Enlarged mediastinal air cyst in a patient with bronchial diverticula localized in the left main bronchus: a case report with surgical and bronchoscopic findings.

Abstract:
BACKGROUND
A mediastinal air cyst is a rare computed tomography (CT) finding. Once the lesion is identified, it is difficult to diagnose and treat. Meanwhile, bronchial diverticula have been reported as a CT finding observed in certain pulmonary pathologic conditions. We encountered the case of an enlarged mediastinal air cyst accompanied with bronchial diverticula and upper lobe-dominant fibrous changes of the lung.

CASE PRESENTATION
A 69-year-old man with a chronic cough who had regularly visited a chest physician for upper lobe-dominant pulmonary fibrosis was referred to our hospital for the examination of an enlarged mediastinal air cyst. Chest CT exhibited an air cyst (size, 30 mm) connected to the lumen of the left main bronchus (LMB) and multiple tiny outpouches only on the LMB. Flexible bronchoscopy showed bubbling from slits or indentations of the bronchial mucosa only in the LMB but not in the right main bronchus or lobar bronchus. For therapeutic diagnosis, we removed the air cyst. Based on clinical, surgical, and pathological findings, we diagnosed the air cyst as an enlarged bronchial diverticulum.

CONCLUSIONS
This is the first case wherein bronchoscopic and surgical findings of bronchial diverticula and an enlarged bronchial diverticulum are reported. There are possible pathogenic mechanisms in cases of pulmonary disease that are attributable to enlargement of the bronchial diverticula.

Mediastinal air cyst
Bronchial diverticula
Upper lobe-dominant pulmonary fibrosis
Surgery


Synthesis of the Galactosyl Derivative of Gluconic Acid With the Transglycosylation Activity of β-Galactosidase.

Abstract: Bionic acids are bioactive compounds demonstrating numerous interesting properties. They are widely produced by chemical or enzymatic oxidation of disaccharides. This paper focuses on the galactosyl derivative of gluconic acid as a result of a new method of bionic acid synthesis which utilises the transglycosylation properties of β-galactosidase and introduces lactose as a substrate. Products obtained in such a process are characterised by different structures (and, potentially, properties) than those resulting from traditional oxidation of disaccharides. The aim of this study is to determine the effect of selected parameters (concentration and ratio of substrates, dose of the enzyme, time, pH, presence of salts) on the course of the reaction carried out with the enzymatic preparation Lactozym, containing β-galactosidase from Kluyveromyces lactis. Research has shown that increased dry matter content in the baseline solution (up to 50%, by mass per volume) and an addition of NaCl contribute to higher yield. On the other hand, reduced content of the derivative is a result of increased pH from 7.0 to 9.0 and an addition of magnesium and manganese salts. Moreover, exceeding the β-galactosidase dose over approx. 35 000 U per 100 g of lactose also leads to reduced yield of the process. The most favourable molar ratio of sodium gluconate to lactose is 2.225:0.675. Depending on the conditions of the synthesis, the product concentration ranged between 17.3 and 118.3 g/L of the reaction mixture, which corresponded to the mass fraction of 6.64-23.7% of dry matter. The data obtained as a result of the present study may be useful for designing an industrial process.

gluconic acid
transglycosylation
β-galactosidase
lactose


Effects of Assam tea extract on growth, skin mucus, serum immunity and disease resistance of Nile tilapia (Oreochromis niloticus) against Streptococcus agalactiae.

Abstract: The present study aimed to assess the possible effects of Assam tea (Camellia sinensis) extract (ATE) on growth performances, immune responses, and disease resistance of Nile tilapia, Oreochromis niloticus against Streptococcus agalactiae. Five levels of ATE were supplemented into the based diet at 0, 1, 2, 4, and 8 g kg-1 feed of Nile tilapia fingerlings (10.9 ± 0.04 g initial weight) in triplicate. After four and eight weeks of feeding, fish were sampled to determine the effects of the tea supplements upon their growth performance, as well as serum and mucosal immune responses. A disease challenge using S. agalactiae was conducted at the end of the feeding trial. Fish fed ATE revealed significantly improved serum lysozyme, peroxidase, alternative complement (ACH50), phagocytosis, and respiratory burst activities compared to the basal control fed fish (P < 0.05). The mucus lysozyme and peroxidase activities were ameliorated through ATE supplementation in the tilapia diets. Supplementation of ATE significantly (P < 0.05) enhanced final body weight, weight gain, and specific growth rate; while a decreased feed conversion ratio was revealed at 2 g kg-1 inclusion level, after four and eight weeks. Challenge test showed that the relative percent survival (RSP) of fish in each treatment was 33.33%, 60.00%, 83.33%, 76.68%, and 66.68% in groups fed 0, 1, 2, 4, and 8 g kg-1, respectively. In summary, diets supplemented with ATE especially at 2 g kg-1 increased the humoral and mucosal immunity, enhanced growth performance, and offered higher resistance against S. agalactiae infection in Nile tilapia.

Van Doan|Hien|H|
Hoseinifar|Seyed Hossein|SH|
Sringarm|Korawan|K|
Jaturasitha|Sanchai|S|
Yuangsoi|Bundit|B|
Dawood|Mahmoud A O|MAO|
Esteban|Maria Ángeles|MÁ|
Ringø|Einar|E|
Faggio|Caterina|C|

Assam tea extract
Disease resistance
Nile tilapia
Growth performance
Mucosal immunity
S. agalactiae
Humoral immunity


Influence of aerobic fitness on gastrointestinal barrier integrity and microbial translocation following a fixed-intensity military exertional heat stress test.

Abstract:
PURPOSE
Exertional-heat stress adversely disrupts gastrointestinal (GI) barrier integrity, whereby subsequent microbial translocation (MT) can result in potentially serious health consequences. To date, the influence of aerobic fitness on GI barrier integrity and MT following exertional-heat stress is poorly characterised.

METHOD
Ten untrained (UT; VO2max = 45 ± 3 ml·kg-1·min-1) and ten highly trained (HT; VO2max = 64 ± 4 ml·kg-1·min-1) males completed an ecologically valid (military) 80-min fixed-intensity exertional-heat stress test (EHST). Venous blood was drawn immediately pre- and post-EHST. GI barrier integrity was assessed using the serum dual-sugar absorption test (DSAT) and plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using plasma Bacteroides/total 16S DNA.

RESULTS
UT experienced greater thermoregulatory, cardiovascular and perceptual strain (p < 0.05) than HT during the EHST. Serum DSAT responses were similar between the two groups (p = 0.59), although Δ I-FABP was greater (p = 0.04) in the UT (1.14 ± 1.36 ng·ml-1) versus HT (0.20 ± 0.29 ng·ml-1) group. Bacteroides/Total 16S DNA ratio was unchanged (Δ; -0.04 ± 0.18) following the EHST in the HT group, but increased (Δ; 0.19 ± 0.25) in the UT group (p = 0.05). Weekly aerobic training hours had a weak, negative correlation with Δ I-FABP and Bacteroides/total 16S DNA responses.

CONCLUSION
When exercising at the same absolute workload, UT individuals are more susceptible to small intestinal epithelial injury and MT than HT individuals. These responses appear partially attributable to greater thermoregulatory, cardiovascular, and perceptual strain.

I-FABP
Exercise
Endotoxemia
Exertional heat stroke
Gut health


Effect of lay-up of sub-waveguide on transmission of S(o) mode from main waveguide to sub-waveguides.

Abstract: This paper focuses on transmission characteristics of fundamental symmetric Lamb mode (So) at the junction of a main waveguide and sub-waveguides in composite laminates. Numerical simulations on transmission of So from the main to sub-waveguide revealed that transmission factors of the modes depend on stacking sequence of plies in the waveguides. Experiments were carried out to verify the observations made in numerical simulations. This work gives an insight on the transmission characteristics of So mode while it propagates from a healthy to a delaminated region in a composite laminate.

Transmission factor
Stacking sequence
Air-coupled probes
Lamb wave


Nitrate pollution reduces bryophyte diversity in Mediterranean springs.

Abstract: Anthropogenic activities and intensive farming are causing nitrate pollution in groundwater bodies. These aquifers are drained by springs which, in the Mediterranean region, act as refugia for preserving biodiversity of species that need continuous water. Some springs are also used for drinking water for wild animals, livestock and humans, so if their water quality is compromised it can become a threat to public health. However, the impact of nitrate pollution on these biotic communities remains unknown. We sampled 338 assemblages of aquatic and semi-aquatic bryophytes (i.e., hygrophytic mosses and liverworts) growing in springs in a gradient of water conductivity, nitrate concentration and climate and distributed across the north-east of the Iberian Peninsula to investigate the impact of nitrate pollution on the diversity of bryophytes and moss functional traits in Mediterranean springs. Based on previous literature suggesting that increased nitrogen load decreases biodiversity in grasslands and freshwater ecosystems, we hypothesised that water nitrate pollution in springs decreases bryophyte diversity at the local and regional scales. Our results indicated that, at the local scale (spring), nitrate pollution reduced the number and the likelihood of finding a rare species in springs. Rare species were found in 4% of the springs with nitrate above 50 mg L-1 but in 32% of the springs with nitrate below 50 mg L-1. Moss, liverwort and overall bryophyte diversity were not directly affected by nitrate at the local scale but nitrate consistently decreased diversity of mosses, liverworts and rare bryophyte species at the regional scale. We also found that warmer and drier springs presented fewer bryophyte species. Our results show that the combination of nitrate pollution, increasing temperature and drought could severely threaten bryophyte diversity in Mediterranean springs. Our results indicate that the absence of rare bryophytes could be used as a bioindicator of nitrate pollution in springs.

Fernández-Martínez|M|M| Corbera|J|J| Domene|X|X| Sayol|F|F| Sabater|F|F| Preece|C|C|

Intensive farming
Groundwater
Mosses
Liverworts
Biodiversity loss


Test-based age-of-acquisition norms for 44 thousand English word meanings.

Abstract: Age of acquisition (AoA) is an important variable in word recognition research. Up to now, nearly all psychology researchers examining the AoA effect have used ratings obtained from adult participants. An alternative basis for determining AoA is directly testing children's knowledge of word meanings at various ages. In educational research, scholars and teachers have tried to establish the grade at which particular words should be taught by examining the ages at which children know various word meanings. Such a list is available from Dale and O'Rourke's (1981) Living Word Vocabulary for nearly 44 thousand meanings coming from over 31 thousand unique word forms and multiword expressions. The present article relates these test-based AoA estimates to lexical decision times as well as to AoA adult ratings, and reports strong correlations between all of the measures. Therefore, test-based estimates of AoA can be used as an alternative measure.

Age of acquisition
Psycholinguistics
Reading
Word learning


Tributyltin induces mitochondrial fission through Mfn1 degradation in human induced pluripotent stem cells.

Abstract: Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT is also known to cause various forms of cytotoxicity, including neurotoxicity and immunotoxicity. However, TBT toxicity has not been identified in normal stem cells. In the present study, we examined the effects of TBT on cell growth in human induced pluripotent stem cells (iPSCs). We found that exposure to nanomolar concentrations of TBT decreased intracellular ATP levels and inhibited cell viability in iPSCs. Because TBT suppressed energy production, which is a critical function of the mitochondria, we further assessed the effects of TBT on mitochondrial dynamics. Staining with MitoTracker revealed that nanomolar concentrations of TBT induced mitochondrial fragmentation. TBT also reduced the expression of mitochondrial fusion protein mitofusin 1 (Mfn1), and this effect was abolished by knockdown of the E3 ubiquitin ligase membrane-associated RING-CH 5 (MARCH5), suggesting that nanomolar concentrations of TBT could induce mitochondrial dysfunction via MARCH5-mediated Mfn1 degradation in iPSCs. Thus, mitochondrial function in normal stem cells could be used to assess cytotoxicity associated with metal exposure.

Yamada|Shigeru|S| Asanagi|Miki|M| Hirata|Naoya|N| Itagaki|Hiroshi|H| Sekino|Yuko|Y| Kanda|Yasunari|Y|

D033681:Mitochondrial Membrane Transport Proteins

Tributyltin
Mitochondrial fission
Induced pluripotent stem cells
Mitofusin


Gelatin blending and sonication of chitosan nanofiber mats produce synergistic effects on hemostatic functions.

Abstract: To improve the hemostatic function of chitosan nanofiber mats, we studied the synergetic effects of gelatin blending and porosity control. Gelatin-blended-chitosan (Chi-Gel) nanofiber mats were evaluated with respect to surface morphology, mechanical properties and wettability, and functionally tested in a blood clotting study. The blood clotting efficiency of Chi-Gel nanofiber mats using rabbit whole blood in vitro was superior to that of chitosan nanofibers. Moreover, Chi-Gel nanofiber mats with enlarged porosity, produced by ultra-sonication, showed improved blood clotting efficiency, cell viability and cell infiltration compared with non-sonicated Chi-Gel nanofiber mats. Field-emission scanning electron microscopy revealed a richer density of platelets on sonicated nanofiber mats than on non-sonicated nanofiber mats after 3 min of blood clotting. The proliferation of human dermal fibroblast cells on sonicated Chi-Gel nanofiber mats using the DNA assay was higher than that on non-sonicated chitosan nanofiber mats after 7 days of culture. Confocal z-stack images showed that sonicated Chi-Gel nanofiber mats with high porosity supported active cell migration and infiltration into the 3-dimensional nanofiber mats. These results suggest that hydrophilic gelatin blending and sonication of chitosan nanofiber mats yields synergistic effects that not only improve hemostatic function but also promote wound repair.

Gu|Bon Kang|BK|
Park|Sang Jun|SJ|
Kim|Min Sup|MS|
Lee|Yong Jin|YJ|
Kim|Jong-Il|JI|
Kim|Chun-Ho|CH|

Sonication
Hemostatics
Gelatin-blended-chitosan nanofiber mats


Systemic Modelling in Bioethics.

Abstract: We present here a new method for bioethics: systemic modelling. In this method, the complex phenomenon being studied (e.g. personalized medicine, genetic testing, gene therapy, genetically modified organisms) is modelled as a whole, to shed light on its organization and functioning, and major (bio)ethical issues and solutions for their resolution are then identified. This systemic modelling method is ideal for use in the identification of solutions, rather than their validation, with other methods then used to test the solutions found. We provide a description and reproducible instructions for the application of systemic modelling in bioethics, together with a brief example of the application of this method to the study of the impact of personalized medicine on French society.

Stoeklé|Henri-Corto|HC| Charlier|Philippe|P| Mamzer-Bruneel|Marie-France|MF| Hervé|Christian|C| Vogt|Guillaume|G|

D001675:Bioethics
D026689:Ethical Analysis
D005820:Genetic Testing
D015316:Genetic Therapy
D006801:Humans
D008962:Models, Theoretical
D030781:Organisms, Genetically Modified
D057285:Precision Medicine
D013597:Systems Analysis

systemic modelling
Bioethics
personalized medicine
complex phenomena


Optimizing the treatment of pain and anxiety in pediatric emergencies: the role of accreditation.

Abstract: Pervasive disparities exist in the treatment of pain and anxiety in pediatric patients presenting to hospitals with emergency conditions. This finding has been demonstrated worldwide, and is especially exacerbated in general emergency departments, which treat both adults and children. Policies to promote appropriate analgesia in the context of pediatric emergency care have been developed by several professional societies and governmental agencies in the United States; however, progress has been uneven, and data regarding these questions is lacking.In their excellent article, Capua and her co-authors address this precise problem through a unique methodology, by surveying nurse directors of both pediatric accredited and non-accredited emergency departments. Survey questions focused on availability of pharmacological and non-pharmacological modalities, and on the prevalence with which providers administered both oral and parenteral medications. The results demonstrated widespread availability of evidence based analgesic and anxiolytic treatment, ranging from medical clowns and specific holding positions, to use of intravenous opiates and conscious sedation. No significant differences were found associated with accreditation.These results are surprising and seem to call into question the value of pediatric accreditation. However, an alternative hypothesis would be that accreditation has succeeded, and the results reflect a large spillover effect, in which providers trained in accredited institutions bring these advanced practices to their local departments. Regionalization has been promoted for emergency care of many acute conditions such as trauma, stroke, and myocardial infarction. These results suggest that for pediatric emergencies, at least in regard to analgesia, the answer likely lies in dissemination of knowledge, rather than super specialization. In other words, bring the expertise to the children, not the children to the experts. Further research in this area could focus on optimal ways to achieve such knowledge translation.

Pain
Pediatric
Emergency
Accreditation
Pediatric emergency medicine


H-NS Family Proteins Drastically Change Their Targets in Response to the Horizontal Transfer of the Catabolic Plasmid pCAR1.

Abstract: H-NS family proteins regulate the expression of many genes by preferably binding to AT-rich genomic regions and altering DNA topology. They are found in both bacterial chromosomes and plasmids, and plasmid-encoded H-NS family proteins have sometimes been suggested to act as a molecular backup of the chromosomally encoded ones. Pmr is an H-NS family protein encoded on the catabolic plasmid pCAR1, which belongs to incompatibility P-7 group. We have investigated the function of Pmr in Pseudomonas putida KT2440, where two H-NS family proteins (TurA and TurB) encoded on the chromosome are expressed predominantly. Previous transcriptome analyses suggested that TurA, TurB, and Pmr cooperatively regulate numerous genes, but the differentially transcribed genes in KT2440ΔturA(pCAR1), KT2440ΔturB(pCAR1), and KT2440(pCAR1Δpmr) compared with those in KT2440(pCAR1) were somewhat different. Here, we performed RNA sequencing analyses to compare the differentially transcribed genes after the deletion of turA or turB in KT2440, and turA, turB or pmr in KT2440(pCAR1). Three pCAR1-free strains (KT2440, KT2440ΔturA, KT2440ΔturB) and four pCAR1-harboring strains [KT2440(pCAR1), KT2440ΔturA(pCAR1), KT2440ΔturB(pCAR1), KT2440(pCAR1Δpmr)], grown until the log and stationary phases, were used. In KT2440, TurA was the major H-NS family protein regulating a large number and wide range of genes, and both TurA and TurB were suggested to functionally compensate each other, particularly during the stationary phase. In KT2440(pCAR1), the numbers of differentially transcribed genes after the deletion of turA or turB drastically increased compared to those in KT2440. Notably, more than half of the differentially transcribed genes in KT2440ΔturA and KT2440ΔturB did not overlap with those in KT2440ΔturA(pCAR1) and KT2440ΔturB(pCAR1). This dynamic change could be explained by the acquisition of pCAR1 itself and the expression of Pmr. After pCAR1 was transferred into the host, TurA and TurB could be detached from the chromosome of KT2440 and they could newly bind to pCAR1. Moreover, Pmr could reconstitute the chromosome-binding heteromeric oligomers which were formed by TurA and TurB. Our study revealed that horizontal transfer of a plasmid changes the transcriptional network of the chromosomally encoded H-NS family proteins.

Nakamura|Taisuke|T| Suzuki-Minakuchi|Chiho|C| Kawano|Hibiki|H| Kanesaki|Yu|Y| Kawasaki|Shinji|S| Okada|Kazunori|K| Nojiri|Hideaki|H|

H-NS
plasmid
Pseudomonas
transcriptome
MvaT
nucleoid-associated proteins


Trapped in a disrupted normality: Survivors' and partners' experiences of life after a sudden cardiac arrest.

Abstract:
AIM OF THE STUDY
Advances in resuscitation science have resulted in a growing number of out-of-hospital cardiac arrest (OHCA) survivors. However, we know very little about the natural history of recovery and the unmet needs of survivors and their partners. This qualitative study sought to address this knowledge gap to improve understanding of the consequences of surviving cardiac arrest.

METHODS
In-depth qualitative interviews were undertaken separately with survivors and their partners between 3 and 12-months following the cardiac arrest. An interpretative phenomenological approach (IPA) to data analysis was adopted. Developing themes were discussed between members of the research team.

RESULTS
8 survivors (41-79 years; 5 male; mean time 6.3 months post-hospital discharge) and 3 partners (1 male) were interviewed. The key (super-ordinate) theme of being 'trapped in a disrupted normality' was identified within the data. Five related subordinate themes included: existential impact, physical ramifications, emotional consequences, limiting participation in social activities and altered family roles.

CONCLUSION
Recovery for survivors is hindered by a wide range of physical, emotional, cognitive, social and spiritual challenges that disrupt perceptions of 'normality'. Survivors and their carers may benefit from focussing on establishing a 'new normal' rather than striving to achieve a pre-cardiac social and physical position. Survivor-centred assessment should support rather than undermine this goal.

Whitehead|Laura|L|
Tierney|Stephanie|S|
Biggerstaff|Deborah|D|
Perkins|Gavin D|GD|
Haywood|Kirstie L|KL|

Survivors
Cardiac arrest
Carers
Experiences of survival


Best Clinical Practice: Current Controversies in Evaluation of Low-Risk Chest Pain-Part 1.

Abstract:
BACKGROUND
Chest pain is a common presentation to the emergency department (ED), though the majority of patients are not diagnosed with acute coronary syndrome (ACS). Many patients are admitted to the hospital due to fear of ACS.

OBJECTIVE
Our aim was to investigate controversies in low-risk chest pain evaluation, including risk of missed ACS, stress test, and coronary computed tomography angiography (CCTA).

DISCUSSION
Chest pain accounts for 10 million ED visits in the United States annually. Many patients are at low risk for a major cardiac adverse event (MACE). With negative troponin and nonischemic electrocardiogram (ECG), the risk of MACE and myocardial infarction (MI) is < 1%. The American Heart Association recommends further evaluation in low- to intermediate-risk patients within 72 h. These modalities add little to further risk stratification. These evaluations do not appropriately risk stratify patients who are already at low risk, nor do they diagnose acute MI. CCTA is an anatomic evaluation of the coronary vasculature with literature support to decrease ED length of stay, though it is associated with downstream testing. Literature is controversial concerning further risk stratification in already low-risk patients.

CONCLUSIONS
With nonischemic ECG and negative cardiac biomarker, the risk of ACS approaches < 1%. Use of stress test and CCTA for risk stratification of low-risk chest pain patients is controversial. These tests may allow prognostication but do not predict ACS risk beyond ECG and troponin. CCTA may be useful for intermediate-risk patients, though further studies are required.


Recent nanobiotechnological advancements in lignocellulosic biomass valorization: A review.

Abstract: Increase in human population, rapid industrialization, excessive utilization of fossil fuel utilization and anthropogenic activities have caused serious threats to the environment in terms of greenhouse gas emissions (GHGs), global warming, air pollution, acid rain, etc. This destruction in sustainability can be averted by a paradigm shift in the fuel production from fossil resources to bioenergy. Amongst different forms of bioenergy, lignocellulosic biomass can be utilized as an attractive substrate for the production of several high-value products owing to its renewability, easy availability, and abundance. Additionally, utilization of these waste biomasses reduces the environmental hazards associated with its disposal. Impedance of lignin and crystalline nature of cellulose pose major bottlenecks in biomass based energy. Though, several physio-chemicals processes are recommended as mitigation route but none of them seems to be promising for large scale application. In recent years, a right fusion of biological treatment combined with nanotechnology for efficient pretreatment and subsequent hydrolysis of biomass by ubiquitous enzymes seems to be promising alternative. In addition, to overcome these difficulties, nanotechnology-based methods have been recently adopted in catalytic valorization of lignocellulosic biomass. The present review has critically discussed the application of nano-biotechnology in lignocellulosic biomass valorization in terms of pretreatment and hydrolysis. A detailed discussion on the application of various nanoparticles in these processes, enzyme immobilization and end-production utilization is presented in this review. Finally, the review emphasizes the major challenges of this process along with different routes and recommendations to address the issues.

Roy|Sharmili|S|
Dikshit|Pritam Kumar|PK|
Sherpa|Knawang Chhunji|KC|
Singh|Anshu|A|
Jacob|Samuel|S|
Chandra Rajak|Rajiv|R|

Lignocellulosics Nanotechnology Pretreatment Hydrolysis Nanoparticle


Multiple environmental exposures in early-life and allergy-related outcomes in childhood.

Abstract:
INTRODUCTION
Early onset and high prevalence of allergic diseases result in high individual and socio-economic burdens. Several studies provide evidence for possible effects of environmental factors on allergic diseases, but these are mainly single-exposure studies. The exposome provides a novel holistic approach by simultaneously studying a large set of exposures. The aim of the study was to evaluate the association between a broad range of prenatal and childhood environmental exposures and allergy-related outcomes in children.

MATERIAL AND METHODS
Analyses of associations between 90 prenatal and 107 childhood exposures and allergy-related outcomes (last 12 months: rhinitis and itchy rash; ever: doctor-diagnosed eczema and food allergy) in 6-11 years old children (n = 1270) from the European Human Early-Life Exposome cohort were performed. Initially, we used an exposome-wide association study (ExWAS) considering the exposures independently, followed by a deletion-substitution-addition selection (DSA) algorithm considering all exposures simultaneously. All the exposure variables selected in the DSA were included in a final multi-exposure model using binomial general linear model (GLM).

RESULTS
In ExWAS, no exposures were associated with the outcomes after correction for multiple comparison. In multi-exposure models for prenatal exposures, lower distance of residence to nearest road and higher di-iso-nonyl phthalate level were associated with increased risk of rhinitis, and particulate matter absorbance (PMabs) was associated with a decreased risk. Furthermore, traffic density on nearest road was associated with increased risk of itchy rash and diethyl phthalate with a reduced risk. DSA selected no associations of childhood exposures, or between prenatal exposures and eczema or food allergy.

DISCUSSION
This first comprehensive and systematic analysis of many environmental exposures suggests that prenatal exposure to traffic-related variables, PMabs and phthalates are associated with rhinitis and itchy rash.

Granum|Berit|B|
Oftedal|Bente|B|
Agier|Lydiane|L|
Siroux|Valerie|V|
Bird|Philippa|P|
Casas|Maribel|M|
Warembourg|Charline|C|
Wright|John|J|
Chatzi|Leda|L|
de Castro|Montserrat|M|
Donaire|David|D|
Grazuleviciene|Regina|R|
Småstuen Haug|Line|L|
Maitre|Lea|L|
Robinson|Oliver|O|
Tamayo-Uria|Ibon|I|
Urquiza|Jose|J|
Nieuwenhuijsen|Mark|M|
Slama|Remy|R|
Thomsen|Cathrine|C|
Vrijheid|Martine|M|

Environmental exposure
Childhood
Allergic disease
Exposome
Pregnancy


PMEPA1, a TGF-β- and hypoxia-inducible gene that participates in hypoxic gene expression networks in solid tumors.

Abstract: Prostate transmembrane protein, androgen induced 1 (PMEPA1) is highly expressed in various solid tumors and is known to play important roles in the transforming growth factor-β (TGF-β) signaling pathway. Here, we demonstrate a novel relationship between PMEPA1 and hypoxia, a common microenvironmental stress condition in solid tumors. We showed that induction of PMEPA1 expression occurred during hypoxia in a manner dependent on both TGF-β signaling and hypoxia-inducible factor-1 (HIF-1) pathways. Furthermore, overexpression and knockdown experiments revealed that PMEPA1 enhanced HIF-1 transcription activity. Bioinformatics analyses of PMEPA1-correlated genes using a gene expression database in clinical settings showed significant enrichment of gene sets defined by TGF-β and hypoxia and these two signaling pathways-related angiogenesis and epithelial-mesenchymal transition in many types of solid tumors. Collectively, our findings indicated that PMEPA1 participates in TGF-β- and hypoxia-regulated gene expression networks in solid tumors and thereby may contribute to tumor progression.

Koido|Masaru|M| Sakurai|Junko|J| Tsukahara|Satomi|S| Tani|Yuri|Y| Tomida|Akihiro|A|

D015972:Gene Expression Regulation, Neoplastic

D047908:Intracellular Signaling Peptides and Proteins


Intrapartal pelvic floor protection: a pragmatic and interdisciplinary approach between obstetrics and urogynecology.

Abstract: Pelvic floor protection is an issue of increasing relevance. This article sought to summarize the session at last year's annual meeting of the German Society of Gynecology and Obstetrics (DGGG) in Stuttgart (10/2016) called "Urogynecology 2020-what is the optimal rate of cesarean section-does urogynecology have to deal with Obstetrics?". The main focus was set on the two important anatomical structures, the levator ani muscle and the anal sphincters. Operative vaginal delivery, epidural anesthesia, and episiotomy are subject to discussion.

Huebner|Markus|M|
Brucker|Sara Y|SY|
Tunn|Ralf|R|
Naumann|Gert|G|
Reisenauer|Christl|C|
Abele|Harald|H|

Pelvic floor protection
Levator ani muscle
OASIS
Vaginal operative delivery


Tr1 cell immunotherapy promotes transplant tolerance via de novo Tr1 cell induction in mice and is safe and effective during acute viral infection.

Abstract: Tr1 cell therapy is considered an emerging approach to improve transplant tolerance and enhance allogeneic graft survival. However, it remains unclear how Tr1 cells promote transplant tolerance and whether they will be safe and stable in the face of an acute viral infection. By employing a mouse model of pancreatic islet transplantation, we report that Tr1 cell therapy promoted transplant tolerance via de novo induction of Tr1 cells in the recipients. Acute viral infection with lymphocytic choriomeningitis virus (LCMV) had no impact on Tr1 cell number and function, neither on the Tr1 cells infused nor on the ones induced, and that was reflected in the robust maintenance of the graft. Moreover, Tr1 cell immunotherapy had no detrimental effect on CD8 and CD4 anti-LCMV effector T-cell responses and viral control. Together, these data suggest that Tr1 cells did not convert to effector cells during acute infection with LCMV, maintained transplant tolerance and did not inhibit antiviral immunity.

Jofra|Tatiana|T|
Di Fonte|Roberta|R|
Galvani|Giuseppe|G|
Kuka|Mirela|M|
Iannacone|Matteo|M|
Battaglia|Manuela|M|
Fousteri|Georgia|G|0000-0001-7745-7517

D016381:Islets of Langerhans Transplantation

Lymphocytic choriomeningitis virus (LCMV)


Examining the effects of birth order on personality.

Abstract: This study examined the long-standing question of whether a person's position among siblings has a lasting impact on that person's life course. Empirical research on the relation between birth order and intelligence has convincingly documented that performances on psychometric intelligence tests decline slightly from firstborns to later-borns. By contrast, the search for birth-order effects on personality has not yet resulted in conclusive findings. We used data from three large national panels from the United States (n = 5,240), Great Britain (n = 4,489), and Germany (n = 10,457) to resolve this open research question. This database allowed us to identify even very small effects of birth order on personality with sufficiently high statistical power and to investigate whether effects emerge across different samples. We furthermore used two different analytical strategies by comparing siblings with different birth-order positions (i) within the same family (within-family design) and (ii) between different families (between-family design). In our analyses, we confirmed the expected birth-order effect on intelligence. We also observed a significant decline of a 10th of a SD in self-reported intellect with increasing birth-order position, and this effect persisted after controlling for objectively measured intelligence. Most important, however, we consistently found no birth-order effects on extraversion, emotional stability, agreeableness, conscientiousness, or imagination. On the basis of the high statistical power and the consistent results across samples and analytical designs, we must conclude that birth order does not have a lasting effect on broad personality traits outside of the intellectual domain.

birth order
personality
siblings
Big Five
within-family analyses


Primary and secondary metabolites of an European edible mushroom and its nutraceutical value: Suillus bellinii (Inzenga) Kuntze.

Abstract: In this work, we report the study on the composition in primary and secondary metabolites of the polar and less-polar fractions obtained from the fruiting bodies of Suillus bellinii (Inzenga) Kuntze collected from Central Italy. Thirteen compounds were identified through a series of classical chromatographic methods and through spectroscopic techniques (nuclear magnetic resonance (NMR) and mass spectrometry (MS)), namely suillin (1), ergosterol (2), glutamic acid (3), isoleucine (4), leucine (5), threonine (6), tyrosine (7), valine (8), D-mannitol (9), sucrose (10), D-sorbitol (11), fumaric acid (12) and alanine (13). These results allowed us to make specific considerations about the possible applications of this mushroom, which vary from medicine, due to the high cytotoxic and antitumor properties of suillin (1), to nutritional values, due to the presence of essential nutrients as amino acids and pre-vitamin D2 (ergosterol), together with low-calories sweeteners, confirming the close association between the identified components and the health-promoting properties of this species.

secondary metabolites
Suillus bellinii (Inzenga) Kuntze
pre-vitamin D2
essential amino acids
meroterpene
primary metabolites


Optimal Sensor and Relay Nodes Power Scheduling for Remote State Estimation with Energy Constraint.

Abstract: We study the sensor and relay nodes' power scheduling problem for the remote state estimation in a Wireless Sensor Network (WSN) with relay nodes over a finite period of time given limited communication energy. We also explain why the optimal infinite time and energy case does not exist. Previous work applied a predefined threshold for the error covariance gap of two contiguous nodes in the WSN to adjust the trade-off between energy consumption and estimation accuracy. However, instead of adjusting the trade-off, we employ an algorithm to find the optimal sensor and relay nodes' scheduling strategy that achieves the smallest estimation error within the given energy limit under our model assumptions. Our core idea is to unify the sensor-to-relay-node way of error covariance update with the relay-node-to-relay-node way by converting the former way of the update into the latter, which enables us to compare the average error covariances of different scheduling sequences with analytical methods and thus finding the strategy with the minimal estimation error. Examples are utilized to demonstrate the feasibility of converting. Meanwhile, we prove the optimality of our scheduling algorithm. Finally, we use MATLAB to run our algorithm and compute the average estimation error covariance of the optimal strategy. By comparing the average error covariance of our strategy with other strategies, we find that the performance of our strategy is better than the others in the simulation.

relay nodes
state estimation
wireless sensor networks


The Neuroprotective Effect of Thiopental on the Postoperative Neurological Complications in Patients Undergoing Surgical Clipping of Unruptured Intracranial Aneurysm: A Retrospective Analysis.

Abstract: Although thiopental improved neurological outcomes in several animal studies, there are still insufficient clinical data examining the efficacy of thiopental for patients undergoing surgical clipping of unruptured intracranial aneurysm (UIA). This study validated the effect of thiopental and investigated risk factors associated with postoperative neurological complications in patients undergoing surgical clipping of UIA. In total, 491 patients who underwent aneurysm clipping were included in this retrospective cohort study. Data regarding demographics, aneurysm characteristics, and use of thiopental were collected from electronic medical records. Propensity score matching and logistic regression analysis were used. After propensity score matching, the thiopental group showed a lower incidence of the postoperative neurological complications than non-thiopental group (5.5% vs. 17.1%, p = 0.001). In multivariate analysis, thiopental reduced the risk of postoperative neurological complications (odds ratio (OR) 0.26, 95% confidence interval (CI) 0.13 to 0.51, p < 0.001) while aneurysm size ≥ 10 mm (OR 4.48, 95% CI 1.69 to 11.87, p = 0.003), and hyperlipidemia (OR 2.24, 95% CI 1.16 to 4.32, p = 0.02) increased the risk of postoperative neurological complications. This study showed that thiopental was associated with the lower risk of neurological complications after clipping of UIA.

Kim|Byung-Gun|BG|
Jeon|Young-Tae|YT|
Han|Jiwon|J|
Bae|Yu Kyung|YK|
Lee|Si Un|SU|
Ryu|Jung-Hee|JH|0000-0001-9331-5658
Koo|Chang-Hoon|CH|0000-0001-8567-5514

thiopental
intracranial aneurysm
neurosurgery
postoperative complications


Self-Assembled Dipeptide Aerogels with Tunable Wettability.

Abstract: Constructing supramolecular materials with tunable properties and functions is a great challenge due to the complex competition between multiple assembly pathways. Herein, we report that dipeptides can self-assemble into aerogels with entirely different surface wettability through precisely controlling the assembly pathways. Charged groups or aromatic residues are selectively exposed on the surface of their nanoscale building blocks which results either in a superhydrophilic or highly hydrophobic surface. With this special property, single component dipeptide aerogels can play diverse roles in medical care applications. This study suggests great promise in the synthesis of supramolecular materials with different targeted functions from the same molecular unit.

Li|Xianbao|X| Li|Qi|Q| Fei|Jinbo|J| Jia|Yi|Y| Xue|Huimin|H| Zhao|Jie|J| Li|Junbai|J|0000-0001-9575-3125

dipeptides
aerogels
wettability
hemostasis
supramolecular assembly


Arabidopsis thaliana receptor-like protein AtRLP23 associates with the receptor-like kinase AtSOBIR1.

Abstract: Plants employ a large number of receptors localizing to the cell surface to sense extracellular signals. Receptor-like proteins (RLPs) form an important group of such trans-membrane receptors, containing an extracellular domain which is involved in signal perception and a short cytoplasmic domain. In contrast to receptor-like kinases (RLKs), RLPs lack a cytoplasmic kinase domain. How intracellular signaling is triggered downstream of RLPs upon perception of an extracellular signal, is therefore still poorly understood. Recently, the RLK SOBIR1 (Suppressor Of BIR1-1) was identified as an essential regulatory RLK of various RLPs involved in plant immunity against fungal pathogens. (1) Given that SOBIR1 appears to be a crucial component of RLP-containing complexes, we aimed to identify additional proteins interacting with SOBIR1. Here, we report on the immunopurification of a functional Arabidopsis thaliana (At)SOBIR1-yellow fluorescent protein (YFP) fusion protein stably expressed in Arabidopsis, followed by mass-spectrometry to identify co-purifying proteins. Interestingly, and in line with various studies showing interaction between RLPs and SOBIR1, we discovered that AtSOBIR1 interacts with AtRLP23, an RLP of which the function is currently unknown.

Bi|Guozhi|G|
Liebrand|Thomas W H|TW|
Cordewener|Jan H G|JH|
America|Antoine H P|AH|
Xu|Xiangyang|X|
Joosten|Matthieu H A J|MH|

D018506:Gene Expression Regulation, Plant

Arabidopsis thaliana
Receptor-like Protein (RLP)
Receptor-Like Kinase (RLK)
plant immunity
plant development
receptor-complex


An assessment of the UK inpatient care for heart failure patients with diabetes.

Abstract:
BACKGROUND
Diabetes is a common co-morbidity for patients with heart failure. Diabetes as a co-morbidity means that inpatient care should focus on both conditions to maximize the treatment regimen. However, this pressing issue is not widely researched and so it is unclear whether the acute care management needs of these patients are being met.

AIMS
(1) To assess the differences in the number of hospital readmissions between patients with heart failure and patients with heart failure-diabetes; (2) to assess the use of integrated care approach for patients with heart failure-diabetes during the index heart failure-related admission; (3) to explore patient experiences of admissions.

METHODS
A mixed methods design was used: we identified heart failure-related admissions between 1 April 2011 and 31 March 2012 in two hospitals, then reviewed medical records and interviewed 14 patients.

RESULTS
Over a 12 month period patients with heart failure-diabetes ( n=172) had more heart failure-related Accident and Emergency attendance episodes (incident rate ratio 1.24, p<0.01) and hospital readmissions (incident rate ratio 1.23, p=0.01) than patients with heart failure ( n=370). We reviewed 72 medical records which met inclusion criteria (adults with heart failure-diabetes, ejection fraction <45%): during admission most of them were reviewed by heart failure specialists but less than one-third were reviewed by diabetes specialists. The interview respondents addressed the need for better integration and co-ordination of care.

CONCLUSIONS
This is one of the first UK studies to assess the integration of inpatient care for those with heart failure and multi-morbidities. The findings suggest that maximal care management during admission should be explored as a way of reducing the frequent readmissions and improving patient outcomes.

Wu|Lihua|L| Cleator|Jackie|J| Mamas|Mamas|M| Deaton|Christi|C|

Inpatient care
diabetes
readmission
heart failure exacerbation


The Relationship of Severe Early Childhood Caries and Body Mass Index in a Group of 3- to 6-year-old Children in Shiraz.

Abstract:
STATEMENT OF PROBLEM
Early childhood caries can cause pain, discomfort and also inability to have a healthy nutrition .Malnutrition can be characterized when there is a weight, height, and body mass index (BMI) deficiency.

PURPOSE
The aim of this study was to evaluate the relationship between the severe early childhood caries (based on the dmft index) and BMI in pre-school children in Shiraz.

MATERIALS AND METHOD
A descriptive analytical cross-sectional study was enrolled on 202 healthy preschool children with the age range of 3-6 years recruited from the kindergartens of different socio- economical parts of Shiraz, Iran. The Anthropometric measurements, weight and height were evaluated. The Z-scores were calculated employing WHO Anthro software (www.who.int/childgrowth/software/en/ index.html) to elucidate the subject's status on the age- and sex-specific growth chart. Every Child who has received two Z-scores under the normal value (< -2) was considered as abnormal. The relationship between dmft index and BMI was then investigated.

RESULTS
The mean of dmft was 4.13. From children with severe early childhood caries, 12.5%were under weight, 5% had height deficiency and 19.5% had BMI deficiency, however, there was no significant relationship between increasing dmft and the height, weight and BMI deficiency.

CONCLUSION
There was not a linear correlation between severe early childhood caries and BMI, height, and weight deficiency. An incidence of 55% was yielded for severe early childhood caries which was an additional finding of this study.

Edalat|A|A| Abbaszadeh|M|M| Eesvandi|M|M| Heidari|A|A|

Body mass index
Preschool children
Software
Dental caries


Is adult attachment associated with engagement with services? A systematic literature review.

Abstract:
BACKGROUND
People with psychosis often experience difficulties engaging in mental health treatments.

AIMS
This review sought to identify, summarise and critically evaluate studies that investigated associations between adult attachment and relationships with mental health services in the context of psychosis.

METHOD
A search was conducted on the following databases from 1980 to February 2019: Web of Science; PubMed; CINAHL; and PsycINFO. Of the 10,683 articles identified, 11 met inclusion criteria for the review. These articles were then quality appraised using the Effective Public Health Practice Project tool (EPHPP).

RESULTS
There was some evidence of associations between insecure attachment (namely avoidant attachment) and therapeutic alliance, and insecure attachment and engagement with services. Secure attachment was also associated with self-reported attachment to services as a whole. There were a number of limitations across the studies; the majority of studies were cross-sectional and it was difficult to make comparisons between studies due to the range of different measures used to assess attachment and alliance.

CONCLUSION
Adult attachment security may be an important factor to consider in determining the way in which service users with psychosis engage with mental health services.

McGonagle|G|G| Bucci|S|S| Varese|F|F| Raphael|J|J| Berry|K|K|

D000328:Adult
D000066505:Help-Seeking Behavior
D006801:Humans
D008605:Mental Health Services
D010358:Patient Participation
D011618:Psychotic Disorders
D057566:Self Report
D000078462:Therapeutic Alliance

attachment engagement Psychosis alliance Schizophrenia help-seeking


Impact of legislative change on waiting time for women accessing surgical abortion services in a rural hospital in the Northern Territory.

Abstract:
BACKGROUND
Women face challenges when accessing abortion, including varied legislation and reduced access to services in rural and remote settings. There are limited clinical guidelines in Australia and little information regarding the patient journey, particularly the timeframe between referral to abortion procedure. Legislation reform in the Northern Territory (NT) legalised early medical abortion (EMA) in primary health care, providing an opportunity to review service provision of elective surgical abortion prior to and after these changes.

AIMS
To review the waiting time to access abortion, percentage eligible for EMA based on ultrasound gestation alone, percentage of Indigenous women accessing abortion in the NT and the effects of the legislation change.

MATERIALS AND METHODS
Retrospective audit-analysed surgical abortion data from 354 patient files who underwent suction curettage of uterus between 2012-2017 in one NT public hospital.

RESULTS
Mean wait-time ranged from 20 to 22 days in 2012-2016 and dropped to 15 days in 2017 following the law reform. Sixty-two percent of women waited longer than that in the recommended clinical guidelines. Indigenous women represented approximately 25% of patients accessing surgical abortion services. Average gestation at surgical abortion procedure increased following reform. Prior to reform up to 95% of patients accessing surgical abortion would have been eligible for EMA at time of referral.

CONCLUSIONS
Results demonstrate potential for changes in service provision of abortion in the NT with increased choice, patient-centred care and reduced waiting times. This audit demonstrated the possibility to move the majority of abortion services into primary health care leading to cost savings.

D000023:Abortion Applicants
D000028:Abortion, Induced
D000029:Abortion, Legal
D005260:Female
D005865:Gestational Age
D006297:Health Services Accessibility
D006780:Hospitals, Rural
D006801:Humans
D000081034:Indigenous Peoples
D015876:Northern Territory
D017060:Patient Satisfaction
D011247:Pregnancy
D012189:Retrospective Studies
D012424:Rural Population
D014619:Vacuum Curettage
D014850:Waiting Lists

rural hospitals
abortion induced
abortion legal
health-care disparities


Multimodality treatment including ONCEPT for canine oral melanoma: A retrospective analysis of 131 dogs.

Abstract: Canine oral melanoma (OM) is an aggressive cancer with a high rate of metastasis. Surgery and/or radiotherapy (RT) are effective local treatments, yet many dogs succumb to distant metastasis. Immunotherapy represents an attractive strategy for this potentially immunogenic tumor. The objective of this multi-institutional retrospective study was to examine the clinical outcome of dogs with OM treated with ONCEPT melanoma vaccine. Most dogs also underwent surgery and/or RT (8 Gy × four weekly fractions). Dogs with distant metastasis at diagnosis and those receiving concurrent chemotherapy were excluded. One hundred thirty-one dogs treated with ONCEPT were included: 62 had adequate local tumor control defined as complete tumor excision or irradiation of residual microscopic disease; 15 were treated in the microscopic disease setting following an incomplete excision without adjuvant RT; and 54 had gross disease. Median time to progression, median progression-free survival, and median tumor-specific overall survival were 304, 260, and 510 days, respectively. In multivariable analysis, presence of gross disease correlated negatively with all measures of clinical outcome. Other negative prognostic indicators were primary tumor ≥2 cm, higher clinical stage (stages 2 and 3), presence of lymph node metastasis at diagnosis, and caudal location in the oral cavity. Radiotherapy had a protective effect against tumor progression. To date, this is the largest reported series of dogs with OM treated with ONCEPT. Several previously reported prognostic indicators were confirmed.

immunotherapy
hypofractionation
radiation
tumor vaccine
veterinary


Efficacy of PSMA PET-Guided Radiotherapy for Oligometastatic Castrate-Resistant Prostate Cancer.

Abstract:
Purpose
To assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC).

Patients and methods
A total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS).

Results
A total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, <0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5).

Conclusion
In well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies.

Henkenberens|Christoph|C|
Derlin|Thorsten|T|
Bengel|Frank|F|
Ross|Tobias L|TL|
Kuczyk|Markus A|MA|
Giordano|Frank A|FA|
Sarria|Gustavo R|GR|
Schmeel|Leonard Christopher|LC|
Christiansen|Hans|H|
von Klot|Christoph A J|CAJ|

PSMA
radiotherapy
castrate-resistant
metastasis-directed therapy
oligometastases


Clinical Characteristics and Short-Term Outcomes of Patients Presenting with Acute Myocardial Infarction having Multi-vessel disease - A Single Middle- eastern Tertiary-Care Center Experience.

Abstract:
OBJECTIVE
Patients with multi-vessel coronary artery disease (MVD) compared to single-vessel coronary artery disease (CAD) have more comorbidities and poor in-hospital outcomes. We aim to analyze MVD-AMI patients regarding clinical data and short-term outcomes.

METHODS
This is a retrospective analysis of the prospectively collected data registry, a single-center study reviewing the clinical details and hospital outcome measures of AMI patients referred to our center for early revascularization from 2016 to 2019.

RESULT
Out of 3041 patients presented with AMI, 491 (16%) had MVD on coronary angiogram. MVD-AMI patients were older, had a higher prevalence of DM, HTN, and prior history of ischemic heart disease compared to the non- MVD -AMI group (p < 0.001 for all). However, they presented more with non-anterior myocardial infarction, showed higher rates of post-myocardial infarction LV dysfunction, and mortality (p < 0.001). Older MVD-AMI patients showed higher rates of in-hospital morbidities and mortality compared to younger ones (p < 0.001). MVD- AMI women and Middle Eastern patients were older and showed a higher prevalence of cardiovascular risk factors compared to MVD-AMI men and South Asian patient population respectively. There were no significant differences recorded among the different subgroups of MVD-AMI patients regarding the hospital outcome measures.

CONCLUSION
Our study highlighted the clinical characters and poor outcomes of a high-risk group of MVD-AMI with different demographic backgrounds. Although age was a strong predictor for in-hospital poor outcomes, neither gender nor ethnicity affected the outcomes in them.

Clinical
Outcomes
Myocardial infarction
Multi-vessel coronary artery disease


Orthopaedic procedures in haemophilia.

Abstract: Haemophilia may nowadays be considered an "ortho paedic" disease given due to the involvement of musculoskeletal system in almost all haemophilic subjects. The modern haematological prophylaxis has dramatically improved the quality of life reducing bleedings and life-threatening complications; however, joint bleedings, progressive and irreversible arthropathy and osteoporosis are still now common challenging issues to be faced. One of the tissues involved by Haemophilia is the bone, particularly in the periarticular zone: poor bone quality and decrease of bone stock are typical patterns, and the worse is the arthropathy, the greater the bone loss. The orthopaedic management of such condition is now mandatory and characterized by several surgical techniques. The purpose of this work is to provide an overview of these options derived from our experience in managing haemophilic patients.

Rizzo|Anna Rosa|AR|
Zago|Manuel|M|
Carulli|Christian|C|
Innocenti|Massimo|M|

haemophilia
bone
bone loss
orthopaedic management
bone grafting
joint fusion
knee arthroplasty
revision


Computational investigation on the host-guest inclusion process of norfloxacin into β-cyclodextrin.

Abstract: A theoretical (1)H NMR spectroscopy and thermodynamic analysis of the host-guest inclusion process involving the norfloxacin (NFX) into β-cyclodextrin (β-CD) was carried out. DFT structure and stabilization energies were obtained in both gas and aqueous phases. We could establish that the complex formation is enthalpy driven, and the hydrogen bonds established between NFX and β-CD play a major role in the complex stabilization. Besides, a theoretical (1)H NMR analysis has shown to be a supplementary proceeding to predict appropriately the inclusion mode of norfloxacin molecule into the β-CD. In this work, a theoretical study of the NFX@β-CD complex is reported for the first time, seeking a deep understanding of topology and thermodynamics of the inclusion complex formation. Graphical Abstract Topology, thermodynamic and (1)H NMR analysis of NFX@β-CD host-guest complexes.

Maia|Pollyanna P|PP|
de Sousa|Sara Maria R|SM|
De Almeida|Wagner B|WB|
Guimarães|Luciana|L|
Nascimento|Clebio S|CS|

Norfloxacin
NMR spectroscopy
Cyclodextrins
DFT calculations
Host–guest inclusion complexes


Surface Nonlinear Optics on Centrosymmetric Dirac Nodal-Line Semimetal ZrSiS.

Abstract: Gapless surface states (SSs) are features of topological semimetals and are extensively observed. Nowadays, the emerging question is whether the SSs possess exotic and applicable properties. Here, associated with the symmetrical selection rule for nonlinear optical materials, the surface nonlinear optics on a centrosymmetric Dirac nodal-line semimetal ZrSiS crystal is studied and it is found that the SSs bring record nonlinear susceptibilities. The unprecedented conversion efficiencies for second and third harmonic generations are 0.11‰ and 0.43‰, respectively, more than ten orders of magnitude larger than the typical surface second harmonic generation. This work discovers a new route toward studying the SSs for applications in nonlinear photonics.

nonlinear optics
surface states
ZrSiS
density functional theory calculations
symmetry breaking


Hand Surgery in Singapore.

Abstract: Singapore as an island nation is one of three countries in the world that has hand and reconstructive microsurgery (HRM) as an independent specialty. The 52 accredited hand surgeons serving a population of 5.7 million facilitate hassle free access to patients. Hand surgery historically is rooted very much in orthopaedic surgery as in most Asian countries with more than five decades of rapid evolution. Singapore pioneered a structured and systematic training program for HRM and the local surgeons have contributed significantly to the body of knowledge in hand surgery with targeted research and publications with three surgeons being awarded international recognition for their contributions. Singapore continues to contribute significantly to surgical volunteerism regionally through active involvement in the training of regional surgeons through their sustainable volunteer activities and through international fellowships in Singapore hospitals. The future of hand surgery in Singapore will be more competency and multidiscipline based on community-centered approach.

Pei-Yein|Tong|T|
Chia|Dawn Sinn Yii|DSY|
Omar|Usama Farghaly|UF|
Das De|Soumen|S|
Sirisena|Renita|R|
Yap|Robert Tze Jin|RTJ|
Tan|Jacqueline Siau Woon|JSW|
Rajaratnam|Vaikunthan|V|

hand surgery
Singapore
reconstructive microsurgery
surgical volunteerism


Neuroimaging Anomalies in Community-Dwelling Asymptomatic Adults With Very Early-Stage White Matter Hyperintensity.

Abstract: White matter hyperintensity (WMH) is common in healthy adults in their 60s and can be seen as early as in their 30s and 40s. Alterations in the brain structural and functional profiles in adults with WMH have been repeatedly studied but with a focus on late-stage WMH. To date, structural and functional MRI profiles during the very early stage of WMH remain largely unexplored. To address this, we investigated multimodal MRI (structural, diffusion, and resting-state functional MRI) profiles of community-dwelling asymptomatic adults with very early-stage WMH relative to age-, sex-, and education-matched non-WMH controls. The comparative results showed significant age-related and age-independent changes in structural MRI-based morphometric measures and resting-state fMRI-based measures in a set of specific gray matter (GM) regions but no global white matter changes. The observed structural and functional anomalies in specific GM regions in community-dwelling asymptomatic adults with very early-stage WMH provide novel data regarding very early-stage WMH and enhance understanding of the pathogenesis of WMH.

Guan|Shuai|S| Kong|Xiangyu|X| Duan|Shifei|S| Ren|Qingguo|Q| Huang|Zhaodi|Z| Li|Ye|Y| Wang|Wei|W| Gong|Gaolang|G| Meng|Xiangshui|X| Ma|Xiangxing|X|

white matter hyperintensity
cerebral small vessel disease
cortical thickness
diffusion tensor imaging
functional magnetic resonance imaging


Efficacy of directly-observed chloroquine-primaquine treatment for uncomplicated acute Plasmodium vivax malaria in northeast Myanmar: A prospective open-label efficacy trial.

Abstract:
BACKGROUND
Chloroquine (CQ) and primaquine (PQ) remain the frontline drugs for radical cure of uncomplicated P. vivax malaria in the Greater Mekong Sub-region (GMS). Recent reports of decreased susceptibility of P. vivax to CQ in many parts of the GMS raise concerns.

METHODS
From April 2014 to September 2016, 281 patients with uncomplicated P. vivax infection attending clinics in border settlements for internally displaced people in northeast Myanmar were recruited into this study. Patients were treated with standard regimen of 3-day CQ and concurrent 14-day PQ (3.5 mg/kg total dose) as directly observed therapy, and followed for recurrent parasitemia within 28 days post-patency.

RESULTS
Within the 28-day follow-up period, seven patients developed recurrent parasitemia, resulting in a cumulative rate of parasite recurrence of 2.6%. Five of the seven parasitemias recurred within two weeks, and two of those failed to clear within seven days, indicating high-grade resistance.

CONCLUSION
Although failure of CQ/PQ treatment of P. vivax was relatively infrequent in northeast Myanmar, this study nonetheless confirms that CQ/PQ-resistant strains do circulate in this area, some of them of a highly resistant phenotype. It is thus recommended that patients who acquire vivax malaria in Myanmar be treated an artemisinin-combination therapy along with hypnozoitocidal primaquine therapy to achieve radical cure.

Xu|Shiling|S|
Zeng|Weilin|W|
Ngassa Mbenda|Huguette Gaelle|HG|
Liu|Huaie|H|
Chen|Xi|X|
Xiang|Zheng|Z|
Li|Cuiying|C|
Zhang|Yanmei|Y|
Baird|J Kevin|JK|
Yang|Zhaoqing|Z|
Cui|Liwang|L|

Efficacy
Plasmodium vivax
Chloroquine
Directly observed therapy
Resistance


Regional Ventilation Is the Main Determinant of Alveolar Deposition of Coarse Particles in the Supine Healthy Human Lung During Tidal Breathing.

Abstract:
BACKGROUND
To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar gamma scintigraphy in seven subjects.

METHODS
Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar gamma scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 μm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data-apices aligned-using a transmission scan as reference. The ratio of fractional alveolar deposition to fractional ventilation of each quartile (r) was used to evaluate ventilation and deposition matching (r > 1, regional aerosol deposition fraction larger than regional ventilation fraction).

RESULTS
r was not significantly different from 1 for all regions (1.04 ± 0.25, 1.08 ± 0.22, 1.03 ± 0.17, 0.92 ± 0.13, apex to diaphragm, p > 0.40) at the alveolar level (r22h). For retention times r0h and r1h30, only the diaphragmatic region at r1h30 differed significantly from 1.

CONCLUSIONS
These results support the hypothesis that alveolar deposition is directly proportional to ventilation for ∼5 μm particles that are inhaled in the supine posture and are consistent with previous simulation predictions that show that convective flow is the main determinant of aerosol transport to the lung periphery.

Sá|Rui Carlos|RC|
Zeman|Kirby L|KL|
Bennett|William D|WD|
Prisk|G Kim|GK|
Darquenne|Chantal|C|

D013671:Technetium Tc 99m Sulfur Colloid

ventilation
human lung
coarse aerosol deposition
multimodal imaging


Development and validation of a simple and robust model to predict 30-day mortality in patients with Clostridioides difficile-associated enterocolitis.

Abstract:
OBJECTIVE
Clostridioides difficile infection (CDI) is a common healthcare-associated infection and associated with high morbidity and mortality. As current guidelines recommend treatment stratified for disease severity, this study aimed to identify predictors of 30-day mortality in order to develop a robust prediction model.

DESIGN
This was a retrospective analysis of 207 inpatients with CDI who were treated at the Jena University Hospital between September 2011 and December 2015. In a training cohort (n=127), predictors of 30-day mortality were identified by receiver operating characteristics analysis and logistic regression. The derived model was validated in an independent cohort of 80 inpatients with CDI.

RESULTS
Within 30 days, 35 (28%) patients in the training cohort died from any cause. C-reactive protein (CRP) of ≥121 mg/L (OR 3.80; 95% CI 1.64 to 7.80; p=0.003) and lower systolic blood pressure of ≤104 mm Hg (OR 3.73; 95% CI 1.63 to 8.53; p=0.002) at diagnosis as well as development of renal impairment (serum creatinine >1.5×baseline; OR 5.61; 95% CI 1.94 to 16.26; p=0.035) within the first 6 days were associated with 30-day mortality in univariate analysis. The use of these parameters enabled correct mortality prediction in 73% of cases on the day of diagnosis and in 76% at day 6. In the validation cohort, 30-day mortality was 18/80 (23%). Our model enabled a 73.7% correct prediction concerning 30-day mortality on day 6 after diagnosis of CDI.

CONCLUSION
Hypotension and CRP elevation on the day of diagnosis as well as occurrence of kidney dysfunction during the first 6 days are suitable parameters to predict 30-day mortality in patients with CDI who need to be treated in the hospital.

infectious diarrhoea
infectious disease
infective colitis


Bone Density and Texture from Minimally Post-Processed Knee Radiographs in Subjects with Knee Osteoarthritis.

Abstract: Plain radiography is the most common modality to assess the stage of osteoarthritis. Our aims were to assess the relationship of radiography-based bone density and texture between radiographs with minimal and clinical post-processing, and to compare the differences in bone characteristics between controls and subjects with knee osteoarthritis or medial tibial bone marrow lesions (BMLs). Tibial bone density and texture was evaluated from radiographs with both minimal and clinical post-processing in 109 subjects with and without osteoarthritis. Bone texture was evaluated using fractal signature analysis. Significant correlations (p < 0.001) were found in all regions (between 0.94 and 0.97) for calibrated bone density between radiographs with minimal and clinical post-processing. Correlations varied between 0.51 and 0.97 (p < 0.001) for FDVer texture parameter and between - 0.10 and 0.97 for FDHor. Bone density and texture were different (p < 0.05) between controls and subjects with osteoarthritis or BMLs mainly in medial tibial regions. When classifying healthy and osteoarthritic subjects using a machine learning-based elastic net model with bone characteristics, area under the receiver operating characteristics (ROCAUC) curve was 0.77. For classifying controls and subjects with BMLs, ROCAUC was 0.85. In conclusion, differences in bone density and texture can be assessed from knee radiographs when using minimal post-processing.

Bone density
Knee
Osteoarthritis
Radiography
Bone marrow lesion
Bone texture


Posttraumatic Stress Disorder in the DSM-5: Controversy, Change, and Conceptual Considerations.

Abstract: The criteria for posttraumatic stress disorder PTSD have changed considerably with the newest edition of the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Changes to the diagnostic criteria from the DSM-IV to DSM-5 include: the relocation of PTSD from the anxiety disorders category to a new diagnostic category named "Trauma and Stressor-related Disorders", the elimination of the subjective component to the definition of trauma, the explication and tightening of the definitions of trauma and exposure to it, the increase and rearrangement of the symptoms criteria, and changes in additional criteria and specifiers. This article will explore the nosology of the current diagnosis of PTSD by reviewing the changes made to the diagnostic criteria for PTSD in the DSM-5 and discuss how these changes influence the conceptualization of PTSD.

Pai|Anushka|A|
Suris|Alina M|AM|
North|Carol S|CS|

posttraumatic stress disorder
DSM-5
diagnostic criteria
trauma
nosology
psychiatric diagnosis


Purification and characterization of a novel high molecular weight alkaline protease produced by an endophytic Bacillus halotolerans strain CT2.

Abstract: A protease-producing strain CT2 isolated from Tunisian potatoes, exhibiting a potent protease activity (prot CT2), was identified as Bacillus halotolerans according to 16S ribosomal DNA sequence analysis. Maximum prot CT2 production was obtained in medium supplemented with bean seed proteins. Proteolytic activity was purified by ammonium sulphate precipitation, Sephacryl S-200 gel filtration and SP-sepharose cation-exchange chromatography. Optimal enzyme activity was reached at pH 9 and temperature of 50 °C. Proteolytic activity was enhanced by Ca2+ and Mn2+ ions, completely inhibited by PMSF suggesting a serine protease nature and exhibited high stability in the presence of commercial detergents. Prot CT2 showed broad substrate specificity towards both synthetic and natural substrates, with a high capacity to hydrolyze legume seed proteins. Using electrophoretic analysis, its molecular weight was around 250 kDa with two major subunit showing important homologies with serine proteases belonging to the subtilisin-like serine proteases. Based on the Lineweaver-Burk plots Km and Vmax values were 10 mg/ml and 50,000 U/mg respectively. This newly described prot CT2 displays relevant properties which highlight its potential use in various industrial and biotechnological applications.

Dorra|Gharbi|G|
Ines|Karkouch|K|
Imen|Ben Slimene|BS|
Laurent|Coquet|C|
Sana|Azaiez|A|
Olfa|Tabbene|T|
Pascal|Cosette|C|
Thierry|Jouenne|J|
Ferid|Limam|L|

High molecular weight
Protease
Detergent compatible
Protein hydrolysis


Induced adaptation of Bacillus sp. to antimicrobial nanosilver.

Abstract: The natural ability of Bacillus sp. to adapt to nanosilver cytotoxicity upon prolonged exposure is reported for the first time. The combined adaptive effects of nanosilver resistance and enhanced growth are induced under various intensities of nanosilver-stimulated cellular oxidative stress, ranging from only minimal cellular redox imbalance to the lethal levels of cellular ROS stimulation. An important implication of the present work is that such adaptive effects lead to the ultimate domination of nanosilver-resistant Bacillus sp. in the microbiota, to which nanosilver cytotoxicity is continuously applied.

Gunawan|Cindy|C|
Teoh|Wey Yang|WY|
Marquis|Christopher P|CP|
Amal|Rose|R|

induced adaptation
cellular oxidative stress
antimicrobial resistance
silver nanoparticles


Early bone formation in mini-lateral window sinus floor elevation with simultaneous implant placement: An in vivo experimental study.

Abstract:
OBJECTIVE
To investigate the early bone formation in beagles with mini-lateral window sinus floor elevation and simultaneous implant placement.

MATERIAL AND METHODS
Six beagles were selected for the split-mouth design procedures. In each animal, one maxillary recess received a 5 mm-diameter mini-round lateral osteotomy (test group), and the contralateral maxillary recess received a large rectangular osteotomy (10 mm long and 8 mm wide), (control group). Simultaneous implant installation was executed on bilateral maxillary recesses. Tetracycline and calcein dyes were administered on the 14th, 13th days and the 4th, 3rd days prior to sacrifice, respectively. After 8 weeks of healing, the beagles were euthanized for fluorescent labeling and histomorphometric analyses.

RESULTS
In both groups, new bone formation initiated from the circumferential native bone of the maxillary recesses and extended toward the central sub-recess cavities. The maxillary recesses with the mini-window procedures exhibited superior mineral apposition rate, bone formation rate, and the percentage of new bone area to those of the group exposed to large osteotomy procedure (p < .05). While there was no significant difference in the value of bone-to-implant contact, the mini-window group displayed a tendency for an increase in this aspect (p > .05). Bone formation rate and new bone amount were not statistically correlated with bone-to-implant contact (p > .05).

CONCLUSION
The hypothesis that mini-lateral window sinus floor elevation with simultaneous implant placement would improve early new bone formation in augmented sinus compared with large lateral window procedure is accepted.

bone substitutes
dental implants
minimally invasive surgical procedures
osseointegration
osteogenesis
sinus floor augmentation


Return to pregnancy after contraceptive discontinuation to become pregnant: a pooled analysis of West and East African populations.

Abstract:
BACKGROUND
The fear of infertility or delayed return to fertility is a common barrier to contraceptive use in sub-Saharan Africa, particularly among young or nulliparous women. Global evidence on return to pregnancy after method discontinuation suggests these fears may be misplaced; yet the topic has not been widely studied in sub-Saharan Africa nor by age and parity group.

METHODS
Reproductive calendar data from recent Demographic and Health Surveys of 15 sub-Saharan African countries were used to analyze time-to-pregnancy following discontinuation of a contraceptive method with the reason to become pregnant. The probability of pregnancy at 12 months was estimated using single-decrement life tables run by type of method discontinued, age and parity. Results are presented by region: francophone West Africa, anglophone West Africa and East Africa.

RESULTS
The 12-month probability of pregnancy after discontinuation of contraception to become pregnant was 73.0% in francophone West Africa, 78.8% in anglophone West Africa, and 82.0% in East Africa. Our results showed significant regional differences in return to pregnancy by 12 months, with probabilities in francophone West Africa being significantly lower than in anglophone West Africa or East Africa. A lower return to pregnancy by 12 months was seen among women ages 35-49 years and was lowest after discontinuation of a hormonal method for all age groups. Differences by parity group were only evident after discontinuation of hormonal methods in francophone West Africa.

CONCLUSIONS
Sustainable gains in increasing contraceptive uptake, especially among youth, may be difficult to achieve without information and counseling that address concerns about infertility and potential delays in return to pregnancy following use of hormonal methods.

Return to pregnancy
Contraceptive discontinuation
Sub-Saharan Africa
West Africa
East Africa
Youth
Fecundity


Heat Driven Transport in Serial Double Quantum Dot Devices.

Abstract: Studies of thermally induced transport in nanostructures provide access to an exciting regime where fluctuations are relevant, enabling the investigation of fundamental thermodynamic concepts and the realization of thermal energy harvesters. We study a serial double quantum dot formed in an InAs/InP nanowire coupled to two electron reservoirs. By means of a specially designed local metallic joule-heater, the temperature of the phonon bath in the vicinity of the double quantum dot can be enhanced. This results in phonon-assisted transport, enabling the conversion of local heat into electrical power in a nanosized heat engine. Simultaneously, the electron temperatures of the reservoirs are affected, resulting in conventional thermoelectric transport. By detailed modeling and experimentally tuning the interdot coupling, we disentangle both effects. Furthermore, we show that phonon-assisted transport is sensitive to excited states. Our findings demonstrate the versatility of our design to study fluctuations and fundamental nanothermodynamics.

quantum dot
thermal energy harvesters
nanowire
phonon assisted transport
thermoelectric effect


Pertussis Accompanying Recent Mycoplasma Infection in a 10-Year-Old Girl.

Abstract: Recently, the incidence of pertussis has been increasing; however, reports on mixed infection of pertussis with other respiratory pathogens are rare in highly immunized populations. We report the case of a 10-year-old girl who presented with cough, post-tussive emesis, and fever. She was subsequently diagnosed with bronchopneumonia. Although she had received five doses of diphtheria-tetanus-acellular pertussis vaccine, polymerase chain reaction of her nasopharyngeal aspirate confirmed Bordetella pertussis infection. In addition, serologic testing for Mycoplasma pneumoniae was also positive. The patient was treated with roxithromycin without any complications. This is the first report of mixed B. pertussis and M. pneumoniae infection in Korea. To avoid under-diagnosis, pertussis should be considered in patients with chronic cough even when other respiratory pathogens have been documented.

Cheon|Mi Kyung|MK|
Na|Hyunju|H|
Han|Seung Beom|SB|
Kwon|Hyo Jin|HJ|
Chun|Yoon Hong|YH|
Kang|Jin Han|JH|

Bordetella pertussis
Mycoplasma pneumoniae
Child
Coinfection


Isotope Composition and Chemical Species of Monthly Precipitation Collected at the Site of a Fusion Test Facility in Japan.

Abstract: The deuterium plasma experiment was started using the Large Helical Device (LHD) at the National Institute for Fusion Science (NIFS) in March 2017 to investigate high-temperature plasma physics and the hydrogen isotope effects towards the realization of fusion energy. In order to clarify any experimental impacts on precipitation, precipitation has been collected at the NIFS site since November 2013 as a means to assess the relationship between isotope composition and chemical species in precipitation containing tritium. The tritium concentration ranged from 0.10 to 0.61 Bq L-1 and was high in spring and low in summer. The stable isotope composition and the chemical species were unchanged before and after the deuterium plasma experiment. Additionally, the tritium concentration after starting the deuterium plasma experiment was within three sigma of the average tritium concentration before the deuterium plasma experiment. These results suggested that there was no impact by tritium on the environment surrounding the fusion test facility.

Akata|Naofumi|N| Tanaka|Masahiro|M| Iwata|Chie|C| Kato|Akemi|A| Nakada|Miki|M| Kovács|Tibor|T| Kakiuchi|Hideki|H|

monthly precipitation
fusion test facility
deuterium plasma experiment
chemical composition
tritium monitoring


Inhibition of Cardiac RIP3 Mitigates Early Reperfusion Injury and Calcium-Induced Mitochondrial Swelling without Altering Necroptotic Signalling.

Abstract: Receptor-interacting protein kinase 3 (RIP3) is a convergence point of multiple signalling pathways, including necroptosis, inflammation and oxidative stress; however, it is completely unknown whether it underlies acute myocardial ischemia/reperfusion (I/R) injury. Langendorff-perfused rat hearts subjected to 30 min ischemia followed by 10 min reperfusion exhibited compromised cardiac function which was not abrogated by pharmacological intervention of RIP3 inhibition. An immunoblotting analysis revealed that the detrimental effects of I/R were unlikely mediated by necroptotic cell death, since neither the canonical RIP3-MLKL pathway (mixed lineage kinase-like pseudokinase) nor the proposed non-canonical molecular axes involving CaMKIIδ-mPTP (calcium/calmodulin-dependent protein kinase IIδ-mitochondrial permeability transition pore), PGAM5-Drp1 (phosphoglycerate mutase 5-dynamin-related protein 1) and JNK-BNIP3 (c-Jun N-terminal kinase-BCL2-interacting protein 3) were activated. Similarly, we found no evidence of the involvement of NLRP3 inflammasome signalling (NOD-, LRR- and pyrin domain-containing protein 3) in such injury. RIP3 inhibition prevented the plasma membrane rupture and delayed mPTP opening which was associated with the modulation of xanthin oxidase (XO) and manganese superoxide dismutase (MnSOD). Taken together, this is the first study indicating that RIP3 regulates early reperfusion injury via oxidative stress- and mitochondrial activity-related effects, rather than cell loss due to necroptosis.

D053422:Receptor-Interacting Protein Serine-Threonine Kinases

receptor-interacting protein kinase 3
necroptosis
myocardial ischemia/reperfusion


Generation of 3D Collagen Gels with Controlled Diverse Architectures.

Abstract: Rat tail collagen solutions have been used as polymerizable in vitro three dimensional (3D) extracellular matrix (ECM) gels for single and collective cell migration assays as well as spheroid formation. Factors such as ECM concentration, pH, ionic concentration, and temperature can alter collagen polymerization and ECM architecture. This unit describes how to generate 3D collagen gels that have distinct architectures ranging from a highly reticular meshwork of short thin fibrils with small pores to a loose matrix consisting of stiff, parallel-bundled long fibrils by changing collagen polymerization temperature. This permits analysis of 3D cell migration in different ECM architectures found in vivo while maintaining a similar ECM concentration. Also included are collagen labeling techniques helpful for ECM visualization during live fluorescence imaging. © 2016 by John Wiley & Sons, Inc.

ECM architecture
3D matrix
fluorescent labelling
rat-tail collagen


Medical Costs Related to Enzyme Replacement Therapy for Mucopolysaccharidosis Types I, II, and VI in Brazil: A Multicenter Study.

Abstract:
BACKGROUND
Mucopolysaccharidosis (MPS) type I (MPS I), MPS type II (MPS II), and MPS type VI (MPS VI) are lysosomal storage disorders for which enzyme replacement therapy (ERT) is available.

OBJECTIVE
The objective of this study was to evaluate the frequency of medical interventions in a cohort of patients with MPS I, II, and VI on ERT to estimate the impact of direct medical costs associated with the treatment of MPS and compare its frequency with that observed among patients not on ERT.

METHODS
This was a multicenter study using a retrospective design including a convenience sampling of Brazilian patients with MPS I, II, and VI. Data on the number and type of medical appointments, hospital admissions, medications used, and surgical procedures performed per patient were obtained through a review of medical records, as were data on ERT. These variables were then compared between patients undergoing ERT and those not on ERT.

RESULTS
Thirty-four patients (27 on ERT) were included in the study. Overall, between-group differences were found in median absolute frequencies of hospital admissions and surgical procedures per year, both of which were higher in the non-ERT group. Furthermore, we observed a high rate of failure to record medication dosage regimens.

CONCLUSIONS
Our findings suggest that Brazilian patients with MPS I, II, and VI who are on ERT undergo fewer medical interventions, which can lead to a reduction in direct medical costs to the publicly funded health care system. The cost of ERT, however, is extremely high and probably outweighs this reduction.

Bitencourt|Fernanda Hendges de|FH|
Vieira|Taiane Alves|TA|
Steiner|Carlos Eduardo|CE|
Neto|Jordão Correa|JC|
Boy|Raquel|R|
Schwartz|Ida Vanessa Doederlein|IVD|

enzyme replacement therapy
mucopolysaccharidosis type I
health technology assessment
mucopolysaccharidosis type II
mucopolysaccharidosis type VI
rare disorders


Relative contributions of hospital versus skilled nursing facility quality on patient outcomes.

Abstract:
BACKGROUND
Hospitals and health systems worldwide have adopted value-based payment to improve quality and reduce costs. In the USA, skilled nursing facilities (SNFs) are now financially penalised for higher-than-expected readmission rates. However, the extent to which SNFs contribute to, and should thus be held accountable for, readmission rates is unknown. To compare the relative contributions of hospital and SNF quality on readmission rates while controlling for unobserved patient characteristics.

METHODS
Retrospective cohort study of Medicare beneficiaries, 2010-2016. Acute care hospitals and SNFs in the USA. Medicare beneficiaries with two hospitalisations followed by SNF admissions, divided into two groups: (1) patients who went to different hospitals but were discharged to the same SNF after both hospitalisations and (2) patients who went to the same hospital but were discharged to different SNFs. Hospital-level and SNF-level quality, using a lagged measure of 30-day risk-standardised readmission rates (RSRRs). Readmission within 30 days of hospital discharge.

RESULTS
There were 140 583 patients who changed hospitals but not SNFs, and 183 232 who changed SNFs but not hospitals. Patients who went to the lowest-performing hospitals (highest RSRR) had a 0.9% higher likelihood of readmission (p=0.005) compared with patients who went to the highest-performing hospitals (lowest RSRR). In contrast, patients who went to the lowest-performing SNFs had a 2% higher likelihood of readmission (p<0.001) compared with patients to went to the highest-performing SNFs.

CONCLUSIONS
The association between SNF quality and patient outcomes was larger than the association between hospital quality and patient outcomes among postacute care patients. Holding postacute care providers accountable for their quality may be an effective strategy to improve SNF quality.

health policy
health services research
quality improvement


A researcher's guide to the galaxy of IRESs.

Abstract: The idea of internal initiation is frequently exploited to explain the peculiar translation properties or unusual features of some eukaryotic mRNAs. In this review, we summarize the methods and arguments most commonly used to address cases of translation governed by internal ribosome entry sites (IRESs). Frequent mistakes are revealed. We explain why "cap-independent" does not readily mean "IRES-dependent" and why the presence of a long and highly structured 5' untranslated region (5'UTR) or translation under stress conditions cannot be regarded as an argument for appealing to internal initiation. We carefully describe the known pitfalls and limitations of the bicistronic assay and artefacts of some commercially available in vitro translation systems. We explain why plasmid DNA transfection should not be used in IRES studies and which control experiments are unavoidable if someone decides to use it anyway. Finally, we propose a workflow for the validation of IRES activity, including fast and simple experiments based on a single genetic construct with a sequence of interest.

D000067556:Internal Ribosome Entry Sites

D010442:Peptide Chain Initiation, Translational

Bicistronic vector
CITE
Cap-independent translation
Cellular IRES
RNA transfection
RRL


Differential inflammatory responses associated with Leishmania major and L tropica in culture.

Abstract:
BACKGROUND
Anthroponotic cutaneous leishmaniasis (ACL) due to Leishmania tropica and zoonotic CL (ZCL) due to L major have different clinical and epidemiological features.

OBJECTIVES
To determine whether pro-inflammatory cytokines are involved in diverse pathogenicity of Leishmania species causing CL.

PATIENTS/METHODS
The capacity of L major/L tropica to modulate expression of IL-1β, IL-8 (CXCL8), IFN-γ, TNF-α and MCP-1 (CCL2) in peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MDMs) was evaluated by real-time RT-PCR technique.

RESULTS
PBMCs from both ZCL and ACL cases expressed significantly higher IFN-γ (P < .001) and TNF-α (P < .05) compared with healthy controls (HC). PBMCs from ACL patients expressed significantly higher IL-1β and IL-8 compared with ZCL patients and HC when stimulated with live L major or L tropica promastigotes (P < .001). After 4 and 10 hours, L major-infected MDMs expressed significantly higher IFN-γ (P < .05), and after 10 hours, L tropica-infected MDMs expressed significantly higher IL-1β, IFN-γ and IL-8 compared with noninfected cells (P < .05).

CONCLUSIONS
This study shows differential parasite-mediated stimulations of the inflammatory response with L major vs L tropica ex vivo. Pro-inflammatory cytokines particularly IL-8 (CXCL8) and IL-1β might contribute in diverse clinical features of CL such as longer duration of lesion persistence in ACL patients.

D016207:Cytokines
D006801:Humans
D018320:Leishmania major
D007895:Leishmania tropica
D016773:Leishmaniasis, Cutaneous
D007963:Leukocytes, Mononuclear

Leishmania major
cutaneous leishmaniasis
Leishmania tropica
pro-inflammatory cytokines
interleukin-1β
interleukin-8


H7K(R2)2-modified pH-sensitive self-assembled nanoparticles delivering small interfering RNA targeting hepatoma-derived growth factor for malignant glioma treatment.

Abstract: The lack of effective glioma therapeutics mandates the development of novel treatment strategies. Hepatoma-derived growth factor (HDGF) has been considered as a potential glioma therapeutic target, and its expression level in gliomas is positively related to the malignant grade. Although there are no effective and specific inhibitors against this target, small interfering RNA targeting HDGF (siHDGF)-mediated RNA interference (RNAi) can inhibit the target protein function by knockdown of HDGF expression. However, the application of siHDGF in glioma research and therapy is hampered by the challenge to safe and effective in vivo systemic delivery of siHDGF to gliomas. To address this question, we develop the peptide H7K(R2)2-modified pH-sensitive self-assembled hybrid nanoparticles encapsulating siHDGF (H7K(R2)2-PSNPs (siHDGF)). The acidic glioma microenvironment is beneficial to the membrane penetration of H7K(R2)2-PSNPs and the encapsulated siHDGF. Following systemic administration, H7K(R2)2-PSNPs (siHDGF) can effectively deliver siHDGF into the brain and malignant glioma cells, and therefore can significantly downregulate HDGF expression, inhibit malignant phenotypes of glioma cells, result in reduced tumor volumes and prolonged survival times in nude mice bearing U251 human glioblastoma. Thus, systemic administration of H7K(R2)2-PSNPs (siHDGF) offers an effective way for the targeted delivery of siHDGF and may serve as a practical malignant glioma therapy.

Zhou|Meiling|M| Jiang|Nan|N| Fan|Junting|J| Fu|Song|S| Luo|Honghua|H| Su|Ping|P| Zhang|Mingwan|M| Shi|Huihui|H| Zeng|Jiaqi|J| Huang|Yuan|Y| Li|Yang|Y| Shen|Hong|H| Zhang|Aixia|A| Li|Rui|R|

D036341:Intercellular Signaling Peptides and Proteins

D023041:Xenograft Model Antitumor Assays

Nanoparticles
Small interfering RNA
Hepatoma-derived growth factor
Malignant gliomas
Targeted delivery


Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters.

Abstract:
BACKGROUND
There is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c - expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS).

METHODS
Fasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c - expected HbA1c ≤-0.5%.

RESULTS
Over 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (<500 cells/mm(3)); a regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or zidovudine; high mean corpuscular volume; and abnormal corpuscular haemoglobin.

CONCLUSION
HbA1c underestimates glycaemia in HIV-infected patients and its use in patients with risk factors for HbA1c discordance may lead to under-diagnosis and to under-treatment of established diabetes mellitus.

Slama|Laurence|L|
Palella|Frank J|FJ|
Abraham|Alison G|AG|
Li|Xiuhong|X|
Vigouroux|Corinne|C|
Pialoux|Gilles|G|
Kingsley|Lawrence|L|
Lake|Jordan E|JE|
Brown|Todd T|TT|

D000293:Adolescent
D000328:Adult
D044966:Anti-Retroviral Agents
D001786:Blood Glucose
D018791:CD4 Lymphocyte Count
D003920:Diabetes Mellitus
D003951:Diagnostic Errors
D016903:Drug Monitoring
D006442:Glycated Hemoglobin A
D015658:HIV Infections
D006801:Humans
D008297:Male
D008875:Middle Aged
D011446:Prospective Studies
D055815:Young Adult

HbA1c
HIV
mean corpuscular volume
diabetes
glycosylated haemoglobin


Comparison of the CapitalBio™Mycobacterium RT-PCR detection test and Xpert MTB/RIF assay for diagnosis of renal tuberculosis.

Abstract: The purpose of this study is to compare the efficiency difference between CapitalBio™Mycobacterium real-time polymerase chain reaction (RT-PCR) detection test and Xpert MTB/RIF assay for the diagnosis of renal tuberculosis (TB). We analyzed 117 samples collected between July 1, 2018, and October 31, 2019, from patients with suspected renal TB to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the CapitalBio™ Mycobacterium RT-PCR detection test for renal TB and to evaluate its diagnostic accuracy compared with Xpert MTB/RIF assay. Five cases were excluded from this study because of incomplete data. Taking clinical diagnosis as the gold standard, for the Xpert MTB/RIF assay, the sensitivity was 87.95% (78.96-94.07%), specificity 96.55% (82.24-99.91%), PPV 98.65% (92.70-99.97%), NPV 73.68% (56.90-86.60%), and AUC 0.92 (0.86-0.96). For the CapitalBio™Mycobacterium RT-PCR detection test, the overall sensitivity was 84.34% (74.71-91.39%), specificity 93.10% (77.23-99.15%), PPV 97.22% (90.32-99.66%), NPV 67.50% (50.87-81.43%), and AUC 0.89(0.81-0.94). The diagnostic efficiency of the CapitalBio™Mycobacterium RT-PCR detection test was similar to that of the Xpert MTB/RIF assay in patients with renal TB. Hence, the CapitalBio™Mycobacterium RT-PCR detection test presents a valuable alternative for the diagnosis of renal TB.

Liu|Pengju|P| Wang|Yeqiang|Y| Hao|Sida|S| Qin|Yong|Y|

D060888:Real-Time Polymerase Chain Reaction


Relating Structure to Efficiency in Surfactant-Free Polymer/Fullerene Nanoparticle-Based Organic Solar Cells.

Abstract: Nanoparticle dispersions open up an ecofriendly route toward printable organic solar cells. They can be formed from a variety of organic semiconductors by using miniemulsions that employ surfactants to stabilize the nanoparticles in dispersion and to prevent aggregation. However, whenever surfactant-based nanoparticle dispersions have been used to fabricate solar cells, the reported performances remain moderate. In contrast, solar cells from nanoparticle dispersions formed by precipitation (without surfactants) can exhibit power conversion efficiencies close to those of state-of-the-art solar cells processed from blend solutions using chlorinated solvents. In this work, we use small-angle neutron scattering measurements and transient absorption spectroscopy to investigate why surfactant-free nanoparticles give rise to efficient organic solar cells. We show that surfactant-free nanoparticles comprise a uniform distribution of small semiconductor domains, similar to that of bulk-heterojunction films formed using traditional solvent processing. This observation differs from surfactant-based miniemulsion nanoparticles that typically exhibit core-shell structures. Hence, the surfactant-free nanoparticles already possess the optimum morphology for efficient energy conversion before they are assembled into the photoactive layer of a solar cell. This structural property underpins the superior performance of the solar cells containing surfactant-free nanoparticles and is an important design criterion for future nanoparticle inks.

small-angle neutron scattering
transient absorption spectroscopy
organic nanoparticle
polymer solar cell
printed electronics