A systematic review with meta-analysis of the role of anxiety and depression in irritable bowel syndrome onset.

Abstract:
BACKGROUND
It is well established that people with irritable bowel syndrome (IBS) have higher levels of anxiety and depression compared with controls. However, the role of these as risk factors is less clearly established. The aims of this systematic review were to investigate: (1) whether anxiety and/or depression predict IBS onset; (2) the size of the relative risk (RR) of anxiety versus depression in IBS onset. Subgroup analyses explored if methodological factors affected the overall findings.

METHOD
Prospective cohort or case-control studies were included if they: (1) focused on the development of IBS in population-based or gastroenteritis cohorts; (2) explored the effects of anxiety and/or depression at baseline as predictors of IBS onset at a future point. In all, 11 studies were included of which eight recruited participants with a gastrointestinal infection. Meta-analyses were conducted.

RESULTS
The risk of developing IBS was double for anxiety cases at baseline compared with those who were not [RR 2.38, 95% confidence interval (CI) 1.58-3.60]. Similar results were found for depression (RR 2.06, 95% CI 1.44-2.96). Anxiety and depression seemed to play a stronger role in IBS onset in individuals with a gastrointestinal infection although this could be attributed to other differences in methodology, such as use of diagnostic interviews rather than self-report.

CONCLUSIONS
The findings suggest that self-reported anxiety and depression provide a twofold risk for IBS onset. There is less support for the role of anxiety or depressive disorder diagnosed using clinical interview. These findings may have implications for the development of interventions focused on IBS prevention and treatment.

Sibelli|A|A| Chalder|T|T| Everitt|H|H| Workman|P|P| Windgassen|S|S| Moss-Morris|R|R|

systematic reviews
Anxiety
depression
irritable bowel syndrome
meta-analyses


Reduction of patient anxiety in PET/CT imaging by improving communication between patient and technologist.

Abstract:
UNLABELLED
Patients experience anxiety during imaging procedures because of the confined space, uncertainty about the procedure, worry about the results, and other concerns. When a patient experiences anxiety during PET/CT imaging, the quality of the scan can be affected in several ways. Current patient-technologist communication is limited in PET/CT because the technologist must be separated from the patient during the course of the imaging workflow. This study investigated the use of a call device enabling rapid communication to reduce patient anxiety.

METHODS
Clinical patients with various oncologic indications and undergoing (18)F-FDG PET/CT imaging were asked to participate in anxiety surveys under several conditions. Metrics were tracked regarding the survey results for comparison between groups and survey conditions. During the course of this study, 2 patient surveys were used. One of the patient populations was asked to fill out a survey on personal perceptions of the use of such a device, with questions related to their comfort with the device and the degree to which they perceived the device to reduce their anxiety. The 2 remaining populations were given a standard Spielberger State Anxiety survey for anxiety assessments against control populations.

RESULTS
Perception survey results indicated that 75% of the respondents experienced a reduction in anxiety and that 84% would request this type of device for other procedures. A correlation was observed between improved patient-technologist communication and perceived feelings of safety, with identical percentages of positive responses. Although responses were mostly positive, 18.8% did not perceive any reduction in anxiety, and the same number indicated they would not use the system in the future. For those patients given the standard Spielberger State Anxiety survey, a statistically significant reduction in anxiety was observed (P < 0.05) in those patients given a call device. Reductions in anxiety were observed for all patient populations, including first-time and repeated-imaging patients.

CONCLUSION
Patient anxiety can be reduced through the use of a tangible device that improves communication between the patient and the imaging staff. Reducing anxiety may have a positive effect on imaging, because involuntary motion may be reduced and there may be improvement in the patients' comfort and in their overall experience with the imaging procedure.

Acuff|Shelley N|SN|
Bradley|Yong C|YC|
Barlow|Patrick|P|
Osborne|Dustin R|DR|


The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat epigastric skin flaps.

Abstract:
BACKGROUND
Ischemia-reperfusion injury may lead to insufficient microcirculation and results in partial flap loss during the free flap surgeries.

OBJECTIVE
This study aimed to investigate the effect of trimetazidine (TMZ) on oxidative stress, inflammation and histopathological changes, using the epigastric skin flap model in rats.

METHODS
40 male Wistar rats were used, that were divided into four groups. Control group, non-treated ischemic (I/R)-group and two trimetazidine treated groups (preischemically, postischemically) were established. To create ischemia in the skin flap, the superficial epigastric vessels were clamped for six hours, followed by twenty-four hours of reperfusion. Blood samples and biopsies from skin flaps were collected at the end of the reperfusion period. The inflammatory response, the degree of oxidative stress (by measuring the plasma level of malondialdehyde (MDA), reduced glutathione (GSH); sulfhydryl (-SH) groups) and histopathological changes were evaluated.

RESULTS
Inflammatory response, and oxidative stress were significantly attenuated in the trimetazidine treated groups, compared to the non-treated ischemic group. Histopathological findings were also correlated with the biochemical results.

CONCLUSION
In our study trimetazidine could reduce the ischaemia-reperfusion injury, even after an unexpected ischemic period, so it is a promising drug during free tissue transfer, replantation or during revascularization procedures in the future.

Petrovics|Laura|L| Nagy|Tibor|T| Hardi|Peter|P| Bognar|Laura|L| Pavlovics|Gabor|G| Tizedes|Gyorgy|G| Takacs|Ildiko|I| Jancso|Gabor|G|

trimetazidine
free flaps
oxidative stress
inflammation
Ischaemia-reperfusion injury
reconstruction


Mutation of Arabidopsis SMC4 identifies condensin as a corepressor of pericentromeric transposons and conditionally expressed genes.

Abstract: In eukaryotes, transcriptionally inactive loci are enriched within highly condensed heterochromatin. In plants, as in mammals, the DNA of heterochromatin is densely methylated and wrapped by histones displaying a characteristic subset of post-translational modifications. Growing evidence indicates that these chromatin modifications are not sufficient for silencing. Instead, they are prerequisites for further assembly of higher-order chromatin structures that are refractory to transcription but not fully understood. We show that silencing of transposons in the pericentromeric heterochromatin of Arabidopsis thaliana requires SMC4, a core subunit of condensins I and II, acting in conjunction with CG methylation by MET1 (DNA METHYLTRANSFERASE 1), CHG methylation by CMT3 (CHROMOMETHYLASE 3), the chromatin remodeler DDM1 (DECREASE IN DNA METHYLATION 1), and histone modifications, including histone H3 Lys 27 monomethylation (H3K27me1), imparted by ATXR5 and ATXR6. SMC4/condensin also acts within the mostly euchromatic chromosome arms to suppress conditionally expressed genes involved in flowering or DNA repair, including the DNA glycosylase ROS1, which facilitates DNA demethylation. Collectively, our genome-wide analyses implicate condensin in the suppression of hundreds of loci, acting in both DNA methylation-dependent and methylation-independent pathways.

Wang|Jing|J|
Blevins|Todd|T|
Podicheti|Ram|R|
Haag|Jeremy R|JR|
Tan|Ek Han|EH|
Wang|Feng|F|
Pikaard|Craig S|CS|0000-0001-8204-7459

D018506:Gene Expression Regulation, Plant

DNA methylation
SMC proteins
chromosome condensation
epigenetic regulation
gene silencing
heterochromatin formation


Acute hypoxic preconditioning prevents palmitic acid-induced cardiomyocyte apoptosis via switching metabolic GLUT4-glucose pathway back to CD36-fatty acid dependent.

Abstract: Metabolic syndrome is a risk factor for the development of cardiovascular diseases. Myocardial cell damage leads to an imbalance of energy metabolism, and many studies have indicated that short-term hypoxia during myocardial cell injury has a protective effect. In our previous animal studies, we found that short-term hypoxia in the heart has a protective effect, but long-term hypoxia increases myocardial cell injury. Palmitic acid (PA)-treated H9c2 cardiomyoblasts and neonatal rat ventricle cardiomyocytes were used to simulate hyperlipidemia model, which suppress cluster of differentiation 36 (CD36) and activate glucose transporter type 4 (GLUT4). We exposed the cells to short- and long-term hypoxia and investigated the protective effects of hypoxic preconditioning on PA-induced lipotoxicity in H9c2 cardiomyoblasts and neonatal rat cardiomyocytes. Preconditioning with short-term hypoxia enhanced both CD36 and GLUT4 metabolism pathway protein levels. Expression levels of phospho-PI3K, phospho-Akt, phospho-AMPK, SIRT1, PGC1α, PPARα, CD36, and CPT1β induced by PA was reversed by short-term hypoxia in a time-dependent manner. PA-induced increased GLUT4 membrane protein level was reduced in the cells exposed to short-term hypoxia and si-PKCζ. Short-term hypoxia, resveratrol and si-PKCζ rescue H9c2 cells from apoptosis induced by PA and switch the metabolic pathway from GLUT4 dependent to CD36 dependent. We demonstrate short-term hypoxic preconditioning as a more efficient way as resveratrol in maintaining the energy metabolism of hearts during hyperlipidemia and can be used as a therapeutic strategy.

D000818:Animals
D000831:Animals, Newborn
D017209:Apoptosis
D018955:CD36 Antigens
D015687:Cell Hypoxia
D002460:Cell Line
D004268:DNA-Binding Proteins
D005227:Fatty Acids
D005947:Glucose
D006352:Heart Ventricles
D006949:Hyperlipidemias
D053858:Metabolic Networks and Pathways
D008954:Models, Biological
D032383:Myocytes, Cardiac
D019308:Palmitic Acid
D051381:Rats
D014157:Transcription Factors

hypoxia
palmitic acid
fatty acid metabolism
glucose metabolism
insulin signaling pathway
ischemia


Glycemic modulation in neuro-oncology: experience and future directions using a modified Atkins diet for high-grade brain tumors.

Abstract: Dietary glycemic modulation through high-fat, low-carbohydrate diets, which induce a state of systemic ketosis and alter systemic metabolic signaling, have been incorporated into the clinical management of patients with neurological disease for more than a century. Mounting preclinical evidence supports the antitumor, proapoptotic, and antiangiogenic effects of disrupting glycolytic metabolism through dietary intervention. In recent years, interest in incorporating such novel therapeutic strategies in neuro-oncology has increased. To date, 3 published studies incorporating novel dietary therapies in oncology have been reported, including one phase I study in neuro-oncology, and have set the stage for further study in this field. In this article, we review the biochemical pathways, preclinical data, and early clinical translation of dietary interventions that modulate systemic glycolytic metabolism in the management of primary malignant brain tumors. We introduce the modified Atkins diet (MAD), a novel dietary alternative to the classic ketogenic diet, and discuss the critical issues facing future study.

Strowd|Roy E|RE|
Cervenka|Mackenzie C|MC|
Henry|Bobbie J|BJ|
Kossoff|Eric H|EH|
Hartman|Adam L|AL|
Blakeley|Jaishri O|JO|

modified Atkins diet
ketogenic diet
cancer metabolism
glioma
seizure


Total resection of the aortic arch intimal sarcoma using the L-incision technique.

Abstract: A 26-year-old male suffering from sudden right lower abdominal pain and lumbago was referred to our hospital. Enhanced computed tomography demonstrated bilateral kidneys and spleen infarctions, and a large tumour was found occupying the aortic arch and thoracic descending aorta. We suspected that these infarctions were due to tumour embolization. The aortic arch and thoracic descending aorta were resected with the tumour and then reconstructed using the L-incision technique. A microscopic examination revealed the presence of an intimal sarcoma. The patient was treated with adjuvant chemotherapy and showed a good postoperative course. Neither recurrence nor metastasis has been observed during the 3 years since the operation.

Onitsuka|Hirofumi|H| Nishida|Takahiro|T| Akashi|Koichi|K| Tominaga|Ryuji|R|


Differentiation of rat pancreatic duct stem cells into insulin-secreting islet-like cell clusters through BMP7 inducement.

Abstract: To cure the epidemic of diabetes, in vitro produced β-like cells are lauded for cell therapy of diabetic patients. In this regard, we investigated the effects of different concentrations of bone morphogenetic protein 7 (BMP7) on the differentiation of rat pancreatic ductal epithelial-like stem cells (PDESCs) into β-like cells. For inducement of the differentiation, PDESCs were cultured in the basal media (H-DMEM + 10 % FBS + 1% penicillin-streptomycin) supplemented with 5 ng/mL, 10 ng/mL, 15 ng/mL, and 20 ng/mL of BMP7 for 28 days. To corroborate the identity of induced cells, they were examined through cell morphology, dithizone (DTZ) staining, immunofluorescence staining, real-time polymerase chain reaction (qPCR), and glucose-stimulated insulin secretion assay (GSIS). The enrichment of induced cells was high among 5 ng/mL, 10 ng/mL, 15 ng/mL, and 20 ng/mL of BMP7 supplemented groups as compared to the control group. Further, the induced cells were positive, while, the control group cells were negative to DTZ staining and the differentiated cells also have shown the upregulated expression of β cell-specific marker genes (Ins1 and Pdx1). The GSIS assay of inducement groups for insulin and C-peptide secretion has shown significantly higher values as compared to the control group (P < 0.01). Hence, the addition of BMP7 to basal medium has effectually induced differentiation of adult rat PDESCs into islet like-cell clusters containing insulin-secreting β-like cells.

Ghani|Muhammad Waseem|MW|
Bin|Liu|L|
Jie|Yang|Y|
Yi|Zhao|Z|
Jiang|Wu|W|
Ye|Li|L|
Cun|Lang Guan|LG|
Birmani|Muhammad Waseem|MW|
Zhuangzhi|Zhao|Z|
Lilong|An|A|
Mei|Xiao|X|

Differentiation
Islet-like cells clusters
Bone morphogenetic protein
PDESCs
Insulin-secreting cells


Changes in smoking among adolescents in the Republic of Karelia, Russia and Eastern Finland from 1995 to 2013.

Abstract:
AIMS
The aim of this study was to compare the prevalence of smoking, smoking experimentation and future intention to smoke in the Pitkäranta district, the Republic of Karelia, Russia and Eastern Finland in the years 1995 and 2013.

METHODS
Cross-sectional studies were carried out among 15-year-old ninth grade adolescents in all schools in the Pitkäranta region (1995: n=385, response rate 95%; 2013: 182, response rate 98%) and a sample of schools in Eastern Finland (1995: n=2098, response rate 91%; 2013: 635 response rate 95%).

RESULTS
The daily smoking prevalence among adolescents did not change either in Eastern Finland or in the Pitkäranta district from 1995 to 2013. However, smoking among Finnish adolescents was more common than among Russians (p<0.001) and boys, in general, smoke more commonly than girls (p<0.001). In Finland, early smoking experimentations declined by half among both genders but in Pitkäranta the girls' smoking experimentations tripled (relative risk 3.03, 95% confidence interval 1.76-5.20) from 1995 to 2013. The combined effect of country and gender was significant (p<0.001) for future intention to smoke. In Finland future intentions to smoke were very similar in boys and girls compared with obvious gender differences in Russia.

CONCLUSIONS
These results suggest that more attention should be paid for programmes that consider better gender and culture-specific issues in preventing initiation of smoking and promoting an anti-smoking climate in societies.

Aura|Annamari|A| Laatikainen|Tiina|T| Isoaho|Hannu|H| Bykachev|Kirsi|K| Lazutkina|Galina|G| Tossavainen|Kerttu|K|

smoking
Adolescent
school
gender
health behaviour


Upper extremity myxofibrosarcoma mimicking an erosive inflammatory arthritis: a case report.

Abstract: Myxofibrosarcoma is a malignant fibroblastic soft tissue neoplasm containing a variable amount of myxoid stroma that commonly presents as a slow-growing mass in elderly patients. The neoplasm may be superficial or deep to the muscle fascia and characteristically has an infiltrative growth pattern with a dominant or multinodular mass. We describe an unusual case of high-grade myxofibrosarcoma of the wrist and forearm that infiltrated the muscles, tendons, and wrist joint, causing bone erosions. The tumor was mistakenly diagnosed as synovitis and a chronic, erosive, inflammatory process. The diffuse nature, absence of a dominant mass, and radiographic appearance complicated the diagnosis. Although neoplasms of the synovial spaces are rare, this case demonstrates that tumors with a highly infiltrative growth pattern can mimic inflammatory synovitis and that neoplasms should be considered in the differential diagnosis when clinical and laboratory features are discordant with the imaging appearance.

Myxofibrosarcoma
Infiltrative growth pattern
Synovitis


How do urban rainfall-runoff pollution control technologies develop in China? A systematic review based on bibliometric analysis and literature summary.

Abstract: Rapid urbanization in China is driving the need of urban rainfall-runoff pollution control technologies due to adverse impacts on water environment. In this study, literature from China National Knowledge Infrastructure, Web of Science and Scopus in 1995/1/1-2019/5/15 are used to review research hotspots, development process and future directions of urban rainfall-runoff pollution control technologies in China and global world. Temporal evolution of publications showed that source reduction played better growing trend in urban rainfall-runoff pollution control field for both China and global world. Furthermore, with bibliometric tool, density visualization maps and co-occurrence network maps were created to identify research hotspots in China and global world. By comprehensively analyzing research hotspots above and development process from extracted literature, future directions of urban rainfall-runoff pollution control technologies were predicted. For model and strategy, both China and global world would concern on the accuracy of models to evaluate combination technologies. For source reduction, China would explore rainwater purification in sponge city, while global world would investigate match characteristics between specific regions and control technologies, combination between model and technologies, and improvement of pollutants removal. For process control, China would enhance ecological gutter inlet performance, whereas global world would concentrate on optimization of rainwater harvesting system. For post treatment, China would estimate modified hydrocylone and coagulation technology, and improve performance of filtration systems, riparian buffers and constructed wetlands, while global world would explore ecological and landscape function of constructed wetlands. Since China ranked first in producing Western publications and was the second most cited country for Western publications recently, China would significantly influence future development of urban rainfall-runoff pollution control technologies around the world. Meanwhile, some directions including infiltration basin and rainwater harvesting system were still shortcomings for China due to a late start of urban rainfall-runoff pollution control technologies in China.

Wang|Zhenbei|Z| Qi|Fei|F| Liu|Longyan|L| Chen|Miao|M| Sun|Dezhi|D| Nan|Jun|J|

Urban rainfall-runoff pollution
Control technologies
Bibliometric analysis
Literature summary
Research hotspots
Development tendency


Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes.

Abstract: The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and functionally essential post-translational modification, the change of a lysine to hypusine. eIF5A is recognized as a promoter of cell proliferation, but it has also been suggested to induce apoptosis. To date, the precise molecular mechanism through which eIF5A affects these processes remains elusive. In the present study, we explored whether eIF5A is involved in controlling the stress-induced expression of the key cellular regulator p53. Our results show that treatment of HCT-116 colon cancer cells with the deoxyhypusine (DHS) inhibitor N1-guanyl-1,7-diamineheptane (GC7) caused both inhibition of eIF5A hypusination and a significant reduction of p53 expression in UV-treated cells, and that eIF5A controls p53 expression at the level of protein synthesis. Furthermore, we show that treatment with GC7 followed by UV-induced stress counteracts the pro-apoptotic process triggered by p53 up-regulation. More in general, the importance of eIF5A in the cellular stress response is illustrated by the finding that exposure to UV light promotes the binding of eIF5A to the ribosomes, whereas UV treatment complemented by the presence of GC7 inhibits such binding, allowing a decrease of de novo synthesis of p53 protein.

Martella|Marianna|M|0000-0003-2389-3975
Catalanotto|Caterina|C|
Talora|Claudio|C|
La Teana|Anna|A|
Londei|Paola|P|
Benelli|Dario|D|0000-0002-1488-8392

D015972:Gene Expression Regulation, Neoplastic


Synergistic Effect of Beauveria bassiana and Trichoderma asperellum to Induce Maize (Zea mays L.) Defense against the Asian Corn Borer, Ostrinia furnacalis (Lepidoptera, Crambidae) and Larval Immune Response.

Abstract: Ostrinia furnacalis, is the major pest of maize causing significant yield losses. So far, many approaches have been used to increase the virulence of entomopathogenic fungal isolates. The current study is an attempt to estimate synergistic effect of Beauveria bassiana and Trichoderma asperellum in order to explore larval immune response through RNA sequencing and differentially expression analysis. In vivo synergism was examined in seven proportions (B. bassiana: T. asperellum = 1:1, 1:2, 1:3, 1:4, 4:1, 3:1, 2:1) and in the in vitro case, two inoculation methods were applied: seed coating and soil drenching. Results revealed significant decrease in plant damage and high larval mortality in fungal treatments. Fungal isolates mediated the plant defense by increasing proline, superoxide dismutase (SOD), peroxidase (POD), polyphenol oxidase (PPO) and protease activities. Seed coating method was proved to be the most effective in case of maize endophytic colonization. In total, 59 immune-related differentially expressed genes DEGs were identified including, cytochrome P450, heat shock protein, ABC transporter, cadherin, peptidoglycan recognition protein (PGRP), cuticlular protein, etc. Further, transcriptomic response was confirmed by qRT-PCR. Our results concluded that, coculture of B. bassiana and T. asperellum has the synergistic potential to suppress the immune response of O. furnacalis and can be used as sustainable approach to induce plant resistance through activation of defense-related enzymes.

Beauveria bassiana
Trichoderma asperellum
Ostrinia furnacalis
transcriptomic response
combine application
entomopathogenic fungi


Structure of a dihydroxycoumarin active-site inhibitor in complex with the RNase H domain of HIV-1 reverse transcriptase and structure-activity analysis of inhibitor analogs.

Abstract: Human immunodeficiency virus (HIV) encodes four essential enzymes: protease, integrase, reverse transcriptase (RT)-associated DNA polymerase, and RT-associated ribonuclease H (RNase H). Current clinically approved anti-AIDS drugs target all HIV enzymatic activities except RNase H, which has proven to be a very difficult target for HIV drug discovery. Our high-throughput screening activities identified the dihydroxycoumarin compound F3284-8495 as a specific inhibitor of RT RNase H, with low micromolar potency in vitro. Optimization of inhibitory potency can be facilitated by structural information about inhibitor-target binding. Here, we report the crystal structure of F3284-8495 bound to the active site of an isolated RNase H domain of HIV-1 RT at a resolution limit of 1.71Å. From predictions based on this structure, compounds were obtained that showed improved inhibitory activity. Computational analysis suggested structural alterations that could provide additional interactions with RT and thus improve inhibitory potency. These studies established proof of concept that F3284-8495 could be used as a favorable chemical scaffold for development of HIV RNase H inhibitors.

Himmel|Daniel M|DM|
Myshakina|Nataliya S|NS|
Ilina|Tatiana|T|
Van Ry|Alexander|A|
Ho|William C|WC|
Parniak|Michael A|MA|
Arnold|Eddy|E|

RNase H inhibitors
HIV ribonuclease H
dihydroxybenzopyrone derivatives
protein–inhibitor complex
structure-based drug design


The role of corchorus in spreading of tomato yellow leaf curl virus on tomato in Jeddah, Saudi Arabia.

Abstract: Corchorus (Corchorus capsularis L. and Corchorus olitorius L.) is one of the most important fiber crops grown in tropical and subtropical regions throughout the world. Field survey was conducted and naturally infected leaf samples were collected from corchorus and tomato plants in Jeddah, Saudi Arabia. The causal virus was transmitted by whiteflies to tomato plants and begomovirus infection was confirmed by Polymerase chain reaction. The complete viral genome and associated betasatellites were amplified, cloned and sequenced from both corchorus and tomato samples. The genetic variability and phylogenetic relationships were determined for both isolates (corchorus and tomato). The complete genome sequences showed highest (99.5 % nt) similarity with tomato yellow leaf curl virus (TYLCV) and formed closest cluster with TYLCV-Tomato reported from Jizan and Al-Qasim, Saudi Arabia and betasatellites sequences showed highest similarity (99.8 % nt) with Tomato yellow leaf curl betasatellites-Jeddah followed by Tomato yellow leaf curl Oman betasatellites and formed closed cluster with TYLCV-Tomato. On the basis of results obtained from whiteflies transmission, sequence similarity and phylogenetic relationships; it is concluded that the identified virus could be a variant of TYLCV circulating in the Kingdom. The significance of this study demonstrated that the corchorus is serving as reservoir and alternative host and playing an important role in spreading the begomovirus associated disease in the Kingdom of Saudi Arabia.

Corchorus
Tomato
Tomato yellow leaf curl virus
Betasatellites
Phylogenetic relationships


Steel slag and biochar amendments decreased CO2 emissions by altering soil chemical properties and bacterial community structure over two-year in a subtropical paddy field.

Abstract: Waste amendments, such as steel slag and biochar, have been reported as a strategy for improving soil fertility, crop productivity, and carbon (C) sequestration in agricultural lands. However, information regarding the subsequent effects of steel slag and biochar on C cycling and the underlying microbial mechanisms in paddy soils remains limited. Hence, this study aimed to examine the effect of these waste amendments (applied in 2015-2017) on total soil CO2 emissions, total and active soil organic C (SOC) contents, and microbial communities in the early and late seasons in a subtropical paddy field. The results showed that despite the exogenous C input from these waste amendments (steel slag, biochar and slag + biochar), they significantly (P < 0.05) decreased total CO2 emissions (e.g., by 41.9-59.6% at the early season), compared to the control soil. These amendments also significantly (P < 0.001) increased soil salinity and pH. The increased soil pH had a negative effect (r = -0.37, P < 0.05) on microbial biomass C (MBC). The biochar and slag + biochar treatments (cf. control) significantly (P < 0.001) increased SOC contents in the both seasons. The amendments altered the soil microbial community structure that associated with soil C cycling: (1) all three amendments increased the relative abundance of Agromyces and Streptomyces, which was associated with higher soil pH (cf. control); and (2) biochar and slag + biochar treatments caused a higher relative abundance of Sphingomonas, which was supported by high SOC contents under those amendments. Overall, this study demonstrated that the steel slag and biochar amendments altered microbial community composition due to changes in key soil properties, such as salinity, pH and SOC contents, with implications for increasing soil C stocks while mitigating CO2 emissions in the paddy field.

Wang|Miaoying|M|
Lan|Xingfu|X|
Xu|Xuping|X|
Fang|Yunying|Y|
Singh|Bhupinder Pal|BP|
Sardans|Jordi|J|
Romero|Estela|E|
Peñuelas|Josep|J|
Wang|Weiqi|W|

Paddy field
C cycling
Soil organic C
Microbial community composition
Active C


Exploring the frequency of blood pressure documentation in emergency departments.

Abstract:
PURPOSE
One of the most commonly performed task in the emergency department (ED) is reported as the monitoring of vital signs, yet there are no published standards of care that provide guidelines for the frequency of obtaining vital signs in the ED. The purpose of this exploratory study was to determine the frequency of documentation of vital signs recorded during ED visits across Veterans Health Administration (VHA) facilities.

METHODS
Deidentified patient level data from the VHA electronic health record (EHR) were abstracted for emergency department visits for 12 randomly selected days in calendar year 2011. The dataset included vital signs data, associated time stamps, facility, length of stay, triage category based on the Emergency Severity Index (ESI), and patient disposition for all patients. Descriptive statistics were used to describe the frequency of the specific vital sign measures, and parametric and nonparametric tests were used to examine study variables by ESI.

FINDINGS
The sample consisted of over 43,232 unique patient visits to 94 VHA EDs with a median length of stay of 173.3 min (interquartile range [IQR], 96.1-286.9). The mean number of times that blood pressure (BP) was recorded per visit was 1.23 (SD 1.175). For the entire sample, median time between blood pressure measurements was 139.7 min (IQR, 81.6-230.1). There was a significant difference in median length of stay and median time between blood pressure by ESI category.

CONCLUSIONS
In this dataset, median time between documentation of BP in the ED was every 2.3 hr for all patients. While the median time was statistically significant between ESI categories, these times may not be clinically relevant. More important was the inconsistent documentation of vital signs of ED patients in the designated fields in the EHR. Most facilities (84.1%) documented BP for >75% of patient visits. However, eight facilities (9.1%) had BP documented in <50% of patient visits.

CLINICAL RELEVANCE
It seems unlikely that vital signs are not monitored in the ED; nurses anecdotally report that vital signs are recorded on a paper chart and later scanned as an image into the EHR. However, lack of consistent process in documentation of vital signs may decrease the care team's ability to note early warning signs of physiological instability or deterioration.

Miltner|Rebecca S|RS|
Johnson|Kimberly D|KD|
Deierhoi|Rhiannon|R|

D001794:Blood Pressure
D004282:Documentation
D057286:Electronic Health Records
D016529:Emergency Nursing
D004636:Emergency Service, Hospital
D006787:Hospitals, Veterans
D006801:Humans
D009737:Nursing Records
D012720:Severity of Illness Index
D014218:Triage
D014481:United States

documentation
emergency department
Emergency Severity Index (ESI)
Vital sign monitoring


Assessment of the paraphilias.

Abstract: Paraphilias are recurrent, persistent, and intense sexual interests in atypical objects or activities. The most commonly encountered paraphilias in sexological or forensic settings are pedophilia, sexual sadism, exhibitionism, and voyeurism. Paraphilias are often comorbid with other sexual, mood, and personality disorders. Assessment and diagnosis require an integration of multiple sources of clinical information, given the limits and biases of self-report (through clinical interview or questionnaires). Clinicians ideally have access to more objective assessment methods, such as phallometric testing of sexual arousal. The accurate assessment and diagnosis of paraphilias is essential to effective treatment and management.

Seto|Michael C|MC|
Kingston|Drew A|DA|
Bourget|Dominique|D|

D011569:Psychiatric Status Rating Scales

Assessment
Paraphilias
Pedophilia
Sexual sadism
Diagnosis


Na/K-ATPase regulates bovine sperm capacitation through raft- and non-raft-mediated signaling mechanisms.

Abstract: Highly dynamic lipid microdomains (rafts) in the sperm plasma membrane contain several signaling proteins that regulate sperm capacitation. Na/K-ATPase isoforms (testis-specific isoform ATP1A4 and ubiquitous isoform ATP1A1) are abundant in bovine sperm plasma membrane. We previously reported that incubation of bovine sperm with ouabain, a specific Na/K-ATPase ligand, induced tyrosine phosphorylation of several sperm proteins during capacitation. The objective of this study was to investigate the roles of lipid rafts and non-rafts in Na/K-ATPase enzyme activity and signaling during bovine sperm capacitation. Content of ATP1A4 and, to a lesser extent, ATP1A1 was increased in raft and non-raft fractions of capacitated sperm, although non-raft enzyme activities of both isoforms were higher than the corresponding activities in rafts from capacitated sperm. Yet, ATP1A4 was the predominant isoform responsible for total Na/K-ATPase activity in both rafts and non-rafts. A comparative increase in phosphorylation of signaling molecules was observed in both raft (CAV1) and non-raft (EGFR and ERK1/2) membrane fractions during capacitation. Although SRC was phosphorylated in both membrane fractions, the non-raft fraction possessed more of this activated form. We also inferred, by immunoprecipitation, that ATP1A4 interacted with CAV1 and EGFR in the raft fraction, whereas interactions of ATP1A4 with SRC, EGFR, and ERK1/2 occurred in the non-raft fraction of ouabain-capacitated sperm; conversely, ATP1A1 interacted only with CAV1 in both fractions of uncapacitated and capacitated sperm. In conclusion, both raft and non-raft cohorts of Na/K-ATPase isoforms contributed to phosphorylation of signaling molecules during bovine sperm capacitation.

D048052:Mitogen-Activated Protein Kinase 3

Na/K-ATPase
ouabain
lipid raft
non-raft
bull sperm


Inhibitory-control event-related potentials correlate with individual differences in alcohol use.

Abstract: Impulsivity is a multidimensional construct that is related to different aspects of alcohol use, abuse, and dependence. Inhibitory control, one facet of impulsivity, can be assayed using the stop-signal task (SST) and quantified behaviorally via the stop-signal reaction time (SSRT) and electrophysiologically using event-related potentials (ERPs). Research on the relationship between alcohol use and SSRTs, and between alcohol use and inhibitory-control ERPs, is mixed. Here, adult alcohol users (n = 79), with a wide range of scores on the Alcohol Use Disorders Identification Test (AUDIT), completed the SST under electroencephalography (EEG) (70% of participants had AUDIT total scores greater than or equal to 8). Other measures, including demographic, self-report, and task-based measures of impulsivity, personality, and psychological factors, were also recorded. A machine-learning method with penalized linear regression was used to correlate individual differences in alcohol use with impulsivity measures. Four separate models were tested, with out-of-sample validation used to quantify performance. ERPs alone statistically predicted alcohol use (cross-validated r = 0.28), with both early and late ERP components contributing to the model (larger N2, but smaller P3, amplitude). Behavioral data from a wide range of impulsivity measures were also associated with alcohol use (r = 0.37). SSRT was a relatively weak statistical predictor, whereas the Stroop interference effect was relatively strong. The addition of nonimpulsivity behavioral measures did not improve the correlation (r = 0.34) and was similar when ERPs were combined with non-ERP data (r = 0.29). These findings show that inhibitory control ERPs are robustly correlated individual differences in alcohol use.

O'Halloran|Laura|L|
Rueda-Delgado|Laura M|LM|
Jollans|Lee|L|
Cao|Zhipeng|Z|
Boyle|Rory|R|
Vaughan|Christina|C|
Coey|Phillip|P|
Whelan|Robert|R|0000-0002-2790-7281

event-related potentials
alcohol
impulsivity
electroencephalography
human adults
machine learning


Transcutaneous blepharoplasty in blepharochalasis.

Abstract: Blepharochalasis is a rare degenerative disease of skin of lids. We report 3 cases of blepharochalasis, out of which two involved upper eyelids and one involved lower eyelids. All the three cases were treated with transcutaneous blepharoplasty with acceptable cosmetic results.

Sacchidanand|Sarvajnamurthy A|SA|
Deepak|Hurkudli Suresh|HS|
Vishal|Chugh|C|
Revathy|Tumkur Narasimhan|TN|

blepharoplasty
Blepharochalasis
ptosis atonica


Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways.

Abstract:
BACKGROUND
Despite recent advances in diagnosis and treatment, prostate cancer (PCa) remains the leading cause of cancer-related deaths in men. Current treatments offered in the clinics are often toxic and have severe side effects. Hence, to treat and manage PCa, new agents with fewer side effects or having potential to reduce side effects of conventional therapy are needed. In this study, we show anti-cancer effects of quercetin, an abundant bioflavonoid commonly used to treat prostatitis, and defined quercetin-induced cellular and molecular changes leading to PCa cell death.

METHODS
Cell viability was assessed using MTT. Cell death mode, mitochondrial outer membrane potential, and oxidative stress levels were determined by flow cytometry using Annexin V-7 AAD dual staining kit, JC-1 dye, and ROS detection kit, respectively. Antibody microarray and western blot were used to delineate the molecular changes induced by quercetin.

RESULTS
PCa cells treated with various concentrations of quercetin showed time- and dose-dependent decrease in cell viability compared to controls, without affecting normal prostate epithelial cells. Quercetin led to apoptotic and necrotic cell death in PCa cells by affecting the mitochondrial integrity and disturbing the ROS homeostasis depending upon the genetic makeup and oxidative status of the cells. LNCaP and PC-3 cells that have an oxidative cellular environment showed ROS quenching after quercetin treatment while DU-145 showed rise in ROS levels despite having a highly reductive environment. Opposing effects of quercetin were also observed on the pro-survival pathways of PCa cells. PCa cells with mutated p53 (DU-145) and increased ROS showed significant reduction in the activation of pro-survival Akt pathway while Raf/MEK were activated in response to quercetin. PC-3 cells lacking p53 and PTEN with reduced ROS levels showed significant activation of Akt and NF-κB pathway. Although some of these changes are commonly associated with oncogenic response, the cumulative effect of these alterations is PCa cell death.

CONCLUSIONS
Our results demonstrated quercetin exerts its anti-cancer effects by modulating ROS, Akt, and NF-κB pathways. Quercetin could be used as a chemopreventive option as well as in combination with chemotherapeutic drugs to improve clinical outcomes of PCa patients.

Quercetin
Prostate cancer
Cell survival
Bioflavonoid
Chemoprevention
Apoptosis


Knowledge and attitudes toward breastfeeding in an African American male population.

Abstract:
OBJECTIVE
To measure knowledge and attitudes toward breastfeeding among African American men.

DESIGN
Cross-sectional survey.

SETTING
Three barbershops in Dallas, Texas.

PARTICIPANTS
African American adult men (N = 81).

METHODS
Surveys were completed by African American men to evaluate their knowledge, attitudes, and involvement in breastfeeding.

RESULTS
One half of the participants were age 26 to 40. Eighty-five percent were U.S.-born, and others were born in several African countries. Education varied from some high school to postgraduate. Most had some college or a degree (78%). One half were fathers (51%), and most were single (61%). Most had witnessed breastfeeding (85%), and 58% preferred their infants to be breastfed. Only 47% knew that breastfeeding helps prevent infant infections, and 15% knew it can prevent breast cancer in the mother. Significant differences were found when comparing knowledge and attitudes by place of birth and age. Almost one half of men age 18 to 25 (43%) and age 25 to 40 (48%) felt that breastfeeding should not occur in public compared to only 4% of men older than 40 (p = .005).

CONCLUSION
Overall, we found that African American men were supportive of breastfeeding, knew that breastfeeding was best for infants, and had positive attitudes toward breastfeeding. However, we found consistent gaps in knowledge about the actual health benefits to mothers and infants and conflicting attitudes toward breastfeeding. Results emphasize the need for health education efforts to improve attitudes toward breastfeeding in public.

Jolly|Lisa|L| Pagels|Patti|P| Woodfin|Grant|G| Silver|Mandy|M| Kindratt|Tiffany|T| Gimpel|Nora|N|

D007722:Health Knowledge, Attitudes, Practice

knowledge
attitudes
breastfeeding
African American
men


The contribution of genome mining strategies to the understanding of active principles of PGPR strains.

Abstract: Pathogenic microorganisms and insects affecting plant health are a major and chronic threat to food production and the ecosystem worldwide. As agricultural production has intensified over the years, the use of agrochemicals has in turn increased. However, this extensive usage has had several detrimental effects, with a pervasive environmental impact and the emergence of pathogen resistance. In addition, there is an increasing tendency among consumers to give preference to pesticide-free food products. Biological control, through the employment of plant growth-promoting rhizobacteria (PGPR), is therefore considered a possible route to the reduction, even the elimination, of the use of agrochemicals. PGPR exert their beneficial influence by a multitude of mechanisms, often involving antibiotics and proteins, to defend the host plant against pathogens. To date, these key metabolites have been uncovered only by systematic investigation or by serendipity; their discovery has nevertheless been propelled by the genomic revolution of recent years, as increasing numbers of genomic studies have been integrated into this field, facilitating a holistic view of this topic and the rapid identification of ecologically important metabolites. This review surveys the highlights and advances of genome-driven compound and protein discovery in the field of bacterial PGPR strains, and aims to advocate for the benefits of this strategy.

Paterson|Julia|J| Jahanshah|Ghazaleh|G| Li|Yan|Y| Wang|Qi|Q| Mehnaz|Samina|S| Gross|Harald|H|

genome mining
PGPR
Bacillus
Pseudomonas
biocontrol strains
rhizosphere bacteria


conLSH: Context based Locality Sensitive Hashing for mapping of noisy SMRT reads.

Abstract: Single Molecule Real-Time (SMRT) sequencing is a recent advancement of Next Gen technology developed by Pacific Bio (PacBio). It comes with an explosion of long and noisy reads demanding cutting edge research to get most out of it. To deal with the high error probability of SMRT data, a novel contextual Locality Sensitive Hashing (conLSH) based algorithm is proposed in this article, which can effectively align the noisy SMRT reads to the reference genome. Here, sequences are hashed together based not only on their closeness, but also on similarity of context. The algorithm has O(nρ+1) space requirement, where n is the number of sequences in the corpus and ρ is a constant. The indexing time and querying time are bounded by Onρ+1·lnnln1P2 and O(nρ) respectively, where P2 > 0, is a probability value. This algorithm is particularly useful for retrieving similar sequences, a widely used task in biology. The proposed conLSH based aligner is compared with rHAT, popularly used for aligning SMRT reads, and is found to comprehensively beat it in speed as well as in memory requirements. In particular, it takes approximately 24.2% less processing time, while saving about 70.3% in peak memory requirement for H.sapiens PacBio dataset.


Association of Body Mass Index and Waist Circumference with All-Cause Mortality in Hemodialysis Patients.

Abstract: In this study based on a large nationally representative sample of Korean adults, we investigated the potential associations of the body mass index (BMI) and waist circumference (WC) with mortality in patients undergoing hemodialysis. We obtained the data of 18,699 participants >20 years of age who were followed up with for 4 years and for whom BMI and WC information were available, using a nationally representative dataset from the Korean National Health Insurance System. Patients were stratified into five levels by their baseline BMI and into six levels by their WC (5-cm increments). A total of 4975 deaths occurred during a median follow-up period of 48.2 months. Participants with a higher BMI had a lower mortality rate than those with a lower BMI. In a fully adjusted Cox regression analysis, being overweight and obese was associated with a significantly lower relative risk of all-cause mortality relative to the reference group. Conversely, the mortality rate was higher among participants with a high WC than among those with a low WC. Participants with the highest WC had a higher risk of mortality, while those with the lowest WC level had a significantly lower risk of mortality. In conclusion, all-cause mortality was positively associated with WC, a measure of abdominal obesity, and inversely associated with BMI, a measure of body volume, in patients undergoing hemodialysis.

Kim|Chang Seong|CS|0000-0001-8753-7641
Han|Kyung-Do|KD|
Choi|Hong Sang|HS|0000-0001-8191-4071
Bae|Eun Hui|EH|
Ma|Seong Kwon|SK|
Kim|Soo Wan|SW|0000-0002-3540-9004

body mass index
waist circumference
mortality
hemodialysis
obesity


Minimum ovarian stimulation involving combined clomiphene citrate and estradiol treatment for in vitro fertilization of Bologna-criteria poor ovarian responders.

Abstract:
AIM
The aim of this study was to assess the efficacy of a minimal ovarian stimulation involving combined clomiphene citrate (CC) and estradiol (E2) administration for poor responders with diminished ovarian reserve (DOR).

MATERIAL AND METHODS
In this case-control study, we recruited 41 consecutive hypergonadotropic poor responders (69 cycles) who met Bologna-criteria and had experienced cancellation of oocyte retrieval. In 10 (20 cycles), 11 (21 cycles) and 20 patients (28 cycles) between 2012 and 2014, follicular development was induced using an E2 cycle, CC cycle and CC + E2 cycle, respectively. After confirmation of high follicle-stimulating hormone levels (15-40 mIU/ml) at menstrual day 3, DOR patients were treated with oral E2 of 1.0 mg/day, CC of 100 mg/day, or both CC and E2 continuously, until ovulation induction. Two days later, we transvaginally aspirated the follicles, performed in vitro fertilization, and cryopreserved the cleavage embryos. One warmed embryo was transferred into the uterus during the hormone replacement cycles.

RESULTS
For the E2, CC, and CC + E2 cycles, the median patient age was 41 years in all groups, and the serum anti-Müllerian hormone levels were 0.2 ± 0.3, 0.4 ± 0.4, and 0.2 ± 0.3 ng/mL, respectively (P = 0.258); follicular development failure rates were 50.0%, 19.0%, and 3.6%, respectively (P < 0.001); numbers of retrieved oocytes (/cycle) were 0.5 ± 0.6, 0.8 ± 0.7, and 1.2 ± 1.1, respectively (P = 0.033); and clinical pregnancy rates (/cycle) were 5.0%, 4.8%, and 10.7%, respectively (P = 0.725).

CONCLUSION
CC + E2 administration for the patients with DOR was effective with a lower cancellation rate of oocyte retrieval and a higher number of retrieved oocytes.

Kuroda|Keiji|K| Kitade|Mari|M| Kumakiri|Jun|J| Jinushi|Makoto|M| Shinjo|Azusa|A| Ozaki|Rie|R| Ikemoto|Yuko|Y| Katoh|Noriko|N| Takeda|Satoru|S|

clomiphene citrate
in vitro fertilization
minimal ovarian stimulation
diminished ovarian reserve
estrogen replacement


Phase II Study of S-1 plus Cisplatin as First-Line Therapy in Patients with Metastatic Esophageal Carcinoma.

Abstract:
BACKGROUND
Patients with metastatic esophageal squamous cell cancer (ESCC) need safer and more efficacious treatments. The aim of this phase II study was to investigate the efficacy and safety of S-1 plus cisplatin as first-line therapy in metastatic ESCC.

PATIENTS AND METHODS
50 patients with metastatic ESCC who had not received prior systemic chemotherapy for metastatic disease were enrolled. Patients received S-1 at 40 mg/m2 divided into 2 daily doses for 14 days and cisplatin at 75 mg/m2 on day 1 or 25 mg/m2 on days 1-3 intravenously, repeated every 21 days with a maximum of 6 cycles.

RESULTS
47 patients were assessable for response and 18 patients achieved a partial response, giving an overall response rate of 38.3%. Among those who had objective responses, a large percentage (72.2%) quickly showed remarkable tumor shrinkage during the first 2 cycles. 18 (38.3%) patients had stable disease. The median progression-free survival was 5.6 months, and the median overall survival was 12.0 months. Toxicity was mild to moderate and generally tolerable.

CONCLUSION
The combination of S-1 plus cisplatin was a well-tolerated and convenient chemotherapy regimen with promising efficacy.

Sun|Si|S| Yu|Hui|H| Wang|Huijie|H| Zhang|Hai|H| Wu|Xianghua|X| Wang|Jialei|J| Chang|Jianhua|J|

D000971:Antineoplastic Combined Chemotherapy Protocols

D000077277:Esophageal Squamous Cell Carcinoma

Metastatic
Chemotherapy
Esophageal cancer
Squamous cell cancer, SCC


Human colorectal cancer-derived carcinoma associated fibroblasts promote CD44-mediated adhesion of colorectal cancer cells to endothelial cells by secretion of HGF.

Abstract:
Background
Carcinoma-associated fibroblasts (CAFs) are dominant components of tumor microenvironment, which has been reported to promote development, progression, and metastasis of cancer. However, the role of CAFs during adhesion process remains unknown. It has been hypothesized that CAFs contribute to adhesion to endothelial cells of colorectal cancer (CRC) via HGF/c-Met pathway.

Methods
Clinical specimen and orthotopic liver metastasis model was used to investigate association between CD44 expression and propensity of metastasis in CRC. Human CRC derived cancer associated fibroblasts was isolated and its effect on migration and adhesion of CRC cells was investigated. We also confirm the conclusion on animal metastasis model.

Results
In this study, clinical specimen and orthotopic liver metastatic model indicated that overexpression of CD44 is associated with CRC metastasis, and we found that colorectal cancer-derived CAFs (CC-CAFs) increased the adhesion and migration of CRC cells in vitro through up-regulation of CD44, we also found that CC-CAFs promoted adhesion and liver or lung metastasis in vivo. Mechanistically, we found that the expression of HGF increased tenfolds compared CC-CAFs with adjacent normal fibroblasts, and HGF promoted adhesion through up-regulation of CD44 via HGF/c-MET signal pathway.

Conclusions
These results indicated that CC-CAFs-derived HGF induced up-regulation of CD44 which mediated adhesion of CRC cells to endothelial cells, and subsequently resulted in enhancement of metastasis of CRC cells, it could provide a novel therapeutic or preventive target.

Zhang|Rongsheng|R| Qi|Fan|F| Shao|Shengli|S| Li|Geng|G| Feng|Yongdong|Y|0000-0001-7686-9480

Adhesion
Colorectal cancer
Metastasis
Cancer associated fibroblasts


A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps.

Abstract:
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation.

OBJECTIVE
This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions.

METHODS
The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry.

RESULTS
Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro.

CONCLUSIONS
This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.

Delemarre|Tim|T|
Holtappels|Gabriele|G|
De Ruyck|Natalie|N|
Zhang|Nan|N|
Nauwynck|Hans|H|
Bachert|Claus|C|
Gevaert|Elien|E|

neutrophils
CRSwNP
type 2 inflammation
Charcot-Leyden crystals
IL-17
CRSsNP
NETosis


Prevalence and trends of obesity among adult Sudanese individuals: Population based study.

Abstract:
AIM
The prevalence of obesity has increased across the globe in particular in Africa. The aim of this study was to determine the prevalence of obesity in Sudan.

MATERIAL AND METHODS
Descriptive, cross sectional study recruited 7239 individuals. Demographic and clinical data were collected by an interview using a pretested standardised questionnaire. Anthropometric measurements including body weight, height and waist circumference have been taken using standardized techniques and calibrated equipment. Body mass index (BMI) has been calculated.

RESULTS
Total of 7239 persons completed the questionnaires; the results showed that prevalence of obesity was found to be 21.2%, with a higher rate of obesity in females than males (26.3% versus 13.8%). The prevalence of central obesity was also higher in women (36.7%) than men (17.6%).The prevalence of overweight was 34.9%. The overall prevalence of overweight/obesity was 56.1%. Obesity determined by BMI was associated with hypertension and diabetes. While central obesity was associated with an increase in age, female, diabetes and hypertension.

CONCLUSION
The prevalence of obesity was 21.2%. Obesity and central obesity have a higher prevalence among Sudanese women. Obesity and central obesity were associated with diabetes and hypertension.

Ahmed|Mohamed H|MH|
Ali|Yasmeen A|YA|
Awadalla|Heitham|H|
Elmadhoun|Wadie M|WM|
Noor|Sufian K|SK|
Almobarak|Ahmed O|AO|


Pyridoxal-5-phosphate induced cardioprotection in aging associated with up-expression of cystathionine-γ-lyase, 3-mercaptopyruvate sulfurtransferase, and ATP-sensitive potassium channels.

Abstract:
BACKGROUND
In the present work, we investigated the cardioprotective potential of pyridoxal-5-phosphate (PLP) in old rats as a cofactor of enzymes that synthesize hydrogen sulphide (H2 S).

MATERIALS AND METHODS
PLP was administered per os in a dose of 0.7 mg per kg daily for 2 weeks. Rats were divided into three groups (adult, old and old +PLP) of 20 animals. The cardiac mRNA levels of genes encoding H2 S-synthesizing enzymes cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), uncoupling proteins (UCP3), subunits of ATP-sensitive potassium (KATP ) channels were determined using real-time polymerase chain reaction analysis. We also studied the effect of PLP-administration on the content of H2 S, oxidative stress, the activities of inducible and constitutive NO-synthase (iNOS, cNOS), arginase and nitrate reductase in the heart homogenates as well as cardiac resistance to ischemia-reperfusion in Langendorff-isolated heart model.

RESULTS
It was shown that PLP restored mRNA levels of CSE, 3-MST and UCP3 genes, and H2 S content and also significantly increased the expression of SUR2 and Kir6.1 (2.2 and 3.3 times, respectively) in the heart of old rats. PLP significantly reduced the formation of superoxide, malondialdehyde, diene conjugates as well as the activity of iNOS and arginase. PLP significantly increased constitutive synthesis of NO and prevented reperfusion disturbances of the heart function after ischemia.

CONCLUSIONS
Thus, PLP-administration in old rats was associated with up-expression of CSE, 3-MST, UCP3 and SUR2 and Kir6.1 subunits of KATP channels, and also increased cNOS activity and reduced oxidative stress and prevented reperfusion dysfunction of the heart in ischemia-reperfusion.

pyridoxal-5-phosphate
ageing
ischemia-reperfusion
KATP channels
H2S-synthesizing enzymes


The effectiveness of EVOSKIN®Palm and sole moisturizing cream in treating capecitabine-associated hand-foot syndrome: a randomized double-blind clinical trial.

Abstract:
BACKGROUND
This study sought to test the effectiveness of EVOSKIN®Palm and sole moisturizing cream (PSMC) in preventing and treating hand-foot syndrome (HFS) during capecitabine chemotherapy.

METHODS
Stage II/III colorectal cancer patients receiving capecitabine adjuvant chemotherapy were randomly allocated to receive either EVOSKINPSMC or physiological saline treatments for their hands and feet. Treatment was initiated along with adjuvant chemotherapy and continued till the end of chemotherapy. Participants' skin responses were evaluated every 3 weeks.

RESULTS
During the study, 51 participants in the EVOSKIN PSMC group and 54 participants in the physiological saline group completed at least three cycles of capecitabine chemotherapy. The total incidence of HFS in the EVOSKIN PSMC group was lower than that in the physiological saline group (56.8% vs. 75.9%, P=0.006), as was the incidence of Grade 3/4 HFS (6.0% vs. 18.5%, P=0.011). The incidence of HFS became significant after 6weeks of chemotherapy. Further, the incidence of severe HFS was significant from as early as 3weeks after the commencement of chemotherapy despite the use of EVOSKIN PSMC to manage the condition. Notably, the incidence of Grade 1/2 HFS was not statistically significant between the two groups (26/51 vs. 32/54, 52.0% vs. 59.2%, P=0.194).

CONCLUSIONS
The incidence of severe HFS among individuals using oral capecitabine can be reduced by the prophylactic treatment of EVOSKIN PSMC, this treatment is reasonable and acceptable for patients with capecitabine chemotherapy.

Lu|Weiqun|W| Huang|Zhiliang|Z| Chen|Shicai|S| Lv|Huizeng|H| Chen|Xinqi|X| Lei|Jian|J| Ke|Chuanfeng|C| Hong|Chuyuan|C| Wei|Yisheng|Y| Su|Rong|R| Chen|Rong|R| Sun|Zheng|Z| Yang|Ping|P| Tan|Xiaojun|X| Liu|Haiying|H|

D000964:Antimetabolites, Antineoplastic
D000069287:Capecitabine
D017024:Chemotherapy, Adjuvant
D015179:Colorectal Neoplasms
D060831:Hand-Foot Syndrome
D006801:Humans

prevention
Hand-foot syndrome (HFS)
capecitabine
colorectal cancer


Fighting and mating success in giant Australian cuttlefish is influenced by behavioural lateralization.

Abstract: Behavioural lateralization is widespread. Yet, a fundamental question remains, how can lateralization be evolutionary stable when individuals lateralized in one direction often significantly outnumber individuals lateralized in the opposite direction? A recently developed game theory model predicts that fitness consequences which occur during intraspecific interactions may be driving population-level lateralization as an evolutionary stable strategy. This model predicts that: (i) minority-type individuals exist because they are more likely to adopt unpredictable fighting behaviours during competitive interactions (e.g. fighting); and (ii) majority-type individuals exist because there is a fitness advantage in having their biases synchronized with other conspecifics during interactions that require coordination (e.g. mating). We tested these predictions by investigating biases in giant Australian cuttlefish during fighting and mating interactions. During fighting, most male cuttlefish favoured the left eye and these males showed higher contest escalation; but minority-type individuals with a right-eye bias achieved higher fighting success. During mating interactions, most male cuttlefish favoured the left eye to inspect females. Furthermore, most male cuttlefish approached the female's right side during a mating attempt and these males achieved higher mating success. Our data support the hypothesis that population-level biases are an evolutionary consequence of the fitness advantages involved in intraspecific interactions.

Schnell|Alexandra K|AK|
Jozet-Alves|Christelle|C|
Hall|Karina C|KC|
Radday|Léa|L|
Hanlon|Roger T|RT|

game theory
fitness consequences
evolutionary stable strategy
cephalopod
frequency-dependent
visual asymmetries


Brain tissue responses to neural implants impact signal sensitivity and intervention strategies.

Abstract: Implantable biosensors are valuable scientific tools for basic neuroscience research and clinical applications. Neurotechnologies provide direct readouts of neurological signal and neurochemical processes. These tools are generally most valuable when performance capacities extend over months and years to facilitate the study of memory, plasticity, and behavior or to monitor patients' conditions. These needs have generated a variety of device designs from microelectrodes for fast scan cyclic voltammetry (FSCV) and electrophysiology to microdialysis probes for sampling and detecting various neurochemicals. Regardless of the technology used, the breaching of the blood-brain barrier (BBB) to insert devices triggers a cascade of biochemical pathways resulting in complex molecular and cellular responses to implanted devices. Molecular and cellular changes in the microenvironment surrounding an implant include the introduction of mechanical strain, activation of glial cells, loss of perfusion, secondary metabolic injury, and neuronal degeneration. Changes to the tissue microenvironment surrounding the device can dramatically impact electrochemical and electrophysiological signal sensitivity and stability over time. This review summarizes the magnitude, variability, and time course of the dynamic molecular and cellular level neural tissue responses induced by state-of-the-art implantable devices. Studies show that insertion injuries and foreign body response can impact signal quality across all implanted central nervous system (CNS) sensors to varying degrees over both acute (seconds to minutes) and chronic periods (weeks to months). Understanding the underlying biological processes behind the brain tissue response to the devices at the cellular and molecular level leads to a variety of intervention strategies for improving signal sensitivity and longevity.

Kozai|Takashi D Y|TD|
Jaquins-Gerstl|Andrea S|AS|
Vazquez|Alberto L|AL|
Michael|Adrian C|AC|
Cui|X Tracy|XT|

Foreign body response
biocompatibility
biointegration
in vivo
inflammation
two-photon


Unravelling the taxonomy of an interstitial fish radiation: Three new species of Gouania (Teleostei: Gobiesocidae) from the Mediterranean Sea and redescriptions of G. willdenowi and G. pigra.

Abstract: The clingfish (Gobiesocidae) genus Gouania Nardo, 1833 is endemic to the Mediterranean Sea and inhabits, unlike any other vertebrate species in Europe, the harsh intertidal environment of gravel beaches. Following up on a previous phylogenetic study, we revise the diversity and taxonomy of this genus by analysing a comprehensive set of morphological (meristics, morphometrics, microcomputed tomography imaging), geographical and genetic (DNA-barcoding) data. We provide descriptions of three new species, G. adriatica sp. nov., G. orientalis sp. nov. and G. hofrichteri sp. nov., as well as redescriptions of G. willdenowi (Risso, 1810) and G. pigra (Nardo, 1827) and assign neotypes for the latter two species. In addition to elucidating the complex taxonomic situation of Gouania, we discuss the potential of this enigmatic clingfish genus for further ecological, evolutionary and biodiversity studies that might unravel even more diversity in this unique Mediterranean fish radiation.

intertidal
DNA-barcoding
blunt-snouted clingfish
cryptobenthic fish
pebble beach


Targeting the potent Beclin 1-UVRAG coiled-coil interaction with designed peptides enhances autophagy and endolysosomal trafficking.

Abstract: The Beclin 1-Vps34 complex, known as "mammalian class III PI3K," plays essential roles in membrane-mediated transport processes including autophagy and endosomal trafficking. Beclin 1 acts as a scaffolding molecule for the complex and readily transits from its metastable homodimeric state to interact with key modulators such as Atg14L or UVRAG and form functionally distinct Atg14L/UVRAG-containing Beclin 1-Vps34 subcomplexes. The Beclin 1-Atg14L/UVRAG interaction relies critically on their coiled-coil domains, but the molecular mechanism remains poorly understood. We determined the crystal structure of Beclin 1-UVRAG coiled-coil complex and identified a strengthened interface with both hydrophobic pairings and electrostatically complementary interactions. This structure explains why the Beclin 1-UVRAG interaction is more potent than the metastable Beclin 1 homodimer. Potent Beclin 1-UVRAG interaction is functionally significant because it renders UVRAG more competitive than Atg14L in Beclin 1 binding and is critical for promoting endolysosomal trafficking. UVRAG coiled-coil mutants with weakened Beclin 1 binding do not outcompete Atg14L and fail to promote endolysosomal degradation of the EGF receptor (EGFR). We designed all-hydrocarbon stapled peptides that specifically targeted the C-terminal part of the Beclin 1 coiled-coil domain to interfere with its homodimerization. One such peptide reduced Beclin 1 self-association, promoted Beclin 1-Atg14L/UVRAG interaction, increased autophagic flux, and enhanced EGFR degradation. Our results demonstrate that the targeting Beclin 1 coiled-coil domain with designed peptides to induce the redistribution of Beclin 1 among its self-associated form or Atg14L/UVRAG-containing complexes enhances both autophagy and endolysosomal trafficking.

Wu|Shuai|S| He|Yunjiao|Y| Qiu|Xianxiu|X| Yang|Wenchao|W| Liu|Wenchao|W| Li|Xiaohua|X| Li|Yan|Y| Shen|Han-Ming|HM| Wang|Renxiao|R| Yue|Zhenyu|Z| Zhao|Yanxiang|Y|0000-0002-9408-9979

D054730:Protein Interaction Domains and Motifs

autophagy
endolysosomal trafficking
Beclin 1
Atg14L
UVRAG


quaddRAD: a new high-multiplexing and PCR duplicate removal ddRAD protocol produces novel evolutionary insights in a nonradiating cichlid lineage.

Abstract: The identification of thousands of variants across the genomes and their accurate genotyping are crucial for estimating the genetic parameters needed to address a host of molecular ecological and evolutionary questions. With rapid advances of massively parallel high-throughput sequencing technologies, several methods have recently been developed to access genomewide data on population variation. One of the most successful and widely used techniques relies on the combination of restriction enzymes and sequencing-by-synthesis: restriction-site-associated DNA sequencing (RADSeq). We developed a new, more time- and cost-efficient double-digest RAD paired-end protocol (quaddRAD) that simplifies and speeds up the identification of PCR duplicates and permits large-scale multiplexing. Assessing its performance on a technical data set, we also applied the quaddRAD method on population samples of a Neotropical cichlid fish lineage (Archocentrus centrarchus) to assess its genetic structure and demographic history. While we identified allopatric interlake genetic divergence, most likely driven by drift, no signature of sympatric divergence was detected. This differs from what has been observed in the clade of Midas cichlids (Amphilophus citrinellus spp.), another cichlid lineage that inhabits the same lakes and shares a similar demographic history, but has evolved into small-scale adaptive radiations via sympatric speciation. We demonstrate that quaddRAD is a robust and efficient method for genotyping a massive number and widely overlapping set of loci with high accuracy. Furthermore, the results on A. centrarchus open new research avenues providing an ideal system to investigate genome-level mechanisms that could alter the speciation potential of different but closely related cichlid lineages.

quaddRAD
PCR duplicates
Archocentrus centrarchus
sympatric speciation
population genomics
reduced representation libraries


MRGBP as a potential biomarker for the malignancy of pancreatic ductal adenocarcinoma.

Abstract: MORF4-related gene-binding protein (MRGBP), which is also known as chromosome 20 open reading frame 20 (C20orf20), is commonly highly expressed in several types of malignant tumors and tumor progression. However, the expression pattern and underlying mechanism of MRGBP in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In the study, we found that MRGBP was frequently upregulated in PDAC tissues and cell lines. In addition, the upregulation of MRGBP was positively associated with TNM stage, T classification, and poor prognosis. Knockdown of MRGBP in the PDAC cell lines ASPC-1 and Mia PaCa-2 by transiently transfected with small interfering RNA (siRNA) drastically attenuated the proliferation, migration, and invasion of those cells, whereas ectopic MRGBP overexpression in BxPC-3 cells produced exactly the opposite effect. Furthermore, we also found that overexpression of MRGBP remarkably led to cell morphological changes and induced an increased expression of mesenchymal marker Vimentin, whereas a decreased expression of epithelial marker E-cadherin. Taken together, this study indicates that MRGBP acts as a tumor oncogene in PDAC and is a promising target of carcinogenesis.

Ding|Feng|F| Zhang|Shuang|S| Gao|Shaoyang|S| Shang|Jian|J| Li|Yanxia|Y| Cui|Ning|N| Zhao|Qiu|Q|

MRGBP
biomarker
pancreatic ductal adenocarcinoma
upregulation


Intestinal obstruction in pregnancy by ondansetron.

Abstract:
BACKGROUND
Ondansetron use for nausea and vomiting during pregnancy has increased in the last years, although its maternal and fetal safety is not conclusive.

CASE
We describe a case of intestinal obstruction in a pregnant woman with severe nausea and vomiting of pregnancy treated with ondansetron, which is known to slow gut motility.

CONCLUSION
The spontaneous reporting system of WHO confirms that this potentially life threatening complication is more common than what the peer review literature may suggest and needs to be looked into carefully, especially in view of the wide spread off-label use for NVP.

Cohen|Rana|R|
Shlomo|Meital|M|
Dil|Dorit Nahlieli|DN|
Dinavitser|Natalia|N|
Berkovitch|Mati|M|
Koren|Gideon|G|

Intestinal obstruction
Pregnancy
Ondansetron
5-HT3 receptor antagonist
Adverse event
Hyperemesis gravidarum


Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

Abstract: Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

Kumar|Hariom|H|
Sharma|B M|BM|
Sharma|Bhupesh|B|

D011297:Prenatal Exposure Delayed Effects

Melatonin receptor agonists
Intestinal motility
Serotonin
Calcium
Mitochondrial function
Neurodevelopment


The diagnostic performance of novel torque technique for endoscopic ultrasound-guided tissue acquisition in solid pancreatic lesions: A prospective randomized controlled trial.

Abstract:
BACKGROUND AND AIM
Although several techniques for improved outcomes in endoscopic ultrasound (EUS)-guided tissue acquisition have been reported, the reported diagnostic yield for pancreatic masses is not satisfactory. The effects of novel technique (torque method) on twisting the scope in the clockwise or counterclockwise direction during EUS-fine needle biopsy (EUS-FNB) are unknown. We compared the diagnostic yield of EUS-FNB for pancreatic masses using the torque and standard techniques.

METHODS
From April 20, 2017, to March 16, 2018, 124 consecutive patients with solid pancreatic mass who underwent EUS-FNB using either the torque or standard technique were randomly assigned. Three passes were made with each technique, comprising 10 uniform to-and-fro movements on each pass with a 10-mL syringe suction. The primary outcome was procurement rates of histologic cores, and the secondary outcomes were the diagnostic performance and technical failure.

RESULTS
There were significant differences between the groups regarding the procurement rate of the histologic core and optimal quality core (standard vs torque: 87.1% [54/62] vs 98.4% [61/62], P = 0.038 and 79.0% [49/62] vs 93.5% [58/62], P = 0.037). The sensitivity, specificity, positive predictive value, and negative predictive values of EUS-FNB were 85.45%, 100%, 100%, and 46.67%, respectively, for the standard technique and 96.49%, 100%, 100%, and 71.43%, respectively, for the torque technique. The diagnostic accuracies of the standard and torque techniques were 87.10% and 96.77%, respectively.

CONCLUSIONS
The torque technique for EUS-FNB offered acceptable technical feasibility and superior diagnostic performance, including optimal histologic core procurement, compared with the standard technique.

torque
tissue acquisition
solid pancreatic lesion
endoscopic ultrasound
histologic core


Colorectal cancer-infiltrating T lymphocytes display a distinct chemokine receptor expression profile.

Abstract:
BACKGROUND
T lymphocytes exert important homeostatic functions in the healthy intestinal mucosa, whereas in case of colorectal cancer (CRC), infiltration of T lymphocytes into the tumor is crucial for an effective anti-tumor immune response. In both situations, the recruitment mechanisms of T lymphocytes into the tissues are essential for the immunological functions deciding the outcome. The recruitment of T lymphocytes is largely dependent on their expression of various chemokine receptors. The aim of this study was to identify potential chemokine receptors involved in the recruitment of T lymphocytes to normal human colonic mucosa and to CRC tissue, respectively, by examining the expression of 16 different chemokine receptors on T lymphocytes isolated from these tissues.

METHODS
Tissues were collected from patients undergoing bowel resection for CRC. Lymphocytes were isolated through enzymatic tissue degradation of CRC tissue and nearby located unaffected mucosa, respectively. The expression of a broad panel of chemokine receptors on the freshly isolated T lymphocytes was examined by flow cytometry.

RESULTS
In the normal colonic mucosa, the frequencies of cells expressing CCR2, CCR4, CXCR3, and CXCR6 differed significantly between CD4+ and CD8+ T lymphocytes, suggesting that the molecular mechanisms mediating T lymphocyte recruitment to the gut differ between CD4+ and CD8+ T lymphocytes. In CRC, the frequencies of cells expressing CCR2 and CXCR5 were significantly lower in both the CD4+ and CD8+ T lymphocyte populations compared to unaffected colonic mucosa, and the frequency of CCR9+ cytotoxic T lymphocytes was significantly decreased in CRC tissue.

CONCLUSIONS
With regard to the normal gut mucosa, the results suggest that the molecular mechanisms mediating T lymphocyte recruitment differ between CD4+ and CD8+ T lymphocytes, which are important for understanding gut homeostasis. Importantly, T lymphocytes from CRC compared to normal colonic tissue displayed a distinct chemokine receptor expression profile, suggesting that mechanisms for recruitment of T lymphocytes to CRC tissue are skewed compared to normal colonic mucosa. Understanding these mechanisms could help in developing new strategies in cancer immunotherapy and to optimize already available alternatives such as immune checkpoint inhibitors.

T lymphocyte
Chemokine receptor
Mucosa
Colorectal cancer
Homing


Outcomes of conventional transarterial chemoembolization for hepatocellular carcinoma ≥10 cm.

Abstract:
AIM
To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm.

METHODS
Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses.

RESULTS
Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients.

CONCLUSION
Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors.


Assessment of HER2 using the 2018 ASCO/CAP guideline update for invasive breast cancer: a critical look at cases classified as HER2 2+ by immunohistochemistry.

Abstract: In 2018, the American Society of Clinical Oncology/College of American Pathologists revised the criteria for HER2 immunohistochemistry (IHC) equivocal (2+) classification in their updated guideline. We reviewed invasive breast cancer specimens originally classified as equivocal (2+) under the 2018 guideline that underwent HER2 fluorescence in situ hybridization (FISH) testing from August 2018 to August 2019 at our Canadian reference hospital to investigate cases with ambiguous staining patterns between the 1+ and 2+ definitions. Demographics, pathologic features, and pre-analytic conditions were recorded. The H&E and corresponding HER2 IHC slides were reviewed to confirm tumor type and grade, and classify as HER2 indeterminate, 0, 1+, 2+, or "Intermediate" (staining features between the 1+ and 2+ classifications). FISH testing was performed on 289 cases and 273 met inclusion criteria. The FISH-amplified rate was 12.1%. Upon IHC review, 44.7% (122/273) of cases were reclassified as Intermediate. These cases had incomplete staining with moderate intensity (43/122, 35.3%) and/or <10% complete weak or moderate staining (102/122, 83.6%). Intermediate cases had a significantly lower frequency of amplified FISH results than 2+ cases (p < 0.0001), with only four (3.3%) FISH positive and two (1.6%) FISH heterogeneous. Our study highlights the ambiguity in the current guideline for classifying some HER2 IHC patterns. As the rate of gene amplification in these cases was low (4.9%), we recommend adhering to the 2018 HER2 2+ criteria for reflex FISH testing. However, cases with <10% moderate complete staining and certain heterogeneous patterns warrant special consideration. Further descriptive clarification of 1+ criteria is needed.

D017404:In Situ Hybridization, Fluorescence

ASCO/CAP guidelines
Invasive breast cancer
HER2 immunohistochemistry
Equivocal
HER2 testing


A Roadmap for Disruptive Applications and Heterogeneous Integration Using Two-Dimensional Materials: State-of-the-Art and Technological Challenges.

Abstract: This Mini Review attempts to establish a roadmap for two-dimensional (2D) material-based microelectronic technologies for future/disruptive applications with a vision for the semiconductor industry to enable a universal technology platform for heterogeneous integration. The heterogeneous integration would involve integrating orthogonal capabilities, such as different forms of computing (classical, neuromorphic, and quantum), all forms of sensing, digital and analog memories, energy harvesting, and so forth, all in a single chip using a universal technology platform. We have reviewed the state-of-the-art 2D materials such as graphene, transition metal dichalcogenides, phosphorene and hexagonal boron nitride, and so forth, and how they offer unique possibilities for a range of futuristic/disruptive applications. Besides, we have discussed the technological and fundamental challenges in enabling such a universal technology platform, where the world stands today, and what gaps are required to be filled.

Heterogeneous Integration
2D
Universal Technology Platform
Graphene
Phosphorene
Disruptive Technology
MoS2
TMDCs
Two-Dimentional Materials
h-BN


Dysregulation of Macropinocytosis Processes in Glioblastomas May Be Exploited to Increase Intracellular Anti-Cancer Drug Levels: The Example of Temozolomide.

Abstract: Macropinocytosis is a clathrin-independent endocytosis of extracellular fluid that may contribute to cancer aggressiveness through nutrient supply, recycling of plasma membrane and receptors, and exosome internalization. Macropinocytosis may be notably triggered by epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR), two well-known markers for glioblastoma aggressiveness. Therefore, we studied whether the expression of key actors of macropinocytosis is modified in human glioma datasets. Strong deregulation has been evidenced at the mRNA level according to the grade of the tumor, and 38 macropinocytosis-related gene signatures allowed discrimination of the glioblastoma (GBM) samples. Honokiol-induced vacuolization was then compared to vacquinol-1 and MOMIPP, two known macropinocytosis inducers. Despite high phase-contrast morphological similarities, honokiol-induced vacuoles appeared to originate from both endocytosis and ER. Also, acridine orange staining suggested differences in the macropinosomes' fate: their fusion with lysosomes appeared very limited in 3-(5-methoxy -2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP)-treated cells. Nevertheless, each of the compounds markedly increased temozolomide uptake by glioma cells, as evidenced by LC-MS. In conclusion, the observed deregulation of macropinocytosis in GBM makes them prone to respond to various compounds affecting their formation and/or intracellular fate. Considering that sustained macropinocytosis may also trigger cell death of both sensitive and resistant GBM cells, we propose to envisage macropinocytosis inducers in combination approaches to obtain dual benefits: increased drug uptake and additive/synergistic effects.

Colin|Margaux|M|
Delporte|Cédric|C|
Janky|Rekin's|R|
Lechon|Anne-Sophie|AS|
Renard|Gwendoline|G|
Van Antwerpen|Pierre|P|
Maltese|William A|WA|
Mathieu|Véronique|V|

macropinocytosis temozolomide glioma vacquinol-1 MOMIPP honokiol methuosis


Three highly acidic Equisetum XTHs differ from hetero-trans-β-glucanase in donor substrate specificity and are predominantly xyloglucan homo-transglucosylases.

Abstract: Transglycanases are enzymes that remodel the primary cell wall in plants, potentially loosening and/or strengthening it. Xyloglucan endotransglucosylase (XET; EC 2.4.1.207), ubiquitous in land plants, is a homo-transglucanase activity (donor, xyloglucan; acceptor, xyloglucan) exhibited by XTH (xyloglucan endotransglucosylase/hydrolase) proteins. By contrast, hetero-trans-β-glucanase (HTG) is the only known enzyme that is preferentially a hetero-transglucanase. Its two main hetero-transglucanase activities are MLG : xyloglucan endotransglucosylase (MXE) and cellulose : xyloglucan endotransglucosylase (CXE). HTG is highly acidic and found only in the evolutionarily isolated genus of fern-allies, Equisetum. We now report genes for three new highly acidic HTG-related XTHs in E. fluviatile (EfXTH-A, EfXTH-H and EfXTH-I). We expressed them heterologously in Pichia and tested the encoded proteins' enzymic activities to determine whether their acidity and/or their Equisetum-specific sequences might confer high hetero-transglucanase activity. Untransformed Pichia was found to secrete MLG-degrading enzyme(s), which had to be removed for reliable MXE assays. All three acidic EfXTHs exhibited very predominantly XET activity, although low but measurable hetero-transglucanase activities (MXE and CXE) were also detected in EfXTH-H and EfXTH-I. We conclude that the extremely high hetero-transglucanase activities of Equisetum HTG are not emulated by similarly acidic Equisetum XTHs that share up to 55.5% sequence identity with HTG.

Holland|Claire|C|
Simmons|Thomas J|TJ|
Meulewaeter|Frank|F|
Hudson|Andrew|A|
Fry|Stephen C|SC|

Equisetum
Hetero-trans-β-glucanase
Xyloglucan endotransglucosylase
Cell elongation
Heterologous expression
Pichia pastoris
Plant cell wall


Sex-based biology and the rational design of influenza vaccination strategies.

Abstract: Biological (ie, sex) differences as well as cultural (ie, gender) norms influence the acceptance and efficacy of vaccines for males and females. These differences are often overlooked in the design and implementation of vaccination strategies. Using seasonal and pandemic influenza vaccines, we document profound differences between the sexes in the acceptance, correlates of protection, and adverse reactions following vaccination in both young and older adults. Females develop higher antibody responses, experience more adverse reactions to influenza vaccines, and show greater vaccine efficacy than males. Despite greater vaccine efficacy in females, both young and older females are often less likely to accept influenza vaccines than their male counterparts. Identification of the biological mechanisms, including the hormones and genes, that underlie differential responses to vaccination is necessary. We propose that vaccines should be matched to an individual's biological sex, which could involve systematically tailoring diverse types of FDA-approved influenza vaccines separately for males and females. One goal for vaccines designed to protect against influenza and even other infectious diseases should be to increase the correlates of protection in males and reduce adverse reactions in females in an effort to increase acceptance and vaccine-induced protection in both sexes.

influenza
vaccine
gender
aging
immunogenicity
reactogenicity
sex difference
sex hormone


Impact of hysterectomy on cardiovascular disease and different subtypes: a meta-analysis.

Abstract:
PURPOSE
To explore the association between hysterectomy and cardiovascular disease (CVD).

METHODS
Observational studies from eight databases and reference lists of relevant studies were systematically searched up to January 2021. Pooled relative risks (RRs) and 95% CIs were calculated by the random-effects model. Subgroup analyses and meta-regressions were performed to explore potential sources of heterogeneity. Small-study effects were estimated by Egger's test and funnel plot.

RESULTS
Seventeen studies from 14 articles were included in our meta-analysis. Hysterectomy was positively related to CVD (1.16; 95% CI 1.03-1.30; sample size: 1,233,495). For the subtype, ischemic heart disease, the pooled RR (95% CI) for hysterectomy versus non-hysterectomy was 1.20 (95% CI 1.08-1.35; sample size: 1,210,504), and the pooled HR (95% CI) was 1.15 (95% CI 1.03-1.29; sample size: 1,181,924). In the association between ischemic heart disease and hysterectomy with ovarian preservation (1.33; 95% CI 1.05-1.68; sample size: 29,058) or hysterectomy with oophorectomy (1.31; 95% CI 1.02-1.67; sample size: 23,257), significant positive associations were observed. A significant association was also found with having hysterectomy before 50 years (1.19; 95% CI 1.01-1.41; sample size: 515,297), but not with after 50 years (1.16; 95% CI 0.87-1.54; sample size: 398,383). In addition, hysterectomy was positively related with hypertension (1.31; 95% CI 1.10-1.56; sample size: 47,831).

CONCLUSION
Hysterectomy was related to the increased risks of ischemic heart disease and hypertension. However, the evidence is not strong.

Hysterectomy
Cardiovascular disease
Ischemic heart disease
Ovarian preservation
Oophorectomy
Age at hysterectomy


Push-Out Bond Strength of Dorifill, Epiphany and MTA-Fillapex Sealers to Root Canal Dentin with and without Smear Layer.

Abstract:
INTRODUCTION
The aim of the present experimental study was to evaluate the push-out bond strength of Dorifill, Epiphany and MTA-Fillapex sealers to root canal dentin in presence and absence of smear layer (SL).

METHODS AND MATERIALS
Sixty human single-rooted teeth were selected and divided into six groups (n=10). The canal irrigation protocol in groups 1, 3 and 5 consisted of 2.5% NaOCl during instrumentation and normal saline at the end of preparation plus a 5-min irrigation with 17% ethylenediaminetetraacetic acid (EDTA). In the remaining groups, normal saline was used for canal irrigation. The root canals were filled with Epiphany/Resilon (groups 1 and 2), Dorifill/gutta-percha (groups 3 and 4) and MTA-Fillapex/gutta-percha (groups 5 and 6). After two weeks of storage in 95% relative humidity at 37(º)C, 2 mm-thick dentin disks were prepared from coronal third of each root. The push-out bond strength test was carried out using a universal testing machine. Data were analyzed with the two-way ANOVA and post hoc Tukey's tests. Statistical significance was defined at 0.05.

RESULTS
The highest (3.06±0.38 MPa) and lowest (1.16±0.32 MPa) push-out bond strength values were recorded in Epiphany/Resilon-NaOCl/EDTA and Dorifill/gutta-percha/normal saline groups, respectively. There were significant differences in the bond strength of sealers (P<0.05). In addition, elimination of the SL significantly increased the bond strength of all sealers (P<0.05).

CONCLUSION
The Epiphany/Resilon group exhibited the highest push-out bond strength in the presence and absence of the SL. Elimination of the SL resulted in a significant increase in the bond strength of all the sealers to dentin.

Forough Reyhani|Mohammad|M|
Ghasemi|Negin|N|
Rahimi|Saeed|S|
Salem Milani|Amin|A|
Mokhtari|Hadi|H|
Shakouie|Sahar|S|
Safarvand|Hossein|H|

Push-Out Bond Strength
Dorifill
MTA-Fillapex
Root Canal
Smear Layer
Epiphany Sealer


Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an adult rat calvarial defect model.

Abstract: DNA/protamine complex paste (D/P) and D/P complex paste with Fibroblast Growth Factor-2 (FGF-2) (D/P-FGF) were prepared to investigate their new bone formation abilities using an ∼40-week-old rat calvarial defect model. It was found that D/P could release FGF-2 proportionally in an in vitro experiment with an enzyme-linked immunosorbent assay. It was also found that aging adversely affected self-bone healing of rats by comparison with the results in a previous study using 10-week-old rats. Microcomputed tomography and histopathological examinations showed that new bone formation abilities of D/P and D/P-FGF were superior to that of the control (sham operation). Control, D/P and D/P-FGF showed newly formed bone areas of 6.7, 58.3, and 67.0%, respectively, 3 months after the operation. Moreover, it was found that FGF-2 could support the osteoanagenesis ability of D/P. It was considered that FGF-2 could play an important role in new bone formation at early stages because it induced the genes such as collagen I, CBFA, OSX, and OPN, which are initiated first in the process of osteogenesis. Therefore, D/P-FGF will be a useful injectable biomaterial with biodegradable properties for the repair of bone defects in the elderly.

Shinozaki|Yosuke|Y| Toda|Masako|M| Ohno|Jun|J| Kawaguchi|Minoru|M| Kido|Hirofumi|H| Fukushima|Tadao|T|

DNA
protamine
fibroblast growth factor-2
elderly
bone regeneration


Clinico-epidemiologic characteristics of the 2019 dengue outbreak in Bangladesh.

Abstract:
BACKGROUND
Dengue fever shows a broad range of clinical presentations worldwide. Here we report on our clinical findings during the 2019 dengue outbreak in one of the largest tertiary care hospitals in Dhaka, the capital of Bangladesh.

METHODS
A total of 747 suspected dengue cases (553 confirmed and 194 probable) were interviewed with a pro forma case record form. Statistical analyses were conducted using SPSS 20.0. Ethical clearance was obtained from the Dhaka Medical College.

RESULTS
The mean age of the dengue cases was 27 y and approximately two-thirds were male. Positive tests for NS1 and anti-dengue immunoglobulin M antibody were present in 91.9% and 59.4% of the cases, respectively. Thrombocytopenia was present in 69% of cases and fever was present in 99.1% of cases. Gastrointestinal (GI) features, including anorexia and/or vomiting (69.4%), abdominal pain (39.8%) and diarrhoea (25.6%), were more prevalent than typical rash and pain symptoms. Hypotension was present in approximately one-quarter of patients (25.4%). Probable and confirmed dengue cases have shown similar clinical characteristics and laboratory findings.

CONCLUSIONS
The 2019 outbreak of dengue fever in Bangladesh was characterized by increased presentation with GI features. Recognition of this trend would permit early diagnosis and proper management of patients.

outbreak
Bangladesh
dengue fever
clinical characteristics
epidemiology


Novel Structured Reporting Systems for Theranostic Radiotracers.

Abstract: Standardized reporting is more and more routinely implemented in clinical practice, and such structured reports have a major impact on a large variety of medical fields, such as laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may increase clinical acceptance of new radiotracers, allow for inter- and intracenter comparisons for quality assurance, and be used in global multicenter studies to ensure comparable results and enable efficient data abstraction. In the last couple of years, several standardized framework systems for PET radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen-targeted PET agents to diagnose and treat prostate cancer, and systems for somatostatin receptor-targeted PET agents to diagnose and treat neuroendocrine neoplasia. In the present review, the framework systems for these 2 types of cancer will be briefly introduced, followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.

Werner|Rudolf A|RA|
Bundschuh|Ralph A|RA|
Bundschuh|Lena|L|
Fanti|Stefano|S|
Javadi|Mehrbod S|MS|
Higuchi|Takahiro|T|
Weich|Alexander|A|
Pienta|Kenneth J|KJ|
Buck|Andreas K|AK|
Pomper|Martin G|MG|
Gorin|Michael A|MA|
Herrmann|Ken|K|
Lapa|Constantin|C|
Rowe|Steven P|SP|

D019937:Diagnostic Techniques and Procedures