparin based on one of the proposed methods, monitor the anticoagulants based on ACT measurement, and determine the additional doses of heparin during the cardiopulmonary bypass based on ACT or protamine titration. It was done only in 4.2% of hospitals and health centers.

CONCLUSION
Current practices of cardiopulmonary perfusion technology in Iran are inappropriate based on the standards of American Society of Cardiovascular Perfusion. This represents the necessity of authorities' attention to the validation programs and development of the caring standards on one hand and continuous assessment of using these standards on the other hand.

Faravan|Amir|A|
Mohammadi|Nooredin|N|
Alizadeh Ghavidel|Alireza|A|
Toutounchi|Mohammad Zia|MZ|
Ghanbari|Ameneh|A|
Mazloomi|Mehran|M|

Perfusion
Standard
Cardiopulmonary bypas


Genital morphology and the mechanics of copulation in the millipede genus Pseudopolydesmus (Diplopoda: Polydesmida: Polydesmidae).

Abstract: Mate choice, copulation, genital morphology, and sperm storage are not very well understood in millipedes. The use of three-dimensional x-ray computed tomography (μCT) provides new morphological data regarding millipede reproductive systems in both the female and male, including chitinous sclerites and membranes, muscles, glands, oviducts, and sperm conduits. Here we present a complete integrated account of the morphology and function of the female genital organs in the family Polydesmidae (Diplopoda: Polydesmida) using μCT, UV fluorescence imaging, and scanning electron microscopy. These data allow us to consider competing hypotheses regarding millipede vulva formation. We additionally present the morphology of copulatory interface in Pseudopolydesmus Attems, 1898 using images of a mating pair in copula and by simulating the interface of the organs using 3D models from μCT, allowing us to tentatively identify a lock-and-key-like mechanism. Finally, we use μCT to reveal the topology of the seminal canal in the gonopod of male Pseudopolydesmus, a topic that has remained unresolved for nearly 80 years.

Zahnle|Xavier J|XJ|
Sierwald|Petra|P|
Ware|Stephanie|S|
Bond|Jason E|JE|

Diplopoda
Female genitalia
Reproductive anatomy
Sexual selection
Ultraviolet fluorescence
X-ray tomography


Haloquinone Chloroimides as Toxic Disinfection Byproducts Identified in Drinking Water.

Abstract: Haloquinone chloroimides (HQCs) are suspected to be highly toxic contaminants, and their production during drinking water disinfection is predicted. However, HQC disinfection byproducts (DBPs) have not been reported in drinking water to date because of analytical limitations. In this study, we developed an analytical method to detect five HQCs, including 2,6-dichloroquinone-4-chloroimide (2,6-DCQC), 2,6-dibromoquinone-4-chloroimide (2,6-DBQC), 2-chloroquinone-4-chloroimide (2-CQC), 3-chloroquinone-4-chloroimide (3-CQC), and 2,6-dichloroquinone-3-methyl-chloroimide (2,6-DCMQC). This method combined a derivatization reaction of HQCs with phenol in alkaline solutions to produce halogenated indophenols, a solid-phase extraction pretreatment using hydrophilic-lipophilic balanced (HLB) cartridges, and a multiple reaction monitoring (MRM) method for quantification. The method was demonstrated to be sensitive and accurate with recoveries of 71-85% and limits of detection of 0.1-0.2 ng/L for the five tested HQCs. Using this method, five tested HQCs were identified in drinking water samples from nine water treatment plants and water distribution systems as new DBPs at concentrations of up to 23.1 ng/L. The cytotoxicity of the five tested HQCs in HepG2 cells was higher than or comparable to that of 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), an emerging DBP that was hundreds to thousands of times more toxic than regulated DBPs. This study presents the first analytical method for HQC DBPs in drinking water and the first set of occurrence and cytotoxicity data of HQC DBPs.

drinking water
haloquinone chloroimides (HQCs)
disinfection byproducts (DBPs)
derivatization
solid-phase extraction
cytotoxicity
UPLC-MS/MS


COVID-19 and diabetes mellitus: implications for prognosis and clinical management.

Abstract:
INTRODUCTION
COVID-19 is a novel coronavirus that emerged from Wuhan, China in December 2019, and within 3 months became a global pandemic.

AREAS COVERED
PubMed search of published data on COVID-19, respiratory infections, and diabetes mellitus (DM). DM associates with impairments of both cellular and humoral immunity. Early emergent global data reveal that severity of clinical outcome from COVID-19 infection (including hospitalization and admission to Intensive Care Unit [ICU]), associate with co-morbidities, prominently DM. The key principles of management of COVID-19 in patients with DM include ongoing focused outpatient management (remotely where necessary) and maintenance of good glycemic control.

EXPERT OPINION
We will remember the dawn of the third decade of the twenty-first century as a time when the world changed, the true scale and impact of which is hard for us to imagine. Like a phoenix from the ashes though, COVID-19 provides us with a great learning opportunity to renew insights into ourselves as individuals, our clinical teams, and the optimized provision of care for our patients. COVID-19 has re-shaped and re-focused our collective societal values, with a sea-changed shift from materialistic to human-centric, from self-centredness to altruism, ultimately for the betterment of patient care and the whole of society.

COVID-19
diabetes mellitus
respiratory infection
immunity
glycemia


About a case of traumatic separation of the cervix from the uterine corpus, diagnosed in a context of infertility.

Abstract: This article reports a case of cervico-isthmic disjunction unnoticed during childhood, diagnosed in a context of primary infertility and endometriosis, and surgically treated. It is an uncommon condition. The diagnosis is most often made as part of an assessment of primary amenorrhea in a young woman with a history of severe pelvic trauma. It is suspected after imaging assessment and confirmed intraoperatively. The treatment consists in an anastomosis between the cervix and the uterine body, after individualizing these two structures, around a drain guiding healing. After this surgery, multiple pregnancies have been successfully carried out.

Vignolle|J|J|
Lefebvre|C|C|
Lucot|J P|JP|
Rubod|C|C|

Infertility
Cervico-isthmic disjunction
Pelvic trauma
Cervico-isthmic anastomosis
Uterine avulsion


Automated identification of malignancy in whole-slide pathological images: identification of eyelid malignant melanoma in gigapixel pathological slides using deep learning.

Abstract:
BACKGROUND/AIMS
To develop a deep learning system (DLS) that can automatically detect malignant melanoma (MM) in the eyelid from histopathological sections with colossal information density.

METHODS
Setting: Double institutional study.

STUDY POPULATION
We retrospectively reviewed 225 230 pathological patches (small section cut from pathologist-labelled area from an H&E image), cut from 155 H&E-stained whole-slide images (WSI).

OBSERVATION PROCEDURES
Labelled gigapixel pathological WSIs were used to train and test a model designed to assign patch-level classification. Using malignant probability from a convolutional neural network, the patches were embedded back into each WSI to generate a visualisation heatmap and leveraged a random forest model to establish a WSI-level diagnosis.

MAIN OUTCOME MEASURE(S)
For classification, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity were used to evaluate the efficacy of the DLS in detecting MM.

RESULTS
For patch diagnosis, the model achieved an AUC of 0.989 (95% CI 0.989 to 0.991), with an accuracy, sensitivity and specificity of 94.9%, 94.7% and 95.3%, respectively. We displayed the lesion area on the WSIs as graded by malignant potential. For WSI, the obtained sensitivity, specificity and accuracy were 100%, 96.5% and 98.2%, respectively, with an AUC of 0.998 (95% CI 0.994 to 1.000).

CONCLUSION
Our DLS, which uses artificial intelligence, can automatically detect MM in histopathological slides and highlight the lesion area on WSIs using a probabilistic heatmap. In addition, our approach has the potential to be applied to the histopathological sections of other tumour types.

Wang|Linyan|L| Ding|Longqian|L| Liu|Zhifang|Z| Sun|Lingling|L| Chen|Lirong|L| Jia|Renbing|R| Dai|Xizhe|X| Cao|Jing|J| Ye|Juan|J|0000-0001-8316-6994


MicroRNA-21 regulates the viability and apoptosis of diffuse large B-cell lymphoma cells by upregulating B cell lymphoma-2.

Abstract: Diffuse large B-cell lymphoma (DLBCL), one of the most frequently diagnosed non-Hodgkin lymphoma (NHL), is partly attributed to hereditary factors. MicroRNA-21 (miR-21) is an oncogenic substance that induces NHL and primarily targets tumor-suppressive molecules, such as B cell lymphoma-2 (Bcl-2). The present study explored whether Bcl-2, targeted by miR-21, would affect the development of NHL. Specimens were harvested from 55 patients with DLBCL who had undergone surgical treatment. Expression levels of miR-21 and Bcl-2 were evaluated through reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. Luciferase-reporter assays were performed to investigate the potential association between miR-21 and Bcl-2. MTT assays, flow cytometric analysis and caspase-3 activity assays were used to evaluate cell viability and apoptosis of DLBCL cells, respectively. Furthermore, statistical analysis was conducted using SPSS 19.0 software and the expression levels of miR-21 and Bcl-2 within DLBCL tissues were significantly upregulated when compared to those in normal tissues (P<0.01). As predicted by TargetScan, perfect base pairing was observed between the seed sequence of mature miR-21 and the 3' untranslated region of Bcl-2 mRNA. Dual luciferase reporter gene assays also revealed that miR-21 significantly facilitated the luciferase activity of Bcl-2 wild-type, with 61% upregulation (P<0.01) observed. MTT assays demonstrated that the viability of OCI-LY3 cells was decreased when cells were transfected with miR-21 inhibitor or Bcl-2 small interfering RNA and compared with those of control and negative control groups (all P<0.05). The apoptosis rate and caspase-3 activity level of the miR-21 group were 2.73±0.48 and 0.47±0.05, respectively, which were both significantly different from the groups with lower levels of miR-21 expression levels (all P<0.01). Since miR-21 may contribute to increased viability and decreased apoptosis of DLBCL cells through targeting Bcl-2, both Bcl-2 and miR-21 are likely to serve as effective targets for developing novel DLBCL treatments in the future.

apoptosis
diffuse large B-cell lymphoma
microRNA-21 B-cell lymphoma-2
proliferation


How deep is the conflict between molecular and fossil evidence on the age of angiosperms?

Abstract: The timing of the origin of angiosperms is a hotly debated topic in plant evolution. Molecular dating analyses that consistently retrieve pre-Cretaceous ages for crown-group angiosperms have eroded confidence in the fossil record, which indicates a radiation and possibly also origin in the Early Cretaceous. Here, we evaluate paleobotanical evidence on the age of the angiosperms, showing how fossils provide crucial data for clarifying the situation. Pollen floras document a Northern Gondwanan appearance of monosulcate angiosperms in the Valanginian and subsequent poleward spread of monosulcates and tricolpate eudicots, accelerating in the Albian. The sequence of pollen types agrees with molecular phylogenetic inferences on the course of pollen evolution, but it conflicts strongly with Triassic and early Jurassic molecular ages, and the discrepancy is difficult to explain by geographic or taphonomic biases. Critical scrutiny shows that supposed pre-Cretaceous angiosperms either represent other plant groups or lack features that might confidently assign them to the angiosperms. However, the record may allow the Late Jurassic existence of ecologically restricted angiosperms, like those seen in the basal ANITA grade. Finally, we examine recently recognized biases in molecular dating and argue that a thoughtful integration of fossil and molecular evidence could help resolve these conflicts.

angiosperms
molecular dating
Cretaceous
Jurassic
paleobotany
palynology


A novel technique of two-hole guide tube for percutaneous anterior odontoid screw fixation.

Abstract:
BACKGROUND CONTEXT
Surgical stabilization is recommended for odontoid fractures with mechanical instability. Compared with C1-C2 fusion, percutaneous anterior odontoid screw fixation has the advantages of preserving C1/C2 motion and being a minimally invasive procedure. However, determining the optimal screw trajectory is often difficult. When an initial suboptimal K-wire hole is drilled, it is especially difficult to drill a second optimal K-wire trajectory because the initial hole will be entered inadvertently.

PURPOSE
To design a novel device, two-hole guide tube, to make drilling a second optimal K-wire trajectory easier, and thus, avoid unnecessary additional surgical time and reduce the likelihood of needing to change the procedure to traditional open surgery.

STUDY DESIGN
A technical report.

METHODS
Fifty-three patients with odontoid fractures were treated by percutaneous anterior odontoid screw fixation in our hospital, and the initial K-wire trajectories of 16 cases (12 men and 4 women) among the 53 patients were imperfect. The two-hole guide tube was applied for drilling the second trajectory in each of these 16 cases.

RESULTS
No complications associated with this technique occurred. Satisfactory results and good screw placement was achieved in all patients. Radiographic fusion was confirmed for 15 of 16 patients. None of the patients experienced clinical symptoms or screw loosening or breakage in this study.

CONCLUSIONS
Our novel device, two-hole guide tube, can be used to reduce the difficulty associated with redrilling an optimal K-wire trajectory if the initial trajectory is imperfect during percutaneous anterior odontoid screw fixation. Moreover, by referring to the initial misplaced K-wire, a more accurate trajectory for the second K-wire can be achieved.

Wu|Ai-Min|AM| Wang|Xiang-Yang|XY| Xia|Dong-Dong|DD| Luo|Peng|P| Xu|Hua-Zi|HZ| Chi|Yong-Long|YL|

Guide tube
Percutaneous
Odontoid fracture
Minimally invasive
Trajectory
K-wire
Technique note


Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis.

Abstract:
BACKGROUND
Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes.

METHODS
A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models.

RESULTS
Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay.

CONCLUSIONS
Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED.

TRIAL REGISTRATION
UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.

Yamamoto|Ryo|R| Fujishima|Seitaro|S|0000-0001-8823-8440 Sasaki|Junichi|J| Gando|Satoshi|S| Saitoh|Daizoh|D| Shiraishi|Atsushi|A| Kushimoto|Shigeki|S| Ogura|Hiroshi|H| Abe|Toshikazu|T| Mayumi|Toshihiko|T| Kotani|Joji|J| Nakada|Taka-Aki|TA| Shiino|Yasukazu|Y| Tarui|Takehiko|T| Okamoto|Kohji|K| Sakamoto|Yuichiro|Y| Shiraishi|Shin-Ichiro|SI| Takuma|Kiyotsugu|K| Tsuruta|Ryosuke|R| Masuno|Tomohiko|T| Takeyama|Naoshi|N| Yamashita|Norio|N| Ikeda|Hiroto|H| Ueyama|Masashi|M| Hifumi|Toru|T| Yamakawa|Kazuma|K| Hagiwara|Akiyoshi|A| Otomo|Yasuhiro|Y| |||

Hyperoxemia
Trauma
ICU length of stay
Critically ill
Hyperoxia
Mortality


Enhancing the Sensitivity of Single-Particle Photothermal Imaging with Thermotropic Liquid Crystals.

Abstract: Individual molecules and nanoparticles can be imaged based on their absorption using photothermal microscopy. This technique relies on the heating-induced changes in the refractive index of the surrounding medium. Here, we demonstrate an order of magnitude larger enhancement of the signal-to-noise ratio in photothermal imaging of 20 nm gold nanoparticles when using a thermotropic liquid crystal (5CB). We show quantitatively that this increase is due to the large change in the thermo-optical properties of 5CB mainly along the nematic director. Enhancing the sensitivity is important for the further development of absorption-based single-molecule spectroscopy techniques.

photothermal imaging
liquid crystals
gold nanoparticles
single-particle spectroscopy
surface plasmon resonance


The peripheral and core regions of virus-host network of COVID-19.

Abstract: Two thousand nineteen novel coronavirus SARS-CoV-2, the pathogen of COVID-19, has caused a catastrophic pandemic, which has a profound and widespread impact on human lives and social economy globally. However, the molecular perturbations induced by the SARS-CoV-2 infection remain unknown. In this paper, from the perspective of omnigenic, we analyze the properties of the neighborhood perturbed by SARS-CoV-2 in the human interactome and disclose the peripheral and core regions of virus-host network (VHN). We find that the virus-host proteins (VHPs) form a significantly connected VHN, among which highly perturbed proteins aggregate into an observable core region. The non-core region of VHN forms a large scale but relatively low perturbed periphery. We further validate that the periphery is non-negligible and conducive to identifying comorbidities and detecting drug repurposing candidates for COVID-19. We particularly put forward a flower model for COVID-19, SARS and H1N1 based on their peripheral regions, and the flower model shows more correlations between COVID-19 and other two similar diseases in common functional pathways and candidate drugs. Overall, our periphery-core pattern can not only offer insights into interconnectivity of SARS-CoV-2 VHPs but also facilitate the research on therapeutic drugs.

Wang|Bingbo|B| Dong|Xianan|X| Hu|Jie|J| Ma|Xiujuan|X| Han|Chao|C| Wang|Yajun|Y| Gao|Lin|L|


Effects of hydroxyapatite-coated nonwoven polyethylene/polypropylene fabric on non-mesodermal lineage-specific differentiation of human adipose-derived stem cells.

Abstract:
OBJECTIVE
Compared to other stem cells, the multipotency of human adipose-derived mesenchymal stem cells (ASCs) is limited. Effective approaches that trigger or enhance lineage-specific transdifferentiation are highly envisaged in the improvement of ASCs-based cell therapies. Using Immunofluorescence assays and the secretion of cardiac troponin T (cTnT) protein, we studied the impact of two substrates: Hydroxyapatite (HAp)-coated nonwoven polyethylene (PET)/polypropylene (PP) fabric and glass surfaces, representing 3 dimensional (D) and 2 D environments respectively, on the induction of cardiomyocytes - a non-mesodermal cell type from ASCs for 1-5 weeks.

RESULTS
ASCs were successfully isolated from human adipose tissue under cGMP conditions. Within 1-3 weeks, expression of cTnT in the induced 3D cultures was overall significantly higher (P < 0.021) than that in the induced 2D cultures or controls (P < 0.0009). Remarkably, after 3 weeks of culture, cTnT secretion in the induced 3D cultures gradually declined, nearly reaching levels observed in the 2D cultures. The results show that HAp-coated nonwoven PE/PP fabric could enhance lineage-specific differentiation of ASCs toward cardiac-like cells. However, the fabric might suppress growth of the transformed cells. These preliminary findings encourage further interest in validating the fabric's potential in improving ASCs transdifferentiation.

Mesenchymal stem cells
Transdifferentiation
Cell therapy
Hydroxyapatite
Cardiomyocytes
Adipose tissue-derived stem cells
Nonwoven scaffold


Multiple episodic evolution events in V1R receptor genes of East-African cichlids.

Abstract: Fish use olfaction to detect a variety of nonvolatile chemical signals, and thus, this sense is key to survival and communication. However, the contribution of the olfactory sense to social-especially reproductive-interactions in cichlids is still controversial. To obtain insights into this issue, we investigated the genes encoding V1Rs-possible candidates for reproductive pheromone receptors-among East-African cichlids. Interestingly, we found an excess of nonsynonymous over synonymous substitutions in four of six V1R genes in multiple cichlid lineages. First, we found that highly dimorphic V1R2 allele groups were shared among the cichlids inhabiting all East-African Great Lakes emerged through the episodic accumulation of the nonsynonymous substitutions prior to the radiation of the Lake Tanganyika species flock. We further detected such episodic events in V1R1 of the tribe Tropheini, and in V1R3 and V1R6 of the tribe Trematocarini. The excess of nonsynonymous substitutions in these examples were indicated as dN/dS > 1, which were all statistically significant by Fisher's exact test. Furthermore, we speculate that the amino acid changes in these episodic events are likely functional switch because they occurred in the putative ligand-binding pocket. Our finding of the occurrence of multiple episodic events and the unexpected gene diversity in one unique gene family is suggestive of the contribution of the V1R to the species diversification and the social interaction in cichlids.

Nikaido|Masato|M|
Ota|Tomoki|T|
Hirata|Tadashi|T|
Suzuki|Hikoyu|H|
Satta|Yoko|Y|
Aibara|Mitsuto|M|
Mzighani|Semvua I|SI|
Sturmbauer|Christian|C|
Hagino-Yamagishi|Kimiko|K|
Okada|Norihiro|N|

dN/dS
accelerated evolution
chemo-detection


Iatrogenic Microperforation Linked to Hemorrhagic Pericardial Effusion Complicated by Cardiac Tamponade.

Abstract: Pericardial effusions have a wide range of etiologies, including infection, inflammation, and malignancy. A complication of pericardial effusion is cardiac tamponade. In instances of cardiac tamponade, prompt echocardiography and stabilization are paramount in preventing mortality. Here, we report a case of iatrogenic microperforation of the right ventricle during a pacemaker lead adjustment causing a delayed pericardial effusion complicated by cardiac tamponade. Lead removal is recommended in cases of valvular endocarditis, pocket infection, thrombosis, or life-threatening dysrhythmias; however, there are no established guidelines in the setting of perforation. In this case, an emergent pericardiocentesis was performed due to cardiac tamponade, but lead extraction was not performed.

pericardial effusion
cardiac tamponade
pacemaker lead perforation


Process model of the pharmaceutical integrated management system.

Abstract:
OBJECTIVE
Introduction: One of the innovative trends in the modern development of the pharmaceutical sector is the introduction of integrated management systems (IMS) at the enterprises for the production and distribution of medicines. The aim: to substantiate and develop a process model and approaches to the regulation and documentation, performance evaluation and improvement of the IMS within the pharmaceutical institution (PI) and hospital pharmaceutical service (HPS).

PATIENTS AND METHODS
Materials and methods: research materials used: international standards, regulations and guidelines of the Ministry of Health of Ukraine, scientific publications, information of PI and hospitals, placed on official websites and collected in the process of direct observation. Research methods are: systemic-review, generalization, observation, documentary, structural-logical and graphic modeling.

RESULTS
Results: Based on the requirements of good practices and international standards in the field of management of quality, ecology, occupational health and safety, social responsibility, a typical process model of the IMS of PI and HPS (pharmaceutical integrated management system - PIMS) has been substantiated and developed. The content of each process of a typical PIMS model is described and structured. The expected results (outputs) of the PIMS processes are determined. The approaches to the regulation and documentation of the PIMS processes in the conditions of functioning of the four-level documented information system are substantiated. A matrix of responsibility and authority of the staff of PI and hospitals within the PIMS is developed. The structurally hierarchical model of the performance evaluation and improvement of the PIMS has been designed and described.

CONCLUSION
Conclusions: The results are the basis for the establishing, regulating and documenting of the PIMS and the development of a system for its performance evaluation and continual improvement.

Ubohov|Serhii H|SH|
Trokhymchuk|Viktor V|VV|
Todorova|Violetta I|VI|
Zahoriy|Volodymyr A|VA|

process model
integrated management system
medicines
pharmaceutical institution
hospital pharmaceutical services


Cervical lymph node metastases of squamous cell carcinoma of unknown origin: the diagnostic value of FDG PET/CT and clinical outcome.

Abstract: FDG PET/CT is perceived as a valuable diagnostic tool in addition to the standard diagnostic workup for patients with isolated neck lymph nodes of squamous cell carcinoma of unknown primary (SCCUP). For patients with SCCUP intended for primary radiotherapy, we hypothesize that the previously reported FDG PET/CT detection rates are too high. From 2008 to 2015, 30 SCCUP patients were examined with FDG PET/CT. The objective of the FDG PET/CT examination was twofold: (1) improve the radiotherapy target definition, and (2) identify the primary cancer. Before the FDG PET/CT, the patients had been through a standard workup consisting of CT of the neck and chest, examination with flexible endoscopy with patient awake, panendoscopy and examination under general anesthesia, tonsillectomy and sometimes blind sampling biopsies, and MRI (floor of the mouth). All FDG PET/CTs were performed applying a flat table, head support and fixation mask as part of the radiotherapy treatment planning. Diagnostic CT with contrast was an integrated part of the PET/CT examination. Only 1/30 patients (cancer of the vallecula) had their primary cancer detected by FDG PET/CT. In addition, a non-biopsied patient with high uptake in the ipsilateral palatine tonsil was included, giving a detection rate of ≤7 % (95 % CI 2-21 %). In this retrospective study, we found that the FDG PET/CT detection rate of the primary for SCCUP patients is lower than previously reported. It is questionable whether FDG PET/CT is necessary for these patients when improved, advanced workup is available.

D000072078:Positron Emission Tomography Computed Tomography

Cervical lymph node metastases
18F-FDG
Cancer of unknown primary
Head and neck cancer
Positron emission tomography


Harnack's inequality for doubly nonlinear equations of slow diffusion type.

Abstract: In this article we prove a Harnack inequality for non-negative weak solutions to doubly nonlinear parabolic equations of the form   where the vector field  fulfills p-ellipticity and growth conditions. We treat the slow diffusion case in its full range, i.e. all exponents  and  with  are included in our considerations.


The effect of meloxicam and cryopreserved placenta extract on initial inflammatory response - an experimental study.

Abstract: Alteration is the first phase of the inflammatory process triggering the entire cascade of inflammation and causing destructive changes in the affected tissues. Therefore, suppression of inflammation at this point is essential for the success of anti-inflammatory therapy. Previous experimental studies have shown that the combined use of nonsteroidal anti-inflammatory drugs and drugs with pleiotropic mechanisms of action may potentiate their anti-inflammatory properties. The purpose of my work was to characterize the combined effect of cryopreserved placenta extract and meloxicam on the alterative phase of the inflammatory process in a model of aseptic skin and subcutaneous tissue inflammation in rats. Subcutaneous administration of acetic acid and of dextran was found to result in formation of necrotic ulcers in 100% of rats by day 7 of the experiment. The most pronounced antialterative effect (23.9%) on day 7 of the experiment was observed with the combined use of meloxicam and cryopreserved placenta extract - the area of necrotic ulcers was 1.3-fold smaller (p < 0.05) as compared with control rats (without treatment). On day 27 of the experiment, the antialterative effect of combined treatment and prophylactic use of meloxicam and cryopreserved placenta extract was 1.7 times higher than the effect in meloxicam monotherapy group, and 1.2 times higher than that in the placenta cryoextract monotherapy group.

meloxicam
cryopreserved placenta extract
alteration
inflammation
probiotics


High-fat diet-induced impairment of skeletal muscle insulin sensitivity is not prevented by SIRT1 overexpression.

Abstract: Skeletal muscle sirtuin 1 (SIRT1) expression is reduced under insulin-resistant conditions, such as those resulting from high-fat diet (HFD) feeding and obesity. Herein, we investigated whether constitutive activation of SIRT1 in skeletal muscle prevents HFD-induced muscle insulin resistance. To address this, mice with muscle-specific overexpression of SIRT1 (mOX) and wild-type (WT) littermates were fed a control diet (10% calories from fat) or HFD (60% of calories from fat) for 12 wk. Magnetic resonance imaging and indirect calorimetry were used to measure body composition and energy expenditure, respectively. Whole body glucose metabolism was assessed by oral glucose tolerance test, and insulin-stimulated glucose uptake was measured at a physiological insulin concentration in isolated soleus and extensor digitorum longus muscles. Although SIRT1 was significantly overexpressed in muscle of mOX vs. WT mice, body weight and percent body fat were similarly increased by HFD for both genotypes, and energy expenditure was unaffected by diet or genotype. Importantly, impairments in glucose tolerance and insulin-mediated activation of glucose uptake in skeletal muscle that occurred with HFD feeding were not prevented in mOX mice. In contrast, mOX mice showed enhanced postischemic cardiac functional recovery compared with WT mice, confirming the physiological functionality of the SIRT1 transgene in this mouse model. Together, these results demonstrate that activation of SIRT1 in skeletal muscle alone does not prevent HFD-induced glucose intolerance, weight gain, or insulin resistance.

White|Amanda T|AT|
Philp|Andrew|A|
Fridolfsson|Heidi N|HN|
Schilling|Jan M|JM|
Murphy|Anne N|AN|
Hamilton|D Lee|DL|
McCurdy|Carrie E|CE|
Patel|Hemal H|HH|
Schenk|Simon|S|

D050154:Adiposity
D000818:Animals
D001823:Body Composition
D059305:Diet, High-Fat
D004734:Energy Metabolism
D018149:Glucose Intolerance
D006321:Heart
D007333:Insulin Resistance
D008297:Male
D008810:Mice, Inbred C57BL
D008822:Mice, Transgenic
D008931:Mitochondria, Muscle
D018482:Muscle, Skeletal
D015428:Myocardial Reperfusion Injury
D009765:Obesity
D010101:Oxygen Consumption
D011897:Random Allocation
D056564:Sirtuin 1
D015854:Up-Regulation
D015430:Weight Gain

skeletal muscle
SIRT1
high-fat diet
insulin resistance


Prophylactic doses of low-molecular weight heparin as periprocedural bridging therapy in mechanical heart valve patients.

Abstract:
BACKGROUND
Mechanical heart valve (MHV) patients undergoing invasive procedures necessitating an interruption of their lifelong anticoagulant therapy, often require bridging with low-molecular weight heparin (LMWH) or unfractionated heparin. The aim of this study was to assess whether bridging MHV patients with prophylactic doses of LMWH undergoing invasive, elective procedures is a safe and effective method.

METHOD
This observational cohort study included all MHV patients on vitamin K anticoagulant therapy in Malmö, registered and monitored via AuriculA (the Swedish national quality registry for atrial fibrillation and anticoagulation), between 1/1/2008 and 31/12/2011. Inclusion criteria were periprocedural bridging therapies conducted via AuriculA. Primary endpoints were mortality, thromboembolic (TE) events or major bleedings (MBE) within 30 days of bridging.

RESULTS
During the study period, 210 patients had undergone 434 bridging therapies managed via AuriculA; 203 due to subtherapeutic INR-values were excluded. The remaining 231 periprocedural bridging therapies were included. All were bridged with prophylactic doses of LMWH. When comparing patients with aortic and/or mitral valve replacements undergoing low- or high-risk interventions, only number of days bridged for a low-risk intervention differed significantly. Patients with a mitral or mitral and aortic valve replacement were bridged for a longer period (p=0.023). No TE events, 1 death (0.4%) and 3 MBEs (1.3%) occurred related to periprocedural bridging.

CONCLUSION
Our study shows a low rate of MBEs, deaths and no TE events when bridging MHV patients undergoing invasive, elective procedures with prophylactic doses of LMWH.

D019918:Heart Valve Prosthesis Implantation

Bridging
Mechanical heart valve
Thromboembolism
Bleeding
Low molecular weight heparin


Heterocumulene Sulfinyl Radical OCNSO.

Abstract: Neutral five-atomic cumulenes formally consisting of two pseudohalogens (e.g., NCO, NNN, NSO) by sharing the central nitrogen atom are exotic species that have been barely studied. Through flash vacuum pyrolysis of CF3 S(O)NCO at ca. 1200 K, sulfinyl isocyanate, bearing resonance structures of O=C-N=S=O and O=C=N-S=O, has been generated in the gas phase and subsequently characterized in cryogenic matrices (Ar and N2 ). Its reversible conformational (syn and anti) interconversion and photodecomposition were observed.

Wu|Zhuang|Z|
Liu|Qifan|Q|
Xu|Jian|J|
Sun|Hailong|H|
Li|Dingqing|D|
Song|Chao|C|
Andrada|Diego M|DM|
Frenking|Gernot|G|
Trabelsi|Tarek|T|
Francisco|Joseph S|JS|
Zeng|Xiaoqing|X|

cumulenes
pseudohalogens
IR spectroscopy
matrix isolation
sulfur-nitrogen compounds


Novel Deoxyvasicinone-Donepezil Hybrids as Potential Multitarget Drug Candidates for Alzheimer's Disease.

Abstract: In this study, we designed and synthesized a series of deoxyvasicinone-donepezil hybrids and determined whether they could be used as novel multitarget inhibitors for Alzheimer's disease. In vitro studies showed that most of the hybrids demonstrated moderate to potent inhibition of hAChE, BACE1, and Aβ1-42 aggregation. In particular, the hybrids 10a, 10d, 11a, and 11j exhibited excellent inhibitory activities against hAChE (IC50 = 56.14, 5.91, 3.29, and 8.65 nM, respectively), BACE1 (IC50 = 0.834, 0.167, 0.129, and 0.085 μM, respectively), and Aβ1-42 aggregation (IC50 = 13.26, 19.43, 9.26, and 5.41 μM, respectively). In addition, 10a and 11a exhibited very low cytotoxicity and showed remarkable neuroprotective activity against Aβ1-42-induced damage in SH-SY5Y cells.

Du|Hongtao|H|0000-0002-6428-2401 Liu|Xinlian|X| Xie|Jusen|J| Ma|Fang|F|

D053829:Amyloid Precursor Protein Secretases

Alzheimer’s disease
acetylcholinesterase
deoxyvasicinone
β-amyloid peptide
β-secretase


Trajectories of psychological dating violence perpetration in adolescence.

Abstract:
BACKGROUND
More than one adolescent out of three will use psychological dating violence (DV) as a strategy to resolve conflict in romantic relationships, which will have major consequences on their partner's well-being. However, over time, most adolescents will learn skills to better interact and face conflicts, suggesting that psychological DV rates should decrease over time. Yet, because of individual characteristics and experiences, evolution over time may differ across adolescents. Risk factors for psychological DV have not been examined specifically, even though it is the most common form of dating violence.

OBJECTIVE
This study aimed to explore latent trajectories of psychological DV perpetration and examine risk factors predicting trajectory group membership.

PARTICIPANTS AND METHODS
A sub-sample of 449 adolescents who reported being in a dating relationship for the three waves of the [blind for review] completed printed and online self-report questionnaires.

RESULTS
Results from the group-based modeling identified 4 trajectories of psychological DV perpetration: absence of violence (30.7%), low violence (61.3%), high descending (4.2%), and moderate elevating (3.8%). Age, DV victimization, exposure to father toward mother violence, low self-esteem, marijuana use, DV victimization of peers, and antisocial behaviors of peers predicted trajectory membership. The model explained 36.7% of the variance.

CONCLUSIONS
These results support the need for a person-oriented approach to study psychological DV and for developing prevention programs adapted to the specific characteristics of vulnerable youth.

Lapierre|Andréanne|A| Paradis|Alison|A| Todorov|Emily|E| Blais|Martin|M| Hébert|Martine|M|

Trajectories
Psychological dating violence
Risk factors
Self-esteem
Peers’ characteristics
Risky behaviors


Quercetin enrich diet during the early-middle not middle-late stage of alzheimer's disease ameliorates cognitive dysfunction.

Abstract: The aim of this study was to evaluate the protective effects of dietary flavonoid quercetin against Alzheimer's disease (AD) and detect the explicit administration of quercetin in early-middle or middle-late stage of AD pathology could play the effect as well as its mechanism of action. In this study, APP/PS1 mice were used to investigate cognitive impairment and related pathologies. The results showed that quercetin enrich diet could play an ameliorated pathology development of AD in APP/PS1 mice. And then we next determined administration of quercetin in early-middle and middle-late stage of AD pathology, which exerted that only quercetin enrich diet during the early-middle stage of AD pathological development period ameliorates cognitive dysfunction and the protection effect was mainly related to increased Aβ clearance and reduced astrogliosis. These findings suggest a possible new protective role for dietary flavonoids on AD. This new role might expand the preventive and/or therapeutic use of AD in conditions.


Data on empirical estimation of the relationship between agency costs and ownership structure in Italian listed companies (2002-2013).

Abstract: The data presented in this article are related to the research article entitled "Do shareholder coalitions affect agency costs? Evidence from Italian-listed companies", Research in International Business and Finance, Forthcoming (Rossi et al., 2018) [1]. The study shows an empirical analysis using an extensive balanced panel dataset of 163 Italian listed companies for the period 2002-2013, which is a sample yielding 1956 firm-year observations. The sample consists primarily of manufacturing firms, but also includes some service enterprises. However all financial firms and regulated utilities are excluded. We collected data on ownership structure for the entire study period. Information was acquired from the Consob website and the individual company reports on corporate governance. Data on firm-level indicators (debt-to-capital ratio, firm size, and age of the firm) for all companies in the sample were collected from Datastream, Bloomberg, and Calepino dell'Azionista, as well as obtained manually from the financial statements of the individual companies being studied. Our dataset contains several measures of ownership structure for Italian listed companies.

Rossi|Fabrizio|F|
Barth|James R|JR|
Cebula|Richard J|RJ|

Generalized method of moments (GMM) estimation


Emotional Responses and Perceived Relative Harm Mediate the Effect of Exposure to Misinformation about E-Cigarettes on Twitter and Intention to Purchase E-Cigarettes among Adult Smokers.

Abstract: There is a gap in knowledge on the affective mechanisms underlying effects of exposure to health misinformation. This study aimed to understand whether discrete emotional responses and perceived relative harm of e-cigarettes versus smoking mediate the effect of exposure to tweets about the harms of e-cigarettes on Twitter and intention to purchase e-cigarettes among adult smokers. We conducted a web-based experiment in November 2019 among 2400 adult smokers who were randomly assigned to view one of four conditions of tweets containing different levels of misinformation. We fitted mediation models using structural equation modeling and bootstrap procedures to assess the indirect effects of exposure to tweets through perceived relative harm of e-cigarettes and six discrete emotions. Our findings support that exposure to tweets about harms of e-cigarettes influence intention to purchase e-cigarettes through perceived relative harm, discrete emotional responses, and serially through emotional responses and perceived relative harm. Feeling worried, hopeful, and happy mediated the effects of condition on intention to purchase e-cigarettes. Feeling scared, worried, angry, and hopeful mediated the effects serially through perceived relative harm. Affective responses and perceived relative harm following exposure to misinformation about e-cigarette harm may mediate the relationship with intention to purchase e-cigarettes among adult smokers.

Liu|Jessica|J|0000-0002-8455-0127
Wright|Caroline|C|
Elizarova|Olga|O|
Dahne|Jennifer|J|
Bian|Jiang|J|
Tan|Andy S L|ASL|

emotions
misinformation
e-cigarettes
Twitter
social media


Real-Color Volume Models Made from Real-Color Sectioned Images of Visible Korean.

Abstract:
Background
Volume models made from magnetic resonance images on computed tomographs can produce horizontal, coronal, sagittal, and oblique planes that are used widely in clinics, although detailed structures cannot be identified. Existing real color volume models are mostly commercial and their production methods have not been released. The aim of this study was to distribute free of charge, real-color volume models produced from sectioned images with the production method.

Methods
The original voxel size of sectioned images was increased appropriately so that the volume model could be handled by typical personal computers. By using Dicom Browser and MRIcroGL, the sectioned images were processed to become the volume models.

Results
On the MRIcroGL, the resultant volume model with the voxel size of 0.5 × 0.5 × 0.5 mm3 could be displayed and freely rotated. By adjusting variables of the software, desired oblique planes could be produced instantly. With overlay function, a model of segmented structure can be overlapped to the entire volume models. The sectioned images with high quality and the segmentation data of Visible Korean enabled the identification of detailed anatomical structures on the planes.

Conclusion
The volume models can be used by medical students and doctors for learning sectional anatomy. Other researchers can utilize the method of this study to produce volume models from their own sectioned images.

Computer Simulation
Cross-Sectional Anatomy
Three-Dimensional Imaging
Visible Human Projects


In Vitro Evaluation of Nasogastric Tube Delivery Performance of Esomeprazole Magnesium Delayed-Release Capsules.

Abstract: Enteral feeding tubes are used to deliver food or drugs to patients who cannot swallow. To deliver delayed-release drugs that are formulated as enteric coated granules to these patients via feeding tubes requires that they be suspended in water before administration. Importantly, the suspension of enteric granules in water of varying pH can cause damage to the enteric coating and affect the bioavailability of the drug. Here, analytical methods for testing acid resistance stability and particle size distribution (PSD) of esomeprazole granules were used to monitor the integrity of the granule enteric coating after water pretreatment and delivery through an oral syringe and nasogastric (NG) tube. Granules from esomeprazole magnesium delayed-release capsules were transferred to an oral syringe, suspended in water, and delivered on the bench through an NG tube. Subsequently, acid resistance stability (i.e., the amount of drug released after 2-h acid dissolution) was determined via high-performance liquid chromatography, and the PSD were measured with a laser diffraction system. All the granules demonstrated acid resistance stability when the granules were delivered immediately (0 min incubation) through the oral syringe and NG tube. In contrast, some granules demonstrated significant drug release during acid exposure after a 15-min incubation period which mimics a possible delay in delivery of the drug from the syringe by the caregiver. A bimodal PSD was observed with these granules, which was attributed to debris from damaged enteric coating and particle agglomeration. The methods developed in this study could be used to distinguish batches with suboptimal product quality for delivery using NG tubes and to confirm the substitutability of generic drug products for this alternative route of administration.

Hoover|Alicia|A| Sun|Dajun|D| Wen|Hong|H| Jiang|Wenlei|W| Cui|Minglei|M| Jiang|Xiaojian|X| Keire|David|D| Guo|Changning|C|

HPLC (high-performance/pressure liquid chromatography)


Overview of research on Bombyx mori microRNA.

Abstract: MicroRNAs (miRNAs) constitute some of the most significant regulatory factors involved at the post-transcriptional level after gene expression, contributing to the modulation of a large number of physiological processes such as development, metabolism, and disease occurrence. This review comprehensively and retrospectively explores the literature investigating silkworm, Bombyx mori L. (Lepidoptera: Bombicidae), miRNAs published to date, including discovery, identification, expression profiling analysis, target gene prediction, and the functional analysis of both miRNAs and their targets. It may provide experimental considerations and approaches for future study of miRNAs and benefit elucidation of the mechanisms of miRNAs involved in silkworm developmental processes and intracellular activities of other unknown non-coding RNAs.

review
silkworm
expression profiling analysis
target gene
prediction
microarray technology


Ventilatory adaptation during eccentric cycling in patients with severe COPD: Potential implications for exercise training.

Abstract:
INTRODUCTION
Eccentric (ECC) cycling is viewed as an alternative to concentric (CON) cycling for exercise training in patients with severe COPD as it induces a much lower ventilatory demand for a given mechanical load than CON cycling. However, a more hyperpneic breathing pattern (i.e., higher fB and lower tidal volume (VT)) during ECC than during CON has been reported in healthy subjects.

RESEARCH QUESTION
Do patients with severe COPD develop a more hyperpneic breathing pattern during ECC than during CON cycling, and is it associated with differences in dynamic hyperinflation, ventilatory efficiency and cardiometabolic adaptation?

METHODS
Fourteen patients with severe COPD performed incremental CON and ECC cardiopulmonary exercise tests (CPET). Several physiological parameters including VT, fB, inspiratory capacity (IC) and oxygen consumption (V̇O2) were recorded at each workload increment during CPET.

RESULTS
At the highest identical minute ventilation (V̇E) achieved during ECC and CON (28.6 ± 4.6 L.min-1), VT was lower (1010 ± 218 vs. 1100 ± 233 mL; p = 0.02), fB was higher (29.0 ± 5.1 vs. 27.0 ± 5.5 min-1; p = 0.03), IC(% baseline) was lower (84 ± 10 vs. 78 ± 9; p < 0.01) and markers of ventilatory efficiency were poorer during ECC than during CON. Similar results were found at the highest identical V̇O2 achieved during ECC and CON.

CONCLUSION
The finding of a more hyperpneic ventilatory pattern during ECC cycling together with a lower IC and a poorer ventilatory efficiency suggests that ECC exercise training should be decided with caution in patients with severe COPD.

Nahmias|Olympe|O| Ritter|Ophélie|O| Sagawa|Yoshimasa|Y| Roux|Pauline|P| Degano|Bruno|B| Soumagne|Thibaud|T|

Eccentric cycling
Ventilation
Chronic obstructive
Electromyography
Pulmonary disease


Anesthesia management in a patient of Apert syndrome.

Abstract: Apert syndrome is autosomal dominant disease associated with multiple craniofacial and limb deformities. These children usually face many orthopedic, orthodental operative procedures. As anesthetist, we face difficulties in airway management due to mid-facial hypoplasia, craniosynostosis. We report a case of Apert syndrome which was referred to us for syndactyly release, focusing on the difficulties and complications related to it.


Stretchy binary classification.

Abstract: In this article, we introduce an analytic formulation for compressive binary classification. The formulation seeks to solve the least ℓp-norm of the parameter vector subject to a classification error constraint. An analytic and stretchable estimation is conjectured where the estimation can be viewed as an extension of the pseudoinverse with left and right constructions. Our variance analysis indicates that the estimation based on the left pseudoinverse is unbiased and the estimation based on the right pseudoinverse is biased. Sparseness can be obtained for the biased estimation under certain mild conditions. The proposed estimation is investigated numerically using both synthetic and real-world data.

Toh|Kar-Ann|KA| Lin|Zhiping|Z| Sun|Lei|L| Li|Zhengguo|Z|

Parameter learning
Pattern classification
Sparse estimation


Food Informatics-Review of the Current State-of-the-Art, Revised Definition, and Classification into the Research Landscape.

Abstract: Background: The increasing population of humans, changing food consumption behavior, as well as the recent developments in the awareness for food sustainability, lead to new challenges for the production of food. Advances in the Internet of Things (IoT) and Artificial Intelligence (AI) technology, including Machine Learning and data analytics, might help to account for these challenges. Scope and Approach: Several research perspectives, among them Precision Agriculture, Industrial IoT, Internet of Food, or Smart Health, already provide new opportunities through digitalization. In this paper, we review the current state-of-the-art of the mentioned concepts. An additional concept is Food Informatics, which so far is mostly recognized as a mainly data-driven approach to support the production of food. In this review paper, we propose and discuss a new perspective for the concept of Food Informatics as a supportive discipline that subsumes the incorporation of information technology, mainly IoT and AI, in order to support the variety of aspects tangent to the food production process and delineate it from other, existing research streams in the domain. Key Findings and Conclusions: Many different concepts related to the digitalization in food science overlap. Further, Food Informatics is vaguely defined. In this paper, we provide a clear definition of Food Informatics and delineate it from related concepts. We corroborate our new perspective on Food Informatics by presenting several case studies about how it can support the food production as well as the intermediate steps until its consumption, and further describe its integration with related concepts.

Internet of Things
Precision Agriculture
Internet of Food
Food Informatics
Food Computing
Food Supply Chain Management
smart agriculture


Hydrogen sulphide as a novel therapy to ameliorate cyclosporine nephrotoxicity.

Abstract:
BACKGROUND
Calcineurin inhibitors have significant nephrotoxic side effects, which can exacerbate ischemia-reperfusion injury in renal transplantation. Novel therapeutic agents such as hydrogen sulphide (H₂S) may reduce these harmful effects. This study investigated the effects of H₂S on cyclosporine (CsA) induced nephrotoxicity.

MATERIALS AND METHODS
Porcine kidneys were subjected to 15 min of warm ischemia and 2 h of static cold storage. They were reperfused for 3 h with oxygenated normothermic autologous whole blood on an isolated organ reperfusion apparatus. Kidneys were treated with CsA during reperfusion (n = 6) or cyclosporine and 0.25 mmol/L of H₂S infused 10 min before and 20 min after reperfusion (n = 6). These were compared with untreated controls (n = 7).

RESULTS
CsA caused a significant reduction in renal blood flow during reperfusion, which was reversed by H₂S (area under the curve renal blood flow CsA 257 ± 93 versus control 477 ± 206 versus CsA + H₂S 478 ± 271 mL/min/100 g.h; P = 0.024). Urine output was higher after 2 h of reperfusion in the CsA + H₂S group (CsA + H₂S 305 ± 218 versus CsA 78 ± 180 versus control 210 ± 45 mL; P = 0.034). CsA treatment was associated with an increase in tubular injury, which was not reversed by H₂S (area under the curve fractional excretion of sodium, control 77 ± 53 versus CsA 100 ± 61 versus CsA + H2S 111 ± 57%.h; P = 0.003). Histologic evaluation showed significant vacuolation and glomerular shrinkage in the CsA group. These were significantly reduced by H₂S (P = 0.005, 0.002).

CONCLUSIONS
H₂S reversed the vasoconstriction changes associated with CsA treatment during reperfusion.

Lee|Gwyn|G|
Hosgood|Sarah A|SA|
Patel|Meeta S|MS|
Nicholson|Michael L|ML|

Hydrogen sulphide
Cyclosporine
Kidney
Ischemia–reperfusion injury


Janus Kinase 3, a Novel Regulator for Smooth Muscle Proliferation and Vascular Remodeling.

Abstract:
OBJECTIVE
Vascular remodeling because of smooth muscle cell (SMC) proliferation is a common process occurring in several vascular diseases, such as atherosclerosis, aortic aneurysm, post-transplant vasculopathy, restenosis after angioplasty, etc. The molecular mechanism underlying SMC proliferation, however, is not completely understood. The objective of this study is to determine the role and mechanism of Janus kinase 3 (JAK3) in vascular remodeling and SMC proliferation.

APPROACH AND RESULTS
Platelet-derived growth factor-BB, an SMC mitogen, induces JAK3 expression and phosphorylation while stimulating SMC proliferation. Janex-1, a specific inhibitor of JAK3, or knockdown of JAK3 by short hairpin RNA, inhibits the SMC proliferation. Conversely, ectopic expression of JAK3 promotes SMC proliferation. Mechanistically, JAK3 promotes the phosphorylation of signal transducer and activator of transcription 3 and c-Jun N-terminal kinase in SMC, 2 signaling pathways known to be critical for SMC proliferation and vascular remodeling. Blockade of these 2 signaling pathways by their inhibitors impeded the JAK3-mediated SMC proliferation. In vivo, knockdown of JAK3 attenuates injury-induced neointima formation with attenuated neointimal SMC proliferation. Knockdown of JAK3 also induces neointimal SMC apoptosis in rat carotid artery balloon injury model.

CONCLUSIONS
Our results demonstrate that JAK3 mediates SMC proliferation and survival during injury-induced vascular remodeling, which provides a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.

Wang|Yung-Chun|YC| Cui|Xiao-Bing|XB| Chuang|Ya-Hui|YH| Chen|Shi-You|SY|

Janus kinase 3
smooth muscle proliferation
vascular remodeling
apoptosis
interleukin


The longer term impact of a novel rural mental health recruitment strategy: A quasi-experimental study.

Abstract:
INTRODUCTION
This study examines the longer term impact of the Gippsland Mental Health Vacation School program, an initiative designed to orientate preregistration allied health and nursing students to rural mental health employment and career opportunities.

METHODS
Student participants from vacation schools held from July 2010 to August 2013 were invited to complete on-line surveys prior to, immediately following and 6 months after the event. Participant rating of Interest in rural work, mental health work and rural mental health work and responses to the student attitudes to rural practice and life questionnaire were analyzed using repeated measure analyses of variance.

RESULTS
There was a large and significant positive increase in pre to post scores for student interest and attitudes to working in and career in the rural mental health sector. These gains in interest and attitudes fell away by approximately 50% in the six months following the program. The changes in attitudes toward rural work remained significant six months after the program, while attitudes to rural life at six months following the program were not-significantly different to the preprogram scores.

CONCLUSIONS
The findings highlight that although a short term program designed to attract students to rural mental health work can positively change participants' interest in and attitudes toward rural work and life, the change diminishes over time. However, interest in rural work and career and rural work attitudes generally maintain significant improvement in the longer term. These differential findings have important implications for developing strategies to overcome rural mental health workforce shortages.

Sutton|Keith P|KP|
Maybery|Darryl|D|
Patrick|Kent J|KJ|

D003156:Community Mental Health Services

rural
recruitment
student
career choice
mental health profession


SBRT planning for liver metastases: A focus on immobilization, motion management and planning imaging techniques.

Abstract:
AIM
To evaluate the different techniques used for liver metastases Stereotactic Body Radiation Therapy (SBRT) planning. We especially focused on immobilization devices, motion management and imaging used for contouring.

BACKGROUND
Although some guidelines exist, there is no consensus regarding the minimal requirements for liver SBRT treatments.

MATERIALS AND METHODS
We reviewed the main liver metastases SBRT publications and guidelines; and compared the techniques used for immobilization, motion management, margins and imaging.

RESULTS
There is a wide variety of techniques used for immobilization, motion management and planning imaging.

CONCLUSIONS
We provide a subjective critical analysis of minimal requirements and ideal technique for liver SBRT planning.

Riou|Olivier|O|
Llacer Moscardo|Carmen|C|
Fenoglietto|Pascal|P|
Deshayes|Emmanuel|E|
Tetreau|Raphaël|R|
Molinier|Jessica|J|
Lenglet|Alexis|A|
Assenat|Eric|E|
Ychou|Marc|M|
Guiu|Boris|B|
Aillères|Norbert|N|
Bedos|Ludovic|L|
Azria|David|D|

SBRT
Planning
Liver metastases
Immobilization
Motion management
Contouring


Supratentorial CAPNON associated with WHO grade II meningioma: A case report.

Abstract: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign tumor of uncertain etiology, arising in the craniospinal axis. CAPNON typically arises in isolation, with only two prior reports of a concurrent second neoplasm. Here, we report the case of a male 17-year-old who presented with new-onset seizures. MRIs revealed a 2 cm extra-axial solid-cystic mass, arising at the left temporo-occipital junction and abutting the dura with marked surrounding parenchymal vasogenic edema. The solid components demonstrated dense calcification and avid enhancement. Gross total surgical resection was performed. Histopathological examination revealed central regions showing characteristic features of CAPNON. Toward the periphery, the CAPNON was intimately associated with and sharply demarcated from a meningioma, which showed up to five mitoses per 10 high-power fields and had invasion into the adjacent brain parenchyma, warranting a WHO grade II designation. This is the first report of CAPNON arising in association with a meningioma. The coexistence of these two tumors raises the possibility of a reactive/dysplastic etiology for CAPNON.

Paolini|Michael A|MA|
Ho|Mai-Lan|ML|
Monahan|Hannah R|HR|
Raghunathan|Aditya|A|

pseudoneoplasm
atypical meningioma
collision tumor
intracranial calcifying tumor
meninges


Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses.

Abstract: The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.

horse
equine melanocytic tumor
oncology
skin neoplasia
topical drug
triterpenoids


In silico analysis of single-cell RNA sequencing data from 3 and 7 days old mouse spermatogonial stem cells to identify their differentially expressed genes and transcriptional regulators.

Abstract: Spermatogonial stem cells (SSCs), which are at the basis of spermatogenesis process, are valuable cells with different applications in biotechnology and regenerative medicine. Understanding the molecular basis of SSC self-renewal and differentiation at various developmental stages of the male organism is crucial to find key factors in the SSCs fate and function. Therefore, this study was aimed to use single-cell RNA-sequencing dataset analysis for identification of differentially expressed genes (DEGs) and their regulators in 3 and 7 days old mouse-derived single SSCs (mSSCs). Results showed 68 upregulated and 203 downregulated genes in 7 days old mouse-derived SSCs compared to 3 days old mSSCs, which were associated with 1493 and 3077 biological processes, respectively. It also found that DAZL, FKBP6, PAIP2, DDX4, H3F3B, TEX15, XRN2, MAEL, and SOD1 are important factors with the higher gene expression pattern, which may be pivotal for mSSCs fate and function during development of germ cells. Moreover, NR3C1, RXRA, NCOA, ESR1, PML, ATF2, BMI1, POU5F1, and CHD1 were the main central regulators for the upregulated DEGs, while HNF1A, C/EBPα, and NFATC1 were the master regulators for the downregulated DEGs. In this regard, two significant protein complexes were found in the protein-protein interactions network for the upregulated DEGs regulators. Furthermore, 24 protein kinases detected upstream of the main central regulators of DEGs. In conclusion, this study presents DEGs and their transcriptional regulators that are crucial for inducing and regulating SSCs commitment during development, and for developing efficient protocols to identify and isolate SSCs for different applications.

D000072956:Adult Germline Stem Cells
D000818:Animals
D003198:Computer Simulation
D020869:Gene Expression Profiling
D005786:Gene Expression Regulation
D008297:Male
D051379:Mice
D060066:Protein Interaction Maps
D017423:Sequence Analysis, RNA
D015398:Signal Transduction
D059010:Single-Cell Analysis
D014158:Transcription, Genetic

spermatogonial stem cell
bioinformatics
differential gene expression
scRNA-seq
transcriptional regulatory proteins


Wolfram Syndrome: Diagnosis, Management, and Treatment.

Abstract: Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. Although there are currently no effective treatments that can delay or reverse the progression of Wolfram syndrome, the use of careful clinical monitoring and supportive care can help relieve the suffering of patients and improve their quality of life. The prognosis of this syndrome is currently poor, and many patients die prematurely with severe neurological disabilities, raising the urgency for developing novel treatments for Wolfram syndrome. In this article, we describe natural history and etiology, provide recommendations for diagnosis and clinical management, and introduce new treatments for Wolfram syndrome.

Wolfram syndrome
Genetic disorder
Neurodegeneration
Blindness
Deafness
Endoplasmic reticulum stress
Type 1 diabetes
Type 2 diabetes
β cells


Assessment of Preclinical Liver and Skeletal Muscle Biomarkers Following Clofibrate Administration in Wistar Rats.

Abstract: Clofibrate is a known rodent hepatotoxicant classically associated with hepatocellular hypertrophy and increased serum activities of cellular alanine aminotransferase/aspartate aminotransferase (ALT/AST) in the absence of microscopic hepatocellular degeneration. At toxic dose, clofibrate induces liver and skeletal muscle injury. The objective of this study was to assess novel liver and skeletal muscle biomarkers following clofibrate administration in Wistar rats at different dose levels for 7 days. In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase. Skeletal muscle injury was evaluated with fatty acid binding protein 3 (Fabp3) and myosin light chain 3 (Myl3). Clofibrate-induced hepatocellular hypertrophy and skeletal muscle degeneration (type I rich muscles) were noted microscopically. CK, Fabp3, and Myl3 elevations correlated to myofiber degeneration. Fabp3 and Myl3 outperformed CK for detection of myofiber degeneration of minimal severity. miR-122 and ARG1 results were significantly correlated and indicated the absence of liver toxicity at low doses of clofibrate, despite increased ALT/AST activities. Moreover, combining classical and novel biomarkers (Fabp3, Myl3, ARG1, and miR-122) can be considered a valuable strategy for differentiating increased transaminases due to liver toxicity from skeletal muscle toxicity.

Maliver|Pierre|P| Festag|Matthias|M| Bennecke|Moritz|M| Christen|Francois|F| Bánfai|Balázs|B| Lenz|Barbara|B| Winter|Michael|M|

D056486:Chemical and Drug Induced Liver Injury

biomarkers
clofibrate
Wistar rats
skeletal muscle degeneration
ALT/AST activity
hepatoxicity


Speciation and Bioavailability of Metals in Sediments from a Stream Impacted by Abandoned Mines in Maoshi Town, Southwest of China.

Abstract: The speciation of metals in surface sediments, as well as metal concentrations in muscle and liver of sharpbelly Hemiculter leucisculus from a stream near the Mo-Ni polymetallic mines in Maoshi town were investigated. The results indicated that metal concentrations were generally highest in the most upstream sampling location that is closest to the former mine operation. The total concentrations of Mn in sediments were higher than other metals. The Cr was mainly associated with residual fraction, while the order of bioavailability of metals (sum of the concentrations of exchangeable, reducible, and oxidizable fractions) was as follows: Cd (89.95%) > Mn (82.32%) > Ni (45.58%) > Mo (29.39%) > Hg (29.23%) > As (22.60%) > Pb (17.38%) > Cr (6.21%). The Cd concentration in muscle of H. leucisculus exceeded the permissible limit which indicated that the fish from this area are not safe for human consumption. The potential ecological risks of Cd cannot be ignored in this study area.

Cai|Shenwen|S| Zhou|Shaoqi|S| Wu|Pan|P| Zhao|Jun|J|

Speciation Bioavailability Metal Sediments


Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions.

Abstract:
OBJECTIVE
Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions.

DESIGN
Cross-sectional design.

SETTING
Hospital-based and community-based screening settings.

PARTICIPANTS
A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings.

INTERVENTIONS
Three types of stool tests with bidirectional endoscopy as the reference standard.

OUTCOMES
Sensitivity, specificity and positive and negative likelihood ratios.

RESULTS
For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values.

CONCLUSIONS
The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection.

TRIAL REGISTRATION
NCT01341197 (ClinicalTrial.gov).

Lee|Yi-Chia|YC|
Chiu|Han-Mo|HM|
Chiang|Tsung-Hsien|TH|
Yen|Amy Ming-Fang|AM|
Chiu|Sherry Yueh-Hsia|SY|
Chen|Sam Li-Sheng|SL|
Fann|Jean Ching-Yuan|JC|
Yeh|Yen-Po|YP|
Liao|Chao-Sheng|CS|
Hu|Tsung-Hui|TH|
Tu|Chia-Hung|CH|
Tseng|Ping-Huei|PH|
Chen|Chien-Chuan|CC|
Chen|Mei-Jyh|MJ|
Liou|Jyh-Ming|JM|
Liao|Wei-Chih|WC|
Lai|Yo-Ping|YP|
Wang|Chen-Ping|CP|
Ko|Jenq-Yuh|JY|
Wang|Hsiu-Po|HP|
Chiang|Hung|H|
Lin|Jaw-Town|JT|
Chen|Hsiu-Hsi|HH|
Wu|Ming-Shiang|MS|


Atypical presentation of cystic schwannoma of the sphenoid sinus: a nonsolitary mass with osseous, intracranial and cavernous sinus invasion.

Abstract: Although nearly half of all schwannomas involve the head and neck region, nasal and paranasal sinus presentations are quite rarely seen. Cystic schwannoma, characterized by cyst formation lined by S-100 protein positive membrane-like structures is very uncommonly seen in sphenoid sinus with only a single previously reported case. Here we report a young patient of cystic schwannoma of the paranasal sinuses having epicenter in the sphenoid sinus. The tumor had caused extensive erosion of the skull base and paranasal sinuses and extended intracranially that radiologically mimicked as infected mucocele causing loss of vision. This case denotes the aggressive behavior of such uncommon tumors.

Dutta|Gautam|G|
Singh|Daljit|D|
Singh|Hukum|H|
Singhal|Ghanshyam|G|
Saran|Ravindra Kumar|RK|

Cystic schwannoma
sphenoid sinus
paranasal sinus
mucocele


Comparison of subjective symptoms associated with exposure to low levels of formaldehyde between students enrolled and not enrolled in a gross anatomy course.

Abstract:
OBJECTIVES
This study aimed to evaluate students' subjective symptoms associated with exposure to low levels of formaldehyde (FA) during a gross anatomy course and to survey how the risk of subjective symptoms was affected by exposure to FA.

METHODS
We conducted three questionnaire surveys of 125 students enrolled in an anatomy course (FA exposure group) and 124 students not enrolled in the course (FA nonexposure group) before, during, and 6 months after the course. The questionnaire included questions inquiring about subjective symptoms, sex, age, and allergies. We analyzed differences in the prevalence of subjective symptoms in distinct survey periods. Furthermore, we analyzed the relationship between the subjective symptoms and exposure to FA after adjusting for allergy, sex, and age using multiple logistic regression analysis.

RESULTS
The prevalence of some of the ocular, nasal, and nonspecific symptoms in the FA exposure group was low before the course, increased during the course and decreased 6 months after the course. A significant positive relationship was observed between exposure to FA and some symptoms after adjusting for allergy, sex, and age.

CONCLUSIONS
We identified some concrete symptoms associated with exposure to FA. We suggest that the exposure to low levels of FA influences students' subjective symptoms.

Mori|Mihoko|M| Matsumoto|Yuuki|Y| Kushino|Nanae|N| Morimatsu|Yoshitaka|Y| Hoshiko|Michiko|M| Saga|Tsuyoshi|T| Yamaki|Koh-ichi|K| Ishitake|Tatsuya|T|

Subjective symptoms
Exposure
Formaldehyde
Gross anatomy course
Allergy


Prolonged Delivery of Apomorphine Through the Buccal Mucosa, Towards a Noninvasive Sustained Administration Method in Parkinson's Disease: In Vivo Investigations in Pigs.

Abstract: In the current work, prolonged systemic delivery of apomorphine via buccal mucosa was shown to be a promising treatment for Parkinson's disease as a substitute for clinically utilized subcutaneous infusions. Due to extensive 'first-pass' metabolism, apomorphine is administered parenterally to bypass liver metabolism. Drawbacks of parenteral administration cause low patient compliance and adherence to treatment. On the other hand, while also bypassing the liver, delivery through buccal mucosa has a superior safety profile, is less costly, lacks pain and discomfort, and possesses excellent accessibility, overall augmenting patient compliance. Current in vivo study in pigs showed: (1) steady plateau levels of apomorphine in plasma were obtained 30 min following administration and remained constant for 8 h until a delivery device was removed, (2) bioavailability of apomorphine was 55%-80% as opposed to <2% peroral and (3) simulation of the pharmacokinetic profile obtained in pigs predicted therapeutically relevant levels of apomorphine in human. Furthermore, antipyrine was incorporated as a permeation marker to enable mechanistic investigation of apomorphine release from the delivery device and its permeation through the buccal mucosa. In addition, limitations of an Ussing diffusion chamber as an ex vivo research tool were also discussed.

Itin|Constantin|C|
Komargodski|Rinat|R|
Barasch|Dinorah|D|
Domb|Abraham J|AJ|
Hoffman|Amnon|A|

Prolonged delivery
Apomorphine
Buccal
Bioavailability
Pharmacokinetics
Antipyrine
Buccal delivery
Controlled delivery
Drug delivery system
Transmucosal drug delivery


The effect of pyruvate on the development and progression of post-stroke depression: A new therapeutic approach.

Abstract: Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood brain barrier (BBB) breakdown, cerebrospinal fluid and blood glutamate levels. Anxiety-like behavior and levels of blood alanine and α-ketoglutarate were measured in naïve rats treated with pyruvate, as a control. Post-stroke neurological deficit with concurrent elevation in glutamate levels were demonstrated, with peak glutamate levels 24 h after MCAO. Treatment with pyruvate led to reduced glutamate levels 24 h after MCAO and improved neurologic recovery. Pyruvate treatment reduced lesion volume, brain edema and the extent of BBB permeability 24 h post-MCAO. Naïve rats treated with pyruvate showed increased levels of α-ketoglutarate. Rats demonstrated post-stroke depressive behavior that was improved by the administration of pyruvate. There was less anxiety-like behavior in post-stroke rats treated with placebo in comparison to the post-stroke rats treated with pyruvate or sham operated rats. Glutamate scavenging with pyruvate appears to be an effective as a method in providing neuroprotection following stroke and as a therapeutic option for the treatment of PSD by reducing the consequent elevations in CNS glutamate levels.

Frank|Dmitry|D|
Kuts|Ruslan|R|
Tsenter|Philip|P|
Gruenbaum|Benjamin F|BF|
Grinshpun|Yulia|Y|
Zvenigorodsky|Vladislav|V|
Shelef|Ilan|I|
Natanel|Dmitry|D|
Brotfain|Evgeny|E|
Zlotnik|Alexander|A|
Boyko|Matthew|M|

D020244:Infarction, Middle Cerebral Artery

Pyruvate
Post-stroke depression
Glutamate scavenging
Neuroprotection
Antidepressants
Anxiety


The timing of solid introduction in an 'obesogenic' environment: a narrative review of the evidence and methodological issues.

Abstract:
OBJECTIVE
To evaluate the evidence for association between obesity risk outcomes >12 months of age and timing of solid introduction in healthy term infants in developed countries, the large majority of whom are not exclusively breastfed to six months of age.

METHODS
Studies included were published 1990 to March 2013.

RESULTS
Twenty-six papers with weight status or obesity prevalence outcomes were identified. Studies were predominantly cohort design, most with important methodological limitations. Ten studies reported a positive association. Of these, only two were large, good-quality studies and both examined the outcome of early (<4 months) introduction of solids. None of the four good-quality studies that directly evaluated current guidelines provided evidence of any clinically relevant protective effect of solid introduction from 4-5 versus ≥6 months of age.

CONCLUSION
The introduction of solids prior to 4 months of age may result in increased risk of childhood obesity but there is little evidence of adverse weight status outcomes associated with introducing solids at 4-6 rather than at six months.

IMPLICATIONS
More and better quality evidence is required to inform guidelines on the 'when, what and how' of complementary feeding.

Daniels|Lynne|L|
Mallan|Kimberley M|KM|
Fildes|Alison|A|
Wilson|Jacinda|J|

D007227:Infant Nutritional Physiological Phenomena

narrative review
obesity
developed countries
complementary feeding


In vitro assessment of the Apico Aortic Blood Pump: anatomical positioning, hydrodynamic performance, hemolysis studies, and analysis in a hybrid cardiovascular simulator.

Abstract: The Apico Aortic Blood Pump (AABP) is a centrifugal continuous flow left ventricular assist device (LVAD) with ceramic bearings. The device is in the initial development phase and is being designed to be attached directly to the left ventricular apex by introducing an inlet cannula. This paper reports results from in vitro experiments. In order to evaluate implantation procedures and device dimensioning, in vitro experiments included an anatomic positioning study for the analysis of surgical implantation procedure and device dimensions and positioning that was performed using the body of a pig. The results revealed no damage caused by the device, and the surgical implantation procedure was considered feasible. Hydrodynamic performance curves were obtained to verify the applicability of the device as an LVAD, showing adequate performance. Mechanical blood trauma was analyzed through 6-h hemolysis tests, with total pressure head of 100 mm Hg and flow of 5 L/min. Mean normalized index of hemolysis was 0.009 g/100 L (±0.002 g/100 L). Studies using a hybrid cardiovascular simulator were conducted for three types of circulatory conditions: normal healthy conditions, concentric hypertrophic heart failure (CHHF), and CHHF with AABP assistance. Analysis of cardiovascular parameters under those three conditions demonstrated that when the AABP was assisting the system, parameters under CHHF conditions went back to normal healthy values, indicating the AABP's effectiveness as CHHF therapy. Our preliminary results indicate that it is feasible to use the AABP as a LVAD. The next steps include long-term in vivo experiments.

da Silva|Bruno Utiyama|BU|
Jatene|Adib Domingos|AD|
Leme|Juliana|J|
Fonseca|Jeison W G|JW|
Silva|Cibele|C|
Uebelhart|Beatriz|B|
Suzuki|Carlos Kenichi|CK|
Andrade|Aron J P|AJ|

Left ventricular assist device
Hemolysis tests
Rotary blood pump


Anticytomegalovirus antibody titres are not associated with caregiving burden in younger caregivers.

Abstract:
OBJECTIVE
This analysis examines whether or not younger caregivers, parents of children with developmental disabilities, differed from controls in terms of cytomegalovirus (CMV) seropositivity and CMV-specific antibody titre. Secondly, it examined whether any particular socio-demographics, health behaviours, or psychological/caregiving variables were associated with a higher CMV antibody titre among caregivers.

DESIGN
Young caregivers and age- and sex-matched controls were compared with respect to their reported health behaviour and psychosocial status as well as latent virus control.

METHODS
One hundred and seventeen parents of children with developmental disabilities and 52 control parents completed standard measures of health behaviours, socio-demographics, perceived stress, depression and anxiety, caregiver burden, child problem behaviours. They also provided a blood sample assayed for the presence of CMV-specific antibody.

RESULTS
Caregivers were no more likely to be CMV positive than controls and did not have higher antibody titres against CMV. In addition, there was no association between CMV antibody titre in seropositive caregivers and any of the psychological/caregiving variables. However, higher CMV antibody titres were significantly associated with a higher BMI, lower exercise levels, smoking, and lower fruit and vegetable and fat intake among seropositive caregivers.

CONCLUSIONS
These data suggest that in the absence of immunosenescence, the chronic stress of caregiving is not sufficient to compromise the immune response to persistent CMV infection. However, an indirect mechanism to poorer health in caregivers might be via adoption of disadvantageous health behaviours in response to stress. Statement of contribution What is already known on this subject? Older caregivers of spouses with dementia show a poorer immune response against latent viruses when compared to age- and sex-matched controls. Younger parental caregivers of children with developmental disabilities show a poorer antibody response to vaccination. What does this study add? The study showed no association between caregiving stress and CMV antibody titre in young caregivers. There were higher CMV antibody titres in the caregivers who engage in unhealthy behaviours.

Vitlic|Ana|A|
Phillips|Anna C|AC|
Gallagher|Stephen|S|
Oliver|Chris|C|
Lord|Janet M|JM|
Moss|Paul|P|

antibody caregiving cytomegalovirus stress


Continuous flow reduction of artemisinic acid utilizing multi-injection strategies-closing the gap towards a fully continuous synthesis of antimalarial drugs.

Abstract: One of the rare alternative reagents for the reduction of carbon-carbon double bonds is diimide (HN=NH), which can be generated in situ from hydrazine hydrate (N2H4⋅H2O) and O2. Although this selective method is extremely clean and powerful, it is rarely used, as the rate-determining oxidation of hydrazine in the absence of a catalyst is relatively slow using conventional batch protocols. A continuous high-temperature/high-pressure methodology dramatically enhances the initial oxidation step, at the same time allowing for a safe and scalable processing of the hazardous reaction mixture. Simple alkenes can be selectively reduced within 10-20 min at 100-120 °C and 20 bar O2 pressure. The development of a multi-injection reactor platform for the periodic addition of N2H4⋅H2O enables the reduction of less reactive olefins even at lower reaction temperatures. This concept was utilized for the highly selective reduction of artemisinic acid to dihydroartemisinic acid, the precursor molecule for the semisynthesis of the antimalarial drug artemisinin. The industrially relevant reduction was achieved by using four consecutive liquid feeds (of N2H4⋅H2O) and residence time units resulting in a highly selective reduction within approximately 40 min at 60 °C and 20 bar O2 pressure, providing dihydroartemisinic acid in ≥93% yield and ≥95% selectivity.

Pieber|Bartholomäus|B|
Glasnov|Toma|T|
Kappe|C Oliver|CO|

reduction
antimalarial drugs
flow chemistry
reactor design
synthetic methods


Glycome complexity of human seminal plasma high molecular mass components: Evaluation of the contribution of acid-soluble glycoproteins/mucins and extracellular vesicles.

Abstract: This study was aimed at evaluation of the contribution of acid-soluble glycoproteins (ASG)/mucins and extracellular vesicles (EVs), yet unexplored components of human seminal plasma (hSP) to the complexity of its glycome. Gaining insight into the native presentation and distribution of glycans across hSP could help establish molecular environments supporting specific biological activities based on unique ligand capacities. Soluble and particulate fractions of hSP from healthy subjects were analyzed by gel filtration, electrophoresis, ion-exchange chromatography and a solid phase assay with immobilized charge-resolved glycospecies to test their reactivity with plant lectins, carbohydrate-binding antibodies and selected human lectins. Common O- and N-glycosylated species were detected on mixed or overlapped underlying protein scaffolds in both soluble and particulate fractions of hSP. Siaα2,6Gal and N-glycans were concentrated on EVs, whereas Siaα2,3Gal, T and Tn antigens were selectively associated with distinct glycospecies of ASG/mucins. Accessible ligands for the lectins, DC-SIGN and Siglec-9, were detected in all hSP components, but they preferentially bound to EVs glycospecies. Insight into the complexity of hSP glycans as recognition signals under normal physiological conditions could be of interest for regulation and possible modulation of its biological activity, as well as for biomarker potential related to male health.

Milutinovic|Bojana|B| Mitic|Ninoslav|N| Roncevic|Jelena|J| Goc|Sanja|S| Jankovic|Miroslava|M|

D063265:Sialic Acid Binding Immunoglobulin-like Lectins

Glycome
Seminal plasma
Mucins
Extracellular vesicles


Ischemic appendicitis due to pelvic adhesions: a case report.

Abstract: Acute appendicitis is one of the most common etiologies of a surgical abdomen. The lifetime risk is estimated to be 7%. Over 300 000 appendectomies occur annually in the USA. The pathophysiology of appendicitis in most patients is believed to be caused by outflow obstruction of the appendiceal lumen leading to increased intraluminal pressure, venous congestion and mucosal ischemia. This can occur due to a variety of internal obstructive causes such as a fecalith, lymphoid hyperplasia, parasites or a tumor. To date, no case reports describing appendicitis secondary to external compression of the appendix leading to outflow obstruction been documented in the literature. This case report describes a 61-year-old female who had a thick, adhesive band compressing the base of her appendix, which created external outflow obstruction leading to the development of appendicitis.

appendicitis
pelvic adhesions
ischemia
intraabdominal adhesions