ZnIn2S4 grown on nitrogen-doped hollow carbon spheres: An advanced catalyst for Cr(VI) reduction.

Abstract: Up to now, the environmental damage by heavy metal is getting worse and worse as the development of industry. Meanwhile, hexavalent chromium (Cr(VI)) in wastewater get special attention as its acute toxicity and potential carcinogencity. To solve this problem, we introduce a simple and efficient way to prepare a photocatalyst, ZnIn2S4 grown on nitrogen-doped hollow carbon spheres (ZIS-NHC), which is an effective catalyst that can used to reduce aqueous Cr(VI). This photocatalyst prepared by a three-step strategy. Benefiting from the excellent electrical conductivity and high specific surface area of the NHC which is superior to other carbon material and the favorable band gap of ZnIn2S4 makes ZIS-NHC has superior light-driven photocatalytic efficiency. The ZIS-NHC exhibits an excellent rate of degradation of aqueous Cr(VI) at a concentration of 50 mg/L within 50 min. Moreover, the ZIS-NHC retained excellent stability after five rounds of cycling experiments which was also discussed.

Cheng|Cheng|C| Chen|Dongyun|D| Li|Najun|N| Xu|Qingfeng|Q| Li|Hua|H| He|Jinghui|J| Lu|Jianmei|J|

Photocatalyst
Hexavalent chromium Cr(VI)
Nitrogen doped hollow carbon sphere
ZnIn(2)S(4)


Sensory stimulus-sensitive drop attacks and basal ganglia calcification: new findings in a patient with FOLR1 deficiency.

Abstract: Loss-of-function mutations in the FOLR1 gene (MIM *136430), encoding the folate receptor alpha, impair cerebral folate transport and lead to a progressive neurometabolic disorder. We report on a 5-year-old boy with progressive ataxia, from the age of 2 years and 6 months, with myoclonic jerks, regression, and impressive myoclonic tonic spasms with drop attacks, which were partially provoked by touching his face or washing his hands. Delayed myelination and cerebellar atrophy on cranial MRI were important clues to the diagnosis of cerebral folate transport deficiency, which was confirmed by homozygosity for the known nonsense mutation p.R204X in the FOLR1 gene. Computed tomography taken after head injury revealed bilateral calcifications in the basal ganglia as a novel finding in a patient with FOLR1 mutation.

Toelle|Sandra P|SP|
Wille|David|D|
Schmitt|Bernhard|B|
Scheer|Ianina|I|
Thöny|Beat|B|
Plecko|Barbara|B|

D020022:Genetic Predisposition to Disease

FOLR1 MTHF drop-attacks hypomyelination myoclonus


Structured Reporting of Rectal Cancer Staging and Restaging: A Consensus Proposal.

Abstract:
BACKGROUND
Structured reporting (SR) in oncologic imaging is becoming necessary and has recently been recognized by major scientific societies. The aim of this study was to build MRI-based structured reports for rectal cancer (RC) staging and restaging in order to provide clinicians all critical tumor information.

MATERIALS AND METHODS
A panel of radiologist experts in abdominal imaging, called the members of the Italian Society of Medical and Interventional Radiology, was established. The modified Delphi process was used to build the SR and to assess the level of agreement in all sections. The Cronbach's alpha (Cα) correlation coefficient was used to assess the internal consistency of each section and to measure the quality analysis according to the average inter-item correlation. The intraclass correlation coefficient (ICC) was also evaluated.

RESULTS
After the second Delphi round of the SR RC staging, the panelists' single scores and sum of scores were 3.8 (range 2-4) and 169, and the SR RC restaging panelists' single scores and sum of scores were 3.7 (range 2-4) and 148, respectively. The Cα correlation coefficient was 0.79 for SR staging and 0.81 for SR restaging. The ICCs for the SR RC staging and restaging were 0.78 (p < 0.01) and 0.82 (p < 0.01), respectively. The final SR version was built and included 53 items for RC staging and 50 items for RC restaging.

CONCLUSIONS
The final version of the structured reports of MRI-based RC staging and restaging should be a helpful and promising tool for clinicians in managing cancer patients properly. Structured reports collect all Patient Clinical Data, Clinical Evaluations and relevant key findings of Rectal Cancer, both in staging and restaging, and can facilitate clinical decision-making.

structured reporting
rectal cancer
staging
magnetic resonance imaging
re-staging


Multiple Lines of Evidence from Mitochondrial Genomes Resolve Phylogenetic Relationships of Parasitic Wasps in Braconidae.

Abstract: The rapid increase in the number of mitochondrial genomes in public databases provides opportunities for insect phylogenetic studies; but it also provides challenges because of gene rearrangements and variable substitution rates among both lineages and sites. Typically, phylogenetic studies use mitochondrial sequence data but exclude other features of the mitochondrial genome from analyses. Here, we undertook large-scale sequencing of mitochondrial genomes from a worldwide collection of specimens belonging to Braconidae, one of the largest families of Metazoa. The strand-asymmetry of base composition in the mitochondrial genomes of braconids is reversed, providing evidence for monophyly of the Braconidae. We have reconstructed a backbone phylogeny of the major lineages of Braconidae from gene order of the mitochondrial genomes. Standard phylogenetic analyses of DNA sequences provided strong support for both Cyclostomes and Noncyclostomes. Four subfamily complexes, that is, helconoid, euphoroid, sigalphoid, and microgastroid, within the Noncyclostomes were reconstructed robustly, the first three of which formed a monophyletic group sister to the last one. Aphidiinae was recovered as a lineage sister to other groups of Cyclostomes, while the Ichneutinae was recovered as paraphyletic. Separate analyses of the subdivided groups showed congruent relationships, employing different matrices and methods, for the internal nodes of the Cyclostomes and the microgastroid complex of subfamilies. This research, using multiple lines of evidence from mitochondrial genomes, illustrates multiple uses of mitochondrial genomes for phylogenetic inference in Braconidae.

Li|Qian|Q|
Wei|Shu-Jun|SJ|
Tang|Pu|P|
Wu|Qiong|Q|
Shi|Min|M|
Sharkey|Michael J|MJ|
Chen|Xue-Xin|XX|

Braconidae
gene rearrangement
phylogeny
Hymenoptera
strand asymmetry


Sex differences in hypothalamic-pituitary-adrenal axis regulation after chronic unpredictable stress.

Abstract:
INTRODUCTION
Exposure to stress, mediated through the hypothalamic-pituitary-adrenal (HPA) axis, elicits sex differences in endocrine, neurological, and behavioral responses. However, the sex-specific factors that confer resilience or vulnerability to stress and stress-associated psychiatric disorders remain largely unknown. The evident sex differences in stress-related disease prevalence suggest the underlying differences in the neurobiological underpinnings of HPA axis regulation.

METHOD
Here, we used a chronic unpredictable stress (CUS) model to investigate the behavioral and biochemical responses of the HPA axis in C57BL/6 mice. Animals were tested in the open field and forced swim test to examine anxiety-like and depressive-like behaviors. Plasma corticosterone levels were measured after behavior and CUS, and glucocorticoid receptor (GR) expression and cytosolic and nuclear fractions of binding protein FKBP51 expression were taken to measure function and regulation of the stress response.

RESULTS
Our results indicate increased depressive-like behavior in males and females which correlated with increased corticosterone levels following CUS. However, females displayed more anxiety-like behaviors with and without CUS. Interestingly, we found trends toward dysregulation of GR protein expression in CUS females, and an increase in the GR inhibitory protein, FKBP51, in the cytosol of CUS males but not females.

CONCLUSION
These results suggest biochemical alterations to the HPA axis regulation which may elicit a glucocorticoid resistance in females after chronic stress and may contribute to the sex-biased vulnerability to stress-related psychiatric disorders.

sex differences
HPA axis
glucocorticoid receptor
FKBP51
chronic stress


Social-Ecological Barriers to Access to Healthcare for Adolescents: A Scoping Review.

Abstract: Access to healthcare for adolescents is often overlooked in the United States due to federal and state-sponsored insurance programs such as Medicaid and the Children's Health Insurance Program. While these types of programs provide some relief, the issue of healthcare access goes beyond insurance coverage and includes an array of ecological factors that hinder youths from receiving services. The purpose of this scoping review was to identify social-ecological barriers to adolescents' healthcare access and utilization in the United States. We followed the PRISMA and scoping review methodological framework to conduct a comprehensive literature search in eight electronic databases for peer-reviewed articles published between 2010 and 2020. An inductive content analysis was performed to thematize the categories identified in the data extraction based on the Social-Ecological Model (SEM). Fifty studies were identified. Barriers across the five SEM levels emerged as primary themes within the literature, including intrapersonal-limited knowledge of and poor previous experiences with healthcare services, interpersonal-cultural and linguistic barriers, organizational-structural barriers in healthcare systems, community-social stigma, and policy-inadequate insurance coverage. Healthcare access for adolescents is a systems-level problem requiring a multifaceted approach that considers complex and adaptive behaviors.

adolescents
healthcare access
health services
healthcare utilization


The American Cancer Society's Cancer Prevention Study 3 (CPS-3): Recruitment, study design, and baseline characteristics.

Abstract:
BACKGROUND
Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology.

METHODS
The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index.

RESULTS
In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years.

CONCLUSIONS
CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society.

Patel|Alpa V|AV|
Jacobs|Eric J|EJ|
Dudas|Daniela M|DM|
Briggs|Peter J|PJ|
Lichtman|Cari J|CJ|
Bain|Elizabeth B|EB|
Stevens|Victoria L|VL|
McCullough|Marjorie L|ML|
Teras|Lauren R|LR|
Campbell|Peter T|PT|
Gaudet|Mia M|MM|
Kirkland|Elizabeth G|EG|
Rittase|Melissa H|MH|
Joiner|Nance|N|
Diver|W Ryan|WR|
Hildebrand|Janet S|JS|
Yaw|Nancy C|NC|
Gapstur|Susan M|SM|

Cancer Prevention Study
recruitment
study design
prospective cohort
epidemiology


Noninvasive monitoring of plasma L-dopa concentrations using sweat samples in Parkinson's disease.

Abstract:
BACKGROUND
L-dopa (l-3,4-dihydroxyphenylalanine) is commonly used for treating Parkinson's disease (PD). However, regardless of its prominent effect, therapeutic range of L-dopa narrows down with disease progression, which leads to development of motor complications including wearing off and dyskinesias. In addition, intestinal absorption of L-dopa is inversely correlated with the amount of oral protein intake, and shows intra- and inter-day variability. Hence, frequent monitoring of plasma L-dopa concentrations is beneficial, but frequent venipuncture imposes physical and psychological burdens on patients with PD.

METHODS
We investigated the usefulness of sweat samples instead of plasma samples for monitoring L-dopa concentrations. With a monolithic silica disk-packed spin column and the high-performance liquid chromatography-electrochemical detection system, L-dopa in sweat samples was successfully quantified and analyzed in 23 PD patients.

RESULTS
We found that the Pearson's correlation coefficient of the plasma and sweat l-dopa concentrations was 0.678. Although the disease durations and severities were not correlated with the deviation of the actual sweat L-dopa concentrations from the fitted line, acquisition of the sweat samples under a stable condition was technically difficult in severely affected patients. The deviations may also be partly accounted for by skin permeability of L-dopa.

CONCLUSIONS
Measuring L-dopa concentrations in sweat is suitable to get further insights into the L-dopa metabolism.

Tsunoda|Makoto|M| Hirayama|Masaaki|M| Tsuda|Takao|T| Ohno|Kinji|K|

Plasma l-dopa
Parkinson's disease
Sweat l-dopa


Citric acid and itaconic acid accumulation: variations of the same story?

Abstract: Citric acid production by Aspergillus niger and itaconic acid production by Aspergillus terreus are two major examples of technical scale fungal fermentations based on metabolic overflow of primary metabolism. Both organic acids are formed by the same metabolic pathway, but whereas citric acid is the end product in A. niger, A. terreus performs two additional enzymatic steps leading to itaconic acid. Despite of this high similarity, the optimization of the production process and the mechanism and regulation of overflow of these two acids has mostly been investigated independently, thereby ignoring respective knowledge from the other. In this review, we will highlight where the similarities and the real differences of these two processes occur, which involves various aspects of medium composition, metabolic regulation and compartmentation, transcriptional regulation, and gene evolution. These comparative data may facilitate further investigations of citric acid and itaconic acid accumulation and may contribute to improvements in their industrial production.

Citric acid
Itaconic acid
Aspergillus niger
Aspergillus terreus
Overflow metabolism
Submerged fermentation


Quantitative cross-linking/mass spectrometry using isotope-labelled cross-linkers.

Abstract:
UNLABELLED
Dynamic proteins and multi-protein complexes govern most biological processes. Cross-linking/mass spectrometry (CLMS) is increasingly successful in providing residue-resolution data on static proteinaceous structures. Here we investigate the technical feasibility of recording dynamic processes using isotope-labelling for quantitation. We cross-linked human serum albumin (HSA) with the readily available cross-linker BS3-d0/4 in different heavy/light ratios. We found two limitations. First, isotope labelling reduced the number of identified cross-links. This is in line with similar findings when identifying proteins. Second, standard quantitative proteomics software was not suitable for work with cross-linking. To ameliorate this we wrote a basic open source application, XiQ. Using XiQ we could establish that quantitative CLMS was technically feasible.

BIOLOGICAL SIGNIFICANCE
Cross-linking/mass spectrometry (CLMS) has become a powerful tool for providing residue-resolution data on static proteinaceous structures. Adding quantitation to CLMS will extend its ability of recording dynamic processes. Here we introduce a cross-linking specific quantitation strategy by using isotope labelled cross-linkers. Using a model system, we demonstrate the principle and feasibility of quantifying cross-linking data and discuss challenges one may encounter while doing so. We then provide a basic open source application, XiQ, to carry out automated quantitation of CLMS data. Our work lays the foundations of studying the molecular details of biological processes at greater ease than this could be done so far.

Fischer|Lutz|L|
Chen|Zhuo Angel|ZA|
Rappsilber|Juri|J|

Quantitation
Cross-linking
Mass spectrometry
Proteomics
Protein dynamics
Structural biology


Patent disclosure requirements for therapeutic antibody patents.

Abstract: Therapeutic antibodies have grown to become an important product class within the biopharmaceutical market. A prerequisite to their commercialization is adequate patent protection. Disclosure requirements and the types of claims available in different jurisdictions can impact the scope of protection available for antibodies. Areas covered: A comparative review of statutory bases, patent office practices and selected decisions in Canada, the United States and the United Kingdom related to disclosure requirements is provided. Expert opinion: Differences in disclosure requirements exist in different jurisdictions which can impact the type of claims obtained and their survival when attacked in litigation. Including a wide variety of claim types is a key strategy to ensuring therapeutic antibodies are adequately protected. Method of use claims may provide advantages and broader protection in some circumstances and should also be considered.

disclosure requirements
Therapeutic antibodies
patent protection
Canada
United States and United Kingdom
sufficiency
support requirements


Artificial Chromosomes in Rice (Oryza sativa).

Abstract: Chromosomes are the carriers of genetic material in biological organisms. Each chromosome has three essential components: a centromere, telomeres, and origins of replication. The understanding of the essential structural and functional organization of chromosomes has made it possible to produce artificial chromosomes (ACs), which are human-engineered minichromosomes. There are two approaches to make ACs: de novo assembly (bottom-up) and truncation of existing chromosomes (top-down). Rice (Oryza sativa) ACs are produced by telomere-mediated chromosome truncation, and may have many applications, such as genetic engineering to stack and express multiple genes in rice to combat diseases caused by bacteria, fungi, and viruses, to enhance tolerance of rice to environmental stresses such as drought, heat, and salinity, and to improve yield and quality. © 2016 by John Wiley & Sons, Inc.

artificial chromosome
minichromosome
genetic engineering
telomere truncation


Morphology and Multi-Gene Phylogeny Reveal Pestalotiopsis pinicola sp. nov. and a New Host Record of Cladosporium anthropophilum from Edible Pine (Pinus armandii) Seeds in Yunnan Province, China.

Abstract: This study contributes new knowledge on the diversity of conidial fungi in edible pine (Pinus armandii) seeds found in Yunnan Province, China and emphasizes the importance of edible seed products to ensure food safety standards. We isolated two fungal species, one on the pine seed coat and the other on the endosperm of the pine seed. The two fungal species were identified as Pestalotiopsis pinicola sp. nov. and a new host record Cladosporium anthropophilum. Characteristic morphological features of Pestalotiopsis pinicola were used alongside results from multi-gene phylogenetic analysis to distinguish it from currently known species within the genus. Cladosporium anthropophilum was identified as a new host record based on morphological features and phylogenetic analysis. In addition, detailed descriptions, scanned electron microscopy morphology, illustrations, and phylogenetic trees are provided to show the placement of these species.

Tibpromma|Saowaluck|S|
Mortimer|Peter E|PE|
Karunarathna|Samantha C|SC|
Zhan|Fangdong|F|0000-0003-4188-8918
Xu|Jianchu|J|
Promputtha|Itthayakorn|I|
Yan|Kai|K|

ascomycota
endophytic fungi
new taxon
saprobic fungi
taxonomy
weak pathogen


Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease.

Abstract: We examined behaviors and neurotransmitter levels in the tgDimer mouse, a model for early Alzheimer's disease, that expresses exclusively soluble amyloid beta (Aβ) dimers and is devoid of Aβ plaques, astrogliosis, and neuroinflammation. Seven-month-old mice were subjected to tests of motor activity, attention, anxiety, habituation learning, working memory, and depression-related behaviors. They were impaired in nonselective attention and motor learning and showed anxiety- and despair-related behaviors. In 7- and 12-month-old mice, levels of acetylcholine, dopamine, and serotonin were measured in neostriatum, ventral striatum, prefrontal cortex, hippocampus, amygdala, and entorhinal cortex by high-performance liquid chromatography. The tgDimer mice had lower serotonin turnover rates in hippocampus, ventral striatum, and amygdala relative to wild type controls. The aged tgDimer mice had less hippocampal acetylcholine than adult tgDimers. Stress-test results, based on corticosterone levels, indicated an intact hypothalamus-pituitary-adrenal axis in 12-month-old mice. Since neither Aβ plaques nor astrogliosis or neuroinflammation was responsible for these phenotypes, we conclude that Aβ dimers contribute to neurotransmitter dysfunction and behavioral impairments, characteristic for the early stages of Alzheimer's disease.

Abdel-Hafiz|Laila|L|
Müller-Schiffmann|Andreas|A|
Korth|Carsten|C|
Fazari|Benedetta|B|
Chao|Owen Y|OY|
Nikolaus|Susanne|S|
Schäble|Sandra|S|
Herring|Arne|A|
Keyvani|Kathy|K|
Lamounier-Zepter|Valéria|V|
Huston|Joseph P|JP|
de Souza Silva|Maria A|MA|

Alzheimer's disease
tgDimer mouse
Memory
Acetylcholine
5-HT
Amyloid β dimer


Identifying jitter outliers in single fiber electromyography: Comparison of four methods.

Abstract:
BACKGROUND
Little is known about how different outlier estimation methods affect cutoff limits for outliers in single fiber electromyography.

METHODS
We compared in a prospective fashion the established 18th jitter value (18thjv) method to three, whole-distribution based, outlier detection methods: the interquartile range (IQR), the log-normal, and the Z-score method. The reference limits were probed in a normal cohort and in myasthenia gravis (MG) patients.

RESULTS
Differences in outlier cutoff values between the different methods were in the range of 2 μs. The number of abnormal muscles according to the computed criteria was similar for all four methods in the control group. Classification metrics (sensitivity, specificity, Youden's statistic, and predictive values) were also similar among the different methods. In the MG group, however, the Z-score method failed to identify the abnormal jitter values. Accordingly, Kappa agreement was substantial to perfect (0.658 to 1) between the three methods (18thjv, IQR, and log-normal), but was equivalent to chance between the three methods and the Z-score in the MG group.

CONCLUSIONS
The established 18thjv method proved largely robust when compared to whole-distribution based methods, and its use in clinical practice is justified. Simple estimation of outlier limits by adding two SDs to the mean of the data, leads to unacceptable deviations from the true cutoff values. Moreover, in a clinical scenario in which the final electrodiagnosis depends only on the number of outliers, it is meaningful to accept a tolerance zone of about 2 μs, which is the approximate variation range among the different methods.

Anagnostou|Evangelos|E| Dimopoulou|Panagiota|P| Sklavos|Sokratis|S| Zouvelou|Vasiliki|V| Zambelis|Thomas|T|

jitter
outliers
single fiber electromyography
reference values
skewed distribution


Absolute Power Spectral Density Changes in the Magnetoencephalographic Activity During the Transition from Childhood to Adulthood.

Abstract: The aim of this study was to define the pattern of reduction in absolute power spectral density (PSD) of magnetoencephalography (MEG) signals throughout development. Specifically, we wanted to explore whether the human skull's high permeability for electromagnetic fields would allow us to question whether the pattern of absolute PSD reduction observed in the human electroencephalogram is due to an increase in the skull's resistive properties with age. Furthermore, the topography of the MEG signals during maturation was explored, providing additional insights about the areas and brain rhythms related to late maturation in the human brain. To attain these goals, spontaneous MEG activity was recorded from 148 sensors in a sample of 59 subjects divided into three age groups: children/adolescents (7-14 years), young adults (17-20 years) and adults (21-26 years). Statistical testing was carried out by means of an analysis of variance (ANOVA), with "age group" as between-subject factor and "sensor group" as within-subject factor. Additionally, correlations of absolute PSD with age were computed to assess the influence of age on the spectral content of MEG signals. Results showed a broadband PSD decrease in frontal areas, which suggests the late maturation of this region, but also a mild increase in high frequency PSD with age in posterior areas. These findings suggest that the intensity of the neural sources during spontaneous brain activity decreases with age, which may be related to synaptic pruning.

Gómez|Carlos M|CM|
Rodríguez-Martínez|Elena I|EI|
Fernández|Alberto|A|
Maestú|Fernando|F|
Poza|Jesús|J|
Gómez|Carlos|C|

Power spectral density
Magnetoencephalography
Development
Electroencephalography


The beneficial effects of game-based exercise using age-appropriate tennis lessons on the executive functions of 6-12-year-old children.

Abstract: This study evaluated the effects of two different types of tennis lessons-those involving a technique-based approach (TBA) and those involving a game-based approach (PLAY+STAY [P+S])-on the executive functions (EFs) of junior tennis players. Eighty-one tennis players (6-12 years old) were recruited and assigned to one of three groups: TBA, P+S, or watching TV (CONT). Subjects completed evaluations of EFs (inhibitory control, working memory, and cognitive flexibility) before and after 50min programs. The overall score for EFs improved significantly for both the P+S and TBA groups but not for the CONT group; indeed the CONT group showed no improvement in overall EFs. Furthermore, the overall EF score improved more for P+S participants than for those in TBA. Looking at components of EFs, the pattern for inhibitory control reflected the pattern for the overall EF index: Improvement in the P+S and TBA groups but not in the CONT group. Only the P+S group improved in working memory. Thus, playing tennis and practicing isolated tennis skills both improved EFs of junior players more than did watching TV, and game-based tennis lessons seem to hold more promise for improving EFs than drills of tennis skills.

Ishihara|Toru|T| Sugasawa|Shigemi|S| Matsuda|Yusuke|Y| Mizuno|Masao|M|

Inhibitory control
Working memory
Cognitive flexibility
Cognitive engaging exercise
Sports activity


Histopathology of gill, muscle, intestine, kidney, and liver on Myxobolus sp.-infected Koi carp (Cyprinus carpio).

Abstract: This research aims to investigate the clinical symptoms of Myxobolus sp.-infected Koi carp (Cyprinus carpio) and to observe fish histopathology including histological alteration in the intestine, kidney, and liver organs. Descriptive method was employed in this research. The fish sample was obtained from Fish Farmer Group at Nglegok Village in Blitar City. The main observed parameters were the alteration of intestine, kidney, and liver of Koi infected with Myxobolus sp. parasite. The observation result of the histopathology of the parasite-infected fish indicated that necrosis and cyst occurred in the intestine. Necrosis also occurred in kidney, while hyaline degeneration occurred in tubule cells. Furthermore, necrosis and inflammation were also found in liver. It is obvious from the result that Myxobolus sp. infection resulted in the damage of Koi carp vital organs.

Maftuch|Maftuch|M|0000-0002-3941-6033
Sanoesi|Ellana|E|
Farichin|Ichfat|I|
Saputra|Bagus Amin|BA|
Ramdhani|Luqman|L|
Hidayati|Sarifa|S|
Fitriyah|Nurul|N|
Prihanto|Asep A|AA|

Histopathology
Intestine
Kidney
Liver
Koi carp
Myxobolus sp.


Twin Atrioventricular Nodal Reentrant Tachycardia Associated with Heterotaxy Syndrome with Malaligned Atrioventricular Canal Defect and Atrioventricular Discordance.

Abstract: There are limited data on the experience of transbaffle access for catheter ablation in patients who have undergone a Fontan palliation for complex congenital heart. Nevertheless, these issues will be encountered more frequently, because patients who have undergone Fontan palliation continue to survive into adulthood and develop a variety of arrhythmias that may be refractory to medical therapy.

D013611:Tachycardia, Atrioventricular Nodal Reentry

Heterotaxy syndrome
Congenital heart disease
Twin atrioventricular nodes


Vascularized solid iris lesion in a 3 year old child: 5 years of follow up.

Abstract:
BACKGROUND
Iris tumors are rare in young patients. When an iris lesion occurs in a pediatric patient, it can be difficult to classify because of the wide spectrum of iris proliferations.

CASE PRESENTATION
We report on an unusual case of a vascularized iris lesion in a three year old Caucasian patient, with no symptoms and no visual impairment. We evaluated in a 50-month follow up with non-invasive diagnostic tools in order to avoid eye biopsy.

CONCLUSION
We focused attention on the differential diagnoses and underlined the role of non-invasive diagnostic tools in a child to avoid or postpone the eye biopsy. We performed a review of the literature to identify the best medical practice in pediatric iris lesions with atypical characteristics.

Fea|Antonio Maria|AM|
Briamonte|Cristina|C|
Aragno|Vittoria|V|
Grignolo|Federico Maria|FM|

Anterior segment optical coherence tomography


Bilateral Internal Auditory Canal Metastasis of Non-small Cell Lung Cancer.

Abstract: We report on a patient with brain metastasis involving bilateral internal auditory canal from non-small cell lung cancer (NSCLC). A 49-year-old woman who had been diagnosed with NSCLC (T2aN1M0) complained of persistent vertigo and bilateral tinnitus for three months. The patient had refused all treatments, including surgery and chemotherapy; however, she sought alternative medicine. The patient's hearing loss showed rapid progression bilaterally, and rotatory vertigo with peripheral-type nystagmus developed. Magnetic resonance imaging of the brain showed irregular nodular enhancement within both internal auditory canals with leptomeningeal enhancement and multiple intracranial metastasis. The patient was treated with epidermal growth factor receptor-tyrosine kinase inhibitor, and the tumor showed partial response. This was a rare case of multiple brain metastases involving bilateral internal auditory canal from known NSCLC presenting with vertigo and hearing loss.

Kim|Chang-Hee|CH|
Shin|Jung Eun|JE|
Kim|Hee Joung|HJ|
Lee|Kye Young|KY|

Internal auditory canal
Vertigo
Hearing loss
Lung neoplasms
Neoplasm metastasis


Protective Role of α-Calcitonin Gene-Related Peptide in Cardiovascular Diseases.

Abstract: α-Calcitonin gene-related peptide (α-CGRP) is a regulatory neuropeptide of 37 amino acids. It is widely distributed in the central and peripheral nervous system, predominantly in cell bodies of the dorsal root ganglion (DRG). It is the most potent vasodilator known to date and has inotropic and chronotropic effects. Using pharmacological and genetic approaches, our laboratory and other research groups established the protective role of α-CGRP in various cardiovascular diseases such as heart failure, experimental hypertension, myocardial infarction, and myocardial ischemia/reperfusion injury (I/R injury). α-CGRP acts as a depressor to attenuate the rise in blood pressure in three different models of experimental hypertension: (1) DOC-salt, (2) subtotal nephrectomy-salt, and (3) L-NAME-induced hypertension during pregnancy. Subcutaneous administration of α-CGRP lowers the blood pressure in hypertensive and normotensive humans and rodents. Recent studies also demonstrated that an α-CGRP analog, acylated α-CGRP, with extended half-life (~7 h) reduces blood pressure in Ang-II-induced hypertensive mouse, and protects against abdominal aortic constriction (AAC)-induced heart failure. Together, these studies suggest that α-CGRP, native or a modified form, may be a potential therapeutic agent to treat patients suffering from cardiac diseases.

Kumar|Ambrish|A|
Potts|Jay D|JD|
DiPette|Donald J|DJ|

cardiovascular diseases
neuropeptide
heart failure
hypertension
myocardial infarction
calcitonin gene-related peptide (CGRP)


Biocompatible cellulose-based supramolecular nanoparticles driven by host-guest interactions for drug delivery.

Abstract: To extend the applications of natural products in nanomedicine, novel cellulose-based supramolecular nanoparticles (SNPs) were fabricated via a host-guest driven self-assembly strategy here. The adamantane-grafted carboxyethyl hydroxyethyl cellulose and β-cyclodextrin-grafted glycerol ethoxylate were synthesized to self-assemble into the SNPs. Furthermore, doxorubicin (DOX)-functionalized β-cyclodextrin was encapsulated into SNPs via an in situ co-assembly process to generate DOX-loaded SNPs (DOX-SNPs). The SNPs exhibited a quasi-spherical morphology with an average diameter of ∼25 nm. The DOX-SNPs with relatively larger diameter possessed a high DOX loading efficiency (∼94 %) and the pH-responsive drug release behaviors, which made them suitable as a drug delivery system. In vitro cytotoxicity assays demonstrated the excellent cytocompatibility of SNPs and the efficient inhibition of Hela cell proliferation of DOX-SNPs. Moreover, the DOX-SNPs could effectively enter Hela cells via endocytosis and release DOX under endo/lysosome pH. Thus, this nanocarrier has promising translational potential in cancer therapy and personalized nanomedicine.

Yang|Xuefeng|X| Jiang|Xueyu|X| Yang|Hongye|H| Bian|Liming|L| Chang|Chunyu|C| Zhang|Lina|L|

1-Adamantylamine (Ad-NH(2), PubChem CID: 2130)

2-Hydroxyethyl cellulose (HEC, PubChem CID: 24846132)

Doxorubicin hydrochloride (DOX·HCl, PubChem CID: 443939)

Glycerol ethoxylate (GE, PubChem CID: 88802)

Tetrabutylammonium hydroxide (TBA-OH, PubChem CID: 2723671)

benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, PubChem CID: 2724699)

p-toluenesulfonyl chloride (TsCl, PubChem CID: 7397)

β-cyclodextrin (CD, PubChem CID: 444041)


Role of Neutrophils on the Ocular Surface.

Abstract: The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.

neutrophil
neutrophil extracellular trap
ocular surface disease
dry eye syndrome


Gold nanoparticles against respiratory diseases: oncogenic and viral pathogens review.

Abstract: Nanoscale size-dependent properties give nanomaterials unique specifications that are robust in many applications of human medicine. Gold nanoparticles (AuNPs) have recently gained attention because of their unique optical, physical and electrical properties. AuNPs increase the efficacy of biomedical applications in diagnostic treatments for infectious diseases, by targeting or labeling target cells/bioactive compounds. However, it is imperative to develop the regimens for more accurate diagnostic tools, preventive care and effective therapy. Our critical and comprehensive review presents emerging avenues of molecular diagnostics as well as therapeutics translated into clinical approaches. This manuscript critically reviews the rampant future of AuNPs in the diagnosis and treatment of the most important diseases, such as cancer and viruses of respiratory system.

V|Raji|R|
Pal|Kaushik|K|
Zaheer|Tean|T|0000-0001-8248-6451
Kalarikkal|Nandakumar|N|
Thomas|Sabu|S|0000-0003-4726-5746
de Souza|Fernando Gomes|FG|
Si|Asiya|A|

gold nanoparticles
therapeutics
cancer
COVID-19
coronavirus
imaging
plasmonic


Investigation into the distinct subcellular effects of docosahexaenoic acid loaded low-density lipoprotein nanoparticles in normal and malignant murine liver cells.

Abstract:
BACKGROUND
Recent studies have shown that low density lipoproteins reconstituted with the natural omega 3 fatty acid docosahexaenoic acid (LDL-DHA) is selectively cytotoxic to liver cancer cells over normal hepatocytes. To date, little is known about the subcellular events which transpire following LDL-DHA treatment.

METHODS
Herein, murine noncancer and cancer liver cells, TIB-73 and TIB-75 respectively, were investigated utilizing confocal microscopy, flow cytometry and viability assays to demonstrate differential actions of LDL-DHA nanoparticles in normal versus malignant cells.

RESULTS
Our studies first showed that basal levels of oxidative stress are significantly higher in the malignant TIB-75 cells compared to the normal TIB-73 cells. As such, upon entry of LDL-DHA into the malignant TIB-75 cells, DHA is rapidly oxidized precipitating global and lysosomal lipid peroxidation along with increased lysosomal permeability. This leakage of lysosomal contents and lipid peroxidation products trigger subsequent mitochondrial dysfunction and nuclear injury. The cascade of LDL-DHA mediated lipid peroxidation and organelle damage was partially reversed by the administration of the antioxidant, N-acetylcysteine, or the iron-chelator, deferoxamine. LDL-DHA treatment in the normal TIB-73 cells was well tolerated and did not elicit any cell or organelle injury.

CONCLUSION
These studies have shown that LDL-DHA is selectively cytotoxic to liver cancer cells and that increased levels of ROS and iron catalyzed reactions promote the peroxidation of DHA which lead to organelle dysfunction and ultimately the demise of the cancer cell.

GENERAL SIGNIFICANCE
LDL-DHA selectively disrupts lysosomal, mitochondrial and nuclear function in cancer cells as a novel pathway for eliminating cancer cells.

Moss|Lacy R|LR|
Mulik|Rohit S|RS|
Van Treuren|Tim|T|
Kim|Soo Young|SY|
Corbin|Ian R|IR|

Liver cancer
Lipid peroxidation
Lysosome membrane permeability
Mitochondrial membrane potential
Omega-3 fatty acid


Second pulmonary resection for a second primary lung cancer: analysis of morbidity and survival.

Abstract:
OBJECTIVES
Evaluating morbidity and survival of patients operated on for a second primary non-small-cell lung cancer (NSCLC).

METHODS
Retrospective collection of data from patients operated on for a second NSCLC between 2009 and 2018.

RESULTS
Fifty-two patients met the inclusion criteria. At the time of second pulmonary resection, the median time between the 2 surgeries was 25 months (5-44.5 months). Patients' median age was 65 years (61-68 years). Median tumour size was 16 mm (10-22 mm). Thoracoscopy was used in 75% of cases. The resection was a pneumonectomy (n = 1), bilobectomy (n = 1), lobectomy (n = 15), segmentectomy (n = 32) or wedge resection (n = 3). The length of stay was 7 days (5-9 days). Mortality was null and morbidity was 36.5%, mainly from grade I-II complications according to the Clavien-Dindo classification. The median follow-up was 28 months (13-50 months). The median overall survival was 67 months (95% confidence interval 60.8-73.1 months). Survival at 5 years and specific survival were 71.1% and 67.7%, respectively.

CONCLUSIONS
A second surgical resection of either synchronous or metachronous NSCLC has a morbidity that is not superior to the morbidity of the first operation. The new tumour is usually diagnosed at an early stage. An anatomical sublobar resection is most likely the best compromise. It might also be considered for the first operation when there is a suspicious synchronous lesion that may require surgery at a later stage.

Lung
Cancer
Survival
Surgery
Sublobar resections
Multiple


Comparative Proteomic Analysis of Slime from the Striped Pyjama Squid, Sepioloidea lineolata, and the Southern Bottletail Squid, Sepiadarium austrinum (Cephalopoda: Sepiadariidae).

Abstract: Sepioloidea lineolata, the striped pyjama squid (family Sepiadariidae), is a small species of benthic bobtail squid distributed along the Southern Indo-Pacific coast of Australia. Like other sepiadariid squids, it is known to secrete large volumes of viscous slime when stressed. In order to identify key proteins involved in the function of sepiadariid slimes, we compared the slime proteome of Sepioloidea lineolata with that of a closely related species, Sepiadarium austrinum. Of the 550 protein groups identified in Sepioloidea lineolata slime, 321 had orthologs in Sepiadarium austrinum, and the abundance of these (iBAQ) was highly correlated between species. Both slimes were dominated by a small number of abundant proteins, and several of these were short secreted proteins with no homologues outside the class Cephalopoda. No mucins were identified within either species' slime, suggesting that it is structurally distinct from mucin polymer-based gels found in many vertebrate and echinoderm secretions. The extent of N-glycosylation in the slime of Sepioloidea lineolata was also studied via glycan cleavage with Peptide: N-glycosidase F (PNGase-F). Although very few (four) proteins showed strong evidence of N-glycosylation, we found that treatment with PNGase-F led to a slight increase in peptide identification rates compared with controls.

proteomics squid Cephalopoda Sepiadariidae N-glycosylation transcriptomics


A RE-AIM Analysis of an Intergenerational Dementia Education Program.

Abstract: Objectives: Children often have a lack of dementia understanding and poor attitudes toward people with dementia. Intergenerational programs are increasingly common, but the effects on knowledge and attitudes related to dementia are mixed, especially in the long-term (6 months). Using a RE-AIM framework, we quantitatively evaluated the effects of an educational dementia program (with and without an intergenerational program) on dementia attitudes in the short and long-term, and qualitatively, which elements of the program facilitated this change. Methods: Eighty-one children (9.63 ± 0.52 years, 35 males) from three classes participated in an 8-week dementia education program and 52 also interacted with older adults through an intergenerational experience. Program reach was measured as the percentage of children who participated in the study. The Kids Insight into Dementia Survey (KIDS) was implemented to measure dementia knowledge and attitudes: efficacy and maintenance. Qualitative interviews with all participant groups informed both adoption and implementation. Cost-benefit analysis was used as a secondary outcome measure for efficacy. Results: The program demonstrated strong levels of impact reaching 93% of school children across the three included classes. Efficacy was demonstrated by a positive change in children's dementia knowledge and attitudes immediately post program, which remained increased (as compared to baseline) 6- months post intervention; there were no differences between groups (those who interacted with older adults and those who did not). Interviews identified positive changes in children's empathy and improved community awareness. Barriers to adoption included the project scope, time constraints incurred by school terms and the management of children-to-adult ratios. Conclusions: These findings provide the first evidence that school-based dementia education improves knowledge of and attitudes toward people with dementia long-term. We demonstrated programs such as this can be successful in both primary school and wider community settings, with support from school and community partners key to the success.

Smith|Ashleigh E|AE|
Kamm|Georgina L|GL|
Lai|Samantha|S|
Hull|Melissa J|MJ|
Baker|Jess R|JR|
Milte|Rachel|R|
Ratcliffe|Julie|J|
Loetscher|Tobias|T|
Keage|Hannah A D|HAD|

RE-AIM
intergenerational program
school-based
dementia-friendly communities
program evaluation


Why older people stop to drive? A cohort study of older patients admitted to a rehabilitation setting.

Abstract: The aim of this study is to describe the predictive factors of driving cessation at 6-month follow-up in older patients discharged from a rehabilitation setting and evaluated by an occupational therapist in a multidisciplinary team. Of 95 patients, at 6-month 27.4% ceased to drive. The reasons for driving cessation were a patients' voluntary choice (42.3%) or a choice of their family (23.1%), and only in 34.6% of the patients the license was revoked by a medical commission. In a multivariate analysis greater functional impairment-measured with the Timed Up and Go test-(OR 12.60, CI 2.74-57.89; p < 0.01) was the only predictor of driving cessation. This study shows that the ability to walk safely and independently is a significant predictor of driving cessation. The simple assessment of this factor using the TUG might be an easy screening tool to prompt a second level evaluation to accurately identify unsafe driving.

Driving
Age
Functional impairment
Occupational therapy
Older adults


Global Mental Health: Interdisciplinary challenges for a field in motion.

Abstract: In recent years, efforts in Global Mental Health (GMH) have evolved alongside critical engagement with the field's claims and interventions. GMH has shifted its agenda and epistemological underpinnings, increased its evidence base, and joined other global policy platforms such as the Sustainable Development Goals. This editorial introduction to a thematic issue traces the recent shifts in the GMH agenda and discusses the changing construct of "mental health" as GMH moves away from a categorical biomedical model toward dimensional and transdiagnostic approaches and embraces digital technologies. We highlight persistent and emerging lines of inquiry and advocate for meaningful interdisciplinary engagement. Taken together, the articles in this special issue of Transcultural Psychiatry provide a snapshot of current interdisciplinary work in GMH that considers the socio-cultural and historical dimensions of mental health important and proposes reflexive development of interventions and implementation strategies.

D054521:Cultural Competency
D005008:Ethnopsychology
D014943:Global Health
D006801:Humans
D033183:Interdisciplinary Communication
D008603:Mental Health
D000076502:Sustainable Development

Global Mental Health
sustainable development
cultural adaptation
ecosocial view
interdisciplinarity
transdiagnostic interventions


Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

Abstract: We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM.

Landau|Heather|H|
Wood|Kevin|K|
Chung|David J|DJ|
Koehne|Guenther|G|
Lendvai|Nikoletta|N|
Hassoun|Hani|H|
Lesokhin|Alexander|A|
Hoover|Elizabeth|E|
Zheng|Junting|J|
Devlin|Sean M|SM|
Giralt|Sergio|S|

D000971:Antineoplastic Combined Chemotherapy Protocols

D018380:Hematopoietic Stem Cell Transplantation

fractionated
myeloma
transplant
Engraftment
symptom burden


New developments in the use of positive airway pressure for obstructive sleep apnea.

Abstract: Obstructive sleep apnea (OSA) is a disorder which afflicts a large number of individuals around the world. OSA causes sleepiness and is a major cardiovascular risk factor. Since its inception in the early 1980's, continuous positive airway pressure (CPAP) has emerged as the major treatment of OSA, and it has been shown to improve sleepiness, hypertension, and a number of cardiovascular indices. Despite its successes, adherence with treatment remains a major limitation. Herein we will review the evidence behind the use of positive airway pressure (PAP) therapy, its various modes, and the methods employed to improve adherence. We will also discuss the future of PAP therapy in OSA and personalization of care.

Donovan|Lucas M|LM|
Boeder|Schafer|S|
Malhotra|Atul|A|
Patel|Sanjay R|SR|

Obstructive sleep apnea (OSA)
positive airway pressure (PAP)
treatment adherence


Recruitment of SH-containing peptides to lipid and biological membranes through the use of a palmitic acid functionalized with a maleimide group.

Abstract: This study presents a novel and easily applicable approach to recruit sulfhydryl-containing biomolecules to membranes by using a palmitic acid which is functionalized with a maleimide group. Notably, this strategy can also be employed with preformed (biological) membranes. The applicability of the assay is demonstrated by characterizing the binding of a Rhodamine-labeled peptide to lipid and cellular membranes using methods of fluorescence spectroscopy, lifetime measurement, and microscopy. Our approach offers new possibilities for preparing biologically active liposomes and manipulating living cells.

Haralampiev|Ivan|I| Mertens|Monique|M| Schwarzer|Roland|R| Herrmann|Andreas|A| Volkmer|Rudolf|R| Wessig|Pablo|P| Müller|Peter|P|

peptides
membranes
palmitic acid
maleimide
liposomes
palmitoylation


Indications and diagnostic value of bone marrow examination in HIV-positive individuals: A 3-year review at Tygerberg Hospital.

Abstract:
Background
Bone marrow examination is a useful diagnostic tool in human immunodeficiency virus (HIV)-positive patients presenting with cytopenias and fever. However, its role in the afebrile and asymptomatic patient presenting with an isolated cytopenia is not well established. This study was conducted to determine the indications for bone marrow examination and its diagnostic yield, in HIV-positive patients at Tygerberg Hospital.

Methods
A retrospective, cross-sectional descriptive study was performed over a 3-year period from 01 September 2015 to 31 August 2018. The bone marrow examination reports for the HIV-positive patients who had a bone marrow examination during the study period were retrieved. Clinical and laboratory information was captured.

Results
Altogether 374 bone marrow reports for HIV-positive patients were found. The indication of the bone marrow examination included investigation of unexplained cytopenias, suspected haematological malignancies, follow-up examination for patients with known haematological diseases, staging of haematological or non-haematological malignancies and investigation of suspected disseminated infection. The patients' median age was 43 years and the interquartile range was 27-60 years. There was a slight female predominance with females 51% and males 49%. The diagnostic yield was 33.7%. Acute leukaemia and lymphoma were the most common diagnoses. Haematinic deficiency and pure red cell aplasia were found in the majority of cases with isolated anaemia. All cases with isolated thrombocytopenia were due to immune thrombocytopenia.

Conclusion
Bone marrow examination is a useful investigation for HIV-positive patients with cytopenias, suspected haematological malignancy and lymphoma staging. However, its early use in patients with isolated anaemia and isolated thrombocytopenia is questionable.

indications
bone marrow examination
diagnostic yield
leukaemia
lymphoma
HIV
diagnostic utility
investigation of cytopenia


Protein-derived Smart Materials for Medical Applications: Elastin-like Polypeptides.

Abstract: A group of stimulus-responsive biopolymers developed from the hydrophobic domain of tropoelastin is collectively known as elastin-like polypeptides (ELPs). These peptides generally consist of repeated pentapeptide units of the form (VPGXG)n, where X can be any amino acid with the exception of proline. ELPs present wide-ranging possibilities in biomedicine due to their many beneficial characteristics, including tunable phase transition behavior and biological compatibility, along with the absence of immunogenic and pyrogenic characteristics. The present paper reviews the physicochemical characteristics of ELPs and outlines a range of applications in biotechnology and medicine.

endoscopic
submucosal injection solution


Diagnostic Performance of Multiparametric Transrectal Ultrasound in Localized Prostate Cancer: A Comparative Study With Magnetic Resonance Imaging.

Abstract:
OBJECTIVES
The aim of this study was to compare the diagnostic performance of multiparametric transrectal ultrasound (TRUS), including grayscale imaging, color Doppler imaging, shear wave elastography, and contrast-enhanced ultrasound, to that of multiparametric magnetic resonance imaging (MRI), including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI, in the diagnosis of localized prostate cancer (PCa; lesions at stage T2 or lower).

METHODS
Seventy-eight patients were prospectively enrolled, including 40 in a benign prostate group and 38 in a localized PCa group (≤T2). The diagnostic performance of multiparametric TRUS and multiparametric MRI in detecting localized PCa was analyzed with surgical and biopsy pathologic results as the references.

RESULTS
Multiparametric TRUS had higher sensitivity, negative predictive value, and accuracy than multiparametric MRI (97.4% versus 94.7%, 96.9% versus 92.3%, and 87.2% versus 76.9%, respectively) for detecting localized PCa. The mean area under the receiver operating characteristic curve ± SD for multiparametric TRUS was 0.874 ± 0.043 (95% confidence interval, 0.790-0.959), and it was 0.774 ± 0.055 (95% confidence interval, 0.666-0.881) for multiparametric MRI.

CONCLUSIONS
Our results suggest that multiparametric TRUS has high diagnostic performance in the diagnosis of localized PCa. Multiparametric TRUS is compatible with multiparametric MRI in the detection of localized PCa (≤T2).

D038524:Diffusion Magnetic Resonance Imaging

transrectal ultrasound
prostate cancer
magnetic resonance imaging


The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism.

Abstract: Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity. We identified the alkylated dicyclohexyl carboxylic acid 2CCA-1 as a potent inducer of autolysin-mediated lysis of S. pneumoniae, while having low activity against Staphylococcus aureus 2CCA-1-resistant strains were found to have inactivating mutations in fakB3, known to be required for uptake of host polyunsaturated fatty acids, as well as through inactivation of the transcriptional regulator gene fabT, vital for endogenous, de novo fatty acid synthesis regulation. Structure activity relationship exploration revealed that, besides the central dicyclohexyl group, the fatty acid-like structural features of 2CCA-1 were essential for its activity. The lysis-inducing activity of 2CCA-1 was considerably more potent than that of free fatty acids and required growing bacteria, suggesting that 2CCA-1 needs to be metabolized to exert its antimicrobial activity. Total lipid analysis of 2CCA-1 treated bacteria identified unique masses that were modeled to 2CCA-1 containing lysophosphatidic and phosphatidic acid in wild-type but not in fakB3 mutant bacteria. This suggests that 2CCA-1 is metabolized as a fatty acid via FakB3 and utilized as a phospholipid building block, leading to accumulation of toxic phospholipid species. Analysis of FabT-mediated fakB3 expression elucidates how the pneumococcus could ensure membrane homeostasis and concurrent economic use of host-derived fatty acids.IMPORTANCE Fatty acid biosynthesis is an attractive antibiotic target, as it affects the supply of membrane phospholipid building blocks. In Streptococcus pneumoniae, it is not sufficient to target only the endogenous fatty acid synthesis machinery, as uptake of host fatty acids may bypass this inhibition. Here, we describe a small-molecule compound, 2CCA-1, with potent bactericidal activity that upon interactions with the fatty acid binding protein FakB3, which is present in a limited number of Gram-positive species, becomes metabolized and incorporated as a toxic phospholipid species. Resistance to 2CCA-1 developed specifically in fakB3 and the regulatory gene fabT These mutants reveal a regulatory connection between the extracellular polyunsaturated fatty acid metabolism and endogenous fatty acid synthesis in S. pneumoniae, which could ensure balance between efficient scavenging of host polyunsaturated fatty acids and membrane homeostasis. The data might be useful in the identification of narrow-spectrum treatment strategies to selectively target members of the Lactobacillales such as S. pneumoniae.

Reithuber|Elisabeth|E|
Nannapaneni|Priyanka|P|
Rzhepishevska|Olena|O|
Lindgren|Anders E G|AEG|
Ilchenko|Oleksandr|O|
Normark|Staffan|S|
Almqvist|Fredrik|F|
Henriques-Normark|Birgitta|B|
Mellroth|Peter|P|

D015964:Gene Expression Regulation, Bacterial

Streptococcus pneumoniae
pneumococci
FakB3
FabT
pneumococcus
DegV
LytA
extracellular fatty acid metabolism
small antimicrobial compound


MINISTOP 2.0: a smartphone app integrated in primary child health care to promote healthy diet and physical activity behaviours and prevent obesity in preschool-aged children: protocol for a hybrid design effectiveness-implementation study.

Abstract:
BACKGROUND
Childhood obesity is still a major health problem in many countries, including Sweden. Childhood obesity and obesity-related behaviours in childhood, such as low physical activity and unhealthy eating habits, tend to track into adulthood, which highlights the need for early prevention. Our aims are to evaluate whether a parent-oriented mobile health app (the MINISTOP 2.0 app) integrated into primary child health care can improve diet and physical activity behaviours and reduce the prevalence of overweight and obesity in preschool-aged children as well as to evaluate the implementation among child health care nurses and parents.

METHODS
This trial uses a hybrid type 1 effectiveness-implementation design. Families (n = 500) who attend a routine visit to one of 15-20 primary child health care centres throughout Sweden, when their child is 2.5 years, are offered participation in a randomised controlled trial (effectiveness evaluation). After acceptance, families will be randomised (1:1) to control or intervention groups. The intervention group receives a 6-month parent-oriented smartphone intervention aimed at improving the dietary and activity behaviours of their child (the MINISTOP 2.0 app) and the control group receives routine child health care. Dietary habits, physical activity and screen time (primary outcomes), body weight and height in children, and parental self-efficacy (secondary outcomes) are measured at baseline and at 6 months post randomisation. Implementation outcomes (i.e. perceived acceptability, appropriateness, and feasibility) of the intervention will be assessed among primary child health care nurses and parents in the trial through questionnaires and qualitative interviews.

DISCUSSION
This trial will evaluate whether the MINISTOP 2.0 app can be used in primary child health care to improve diet and physical activity behaviours, and prevent overweight and obesity, in preschool-aged children. If effectiveness is proven, and the MINISTOP 2.0 app is considered acceptable, appropriate and feasible, it can be implemented nationally as part of the preventive strategies to combat childhood obesity provided by routine child health care.

TRIAL REGISTRATION
The trial was registered at the Clinicaltrials.gov register platform (ID NCT04147039 ) on 31 October 2019.

Primary child health care
Diet
Physical activity
Childhood obesity
Randomised controlled trial
Preschool
mHealth


Clinical application of whole transcriptome sequencing for the classification of patients with acute lymphoblastic leukemia.

Abstract:
BACKGROUND
Considering the clinical and genetic characteristics, acute lymphoblastic leukemia (ALL) is a rather heterogeneous hematological neoplasm for which current standard diagnostics require various analyses encompassing morphology, immunophenotyping, cytogenetics, and molecular analysis of gene fusions and mutations. Hence, it would be desirable to rely on a technique and an analytical workflow that allows the simultaneous analysis and identification of all the genetic alterations in a single approach. Moreover, based on the results with standard methods, a significant amount of patients have no established abnormalities and hence, cannot further be stratified.

METHODS
We performed WTS and WGS in 279 acute lymphoblastic leukemia (ALL) patients (B-cell: n = 211; T-cell: n = 68) to assess the accuracy of WTS, to detect relevant genetic markers, and to classify ALL patients.

RESULTS
DNA and RNA-based genotyping was used to ensure correct WTS-WGS pairing. Gene expression analysis reliably assigned samples to the B Cell Precursor (BCP)-ALL or the T-ALL group. Subclassification of BCP-ALL samples was done progressively, assessing first the presence of chromosomal rearrangements by the means of fusion detection. Compared to the standard methods, 97% of the recurrent risk-stratifying fusions could be identified by WTS, assigning 76 samples to their respective entities. Additionally, read-through fusions (indicative of CDKN2A and RB1 gene deletions) were recurrently detected in the cohort along with 57 putative novel fusions, with yet untouched diagnostic potentials. Next, copy number variations were inferred from WTS data to identify relevant ploidy groups, classifying an additional of 31 samples. Lastly, gene expression profiling detected a BCR-ABL1-like signature in 27% of the remaining samples.

CONCLUSION
As a single assay, WTS allowed a precise genetic classification for the majority of BCP-ALL patients, and is superior to conventional methods in the cases which lack entity defining genetic abnormalities.

Walter|Wencke|W| Shahswar|Rabia|R| Stengel|Anna|A| Meggendorfer|Manja|M| Kern|Wolfgang|W| Haferlach|Torsten|T| Haferlach|Claudia|C|

D017404:In Situ Hybridization, Fluorescence

D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma

Whole transcriptome sequencing
Gene expression profiling
Fusion transcript calling
Patient classification


MRI visualization of optic nerve avulsion due to ocular perforation from BB gun projectile.

Abstract: To report a case of optic nerve avulsion after a perforating injury by an air-soft/BB gun that was successfully captured with magnetic resonance imaging.

MRI
Optic nerve avulsion
BB
Perforating injury
Air-soft gun


microRNA-485-5p inhibits the progression of hepatocellular carcinoma through blocking the WBP2/Wnt signaling pathway.

Abstract: microRNA-485-5p (miR-485-5p) has been shown to act as a tumor-suppressor gene in some cancers, such as ovarian epithelial tumors and oral tongue squamous cell carcinoma. However, with regard to the anti-tumor role of miR-485-5p in hepatocellular carcinoma (HCC), evidence is unexpectedly limited. In the present study, we investigated the expression and the role of miR-485-5p in the progression of HCC. Microarray analysis revealed that miR-485-5p was downregulated and WBP2 was upregulated in HCC, which was consistent with RT-qPCR and immunohistochemistry assays in the HCC tissues we collected. A negative correlation between the expression of miR-485-5p and WBP2 was also found in HCC tissues. It was predicted and confirmed that miR-485-5p could bind to WW domain binding protein 2 (WBP2) through in silico analysis of genetic sequences and an in vitro dual-luciferase reporter gene assay. Next, gain- or loss-of-function studies were applied in the HCC cell line (Huh7) to examine the effects of miR-485-5p and WBP2 on HCC cell behavior. The effects of miR-485-5p and WBP2 on the Wnt/β-catenin signaling pathway were determined by TOP/FOP flash luciferase assays. miR-485-5p was shown to downregulate WBP2 and block the Wnt/β-catenin signaling pathway. As expected, elevated miR-485-5p levels and inhibition of WBP2 protein expression exerted inhibitory effects on HCC cell proliferation, migration and invasion and, induced apoptosis. In vivo experiments were finally conducted, which confirmed that upregulation of miR-485-5p or depletion of WBP2 attenuated tumor growth. Collectively, our results suggest miR-485-5p can downregulate WBP2 to inhibit the development of HCC by the blockade of the Wnt/β-catenin signaling, providing a novel molecular target for HCC treatment.

Gao|Jun|J| Dai|Chao|C| Yu|Xin|X| Yin|Xiang-Bao|XB| Zhou|Fan|F|

D015972:Gene Expression Regulation, Neoplastic

microRNA-485-5p
Hepatocellular carcinoma
WW domain binding protein 2
Wnt/β-catenin signaling


The theoretical and empirical basis of a BioPsychoSocial (BPS) risk screener for detection of older people's health related needs, planning of community programs, and targeted care interventions.

Abstract:
BACKGROUND
This study introduces the conceptual basis and operational measure, of BioPyschoSocial (BPS) health and related risk to better understand how well older people are managing and to screen for risk status. The BPS Risk Screener is constructed to detect vulnerability at older ages, and seeks to measure dynamic processes that place equal emphasis on Psycho-emotional and Socio-interpersonal risks, as Bio-functional ones. We validate the proposed measure and describe its application to programming.

METHODS
We undertook a quantitative cross-sectional, psychometric study with n = 1325 older Singaporeans, aged 60 and over. We adapted the EASYCare 2010 and Lubben Social Network Scale questionnaires to help determine the BPS domains using factor analysis from which we derive the BPS Risk Screener items. We then confirm its structure, and test the scoring system. The score is initially validated against self-reported general health then modelled against: number of falls; cognitive impairment; longstanding diseases; and further tested against service utilization (linked administrative data).

RESULTS
Three B, P and S clusters are defined and identified and a BPS managing score ('doing' well, or 'some', 'many', and 'overwhelming problems') calculated such that the risk of problematic additive BPS effects, what we term health 'loads', are accounted for. Thirty-five items (factor loadings over 0.5) clustered into three distinct B, P, S domains and were found to be independently associated with self-reported health: B: 1.99 (1.64 to 2.41), P: 1.59 (1.28 to 1.98), S: 1.33 (1.10 to 1.60). The fit improved when combined into the managing score 2.33 (1.92 to 2.83, < 0.01). The score was associated with mounting risk for all outcomes.

CONCLUSIONS
BPS domain structures, and the novel scoring system capturing dynamic BPS additive effects, which can combine to engender vulnerability, are validated through this analysis. The resulting tool helps render clients' risk status and related intervention needs transparent. Given its explicit and empirically supported attention to P and S risks, which have the potential to be more malleable than B ones, especially in the older old, this tool is designed to be change sensitive.

Hildon|Zoe J-L|ZJ|
Tan|Chuen Seng|CS|
Shiraz|Farah|F|
Ng|Wai Chong|WC|
Deng|Xiaodong|X|
Koh|Gerald Choon Huat|GCH|
Tan|Kelvin Bryan|KB|
Philp|Ian|I|
Wiggins|Dick|D|
Aw|Su|S|
Wu|Treena|T|
Vrijhoef|Hubertus J M|HJM|

Integrated care delivery in the community


Achiral Molecular Recognition of Aromatic Position Isomers by Polysaccharide-Based CSPs in Relation to Chiral Recognition.

Abstract: Chromatographic separation of several sets of aromatic position isomers on three cellulose- and one amylose-based chiral stationary phases was performed to evaluate the potential of a polysaccharide-based chiral stationary phase (CSP) in the separation of isomeric or closely similar molecules, and to understand the interaction mechanism of this type of CSP with analytes. Their ability of molecular recognition was quite outstanding, but the selection rule was particular to each polysaccharide derivative. In the series of analytes, cellulose tris(4-methylbenzoate) and tris(3,5-dimethylphenylcarbamate) exhibited a contrasting selection rule, and the recognition mechanism was considered based on the computer-simulation of the former polymer.

Shibata|Tohru|T| Shinkura|Satoshi|S| Ohnishi|Atsushi|A| Ueda|Kazuyoshi|K|

D002851:Chromatography, High Pressure Liquid

achiral
position isomer
chiral stationary phase
cellulose
amylose
chromatography
simulation


Assessing the Current Curriculum of the Nursing and Midwifery Informatics Course at All Nursing and Midwifery Institutions in Ghana.

Abstract: The use of computers in the delivery of health care has significantly improved the way health service is delivered to clients and patients in the world. Despite the importance of computing to the delivery of health service, developing countries have not greatly benefited from it. Nursing informatics has been in existence and part of academic curriculum for the past 2 decades in some advanced countries. The Ghana Nursing and Midwifery Council introduced the nursing and midwifery informatics course during the 2015/2016 academic year. This seeks to train student nurses on the relevance of computers to health care. Two separate workshops were organised to ascertain the preparedness of tutors (teachers at the nursing and midwifery training institutions) for teaching the new nursing and midwifery informatics course as well as to compare the curriculum with other international recommendations. The nursing and midwifery informatics course is taught at the first year where students have not been introduced to the nursing processes for them to appreciate the use of nursing informatics skills. It would be better if the nursing and midwifery informatics course is rather introduced during the second year second semester when students are about going for the hands-on training at the various health care institutions. Examining the course content reveals that the practical aspect within the course is very small. It is expected that more practical contents will be introduced. Tutors are not adequately prepared to teach this new course. More training is therefore needed to make tutors fully prepared to teach both the theory and practical aspects of the nursing and midwifery informatics course. It is expected that the nursing and midwifery informatics course would prepare student nurses on all nursing informatics competencies. It is essential that nurse educators incorporate the entire concept of informatics into the education of nurses.

Nursing and midwifery informatics
health care


Impact of Clinical Pharmacist's Interventions on Potential Drug-Drug Interactions in the Cardiac Care Units of Two University Hospitals in Shiraz, South of Iran.

Abstract:
Objective
The main objective of this study aimed to assess drug-drug interactions (DDIs) in the cardiac care unit (CCU) and cardiac surgery units and the role of a clinical pharmacist in detecting and preventing the expected DDIs.

Methods
This cross-sectional study was conducted in the CCU Units of Nemazee and Shahid Faghihi Hospitals, two referral hospitals in Shiraz, South of Iran, from August to February 2016. Patients older than 18 years, who were admitted and had received >24 h of inpatient services in these wards with two or more medication orders, were included in this study. All medication orders were evaluated by a pharmacist and DDIs were examined based on the Lexi-Interact™ software. In cases with serious DDIs (D or X), the physicians and nurses were informed, and intervention was conducted by a clinical pharmacist.

Findings
A total of 3706 medical orders were evaluated. 6478 DDIs were detected, of which, 446 (6.88%) belonged to Classes D and X, and a total of 43.43% of all hospitalizations had at least one DDI. Factors with the most considerable influence on DDIs included an increased number of prescribed medications and patients underlying disease. The physicians accepted 62% of the interventions. The most frequent drugs responsible for interactions of Classes C, D, and X were aspirin, warfarin, and clopidogrel, respectively.

Conclusion
This study shows that a significant number of clinical DDIs exist in hospitalized patients, especially among consumers of warfarin and aspirin. The role of a clinical pharmacist in preventing such interactions and safer pharmacotherapy management for hospitalized patients is essential.

Shafiekhani|Mojtaba|M| Moosavi|Negin|N| Firouzabadi|Dena|D| Namazi|Soha|S|

clinical pharmacist
Cardiovascular care unit
drug–drug interactions


Genetic epidemiology of tooth agenesis in Japan: a population- and family-based study.

Abstract: Tooth agenesis is one of the most common congenital anomalies in humans. However, the etiology of tooth agenesis remains largely unclear, as well as evidence base useful for genetic counseling. Therefore, we estimated the prevalence and sibling recurrence risk, and investigated agenetic patterns systematically. Tooth agenesis was classified into two subtypes: hypodontia (one to five missing teeth) and oligodontia (six or more missing teeth). The prevalence of these two subtypes were 6.8% [95% confidence interval (CI): 6.1-7.7%] and 0.1% (95% CI: 0.04-0.3%), respectively, and sibling recurrence risk of these were 24.5% (95% CI: 13.8-38.3%) and 43.8% (95% CI: 26.4-62.3%), respectively. This result suggests that the severe phenotype, oligodontia, might be mostly transmitted in a dominant fashion. Using a simple statistical modeling approach, our data were found to be consistent with a bilateral symmetry model, meaning that there was equal probability of missing teeth from the right and left sides.

Machida|J|J| Nishiyama|T|T| Kishino|H|H| Yamaguchi|S|S| Kimura|M|M| Shibata|A|A| Tatematsu|T|T| Kamamoto|M|M| Yamamoto|K|K| Makino|S|S| Miyachi|H|H| Shimozato|K|K| Tokita|Y|Y|

tooth agenesis
prevalence
sibling recurrence risk
hypodontia
oligodontia


Power reflectance testing in newborns and infants.

Abstract:
INTRODUCTION
Auditory screening in newborns allows for detection of hearing problems early in life. However, middle ear diseases can make the diagnosis more difficult.

OBJECTIVE
To evaluate the power reflectance test as an indicator of the middle ear disease and to compare it to tympanometry.

METHODS
Case study evaluating 105 newborns and infants who participated in the audiology screening in 2013. The following exams were performed: transient otoacoustic emissions, power reflectance, and tympanometry.

RESULTS
In the optoacoustic emission evaluation, approximately 95% of the subjects passed the test. The specificity of power reflectance in all frequencies studied ranged from 75.3% to 95.9%, and that of tympanometry at 1000Hz ranged from 83% to 87.2%; there was agreement among these exams.

CONCLUSION
The outcome of power reflectance tests at 2000Hz and 3000Hz showed a correlation with tympanometry and otoacoustic emissions, and these were the most appropriate frequencies to determine middle ear disease through power reflectance measurement. It was also observed that values of power reflectance above reference levels suggested the presence of fluid in the middle ear, and thus a conductive hearing loss.

Lima|Ticianna Garambone de Cerqueira|TG|

Middle ear
Hearing tests
Neonatal screening
Orelha média
Testes auditivos
Triagem neonatal


Regulation of IL-10 and IL-17 mediated experimental autoimmune encephalomyelitis by S-nitrosoglutathione.

Abstract: In this study, we investigated IL-10 and IL-17 specific immunomodulatory potential of S-nitrosoglutathione (GSNO), a physiological nitric oxide carrier molecule, in experimental autoimmune encephalomyelitis (EAE). In active EAE model, GSNO treatment attenuated EAE severity and splenic CD4+ T cells isolated from these mice exhibited decreased IL-17 expression without affecting the IFN-γ expression compared to the cells from untreated EAE mice. Similarly, adoptive transfer of these cells to nave mice resulted in reduction in IL-17 expression in the spinal cords of recipient mice with milder EAE severity. CD4+ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, still expressed lower levels of IL-17 under TH17 skewing conditions, but expressed similar levels of IFN-γ under TH1 skewing condition. Interestingly, under both TH17 and TH1 skewing condition, CD4+ T cells isolated from GSNO treated EAE mice, as compared to untreated EAE mice, expressed higher levels of IL-10 and adoptive transfer of these TH17 and TH1 skewed cells seemingly exhibited milder EAE disease. In addition, adoptive transfer of CD4+ T cells from GSNO treated EAE mice to active EAE mice also ameliorated EAE disease with induction of spinal cord expression of IL-10 and reduction in of IL-17, thus suggesting the participation of IL-10 mechanism in GSNO mediated immunomodulation. GSNO treatment of mice passively immunized with CD4+ T cells either from GSNO treated EAE mice or untreated mice further ameliorated EAE disease, supporting efficacy of GSNO for prophylaxis and therapy in EAE. Overall, these data document a modulatory role of GSNO in IL-17/IL-10 axis of EAE and other autoimmune diseases.

Singh|Inderjit|I|
Nath|Narender|N|
Saxena|Nishant|N|
Singh|Avtar K|AK|
Won|Je-Seong|JS|

Experimental autoimmune encephalomyelitis (EAE)


Optimization and evaluation of MALDI TOF mass spectrometric imaging for quantification of orally dosed octreotide in mouse tissues.

Abstract: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-TOF-MSI) has received considerable attention in recent years since it allows molecular mapping of diverse bimolecular in animal/plant tissue sections, although some barriers still exist in absolute pixel-to-pixel quantification. Octreotide, a synthetic somatostatin analogue, has been widely used to prevent gastrointestine bleeding in the clinic. The aim of the present study is to develop a MALDI-TOF-MSI method for quantitatively visualizing spatial distribution of octreotide in mouse tissues. In this process, a structurally similar internal standard was spotted onto tissue section together with matrix solution to minimize signal variation and give excellent quantitative results. The 2,5-dihydroxybenzoic acid was chosen as the most suitable matrix via comparing the signal/noise generated by MALDI-TOF-MSI after cocrystallization of octreotide with different matrix candidates. The reliability of MALDI-TOF-MSI, with respect to linearity, sensitivity and precision, was tested via measuring octreotide in fresh tissue slices at different concentrations. The validated method was then successfully applied to visualize the distribution of octreotide in mouse tissues after oral administration of octreotide at 20mg/kg. The results demonstrated that MALDI-TOF-MSI could not only clearly visualize the spatial distribution of octreotide, but also make the calculation of the key pharmacokinetic parameters (Tmax and t1/2) possible. More importantly, the tissue concentration-time curves of octreotide determined by MALDI-TOF-MSI agreed well with those measured based on LC-MS/MS.These findings illustrate the potential of MALDI-TOF-MSI in pharmacokinetic profiling during drug development.

Rao|Tai|T| Shen|Boyu|B| Zhu|Zhangpei|Z| Shao|Yuhao|Y| Kang|Dian|D| Li|Xinuo|X| Yin|Xiaoxi|X| Li|Haofeng|H| Xie|Lin|L| Wang|Guangji|G| Liang|Yan|Y|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Octreotide MALDI-TOF-MSI Distribution Pharmacokinetics LC–MS/MS


Investigation of thoracic four-dimensional CT-based dimension reduction technique for extracting the robust radiomic features.

Abstract: Robust feature selection in radiomic analysis is often implemented using the RIDER test-retest datasets. However, the CT Protocol between the facility and test-retest datasets are different. Therefore, we investigated possibility to select robust features using thoracic four-dimensional CT (4D-CT) scans that are available from patients receiving radiation therapy. In 4D-CT datasets of 14 lung cancer patients who underwent stereotactic body radiotherapy (SBRT) and 14 test-retest datasets of non-small cell lung cancer (NSCLC), 1170 radiomic features (shape: n = 16, statistics: n = 32, texture: n = 1122) were extracted. A concordance correlation coefficient (CCC) > 0.85 was used to select robust features. We compared the robust features in various 4D-CT group with those in test-retest. The total number of robust features was a range between 846/1170 (72%) and 970/1170 (83%) in all 4D-CT groups with three breathing phases (40%-60%); however, that was a range between 44/1170 (4%) and 476/1170 (41%) in all 4D-CT groups with 10 breathing phases. In test-retest, the total number of robust features was 967/1170 (83%); thus, the number of robust features in 4D-CT was almost equal to that in test-retest by using 40-60% breathing phases. In 4D-CT, respiratory motion is a factor that greatly affects the robustness of features, thus by using only 40-60% breathing phases, excessive dimension reduction will be able to be prevented in any 4D-CT datasets, and select robust features suitable for CT protocol of your own facility.

Tanaka|Shohei|S| Kadoya|Noriyuki|N| Kajikawa|Tomohiro|T| Matsuda|Shohei|S| Dobashi|Suguru|S| Takeda|Ken|K| Jingu|Keiichi|K|

Radiomics
4D-CT
Lung cancer
Radiotherapy


Evaluation of sampling frequency, window size and sensor position for classification of sheep behaviour.

Abstract: Automated behavioural classification and identification through sensors has the potential to improve health and welfare of the animals. Position of a sensor, sampling frequency and window size of segmented signal data has a major impact on classification accuracy in activity recognition and energy needs for the sensor, yet, there are no studies in precision livestock farming that have evaluated the effect of all these factors simultaneously. The aim of this study was to evaluate the effects of position (ear and collar), sampling frequency (8, 16 and 32 Hz) of a triaxial accelerometer and gyroscope sensor and window size (3, 5 and 7 s) on the classification of important behaviours in sheep such as lying, standing and walking. Behaviours were classified using a random forest approach with 44 feature characteristics. The best performance for walking, standing and lying classification in sheep (accuracy 95%, F-score 91%-97%) was obtained using combination of 32 Hz, 7 s and 32 Hz, 5 s for both ear and collar sensors, although, results obtained with 16 Hz and 7 s window were comparable with accuracy of 91%-93% and F-score 88%-95%. Energy efficiency was best at a 7 s window. This suggests that sampling at 16 Hz with 7 s window will offer benefits in a real-time behavioural monitoring system for sheep due to reduced energy needs.

Walton|Emily|E|
Casey|Christy|C|
Mitsch|Jurgen|J|
Vázquez-Diosdado|Jorge A|JA|
Yan|Juan|J|
Dottorini|Tania|T|
Ellis|Keith A|KA|
Winterlich|Anthony|A|
Kaler|Jasmeet|J|0000-0002-3332-7064

sensor
sheep behaviour
accelerometer and gyroscope
classification algorithm
precision livestock monitoring
signal processing


Comparison of predictive grading systems for procedural risk in endovascular treatment of brain arteriovenous malformations: analysis of 104 consecutive patients.

Abstract:
OBJECTIVE
Several grading systems for procedural risk in the endovascular treatment of brain arteriovenous malformations (AVMs) have been proposed, including the Buffalo, Puerto Rico, and AVM embocure scoring systems. The authors sought to validate these systems in an independent patient cohort and compare each system to the established Spetzler-Martin (SM) scale.

METHODS
One hundred four consecutive patients underwent adjunctive endovascular embolization of brain AVMs between 2002 and 2016 with the goal of reducing the surgical or hemorrhagic risk before definitive radiosurgical treatment. Baseline clinical and AVM characteristics, complications, and degree of AVM nidus reduction were obtained retrospectively. Univariate and multivariate comparisons and receiver operating characteristic (ROC) curve analyses were performed.

RESULTS
Ten major (9.6%) and 16 minor (15.4%) complications were encountered in 24 patients (23.1%). An arterial pedicle size < 1 mm (p = 0.001) and a greater number of pedicles (p = 0.039) were predictors of complication occurrence. Only the Buffalo score predicted the complication rate on univariate (p = 0.039) and multivariate (p = 0.001) analyses. ROC curve analysis revealed a greater area under the curve (AUC) of the Buffalo score (0.703) compared to the Puerto Rico score (p = 0.028), AVM embocure score (AVMES; p = 0.010), and SM grade (SMG; p = 0.030). The Buffalo score, Puerto Rico score, and AVMES but not the SMG predicted > 85% nidus reduction. The AUCs for the different scoring systems were not significantly different.

CONCLUSIONS
The major complication rate of 9.6% is within the range of rates reported in the literature and emphasizes that brain AVM embolization is not a low-risk procedure. The Buffalo score but not the Puerto Rico score, AVMES, or SMG predicted the endovascular procedural risk. All three endovascular scores but not the SMG predicted a > 85% nidus reduction rate in this cohort embolized as part of a multimodal AVM treatment.

Pulli|Benjamin|B|
Stapleton|Christopher J|CJ|
Walcott|Brian P|BP|
Koch|Matthew J|MJ|
Raymond|Scott B|SB|
Leslie-Mazwi|Thabele M|TM|
Rabinov|James D|JD|
Patel|Aman B|AB|

prediction
risk
AVM
embolization
AUC = area under the curve
AVM = arteriovenous malformation
AVMES = AVM embocure score
NBCA = N-butyl cyanoacrylate
ROC = receiver operating characteristic
SMG = Spetzler-Martin grade
mRS = modified Rankin Scale
vascular disorders


HP1717 Contributes to Streptococcus suis Virulence by Inducing an Excessive Inflammatory Response and Influencing the Biosynthesis of the Capsule.

Abstract: Streptococcus suis 2 (SS2) is an important zoonotic pathogen that substantially harms the swine industry and poses threats to human health. Excessive inflammation is considered to be a hallmark of SS2 infection because it is responsible for most clinical signs of SS2, especially streptococcal toxic shock-like syndrome. However, the current knowledge of SS2-induced excessive inflammation remains limited. In this study, we identified HP1717 as a novel extracellular pro-inflammatory protein in SS2 that can induce robust expression of inflammatory cytokines in RAW264.7 macrophages. Notably, the pro-inflammatory ability of HP1717 was dose-dependent and heat-sensitive, and it required the recognition of Toll-like receptor 2 (TLR2) and the phosphorylation of both extracellular signal-regulated kinases 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Further, by constructing a deletion mutant, we demonstrated that HP1717 significantly influenced the biosynthesis of the bacterial capsule, which plays a critical role in the virulence of SS2 by interfering with the ability of host immune cells to phagocytize and kill the pathogen. Indeed, the mutant strain displayed reduced resistance to whole-blood killing compared with the wild strain. Finally, murine experiments indicated that the deletion of hp1717 in SS2 reduced the lethality, pro-inflammatory activity, and bacterial loads in mice. Collectively, our data reveal HP1717 as a novel virulence-related factor of SS2 that can induce an excessive inflammatory response and significantly affect the bacterial capsule, thus expanding our understanding of the pathogenesis of S. suis.

Liu|Liang|L| Zhang|Qiang|Q| Xu|Zhongmin|Z| Huang|Jingjing|J| Zhu|Weifeng|W| Zhang|Anding|A| Sun|Xiaomei|X| Jin|Meilin|M|

Streptococcus suis
virulence
inflammatory
capsule
streptococcal toxic shock-like syndrome


Three-dimensional functional workspace of thumb prehension.

Abstract:
BACKGROUND
Clinical assessment of thumb motion is challenging, due to the complex anatomy and motion of the thumb. It is especially difficult to measure hand movement during activity, and to measure the effects of surgery that changes the morphology of the thumb. A three-dimensional model of the hand may enable clinicians to better assess prehension and thumb motion at baseline, and following surgical intervention.

METHODS
A kinematic model of the hand was developed to measure thumb and finger position during functional tasks, enabling the calculation of the volume of space in which prehension could occur. This method was validated by application to a mechanical model of the hand, and then applied to ten adult participants, using three-dimensional motion analysis with a marker array developed for the purpose of this study.

FINDINGS
This method can be used to accurately measure three-dimensional thumb joint range of motion (RoM) and predicted functional workspace during functional activities. The thumb carpometacarpal joint was predominantly responsible for thumb position during functional tasks. Predicted functional workspace is proportional to hand morphometric measurements.

INTERPRETATION
A kinematic model of the hand measures thumb RoM and predicts functional workspace during functional activities.

Curran|Patrick F|PF|
Bagley|Anita M|AM|
Sison-Williamson|Mitell|M|
James|Michelle A|MA|

Prehension
Kinematics
Motion analysis
Functional thumb motion
Hand biomechanics


Comparative effects of traditional Chinese and Western migraine medicines in an animal model of nociceptive trigeminovascular activation.

Abstract: Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.

Zhao|Yonglie|Y|
Martins-Oliveira|Margarida|M|
Akerman|Simon|S|
Goadsby|Peter J|PJ|

migraine
Gastrodin
ligustrazine
trigeminocervical complex
headache


Does resident participation influence otolaryngology-head and neck surgery morbidity and mortality?

Abstract:
OBJECTIVES/HYPOTHESIS
Patients may perceive resident procedural participation as detrimental to their outcome. Our objective is to investigate whether otolaryngology-head and neck surgery (OHNS) housestaff participation is associated with surgical morbidity and mortality.

STUDY DESIGN
Case-control study.

METHODS
OHNS patients were analyzed from the American College of Surgeons National Surgical Quality Improvement Program 2006 to 2013 databases. We compared the incidence of 30-day postoperative morbidity, mortality, readmissions, and reoperations in patients operated on by resident surgeons with attending supervision (AR) with patients operated on by an attending surgeon alone (AO) using cross-tabulations and multivariable regression.

RESULTS
There were 27,018 cases with primary surgeon data available, with 9,511 AR cases and 17,507 AO cases. Overall, 3.62% of patients experienced at least one postoperative complication. The AR cohort had a higher complication rate of 5.73% than the AO cohort at 2.48% (P < .001). After controlling for all other variables, there was no significant difference in morbidity (odds ratio [OR] = 1.05 [0.89 to 1.24]), mortality (OR = 0.91 [0.49 to 1.70]), readmission (OR = 1.29 [0.92 to 1.81]), or reoperation (OR = 1.28 [0.91 to 1.80]) for AR compared to AO cases. There was no difference between postgraduate year levels for adjusted 30-day morbidity or mortality.

CONCLUSIONS
There is an increased incidence of morbidity, mortality, readmission, and reoperation in OHNS surgical cases with resident participation, which appears related to increased comorbidity with AR patients. After controlling for other variables, resident participation was not associated with an increase in 30-day morbidity, mortality, readmission, or reoperation odds. These data suggest that OHNS resident participation in surgical cases is not associated with poorer short-term outcomes.

LEVEL OF EVIDENCE
3b Laryngoscope, 126:2263-2269, 2016.

Abt|Nicholas B|NB|
Reh|Douglas D|DD|
Eisele|David W|DW|
Francis|Howard W|HW|
Gourin|Christine G|CG|


Trajectory of sleep disturbances in patients undergoing lung cancer surgery: a prospective study.

Abstract:
OBJECTIVES
Patients with lung cancer report sleep difficulties to be frequent and bothersome symptoms. This study describes the trajectory of sleep from before and up to 12 months after surgery for lung cancer. Further, it investigates possible associations between sleep disturbance, demographic and clinical characteristics before surgery.

METHODS
This study is part of a longitudinal multicentre study. Sleep disturbance was measured by The General Sleep Disturbance Scale (GSDS) that investigates frequencies of sleep difficulties (21 items) and a total sum score ≥43 indicates a clinically meaningful level of sleep disturbance (score range 0-147). Linear mixed models were used to study changes in sleep from baseline to 1, 5, 9 and 12 months after surgery.

RESULTS
The percentage of patients (n = 264) reporting sleep disturbances was 60.9% at baseline, 68.5% at Month 1, 55.4% at Month 5, 51.3% at Month 9 and 49.7% at Month 12. The increase to and decrease from Month 1 was the only significant alteration in the occurrence of sleep disturbance. The patients reported most problems within the subscales sleep quantity, early awakenings and sleep quality. Factors associated with sleep disturbance were lower age, use of pain medication and psychotropic medication and higher comorbidity score.

CONCLUSIONS
Lung cancer patients sleep poorly, before as well as after surgery. There is a need to address sleeping disturbance routinely in clinical practice and screening for sleeping problems is indicated. Further studies are warranted concerning factors that contribute to sleep disturbance and how they best can be treated.

Halle|Ingrid Helene|IH|
Westgaard|Therese Krystad|TK|
Wahba|Alexander|A|
Oksholm|Trine|T|
Rustøen|Tone|T|
Gjeilo|Kari Hanne|KH|

Sleep
Lung cancer
Surgery
Symptoms
Patient-reported outcomes