Polymorphisms in AURKA and AURKB are associated with the survival of triple-negative breast cancer patients treated with taxane-based adjuvant chemotherapy.

Abstract:
Purpose
Triple-negative breast cancer (TNBC) is more than a single disease. Identifying biomarkers to further subdivide TNBC patients with distinct outcome is of great importance. It has been reported that single-nucleotide polymorphisms (SNPs) in Aurora kinase A (AURKA) or Aurora kinase B (AURKB) are associated with the risk and survival of several cancers. But till now, there is no research about these polymorphisms in TNBC patients.

Materials and methods
In this study, we investigated the association between polymorphisms in AURKA or AURKB gene and prognosis of TNBC patients treated with taxane-based adjuvant chemotherapy. A total of 273 TNBC patients were enrolled. Haploview 4.2 software was used to identify Tag SNPs. Genotyping was conducted using the MassARRAY MALDI-TOF system.

Results
We found that AURKA rs6099128 GG genotype carriers had significantly worse overall survival (OS) than TT+ TG genotype carriers (P = 0.003, HR = 12.499, 95% CI = 2.357-66.298). AURKB rs11651993 TT genotype carriers had better disease-free survival (DFS) than TC + CC genotype carriers (P = 0.018, HR = 1.876, 95% CI = 1.116-3.154). AURKB rs2289590 CC genotype carriers had worse DFS than CA + AA genotype carriers (P = 0.021, HR = 0.536, 95% CI = 0.315-0.912). After subgroup analysis, rs11651993 TC + CC genotype predicted worse DFS in subgroups of age ≤ 50, post-menopausal, grade unknown (UK), tumor size >2 cm, and lymph node negative. Rs2289590 CA + AA genotype could predict favorable DFS in pre-menopausal, grade 3 and lymph node-positive patients.

Conclusion
We first demonstrated that polymorphisms in AURKA or AURKB gene might predict the OS or DFS of TNBC patients treated with taxane-based adjuvant chemotherapy.

Liao|Yuqian|Y| Liao|Yulu|Y| Li|Jun|J| Li|Junyu|J| Fan|Ying|Y| Xu|Binghe|B|

polymorphism
TNBC
Aurora kinase
prognosis


An Electrophysiological Dissociation of Encoding vs. Maintenance Failures in Visual-Spatial Working Memory.

Abstract: Working memory (WM) performance varies substantially among individuals but the precise contribution of different WM component processes to these functional limits remains unclear. By analyzing different types of responses in a spatial WM task, we recently demonstrated a functional dissociation between confident and not-confident errors reflecting failures of WM encoding and maintenance, respectively. Here, we use event-related brain potentials to further explore this dissociation. Healthy participants performed a delayed orientation-discrimination task and rated their response confidence for each trial. The encoding-related N2pc component was significantly reduced for confident errors compared to confident correct responses, which is indicative of an encoding failure. In contrast, the maintenance-related contra-lateral delay activity was similar for these response types indicating that in confident error trials, WM representations - potentially the wrong ones - were maintained accurately and with stability throughout the delay interval. However, contra-lateral delay activity measured during the early part of the delay period was decreased for not-confident errors, potentially reflecting compromised maintenance processes. These electrophysiological findings contribute to a refined understanding of the encoding and maintenance processes that contribute to limitations in WM performance and capacity.

Mayer|Jutta S|JS|
Korinth|Sebastian|S|
Peters|Benjamin|B|
Fiebach|Christian J|CJ|

encoding
maintenance
working memory
N2
contralateral delay activity
orientation


Household Coverage with Adequately Iodized Salt Varies Greatly between Countries and by Residence Type and Socioeconomic Status within Countries: Results from 10 National Coverage Surveys.

Abstract: Background: Household coverage with iodized salt was assessed in 10 countries that implemented Universal Salt Iodization (USI).Objective: The objective of this paper was to summarize household coverage data for iodized salt, including the relation between coverage and residence type and socioeconomic status (SES).Methods: A review was conducted of results from cross-sectional multistage household cluster surveys with the use of stratified probability proportional to size design in Bangladesh, Ethiopia, Ghana, India, Indonesia, Niger, the Philippines, Senegal, Tanzania, and Uganda. Salt iodine content was assessed with quantitative methods in all cases. The primary indicator of coverage was percentage of households that used adequately iodized salt, with an additional indicator for salt with some added iodine. Indicators of risk were SES and residence type. We used 95% CIs to determine significant differences in coverage.Results: National household coverage of adequately iodized salt varied from 6.2% in Niger to 97.0% in Uganda. For salt with some added iodine, coverage varied from 52.4% in the Philippines to 99.5% in Uganda. Coverage with adequately iodized salt was significantly higher in urban than in rural households in Bangladesh (68.9% compared with 44.3%, respectively), India (86.4% compared with 69.8%, respectively), Indonesia (59.3% compared with 51.4%, respectively), the Philippines (31.5% compared with 20.2%, respectively), Senegal (53.3% compared with 19.0%, respectively), and Tanzania (89.2% compared with 57.6%, respectively). In 7 of 8 countries with data, household coverage of adequately iodized salt was significantly higher in high- than in low-SES households in Bangladesh (58.8% compared with 39.7%, respectively), Ghana (36.2% compared with 21.5%, respectively), India (80.6% compared with 70.5%, respectively), Indonesia (59.9% compared with 45.6%, respectively), the Philippines (39.4% compared with 17.3%, respectively), Senegal (50.7% compared with 27.6%, respectively) and Tanzania (80.9% compared with 51.3%, respectively).Conclusions: Uganda has achieved USI. In other countries, access to iodized salt is inequitable. Quality control and regulatory enforcement of salt iodization remain challenging. Notable progress toward USI has been made in Ethiopia and India. Assessing progress toward USI only through household salt does not account for potentially iodized salt consumed through processed foods.

Knowles|Jacky M|JM|
Garrett|Greg S|GS|
Gorstein|Jonathan|J|
Kupka|Roland|R|
Situma|Ruth|R|
Yadav|Kapil|K|
Yusufali|Rizwan|R|
Pandav|Chandrakant|C|
Aaron|Grant J|GJ|
|||

coverage survey
salt iodization
iodine
USI
elimination of IDD
iodine deficiency
micronutrient


Clinical application values of neutrophil-to-lymphocyte ratio in intracranial aneurysms.

Abstract: Inflammation plays an important role in the pathogenesis and growth of intracranial aneurysms (IAs). We investigated the clinical value of the neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic subclinical inflammation in patients with IAs. Consecutive patients with IAs who underwent endovascular treatment (EVT) were enrolled in the study. The evaluation indicators were aneurysm size and rupture, a poor outcome at 3 to 6 months, and delayed cerebral ischemia (DCI) during hospitalization. In total, 532 patients with IAs underwent EVT (mean age, 54.0 years; 62.4% female). Among patients with ruptured IAs, those with a higher NLR had an increased risk of a poor outcome at 3 to 6 months and DCI during hospitalization than those with a lower NLR. A higher NLR was significantly more strongly associated with the size of unruptured aneurysms and aneurysm rupture than a lower NLR. The NLR and C-reactive protein concentration showed similar predictive ability for aneurysm size and treatment prognosis. The NLR was lower at discharge than admission for patients with ruptured IAs and DCI. An elevated NLR was significantly associated with the size of unruptured IAs, an increased risk of a poor outcome, and DCI in patients with ruptured IAs.

Zhang|Baorui|B| Lin|Lin|L| Yuan|Fei|F| Song|Guangrong|G| Chang|Qing|Q| Wu|Zhongxue|Z| Miao|Zhongrong|Z| Mo|Dapeng|D| Huo|Xiaochuan|X| Liu|Aihua|A|

neutrophil-to-lymphocyte ratio
aneurysm
inflammation
endovascular treatment


Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.

Abstract: Equine herpesvirus type 1 (EHV-1) continues to cause severe outbreaks of abortions or myeloencephalopathy in horses despite widely used vaccination. The aim of this work was to determine the effects of frequent vaccination with an inactivated EHV vaccine on immune development in horses. Fifteen EHV-1 naïve mares were vaccinated a total of 5 times over a period of 8 months with intervals of 20, 60, 90 and 60 days between vaccine administrations. Total antibody and antibody isotype responses were evaluated with a new sensitive EHV-1 Multiplex assay to glycoprotein C (gC) and gD for up to 14 months after initial vaccination. Antibodies peaked after the first two vaccine doses and then declined despite a third administration of the vaccine. The fourth vaccine dose was given at 6 months and the gC and gD antibody titers increased again. Mixed responses with increasing gC but decreasing gD antibody values were observed after the fifth vaccination at 8 months. IgG4/7 isotype responses mimicked the total Ig antibody production to vaccination most closely. Vaccination also induced short-lasting IgG1 antibodies to gC, but not to gD. EHV-1-specific cellular immunity induced by vaccination developed slower than antibodies, was dominated by IFN-γ producing T-helper 1 (Th1) cells, and was significantly increased compared to pre-vaccination values after administration of 3 vaccine doses. Decreased IFN-γ production and reduced Th1-cell induction were also observed after the second and fourth vaccination. Overall, repeated EHV vaccine administration did not always result in increasing immunity. The adverse effects on antibody and cellular immunity that were observed here when the EHV vaccine was given in short intervals might in part explain why EHV-1 outbreaks are observed worldwide despite widely used vaccination. The findings warrant further evaluation of immune responses to EHV vaccines to optimize vaccination protocols for different vaccines and horse groups at risk.

Wagner|B|B|
Goodman|L B|LB|
Babasyan|S|S|
Freer|H|H|
Torsteinsdóttir|S|S|
Svansson|V|V|
Björnsdóttir|S|S|
Perkins|G A|GA|

D000818:Animals
D000914:Antibodies, Viral
D000917:Antibody Formation
D018414:CD8-Positive T-Lymphocytes
D005260:Female
D006566:Herpesviridae Infections
D004861:Herpesvirus 1, Equid
D022283:Herpesvirus Vaccines
D006734:Horse Diseases
D006736:Horses
D007111:Immunity, Cellular
D007074:Immunoglobulin G
D007371:Interferon-gamma
D009500:Neutralization Tests
D011247:Pregnancy
D018417:Th1 Cells
D015164:Vaccines, Inactivated
D014759:Viral Envelope Proteins

Equine herpesvirus
Horse
Th1-cell
EHV Multiplex assay
IgG isotype
Interferon-gamma


The effects of individual cubicle research on the social interactions and individual behavior of brown capuchin monkeys (Sapajus apella).

Abstract: Primates are increasingly being tested individually in purpose-built research centers within zoos. The voluntary nature of research testing indicates that participation is enriching for the primate subjects, but previous studies have generally focused only on stress-related behavior, indicating that the research does not have a negative effect. Few data are available on the effects that individual research may have on social behavior, yet given primates' complex social lives and their responses to how conspecifics are treated, it is important to determine whether individual testing impacts upon their social interactions. The current study compared the social and individual behavior of 11 brown capuchin monkeys (Sapajus apella) between three conditions: (1) directly after undergoing individual testing, (2) a control, and (3) upon returning to the group having voluntarily left. The results indicate that individual and stress-related behaviors were affected very little by individual research testing and that social behaviors increased. However, although affiliative interactions were enhanced, aggressive interactions were also seen to increase in the condition following individual testing compared with the return to group condition. Suggestions for minimizing the negative interactions are given. Provided that these suggestions are taken into account by researchers, our results provide support for developing research centers within zoos given the important findings emerging on our closest living relatives, combined with the potentially positive effects the research has on their welfare.

social interactions
research testing
Cebus
human interactions


Evaluation of the clinical performance of single-, dual-, and triple-target SARS-CoV-2 RT-qPCR methods.

Abstract:
BACKGROUND
The coronavirus disease 2019 (COVID-19) has become a pandemic. Reverse transcription quantitative PCR (RT-qPCR) has played a vital role in the diagnosis of COVID-19, but the rates of false negatives is not ideal in dealing with this highly infectious virus. It is thus necessary to systematically evaluate the clinical performance of the single-, dual-, triple-target detection kits to guide the clinical diagnosis of this disease.

METHODS
A series of reference materials calibrated by droplet digital PCR (ddPCR) and 57 clinical samples were used to evaluate the clinical performance of six single-, dual-, triple-target SARS-CoV-2 nucleic acid detection kits based on RT-qPCR.

RESULTS
The dual-target kits, kit B and kit C had the highest and the lowest detection sensitivity, which was 125 copies/mL and 4000 copies/mL, respectively. Among the 57 clinical samples from patients with COVID-19, 47 were tested positive by the kit B, while 35, 29, 28, 30, and 29 were found positive by the kits A, C, D, E, and F, respectively. The number of targets in a detection kit is not a key factor affecting sensitivity, while the amount of sample loading may influence the performance of a detection kit.

CONCLUSIONS
This study provides a guide when choosing or developing a nucleic acid detection kit for the diagnosis of COVID-19. Also, the absolute-quantification feature and high-sensitivity performance of ddPCR, suggesting that it can be used to review clinically suspected samples.

Hu|Xiaomei|X|
Zhu|Lingxiang|L|
Luo|Yijun|Y|
Zhao|Qinfei|Q|
Tan|Chianru|C|
Chen|Xiao|X|
Zhang|Huijuan|H|
Hu|Xiaojun|X|
Lu|Linping|L|
Xiao|Yongwei|Y|
Huang|Shao|S|
He|Yingke|Y|
Sim|Jacqueline Xiu Ling|JXL|
Su|Shisheng|S|
Wang|Fang|F|
Peng|Yanke|Y|
Wang|Jigang|J|
Guo|Yong|Y|
Zhong|Tianyu|T|

D020133:Reverse Transcriptase Polymerase Chain Reaction

COVID-19
Reverse transcription quantitative PCR
Diagnosis
Detection kit
Digital PCR
Sensitivity


Proteome changes in the small intestinal mucosa of growing pigs with dietary supplementation of non-starch polysaccharide enzymes.

Abstract:
BACKGROUND
Non-starch polysaccharide enzymes (NSPEs) have long been used in monogastric animal feed production to degrade non-starch polysaccharides (NSPs) to oligosaccharides in order to promote growth performance and gastrointestinal (GI) tract health. However, the precise molecular mechanism of NSPEs in the improvement of the mammalian small intestine remains unknown.

METHODS
In this study, isobaric tags were applied to investigate alterations of the small intestinal mucosa proteome of growing pigs after 50 days of supplementation with 0.6% NSPEs (mixture of xylanase, β-glucanase and cellulose) in the diet. Bioinformatics analysis including gene ontology annotation was performed to determine the differentially expressed proteins. A protein fold-change of ≥ 1.2 and a P-value of < 0.05 were selected as thresholds.

RESULTS
Dietary supplementation of NSPEs improved the growth performance of growing pigs. Most importantly, a total of 90 proteins were found to be differentially abundant in the small intestinal mucosa between a control group and the NSPE group. Up-regulated proteins were related to nutrient metabolism (energy, lipids, protein and mineral), immunity, redox homeostasis, detoxification and the cell cytoskeleton. Down-regulated proteins were primarily related to transcriptional and translational regulation. Our results indicate that the effect of NSPEs on the increase of nutrient availability in the intestinal lumen facilitates the efficiency of nutrient absorption and utilization, and the supplementation of NSPEs in growing pigs also modulates redox homeostasis and enhances immune response during simulating energy metabolism due to a higher uptake of nutrients in the small intestine.

CONCLUSIONS
These findings have important implications for understanding the mechanisms of NSPEs on the small intestine of pigs, which provides new information for the better utilization of this feed additive in the future.

Zhang|Jize|J| Gao|Yang|Y| Lu|Qingping|Q| Sa|Renna|R| Zhang|Hongfu|H|

Proteomics
Small intestinal mucosa
Growing pigs
Non-starch polysaccharide enzymes


HCMV-controlling NKG2C+ NK cells originate from novel circulating inflammatory precursors.

Abstract:
BACKGROUND
There is limited knowledge on the origin and development from CD34+ precursors of the ample spectrum of human natural killer (NK) cells, particularly of specialized NK subsets.

OBJECTIVE
This study sought to characterize the NK-cell progeny of CD34+DNAM-1brightCXCR4+ and of other precursors circulating in the peripheral blood of patients with chronic viral infections (eg, HIV, hepatitis C virus, cytomegalovirus reactivation).

METHODS
Highly purified precursors were obtained by flow cytometric sorting and cultured in standard NK-cell differentiation media (ie, SCF, FLT3, IL-7, IL-15). Phenotypic and functional analyses on progenies were performed by multiparametric cytofluorimetric assays. Transcriptional signatures of NK-cell progenies were studied by microarray analysis. Inhibition of cytomegalovirus replication was studied by PCR.

RESULTS
Unlike conventional CD34+ precursors, Lin-CD34+DNAM-1brightCXCR4+ precursors from patients with chronic infection, rapidly differentiate into cytotoxic, IFN-γ-secreting CD94/NKG2C+KIR+CD57+ NK-cell progenies. An additional novel subset of common lymphocyte precursors was identified among Lin-CD34-CD56-CD16+ cells and characterized by expression of CXCR4 and lack of perforin and CD94. Lin-CD34-CD56-CD16+Perf-CD94-CXCR4+ precursors are also endowed with generation potential toward memory-like NKG2C+NK cells. Maturing NK-cell progenies mediated strong human cytomegalovirus-inhibiting activity. Microarray analysis confirmed a transcriptional signature compatible with NK-cell progenies and with maturing adaptive NK cells.

CONCLUSIONS
During viral infections, precursors of adaptive NK cells are released and circulate in the peripheral blood.

Bozzano|Federica|F|
Della Chiesa|Mariella|M|
Pelosi|Andrea|A|
Antonini|Francesca|F|
Ascierto|Maria Libera|ML|
Del Zotto|Genny|G|
Moretta|Francesca|F|
Muccio|Letizia|L|
Luganini|Anna|A|
Gribaudo|Giorgio|G|
Cenderello|Giovanni|G|
Dentone|Chiara|C|
Nicolini|Laura|L|
Moretta|Alessandro|A|
Moretta|Lorenzo|L|
De Maria|Andrea|A|

D055654:NK Cell Lectin-Like Receptor Subfamily C

viral infection
HIV
common lymphocyte precursors
HCMV
HCV
Lin(−)CD34(+)DNAM-1(bright)
NKG2C
Natural killer cells
hematopoietic stem cells


A split-face comparison of a fractional microneedle radiofrequency device and fractional radiofrequency therapy for moderate-to-severe acne vulgaris.

Abstract:
PURPOSE
Radiofrequency equipment, including invasive fractional microneedle radiofrequency (FMR) and noninvasive fractional radiofrequency (FR), has facilitated progress in the field of active acne treatment, but clinical data are limited. This study aimed to compare the efficacy and safety of FMR and FR in the treatment of moderate-to-severe acne vulgaris.

METHODS
Ten patients with moderate-to-severe acne were enrolled in a 24-week, prospective, single-blind, randomized, comparative clinical trial with a split-face design. Fractional microneedle radiofrequency treatment was provided on one side of the face and FR on the opposite side. Three consecutive treatments were performed at 4-week interval. Objective assessment of efficacy was performed using the Acne Severity Index (ASI), and acne inflammatory lesions and noninflammatory lesions were evaluated.

RESULTS
After the first treatment, ASI and both inflammatory and noninflammatory lesions of the FMR-treated side were improved to a greater degree than the FR-treated side. Patients' subjective satisfaction was also better regarding the FMR-treated side. After subsequent treatments, efficacy improves for both groups, and no significant differences in the above efficacy parameters between the two groups were observed. Pain scores were significantly higher for the FR-treated side than the FMR-treated side.

CONCLUSION
Fractional microneedle radiofrequency is faster and more effective than FR for the treatment of moderate and severe acne after only one treatment. However, after several treatment sessions, both FMR and FR proved to be safe and effective for long-term treatment of moderate-to-severe acne. Therefore, invasive radiofrequency, such as FMR, or noninvasive radiofrequency, such as FR, can successfully treat active acne.

D000152:Acne Vulgaris
D006801:Humans
D011446:Prospective Studies
D000078702:Radiofrequency Therapy
D016037:Single-Blind Method
D016896:Treatment Outcome

fractional microneedle radiofrequency
fractional radiofrequency
acne vulgaris
randomized controlled trial


Investigation of serotype distribution and resistance genes profile in group B Streptococcus isolated from pregnant women: a Chinese multicenter cohort study.

Abstract: We surveyed the group B Streptococcus (GBS) strains isolated from four teaching hospitals during 1-year period to investigate the current serotypes and antimicrobial resistance status of these strains. A total of 231 non-duplicate colonizing GBS isolates were collected from pregnant women. Antimicrobial susceptibility of these isolates was tested by the disk diffusion method. Serotype was performed by a multiplex polymerase chain reaction (PCR) method. Analysis of the resistance mechanisms was performed by PCR amplification and DNA sequencing. Seven serotypes (Ia, Ib, II, III, V, VI, and VIII) were identified, and the prevalence ranged from 0.9 to 35.9%. All isolates were susceptible to the penicillin, ceftriaxone, and vancomycin. The resistance of all the isolates to erythromycin, clindamycin, and levofloxacin was 61.5, 51.9, and 35.5%, respectively. The erythromycin resistance was mainly associated with the genes ermB and ermB-mef(A/E) (69.8%). The most predominant phenotype was cMLSB (77.5%). Five gene panels, including gyrA, parC, parE, gyrA-parC, and gyrA-parC-parE, were detected. The most predominant genotype was gyrA-parC-parE triple mutation (69.5%). The S81L in gyrA gene, S79Y mutation in parC gene, and H225Y mutation in parE gene were discovered. The isolates with serotype III, V, and Ia were the most important clone concerning the prevalence and resistance.

Yan|Yuzhong|Y| Hu|Hua|H| Lu|Tingyan|T| Fan|Huiqing|H| Hu|Yan|Y| Li|Gang|G| Zhang|Xianhua|X| Shi|Yi|Y| Xia|Rong|R|

D052978:Disk Diffusion Antimicrobial Tests

D060885:Multiplex Polymerase Chain Reaction

serotype
Group B Streptococcus
antimicrobial susceptibility
phenotype


Processing inferences at the semantics/pragmatics frontier: disjunctions and free choice.

Abstract: Linguistic inferences have traditionally been studied and categorized in several categories, such as entailments, implicatures or presuppositions. This typology is mostly based on traditional linguistic means, such as introspective judgments about phrases occurring in different constructions, in different conversational contexts. More recently, the processing properties of these inferences have also been studied (see, e.g., recent work showing that scalar implicatures is a costly phenomenon). Our focus is on free choice permission, a phenomenon by which conjunctive inferences are unexpectedly added to disjunctive sentences. For instance, a sentence such as "Mary is allowed to eat an ice-cream or a cake" is normally understood as granting permission both for eating an ice-cream and for eating a cake. We provide data from four processing studies, which show that, contrary to arguments coming from the theoretical literature, free choice inferences are different from scalar implicatures.

Processing
Inferences
Pragmatics
Free choice
Scalar implicatures


A review of the prognostic value of irrigation on root canal treatment success.

Abstract: The aim of this review is to discuss the requirements for effective irrigation of the root canal system and its role in treatment outcome. A review of the literature regarding irrigants, methods of irrigation and regimens was undertaken. It indicates that irrigation is comprised of a multitude of factors, and that effective irrigant delivery and agitation achieves mechanical, chemical and microbiological functions, which are prerequisites for obtaining a clean canal system. However, most studies are ex vivo and assess intermediate outcome values rather than treatment success. Additionally, there is an absence of high-level evidence evaluating the effect of irrigation on the outcome of root canal treatment. Therefore, citing irrigation as a significant factor that affects root canal treatment success cannot be done. This highlights the need to further investigate the prognostic value of irrigation on root canal treatment success.

D003786:Dental Pulp Cavity
D006801:Humans
D011379:Prognosis
D012388:Root Canal Irrigants
D018915:Root Canal Preparation
D007507:Therapeutic Irrigation
D016896:Treatment Outcome

irrigant
irrigant
root canal treatment
outcome
delivery
agitation
irrigation


Challenges in the management of people with heart failure with preserved ejection fraction (HFpEF) in primary care: A qualitative study of general practitioner perspectives.

Abstract:
OBJECTIVES
To explore the perspectives of general practitioners (GPs) on the identification and management of people, including those from ethnic minority groups, with Heart Failure with Preserved Ejection Fraction (HFpEF).

METHODS
Qualitative study. Semi-structured, face-to-face or telephone interviews and focus groups were conducted with 35 GPs in England, which were audio-recorded and transcribed verbatim. Framework analysis was used to manage and interpret data.

RESULTS
Themes presented reflect four inter-related challenges: GPs' 1) lack of understanding HFpEF, impacting on 2) difficulties in communicating the diagnosis, leading to 3) uncertainty in managing people with HFpEF, further hindered by (4) discontinuity across the primary/secondary interface. All were considered more challenging by GPs when managing people from different cultures and languages.

DISCUSSION
HFpEF is not well understood by GPs, leading to diagnostic difficulty, management uncertainty and potential inequity in care offered. People with HFpEF are seen as complex, with multiple long-term conditions and requiring personalised care. Challenges in their management occur across the healthcare system. This study has identified learning needs for GPs around identification and on-going support for people with HFpEF in primary care. It will contribute to the development of more flexible and patient-centred pathways across the primary/secondary care interface.

heart failure
HFpEF
primary care
General practitioners
qualitative methods


Phaeodactylum tricornutum microalgae as a rich source of omega-3 oil: Progress in lipid induction techniques towards industry adoption.

Abstract: Diatoms are a major group of high omega 3-fatty acid producing algae that play a key role in global climate change and ecosystem function. Phaeodactylum tricornutum is one of only two diatoms whose genomes have been completely sequenced, leading to metabolic engineering of high eicosapentaenoic acid producing strains. Based on its rapid growth, high lipid content, and especially omega-3 long chain unsaturated fatty acids, P. tricornutum exhibits a large commercial potential. However, until now, it is predominately produced as feed for the aquaculture industry, rather than food supplement. This review compares the change of P. tricornutum lipid composition under different treatments, and identifies suitable lipid induction, cultivation and harvesting methods for industry adoption. If produced in a biorefinery setting, P. tricornutum has strong potential for value generation from human health products (omega-3-rich oil and high-value protein) with cost estimates of AU$6.14 per kg dry weight and AU$20.47 for omega-3-rich oil.

Cui|Yi|Y|
Thomas-Hall|Skye R|SR|
Schenk|Peer M|PM|

D002245:Carbon Dioxide
D017377:Diatoms
D015118:Eicosapentaenoic Acid
D015525:Fatty Acids, Omega-3
D019649:Food Industry
D006863:Hydrogen-Ion Concentration
D008055:Lipids

Docosahexaenoic Acid (PubChem CID: 445580)

eicosapentaenoic acid (PubChem CID: 446284)


The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or Endothelial, Is Impaired in Rats with Adjuvant-Induced Arthritis. Connection with Endothelial Dysfunction.

Abstract: Cognitive abilities are largely dependent on activation of cerebral tropomyosin-related kinase B receptors (TrkB) by brain-derived neurotrophic factor (BDNF) that is secreted under a bioactive form by both neurons and endothelial cells. In addition, there is mounting evidence for a link between endothelial function and cognition even though the underlying mechanisms are not well known. Therefore, we investigated the cerebral BDNF pathway, either neuronal or endothelial, in rheumatoid arthritis (RA) that combines both endothelial dysfunction (ED) and impaired cognition. Adjuvant-induced arthritis (AIA) in rats was used as a model of RA. Clinical inflammatory symptoms were evaluated from an arthritis score and brains were collected at day 31 ± 2 post-immunization. Neuronal expression of BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was examined in brain slices. Endothelial BDNF and p-TrkB expression was examined on both brain slices (hippocampal arterioles) and isolated cerebral microvessels-enriched fractions (vessels downstream to arterioles). The connection between endothelial nitric oxide (NO) and BDNF production was explored on the cerebrovascular fractions using endothelial NO synthase (eNOS) levels as a marker of NO production, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) as a NOS inhibitor and glyceryl-trinitrate as a slow releasing NO donor. Brain slices displayed lower BDNF and p-TrkB staining in both neurons and arteriolar endothelial cells in AIA than in control rats. For endothelial cells but not neurons, a strong correlation was observed between BDNF and p-TrkB staining. Of note, a strong correlation was also observed between neuronal p-TrkB and endothelial BDNF staining. In cerebral microvessels-enriched fractions, AIA led to decreased BDNF and eNOS levels with a positive association between the 2 parameters. These effects coincided with decreased BDNF and p-TrkB staining in endothelial cells. The exposure of AIA cerebrovascular fractions to GTN increased BDNF levels while the exposure of control fractions to L-NAME decreased BDNF levels. Changes in the cerebral BDNF pathway were not associated with arthritis score. The present study reveals that AIA impairs the endothelial and neuronal BDNF/TrkB pathway, irrespective of the severity of inflammatory symptoms but dependent on endothelial NO production. These results open new perspectives for the understanding of the link between ED and impaired cognition.

Pedard|Martin|M| Quirié|Aurore|A| Garnier|Philippe|P| Tessier|Anne|A| Demougeot|Céline|C| Marie|Christine|C|


In search of compassion: a new taxonomy of compassionate physician behaviours.

Abstract:
BACKGROUND
Compassion has been extolled as a virtue in the physician-patient relationship as a response to patient suffering. However, there are few studies that systematically document the behavioural features of physician compassion and the ways in which physicians communicate compassion to patients.

OBJECTIVE
To develop a taxonomy of compassionate behaviours and statements expressed by the physician that can be discerned by an outside observer.

DESIGN
Qualitative analysis of audio-recorded office visits between oncologists and patients with advanced cancer.

SETTING AND PARTICIPANTS
Oncologists (n = 23) and their patients with advanced cancer (n = 49) were recruited in the greater Rochester, New York, area. The physicians and patients were surveyed and had office visits audio recorded.

MAIN OUTCOME MEASURES
Audio recordings were listened to for qualitative assessment of communication skills.

RESULTS
Our sensitizing framework was oriented around three elements of compassion: recognition of the patient's suffering, emotional resonance and movement towards addressing suffering. Statements of compassion included direct statements, paralinguistic expressions and performative comments. Compassion frequently unfolded over the course of a conversation rather than being a single discrete event. Additionally, non-verbal linguistic elements (e.g. silence) were frequently employed to communicate emotional resonance.

DISCUSSION AND CONCLUSIONS
This study is the first to systematically catalogue instances of compassionate communication in physician-patient dialogues. Further refinement and validation of this preliminary taxonomy can guide future education and training interventions to facilitate compassion in physician-patient interactions.

Cameron|Rachel A|RA|
Mazer|Benjamin L|BL|
DeLuca|Jane M|JM|
Mohile|Supriya G|SG|
Epstein|Ronald M|RM|

compassion
patient suffering
communication
oncology


Mechanisms of Defect Generation and Clustering in CH3S Self-Assembled Monolayers on Au(111).

Abstract: Periodic density functional calculations probe that step edges play a key role as source of defects during self-assembly. It is shown that the self-assembly process strongly reduces the energy required to strip an atom from the gold surface, locally increasing the concentration of surface defects. The thermodynamic driving force for the atom stripping is considerably more favorable along step-edge lines within the self-assembly than on the higher-coordinated terrace sites. Furthermore, the clustering of surface defects is considered, and we probe that the formation of aggregates of vacancies in the form of vacancy pits significantly stabilizes the self-assembly on the terraces of gold, where the role of the step edges is expected to be less significant. The high stability of pit-like structures arises from a balance between the corrugation and the enhanced bonding of defect-rich substrates. Our results demonstrate the important role that step edges play during assembly and could be very valuable for discovering defect-free assembled structures.

Carro|P|P|
Torres|D|D|
Diaz|R|R|
Salvarezza|R C|RC|
Illas|F|F|

density functional
step edge
surface defects
terrace
vacancy pit


Auditory feedback in error-based learning of motor regularity.

Abstract: Music and speech are skills that require high temporal precision of motor output. A key question is how humans achieve this timing precision given the poor temporal resolution of somatosensory feedback, which is classically considered to drive motor learning. We hypothesise that auditory feedback critically contributes to learn timing, and that, similarly to visuo-spatial learning models, learning proceeds by correcting a proportion of perceived timing errors. Thirty-six participants learned to tap a sequence regularly in time. For participants in the synchronous-sound group, a tone was presented simultaneously with every keystroke. For the jittered-sound group, the tone was presented after a random delay of 10-190 ms following the keystroke, thus degrading the temporal information that the sound provided about the movement. For the mute group, no keystroke-triggered sound was presented. In line with the model predictions, participants in the synchronous-sound group were able to improve tapping regularity, whereas the jittered-sound and mute group were not. The improved tapping regularity of the synchronous-sound group also transferred to a novel sequence and was maintained when sound was subsequently removed. The present findings provide evidence that humans engage in auditory feedback error-based learning to improve movement quality (here reduce variability in sequence tapping). We thus elucidate the mechanism by which high temporal precision of movement can be achieved through sound in a way that may not be possible with less temporally precise somatosensory modalities. Furthermore, the finding that sound-supported learning generalises to novel sequences suggests potential rehabilitation applications.

van Vugt|Floris T|FT|
Tillmann|Barbara|B|

Auditory feedback
Music
Timing
Motor learning
Feedback error-based learning
Action–perception coupling
Movement variability


Mesenchymal Stem Cells Derived from Human Inflamed Dental Pulp Exhibit Impaired Immunomodulatory Capacity In Vitro.

Abstract:
INTRODUCTION
Dental pulp stem cells (DPSC) are very attractive in regenerative medicine. In this study, we focused on the characterization of the functional properties of mesenchymal stem cells derived from DPSCs. Currently, it is unknown whether inflammatory conditions present in an inflamed dental pulp tissue could alter the immunomodulatory properties of DPSCs. This study aimed to evaluate the immunomodulatory capacity in vitro of DPSCs derived from healthy and inflamed dental pulp.

METHODS
DPSCs from 10 healthy and inflamed dental pulps (irreversible pulpitis) were characterized according to the minimal criteria of the International Society for Cell Therapy, proliferation, differential potential, and colony-forming units. Furthermore, the immunomodulatory capacity of DPSCs was tested on the proliferation of T lymphocytes by flow cytometry and the in vitro enzyme activity of indoleamine 2, 3-dioxygenase.

RESULTS
There were no significant differences in the DPSC characteristics and properties such as immunophenotype, tridifferentiation, colony-forming units, and proliferation of the DPSCs derived from normal and inflamed pulp tissue. Furthermore, there were significant differences in the immunomodulatory capacity of DPSCs obtained from human healthy dental pulp and with the diagnosis of irreversible pulpitis.

CONCLUSIONS
Our results showed that DPSCs isolated from inflamed dental pulp showed typical characteristics of MSCs and diminished immunosuppressive capacity in vitro in comparison with MSCs derived from healthy dental pulp. Further investigation in vivo is needed to clarify the mechanism of this diminished immunosuppressive capacity.

Inostroza|Carolina|C|
Vega-Letter|Ana María|AM|
Brizuela|Claudia|C|
Castrillón|Luis|L|
Saint Jean|Nicole|N|
Duran|Carol Mira|CM|
Carrión|Flavio|F|

D002454:Cell Differentiation
D049109:Cell Proliferation
D002478:Cells, Cultured
D003782:Dental Pulp
D006801:Humans
D059630:Mesenchymal Stem Cells

mesenchymal stem cells
inflamed dental pulp
pulpitis
Healthy dental pulp


CORTICAL FOLDINGPRINTS FOR INFANT IDENTIFICATION.

Abstract: Cortical folding of the adult brain is highly convoluted and encodes inter-subject variable characteristics. Recent studies suggest that it is useful for individual identification in adults. However, little is known about whether the infant cortical folding, which undergoes dynamic postnatal development, can be used for individual identification. To fill this gap, we propose to explore cortical folding patterns for infant subject identification. This study thus aims to address two important questions in neuroscience: 1) whether the infant cortical folding is unique for individual identification; and 2) considering the region-specific inter-subject variability, which cortical regions are more distinct and reliable for infant identification. To this end, we propose a novel discriminative descriptor of regional cortical folding based on multi-scale analysis of curvature maps via spherical wavelets, called FoldingPrint. Experiments are carried out on a large longitudinal dataset with 1,141 MRI scans from 472 infants. Despite the dramatic development in the first two years, successful identification of 1-year-olds and 2-year-olds using their neonatal cortical folding (with accuracy > 98%) indicates the effectiveness of the proposed method. Moreover, we reveal that regions with high identification accuracy and large inter-subject variability mainly distribute in high-order association cortices.

Duan|Dingna|D|
Xia|Shunren|S|
Wu|Zhengwang|Z|
Wang|Fan|F|
Wang|Li|L|
Lin|Weili|W|
Gilmore|John H|JH|
Shen|Dinggang|D|
Li|Gang|G|

infant
cortical folding
individual identification
multi-scale curvatures


Prenatal diet and children's trajectories of hyperactivity-inattention and conduct problems from 3 to 8 years: the EDEN mother-child cohort.

Abstract:
BACKGROUND
Evidence shows that diet contributes substantially to lifelong physical and mental health. Although dietary exposure during gestation and early postnatal life is critical, human epidemiological data are limited regarding its link with children's subsequent externalizing issues. The aim of this study was to investigate the role of maternal diet during pregnancy in offspring's symptoms of hyperactivity-inattention and conduct problems from ages 3 to 8 years.

METHODS
We used data of 1,242 mother-child pairs from a French cohort followed up from pregnancy until the children were 8 years of age. Dietary patterns (DP) of the mother during pregnancy were assessed with food frequency questionnaires. Children's externalizing behavior was assessed with the Strength and Difficulties Questionnaire at ages 3, 5, and 8 years, from which trajectories of hyperactivity-inattention symptoms and conduct problems were derived. We conducted multivariable logistic models to study associations adjusted for a range of potential confounders.

RESULTS
Results showed significant relationships between maternal 'low Healthy diet' (adjusted Odds Ratio (aOR) = 1.61; IC 95%: 1.09-2.37) and 'high Western diet' (aOR = 1.67; IC 95%: 1.13-2.47) during pregnancy and children's trajectories of high symptoms of hyperactivity-inattention. The associations took into account relevant confounders such as DP of the children at age 2 years, maternal stress and depression, gestational diabetes, and socioeconomic variables.

CONCLUSIONS
Maternal diet during pregnancy was independently associated with children's hyperactivity-inattention symptoms but not with conduct problems. Early prevention addressing lifestyle should specifically target diet in pregnant women.

Galera|Cédric|C|
Heude|Barbara|B|
Forhan|Anne|A|
Bernard|Jonathan Y|JY|
Peyre|Hugo|H|
Van der Waerden|Judith|J|
Pryor|Laura|L|
Bouvard|Manuel-Pierre|MP|
Melchior|Maria|M|
Lioret|Sandrine|S|
de Lauzon-Guillain|Blandine|B|
|||

D001289:Attention Deficit Disorder with Hyperactivity

D011297:Prenatal Exposure Delayed Effects

attention deficit hyperactivity disorder


The effect of Calendula officinalis versus metronidazole on bacterial vaginosis in women: A double-blind randomized controlled trial.

Abstract: Bacterial vaginosis (BV) is a common disorder among women of reproductive age. This study aimed to compare the effect of a Calendula officinalis extract-based cream and metronidazole on BV among women of reproductive age. In this study, 80 women of reproductive age with BV were randomly assigned to the C. officinalis (n = 40) or metronidazole (n = 40). Diagnosis of BV was confirmed when at least 3 of the 4 Amsel criteria were met (pH >4.5, whitish grey or thin homogeneous discharge, release of a fishy odor on adding 10% KOH, and detection of clue cells on microscopic examination). For each group, either a methanol extract of C. officinalis or metronidazole vaginal cream (5 g) was used for 1 week intravaginally, and all signs and symptoms were assessed 1 week after treatment completion. Before the intervention, the two groups did not differ significantly with regard to vaginal burning, odor, dysuria, and dyspareunia, but itching was significantly more common in the C. officinalis group than in the metronidazole group (22.5% vs. 2.5%, P = 0.01). One week after the intervention, all women in both groups were free of symptoms, including vaginal itching and burning sensation, odor, dysuria, and dyspareunia. None of the women in either group suffered any side effects from C. officinalis or metronidazole. C. officinalis was effective for the treatment of BV in women of reproductive age, without any side effects. This herb could be recommended for women of reproductive age who uncomfortable with the potential side effects of synthetic drugs.

Pazhohideh|Zahra|Z| Mohammadi|Solmaz|S| Bahrami|Nosrat|N| Mojab|Faraz|F| Abedi|Parvin|P| Maraghi|Elham|E|

Calendula officinalis
metronidazole
Bacterial
vaginitis


Competency of groundwater recharge of irrigated cotton field subjacent to sowing methods, plastic mulch, water productivity, and yield under climate change.

Abstract: Irrigated agriculture is a foremost consumer of water resources to fulfill the demand for food and fiber with an increasing population under climate changes; cotton is no exception. Depleting groundwater recharge and water productivity is critical for the sustainable cotton crop yield peculiarly in the semiarid region. This study investigated the water productivity and cotton yield under six different treatments: three sowing methods, i.e., flat, ridge, and bed planting with and without plastic mulch. Cotton bed planting without mulch showed maximum water productivity (0.24 kg.m-3) and the highest cotton yield (1946 kg.ha-1). Plastic mulching may reduce water productivity and cotton yield. HYDRUS-1D unsaturated flow model was used to access the groundwater recharge for 150 days under six treatments after model performance evaluation. Maximum cumulative recharge was observed 71 cm for the flat sowing method without plastic mulch. CanESM2 was used to predict climate scenarios for RCP 2.6, 4.5, and 8.5 for the 2050s and 2080s by statistical downscale modeling (SDSM) using historical data from 1975 to 2005 to access future groundwater recharge flux. Average cumulative recharge flux declined 36.53% in 2050 and 22.91% in 2080 compared to 2017 without plastic mulch. Multivariate regression analysis revealed that a maximum 23.78% reduction in groundwater recharge could influence future climate change. Further study may require to understand the remaining influencing factor of depleting groundwater recharge. Findings highlight the significance of climate change and the cotton sowing method while accessing future groundwater resources in irrigated agriculture.

Groundwater
Cotton
Climate change
HYDRUS-1D
Recharge flux


Utilization and Expenditures of Vertebral Augmentation Continue to Decline: An Analysis in Fee-For-Service (FFS) Recipients from 2009 to 2018.

Abstract:
BACKGROUND
Despite the high prevalence of vertebral compression fractures (VCFs) associated with refractory pain, deformity, or progressive neurological symptoms, minimally invasive vertebral augmentation procedures, including vertebroplasty and kyphoplasty, have been declining in their relative utilization, along with expenditures.

OBJECTIVES
This investigation was undertaken to assess utilization and expenditures for vertebral augmentation procedures, including vertebroplasty and kyphoplasty, in the fee-for-service (FFS) Medicare population from 2009 to 2018.

STUDY DESIGN
The present study was designed to assess utilization and expenditures in all settings, for all providers in the FFS Medicare population from 2009 to 2018 in the United States. In this manuscript:• A patient was described as receiving vertebral augmentation over the course of the year.• An episode was considered as one treatment per region per day utilizing primary codes only. • Services or procedures were considered to be procedures including multiple levels.A standard 5% national sample of the Centers for Medicare and Medicaid Services (CMS) physician outpatient billing claims data for those enrolled in the FFS Medicare program from 2009 to 2018 was utilized. All the expenditures were presented with allowed costs and adjusted for inflation to 2018 US dollars.

RESULTS
In 2009, there were 76,860 episodes of vertebral augmentation with a rate of 168 per 100,000 Medicare population, which declined to 58,760, or 99 per 100,000 population for a total decline of 41%, or an annual rate of decline of 5.7% per 100,000 Medicare population. Vertebroplasty interventions declined more dramatically than kyphoplasty from 2009. Total episodes of vertebroplasty were 27,380 with an annual rate of 60 per 100,000 Medicare population, decreasing to 9,240, or 16 per 100,000 Medicare population, a 66% decline in episodes and a 74% decline in overall rate with an annual decline of 11.4% and 13.9%. In contrast, kyphoplasty interventions were 49,480, for a rate per 100,000 population of 108 in 2009 compared to 49,520 in 2018 with a rate of 83, for a decrease of 23% and 2.9% annual decrease. Evaluation of expenditures showed a net decrease of $30,102,809, or 8%, from $378,758,311 in 2009 to $348,655,502 in 2018. However, inflation-adjusted expenditures decreased overall by 21% and 3% annually from $443,147,324 in 2009 to $345,655,502 in 2018. In addition, inflation-adjusted total expenditures per 100,000 Medicare population decreased from $967,549 to $584,992, for an overall decrease of 40%, or an annual decrease of 5%. Per patient expenditures decreased 2% overall with 0% decrease per year.

LIMITATIONS
Vertebral augmentation procedures were assessed only in the FFS Medicare service population. This excluded over 30% of the Medicare population, which is enrolled in Medicare Advantage plans.

CONCLUSIONS
This study shows a significant decline in relative utilization patterns of vertebroplasty and kyphoplasty procedures, along with reductions in overall expenditures. The inflation-adjusted total expenditures of kyphoplasty and vertebroplasty decreased 21% with an annual decline of 3%. The inflation-adjusted expenditures per 100,000 of Medicare population decreased 40% overall and 5% per year. In addition, vertebroplasty has seen substantial declines in utilization and expenditure patterns compared to kyphoplasty procedures, which showed trends of decline.

Manchikanti|Laxmaiah|L|
Senapathi|Sri Harsha Vardhan|SHV|
Milburn|James M|JM|
Brook|Allan L|AL|
Vangala|Brahma Prasad|BP|
Pampati|Vidyasagar|V|
Sanapati|Mahendra R|MR|
Hirsch|Joshua A|JA|

utilization
expenditures
vertebral augmentation
vertebroplasty
kyphoplasty
inflation-adjusted
osteoporotic compression fracture
Osteoporosis


Ranking of Dystonia Severity by Pairwise Video Comparison.

Abstract:
Background
Reviewers of dystonia rating scales agree on the need to assess symptoms more comprehensively. During the development of a quantitative dystonia assessment by video-perceptive computing, we devised a video-based severity ranking as a procedure to create a validation standard without the use of clinical scales.

Methods
Thirty-four patients with dystonia (17 with dystonic tremor) and 2 controls were assessed with clinical scales and video-recordings of 24 short movement tasks. Two to 4 raters compared multiple permutations of videos from 22 subjects, including 2 healthy controls, until a complete rank order was achieved. Inter-rater agreement was expressed as normalized Kendall tau distance. Spearman correlations of video rank order with clinical scales and self-rating were repeated for tremor/nontremor subgroups.

Results
Normalized Kendall tau distances were <0.3 for 15 items. The video rank order for sitting and head movements correlated with clinical scales for the whole group (rho 0.52-0.87) and in the subgroup without tremor. In the tremor subgroup such correlation was perceived in the 2 items involving sitting. Video rank order correlated with quality of life self-rating only in 1 item (arms held in front, palm down).

Conclusions
The agreement of video rankings between raters is remarkable. The lack of correlation in the tremor subgroup in several items may be interpreted as tremor being considered in video comparisons but not in clinical scales. This supports video-based ranking as a more comprehensive rating of dystonia and as a possible validation instrument applicable in situations in which no reference standard is available.

Ellermeyer|Tobias|T|
Otte|Karen|K|
Heinrich|Felix|F|
Mansow-Model|Sebastian|S|
Kayser|Bastian|B|
Lipp|Axel|A|
Seidel|Adrian|A|
Krause|Patricia|P|
Lauritsch|Katharina|K|
Gusho|Elona|E|
Paul|Friedemann|F|
Kühn|Andrea A|AA|
Brandt|Alexander U|AU|
Schmitz-Hübsch|Tanja|T|

dystonia
quantitative assessment
validation tool


Paraneoplastic Syndrome Presenting with Polymyalgia Rheumatica-like Accumulations on 18F-fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography.

Abstract: A 70-year-old woman presented with a fever and pain in both lower extremities and the right shoulder and right upper arm continuously for approximately 3 months. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG/PET-CT) revealed the accumulation of FDG in the right shoulder, lumbar spinous processes, both ischial tuberosities, and both hips and greater trochanters, indicating polymyalgia rheumatica (PMR). In addition, upper gastrointestinal endoscopy revealed esophageal carcinoma. After endoscopic submucosal dissection was performed, her musculoskeletal symptoms spontaneously improved, and the 18F-FDG/PET-CT findings decreased. In light of these findings, she was diagnosed with paraneoplastic syndrome. When atypical features of PMR, such as asymmetric symptoms occur, we should search for malignancies.

Umetsu|Ayaka|A| Shimizu|Toshimasa|T| Iwamoto|Naoki|N| Hashiguchi|Keiichi|K| Eguchi|Mizuna|M| Okamoto|Momoko|M| Endo|Yushiro|Y| Tsuji|Sosuke|S| Takatani|Ayuko|A| Igawa|Takashi|T| Sumiyoshi|Remi|R| Koga|Tomohiro|T| Kawashiri|Shin-Ya|SY| Ichinose|Kunihiro|K| Tamai|Mami|M| Nakamura|Hideki|H| Origuchi|Tomoki|T| Kawakami|Atsushi|A|

D000072078:Positron Emission Tomography Computed Tomography

paraneoplastic syndrome
18F-FDG/PET-CT
polymyalgia rheumatica


Stearoyl lysophosphatidylcholine enhances the phagocytic ability of macrophages through the AMP-activated protein kinase/p38 mitogen activated protein kinase pathway.

Abstract: A previous study showed that stearoyl lysophosphatidylcholine (sLPC) suppressed extracellular high mobility group box 1 translocation in macrophages stimulated with lipopolysaccharide through AMP-activated protein kinase (AMPK) activation. In the present study, we investigated whether sLPC-induced AMPK activation could enhance macrophages phagocytosis of bacteria. We found that sLPC increased phosphorylation of AMPK and acetyl-CoA carboxylase, a downstream target of AMPK, in a time- and dose-dependent manner in macrophages. Furthermore, sLPC increased the uptake of FITC-conjugated Escherichia coli by macrophages in a dose-dependent manner, and treatment with an AMPK inhibitor (compound C) or siRNA to AMPKα1 reversed this uptake. sLPC increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), but inhibition of AMPK activity with compound C or siRNA to AMPKα1 prevented the sLPC-induced increase in p38 MAPK phosphorylation. SB203580, a p38 MAPK inhibitor, decreased sLPC-induced phagocytosis. In vivo, systemic administration of sLPC to mice led to increased AMPK and p38 MAPK activity in the lung and to increased phagocytosis of fluorescent E. coli in bronchoalveolar lavage cells. These results suggest that sLPC increases macrophages phagocytosis through activation of the AMPK/p38 MAPK pathway. Therefore, sLPC is a candidate pharmacological agent for the treatment of bacterial infections in clinically relevant conditions.

Quan|Hui|H| Hur|Young-Hoe|YH| Xin|Chun|C| Kim|Joung-Min|JM| Choi|Jeong-Il|JI| Kim|Man-Young|MY| Bae|Hong-Beom|HB|

D048051:p38 Mitogen-Activated Protein Kinases

Stearoyl lysophosphatidylcholine
Macrophage
AMP-activated protein kinase
Phagocytosis
p38 mitogen-activated protein kinase


Using Mobile Technology (pMOTAR) to Assess Reactogenicity: Protocol for a Pilot Randomized Controlled Trial.

Abstract:
BACKGROUND
Accurate safety monitoring in HIV vaccine trials is vital to eventual licensure and consequent uptake of products. Current practice in preventive vaccine trials, under the HIV Vaccine Trials Network (HVTN), is to capture related side effects in a hardcopy tool. The reconciliation of this tool, 2 weeks after vaccination at the safety visit, is time consuming, laborious, and fraught with error. Unstructured Supplementary Service Data (USSD), commonly used to purchase airtime, has been suggested for collection of safety data in vaccine trials. With saturated access to mobile phones in South Africa, this cheap, accessible tool may improve accuracy and completeness of collected data and prove feasible and acceptable over the hardcopy tool.

OBJECTIVE
The objective of our study is to develop and implement a USSD tool for real-time safety data collection that is feasible and acceptable to participants and staff, allowing for a comparison with the hardcopy tool in terms of completeness and accuracy.

METHODS
This feasibility study is being conducted at a single study site, the Centre for the AIDS Programme of Research in South Africa eThekwini Clinical Research site, in South Africa. The feasibility study is nested within a parent phase 1/2a preventive HIV vaccine trial (HVTN 108) as an open-label, randomized controlled trial, open to all consenting parent trial participants. Participants are randomly assigned in a 1:1 ratio to the hardcopy or USSD tool, with data collection targeted to the third and fourth injection time points in the parent trial. Online feasibility and acceptability surveys will be completed by staff and participants at the safety visit. We will itemize and compare error rates between the hardcopy tool and the USSD printout and associated source documentation. We hypothesize that the USSD tool will be shown to be feasible and acceptable to staff and participants and to have superior quality and completion rates to the hardcopy tool.

RESULTS
The study has received regulatory approval. We have designed and developed the USSD tool to include all the data fields required for reactogenicity reporting. Online feasibility and accessibility surveys in both English and isiZulu have been successfully installed on a tablet. Data collection is complete, but analysis is pending.

CONCLUSIONS
Several HIV preventive vaccine trials are active in Southern Africa, making tools to improve efficiencies and minimize error necessary. Our results will help to determine whether the USSD tool can be used in future vaccine studies and can eventually be rolled out.

TRIAL REGISTRATION
ClincalTrials.gov NCT02915016; https://clinicaltrials.gov/ct2/show/NCT02915016 (Archived by WebCite at http://www.webcitation.org/71h0cztDM).

REGISTERED REPORT IDENTIFIER
RR1-10.2196/9396.

HIV preventive vaccines
AIDS vaccines
mobile applications
mobile health application
research protocol
telemedicine


Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom, and Notch signaling.

Abstract: The zebrafish pronephros provides a conserved model to study kidney development, in particular to delineate the poorly understood processes of how nephron segment pattern and cell type choice are established. Zebrafish nephrons are divided into distinct epithelial regions that include a series of proximal and distal tubule segments, which are comprised of intercalated transporting epithelial cells and multiciliated cells (MCC). Previous studies have shown that retinoic acid (RA) regionalizes the renal progenitor field into proximal and distal domains and that Notch signaling later represses MCC differentiation, but further understanding of these pathways has remained unknown. The transcription factor mecom (mds1/evi1 complex) is broadly expressed in renal progenitors, and then subsequently marks the distal tubule. Here, we show that mecom is necessary to form the distal tubule and to restrict both proximal tubule formation and MCC fate choice. We found that mecom and RA have opposing roles in patterning discrete proximal and distal segments. Further, we discovered that RA is required for MCC formation, and that one mechanism by which RA promotes MCC fate choice is to inhibit mecom. Next, we determined the epistatic relationship between mecom and Notch signaling, which limits MCC fate choice by lateral inhibition. Abrogation of Notch signaling with the γ-secretase inhibitor DAPT revealed that Notch and mecom did not have additive effects in blocking MCC formation, suggesting that they function in the same pathway. Ectopic expression of the Notch signaling effector, Notch intracellular domain (NICD), rescued the expansion of MCCs in mecom morphants, indicating that mecom acts upstream to induce Notch signaling. These findings suggest a model in which mecom and RA arbitrate proximodistal segment domains, while MCC fate is modulated by a complex interplay in which RA inhibition of mecom, and mecom promotion of Notch, titrates MCC number. Taken together, our studies have revealed several essential and novel mechanisms that control pronephros development in the zebrafish.

Li|Yue|Y|
Cheng|Christina N|CN|
Verdun|Valerie A|VA|
Wingert|Rebecca A|RA|

D018507:Gene Expression Regulation, Developmental

D000074008:MDS1 and EVI1 Complex Locus Protein

Nephrogenesis
Retinoic acid
Retinoic acid
mecom
Notch
Pronephros
Segmentation
multiciliated cell
MCC
RA
mds1/evi1 complex
Notch intracellular domain
NICD
4-diethylamino-benzaldehyde
CS
DE
DEAB
DL
G
IM
MET
N
PCT
PD
PM
PST
RARE
corpuscle of Stannius
days post-fertilization
distal early
distal late
dpf
glomerulus
hours post-fertilization
hpf
intermediate mesoderm
mesenchymal to epithelial transition
neck
paraxial mesoderm
pronephric duct
proximal convoluted tubule
proximal straight tubule
retinoic acid
retinoic acid response element

P P P P P P P P P P P P P U U U U U U U U U U U U U U M U M M U U U U U M U U U M M P M


In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

Abstract: The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease.

Pessetto|Ziyan Y|ZY|
Chen|Bin|B|
Alturkmani|Hani|H|
Hyter|Stephen|S|
Flynn|Colleen A|CA|
Baltezor|Michael|M|
Ma|Yan|Y|
Rosenthal|Howard G|HG|
Neville|Kathleen A|KA|
Weir|Scott J|SJ|
Butte|Atul J|AJ|
Godwin|Andrew K|AK|

D000971:Antineoplastic Combined Chemotherapy Protocols

D004354:Drug Screening Assays, Antitumor

D015972:Gene Expression Regulation, Neoplastic

Ewing sarcoma
auranofin
ganetespib
drug repurposing
high-throughput screening


Determination of trace elements, heavy metals, and antimony in polyethylene terephthalate-bottled local raw cow milk of Iğdır region in Turkey.

Abstract: The presence of several trace elements, heavy metals, and antimony in polyethylene terephthalate-bottled local raw cow milk samples of Iğdır region in Turkey was investigated. The milk samples were analyzed by inductively coupled plasma mass spectrometry after microwave-assisted digestion. Milk samples were categorized into three groups according to the element level intensity in the sample. While 70% of samples showed 2.5 times the maximum Turkish and European permissible level of lead, the lowest lead-contaminated sample exhibited 1.25 times this level. All the examined samples exceeded the maximum permissible limit administrated for arsenic and 35% of samples exhibited 5 times this limit. Results showed 40% of samples contain an antimony level higher than the Turkish maximum allowable concentration. The high antimony content of raw milk samples may be related to the release of antimony from the PET (polyethylene terephthalate) bottles. This study showed high contamination levels of the most toxic trace elements, i.e., lead and arsenic in milk and possible antimony contamination from PET bottles which may cause many health hazards for the consumers.

Trace element
Heavy metal
Antimony
Raw cow milk
PET bottle


Skin Toxicities During Colorectal Cancer Chemotherapy: Incidence and Pearls of Treatment in Our Experience.

Abstract:
INTRODUCTION
Medical treatment of advanced colorectal cancer is effective in prolonging the survival of patients. The aim of this study was to describe the most common skin toxicities that occur in those patients, analyzing the association between the type of reaction and the different chemotherapeutic drugs; and to evaluate the importance of an outpatient dermatologic service to improve quality of life.

PATIENTS AND METHODS
Seventy-two patients with skin reactions from advanced colorectal cancer chemotherapy were included. Each patient underwent physical examination and digital photographic imaging, and completed a quality-of-life questionnaire (Dermatology Life Quality Index [DLQI]).

RESULTS
Papulopustular rash was the most common side effect observed. It was statistically associated with EGFRi + irinotecan, EGFRi + FOLFOX, and EGFRi. Xerosis occurred in 50% of patients during EGFRi therapy. Periungual pyogenic granuloma-like lesions occurred in 30% of patients during EGFRi therapy. Our data underline a statistically significant association between capecitabine, FOLFOX + EGFRi, FOLFIFI + EGFRi, and hand-foot syndrome (P < .001). Because none of patients treated with EGFRi alone developed this kind of reaction, we suppose that it is associated with the use of 5-fluorouracil. Fifty percent of patients receiving anti-epidermal growth factor receptor (EGFR) therapy developed trichomegaly. These data underline a statistically significant association between these reactions and this specific drug.

CONCLUSION
A dermatologic visit is useful, both for the correct diagnosis of and for the adequate therapy of chemotherapy side effects. The prevention and treatment of these toxicities are important, not only to improve quality of life but also to avoid unnecessary dose reduction or interruption, which can have a negative effect on treatment outcome.

Panariello|Luigia|L|
Donnarumma|Marianna|M|
Iaffaioli|Rosario Vincenzo|RV|
Chiodini|Paolo|P|
Annunziata|Maria Carmela|MC|
Peduto|Tiziana|T|
Fabbrocini|Gabriella|G|

Skin reactions
Papulopustular rash
Xerosis
Trichomegaly
EGFR inhibitors


3D Printed Laminated CaCO3-Nanocellulose Films as Controlled-Release 5-Fluorouracil.

Abstract: Drug delivery constitutes the formulations, technologies, and systems for the transport of pharmaceutical compounds to specific areas in the body to exert safe therapeutic effects. The main criteria for selecting the correct medium for drug delivery are the quantity of the drug being carried and the amount of time required to release the drug. Hence, this research aimed to improve the aforementioned criteria by synthesizing a medium based on calcium carbonate-nanocellulose composite and evaluating its efficiency as a medium for drug delivery. Specifically, the efficiency was assessed in terms of the rates of uptake and release of 5-fluorouracil. Through the evaluation of the morphological and chemical properties of the synthesized composite, the established 3D printing profiles of nanocellulose and CaCO3 took place following the layer-by-layer films. The 3D printed double laminated CaCO3-nanocellulose managed to release the 5-fluorouracil as an effective single composition and in a time-controlled manner.

3D printing
drug delivery
nanocellulose
5-FU
liquid deposition modelling


White Matter Integrity Dissociates Verbal Memory and Auditory Attention Span in Emerging Adults with Congenital Heart Disease.

Abstract: White matter disruptions have been identified in individuals with congenital heart disease (CHD). However, no specific theory-driven relationships between microstructural white matter disruptions and cognition have been established in CHD. We conducted a two-part study. First, we identified significant differences in fractional anisotropy (FA) of emerging adults with CHD using Tract-Based Spatial Statistics (TBSS). TBSS analyses between 22 participants with CHD and 18 demographically similar controls identified five regions of normal appearing white matter with significantly lower FA in CHD, and two higher. Next, two regions of lower FA in CHD were selected to examine theory-driven differential relationships with cognition: voxels along the left uncinate fasciculus (UF; a tract theorized to contribute to verbal memory) and voxels along the right middle cerebellar peduncle (MCP; a tract previously linked to attention). In CHD, a significant positive correlation between UF FA and memory was found, r(20)=.42, p=.049 (uncorrected). There was no correlation between UF and auditory attention span. A positive correlation between MCP FA and auditory attention span was found, r(20)=.47, p=.027 (uncorrected). There was no correlation between MCP and memory. In controls, no significant relationships were identified. These results are consistent with previous literature demonstrating lower FA in younger CHD samples, and provide novel evidence for disrupted white matter integrity in emerging adults with CHD. Furthermore, a correlational double dissociation established distinct white matter circuitry (UF and MCP) and differential cognitive correlates (memory and attention span, respectively) in young adults with CHD.

Brewster|Ryan C|RC|
King|Tricia Z|TZ|
Burns|Thomas G|TG|
Drossner|David M|DM|
Mahle|William T|WT|

Memory
Attention
Adults
Congenital heart disease
Adolescents
Diffusion tensor imaging


Insertional Achilles Tendinopathy: Analysis of 166 Procedures and Return to Activity.

Abstract: The surgical procedure for Insertional Achilles tendinopathy (IAT) varies widely with no consensus as to approach and documenting return to activity (RTA). This study presents outcomes of surgery for IAT by a single surgeon, documenting activity level and return to activity. From January 2001 through January 2018, 166 procedures were reviewed. Surgery included debridement of the Achilles insertion, resection of the superior calcaneus and bursa, and re-attachment with suture anchors. There were 110 males and 56 females. The majority of patients in the entire cohort were runners (n = 54). The average age of the cohort was 50.3 ± 12.1 years (range 20-80). Average follow-up was 114.0 ± 63.5 months (range 6-222 months). Average RTA for males and females were 6.43 months and 7.22 months, (p = .2), respectively. There was no difference in RTA between patients who had calcific tendinosis (n = 84) and noncalcific tendinosis (n = 82). Complications were 2 infections, 2 DVTs, and 17 deep suture reactions with a total complication rate of 12.6%; there were no re-ruptures postoperatively. There was no significant difference in number of complications between absorbable and nonabsorbable suture in the anchors (p = .41). The average RM score was 1.5 ± 0.7. The RM scores were better for males (p = .002), but there were no differences in RTA or complications between sexes. Overall, 95.8% of the procedures resulted in improved outcome and ability to return to activity including sports. This retrospective investigation shows surgical intervention for IAT yields good results with an average return to activity including sports in approximately 7 months.

Saxena|Amol|A|
Maffulli|Nicola|N|
Jin|Anqi|A|
Isa|Eghosa|E|
Arthur|William Philip|WP|
Wahl|Alanna|A|

insertion
suture anchors
sports
retrocalcaneal


Unilateral hemidiaphragm weakness is associated with positional hypoxemia in REM sleep.

Abstract:
BACKGROUND
Patients with unilateral diaphragmatic paralysis (UDP) have been reported to have varied respiratory symptoms and often reduced lung function. We sought to describe the polysomnographic respiratory characteristics in patients with UDP without obstructive sleep apnea.

METHODS
We prospectively collected 5 cases with clinical investigation regarding symptoms, lung function, and nocturnal polysomnography. The respiratory sleep characteristics were analyzed with standardized scoring of respiratory events in 30-sec epochs and comparison according to sleep-wake stages and body position with respect to oximetry. The cases were compared to 5 controls matched for age, gender, and body mass index.

RESULTS
Three of 5 patients had significant awake lung restriction with a mean (range) forced vital capacity of 1.89 (1.48-2.24) liters, 72% (45% to 102%) predicted. All had REM sleep with few apneas and episodes of prolonged hypopneas characterized by important desaturation noted on oximetry. These desaturations were greatest during REM sleep when the patients slept supine with a mean (SD) saturation of 90.8% (4.5%) and minimum of 64% or on the side unaffected by UDP with a mean saturation of 87.8% (5.3%) and minimum of 67% (p < 0.0001 compared to same positions awake). Other sleep stages had few, if any significant desaturations and these events rarely occurred when the patient slept in the supine position. Saturation was lower in all sleep-wake stages and sleep positions compared to controls (p < 0.0001).

CONCLUSION
Patients with UDP demonstrate position-dependent hypopneas in REM sleep with frequent desaturations.

Baltzan|Marcel A|MA|
Scott|Adrienne S|AS|
Wolkove|Norman|N|

hypoxemia
sleep
Unilateral diaphragmatic paralysis
polysomnography
diaphragmatic disorders
sleep disordered breathing


Identification of drought tolerant genotypes using physiological traits in soybean.

Abstract: In plant breeding programs, screening for drought-tolerance is often a bottleneck. An experiment was conducted in the field and rainout shelters to: (1) identify physiological traits in breeding programs that can be used as criteria for selecting drought tolerance soybean genotypes [Glycine max (L.) Merr], (2) evaluate genotypic differences to drought tolerance, and (3) identify genotypes with superior drought tolerance. Sixteen genotypes were evaluated in split plot design under irrigated and drought conditions. Various physiological traits were measured in irrigated and drought stressed plants such as canopy temperature, root length, specific leaf weight, photosynthetic rate, chlorophyll, and epicuticular wax content. As compared with irrigated conditions, the percent reduction in mean soybean yield under rainout shelter was 40%. The mean yields of soybean genotypes ranged from 1162 kg/ha (NRC 12) to 2610 kg/ha (JS 335) under irrigated conditions, whereas, under water stress conditions, yields ranged from 852 kg/ha (Samrat) to 1654 kg/ha (EC 538828). Genotypes EC 538828, JS 97-52, EC 456548, and EC 602288 had better avoidance to drought than other genotypes. The superior drought tolerance of the four genotypes was related to their low canopy temperature, deep root system, and high values for root/shoot weight ratio, specific leaf weight, chlorophyll content, photosynthetic rate, epicuticular wax content, and Photosystem II (PSII) efficiency. Therefore, when genetic diversity of these physiological traits is established in breeding programs, these traits can be used as a selection criterion for selecting drought tolerant genotypes.

Soybean
Drought stress
Phenotyping
Root traits
Seed yield


Genetic Characterization of a Novel Reassortant H5N6 Avian Influenza Virus Identified from a 10-Year-Old Girl.

Abstract: A 10-year-old girl was confirmed, by laboratory tests, to be infected with the H5N6 subtype of the highly pathogenic avian influenza virus in Suzhou city in November, 2018 (JSSZ01). The hemagglutinin (HA) gene of this H5N6 virus belonged to the 2.3.4.4 H5 clade, and the HA linkage peptide of the JSSZ01 strain was RERRRKR↓GLF with multiple basic amino acids. Q226L and G228S mutations were not observed, but S128P, S137A, and T160A substitutions were identified in the receptor binding sites. The resistance mutation D198N in the neuraminidase (NA) protein was also identified in this strain. Additionally, an 11 amino acid (AA positions 59-69) deletion was identified in the NA stalk region. Most genes of JSSZ01 exhibited highest identity with previously characterized H5N6 viruses, but its PA segment sequence was highly similar to previously identified avian H3 viruses (Accession Number: EPI596567 or EPI590058), indicating that JSSZ01 may be created by gene reassortment.

Dong|Zefeng|Z| Ya|Xuerong|X| Wang|Di|D| Liu|Cheng|C| Shen|Qiang|Q| Xia|Yu|Y|

D019267:Hemagglutinin Glycoproteins, Influenza Virus

reassortment
avian influenza virus
hemagglutinin (HA)
mutation
neuraminidase (NA)


Characterization of Magnitude and Antigen Specificity of HLA-DP, DQ, and DRB3/4/5 Restricted DENV-Specific CD4+ T Cell Responses.

Abstract: Background: Dengue Virus (DENV) associated disease is a major public health problem. Assessment of HLA class II restricted DENV-specific responses is relevant for immunopathology and definition of correlates of protection. While previous studies characterized responses restricted by the HLA-DRB1 locus, the responses associated with other class II loci have not been characterized to date. Accordingly, we mapped HLA-DP, DQ, and DRB3/4/5 restricted DENV-specific CD4 T cell epitopes in PBMCs derived from the DENV endemic region Sri Lanka. Methods: We studied 12 DP, DQ, and DRB3/4/5 alleles that are commonly expressed and provide worldwide coverage >82% for each of the loci analyzed and >99% when combined. CD4+ T cells purified by negative selection were stimulated with pools of HLA-predicted binders for 2 weeks with autologous APC. Epitope reactive T cells were enumerated using IFNγ ELISPOT assay. This strategy was previously applied to identify DRB1 restricted epitopes. In parallel, membrane expression levels of HLA-DR, DP, and DQ proteins was assessed using flow cytometry. Results: Epitopes were identified for all DP, DQ, and DRB3/4/5 allelic variants albeit with magnitudes significantly lower than the ones previously observed for the DRB1 locus. This was in line with lower membrane expression of HLA-DP and DQ molecules on the PBMCs tested, as compared to HLA-DR. Significant differences between loci were observed in antigen immunodominance. Capsid responses were dominant for DRB1/3/4/5 and DP alleles but negligible for the DQ alleles. NS3 responses were dominant in the case of DRB1/3/4/5 and DQ but absent in the case of DP. NS1 responses were prominent in the case of the DP alleles, but negligible in the case of DR and DQ. In terms of epitope specificity, repertoire was largely overlapping between DRB1 and DRB3/4/5, while DP and DQ loci recognized largely distinct epitope sets. Conclusion: The HLA-DP, DQ, and DRB3/4/5 loci mediate DENV-CD4 specific immune responses of lower magnitude as compared to HLA-DRB1, consistent with their lower levels of expression. The responses are associated with distinct and characteristic patterns of immunodominance, and variable epitope overlap across loci.

Grifoni|Alba|A|
Moore|Eugene|E|
Voic|Hannah|H|
Sidney|John|J|
Phillips|Elizabeth|E|
Jadi|Ramesh|R|
Mallal|Simon|S|
De Silva|Aruna D|AD|
De Silva|Aravinda M|AM|
Peters|Bjoern|B|
Weiskopf|Daniela|D|
Sette|Alessandro|A|

HLA-DP
DENV
CD4+T cells
HLA-DQ
HLA-DRB3/4/5
adaptive immunity


In Situ Pulmonary Artery Thrombosis: Unrecognized Complication of Radiation Therapy.

Abstract: OBJECTIVE. The purpose of this study is to evaluate the CT and clinical characteristics of in situ pulmonary artery thrombosis (PAT) associated with radiation therapy (RT). MATERIALS AND METHODS. A database search was performed to identify patients who had PAT develop after receiving RT. The CT characteristics of PAT, including the number, location, and appearance of filling defects as well as the presence of associated lung fibrosis, were recorded. The terminology (in situ thrombosis vs acute or chronic pulmonary embolism) used by the interpreting radiologists to describe PAT, the time between the completion of RT and development of PAT, the change in the size of the PAT, and observation of any new thrombi and emboli on follow-up imaging, were also recorded. RESULTS. Of the 27 patients in the study cohort, 22 (81%) had lung cancer and five (19%) had mesothelioma. Most PATs were solitary (93%) and nonocclusive (96%) and formed an obtuse angle to the vessel wall (89%). All PATs were eccentric within the involved PA and were located within the RT volume. The time from completion of RT to initial diagnosis of PAT on CT ranged from 53 to 2522 days (mean, 675 days). Radiation-induced lung fibrosis was present in the ipsilateral lung in all patients. No evidence of additional PA filling defects that suggested embolization were seen on follow-up images of any of the patients, even those who did not receive anticoagulant therapy. CONCLUSION. In situ PAT associated with RT, which to our knowledge has not previously been described in the English literature, has imaging features different from those of acute pulmonary emboli and does not appear to embolize. Radiologist awareness of PAT can facilitate accurate diagnosis and impact management.

Ahuja|Jitesh|J|
Shroff|Girish S|GS|
Benveniste|Marcelo F|MF|
Marom|Edith M|EM|
Truong|Mylene T|MT|
Wu|Carol C|CC|

pulmonary artery
thrombosis
radiation therapy


Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function.

Abstract: Insomnia is one of the most common sleep problems with an estimated prevalence of 10%-15% in the general population. Although adenosine A2A receptor (A2AR) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous A2AR signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness. In the present study, we found that 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, denoted A2AR positive allosteric modulator (PAM)-1, enhanced adenosine signaling at the A2AR and induced slow wave sleep (SWS) without affecting body temperature in wild-type male mice after intraperitoneal administration, whereas the SWS-inducing effect of this benzoic acid derivative was abolished in A2AR KO mice. In contrast to the A2AR agonist CGS 21680, the A2AR PAM-1 did not affect blood pressure or heart rate. These findings indicate that enhancing A2AR signaling promotes SWS without cardiovascular effects. Therefore, small molecules that allosterically modulate A2ARs could help people with insomnia to fall asleep.

Korkutata|Mustafa|M| Saitoh|Tsuyoshi|T| Cherasse|Yoan|Y| Ioka|Shuji|S| Duo|Feng|F| Qin|Rujie|R| Murakoshi|Nobuyuki|N| Fujii|Shinya|S| Zhou|Xuzhao|X| Sugiyama|Fumihiro|F| Chen|Jiang-Fan|JF| Kumagai|Hidetoshi|H| Nagase|Hiroshi|H| Lazarus|Michael|M|

D000241:Adenosine
D058908:Adenosine A2 Receptor Agonists
D000494:Allosteric Regulation
D000818:Animals
D001794:Blood Pressure
D001831:Body Temperature
D016466:CHO Cells
D003412:Cricetulus
D004353:Drug Evaluation, Preclinical
D006339:Heart Rate
D006993:Hypnotics and Sedatives
D008297:Male
D008810:Mice, Inbred C57BL
D018345:Mice, Knockout
D010627:Phenethylamines
D011897:Random Allocation
D043705:Receptor, Adenosine A2A
D015398:Signal Transduction
D000077310:Sleep, Slow-Wave
D014851:Wakefulness

Body temperature
Cardiovascular function
Insomnia
Allosteric modulator
Adenosine A(2A) receptor
Slow-wavesleep


GRP78 Interacting Partner Bag5 Responds to ER Stress and Protects Cardiomyocytes From ER Stress-Induced Apoptosis.

Abstract: Bag5 is a member of the BAG family of molecular chaperone regulators and is unusual in that it consists of five BAG domains, which function as modulators of chaperone activity. Bag family proteins play a key role in cellular as well as in cardiac function and their differential expression is reported in heart failure. In this study, we examined the importance of a Bag family member protein, Bag5, in cardiomyocytes during endoplasmic reticulum (ER) stress. We found that expression of Bag5 in cardiomyocytes is significantly increased with the induction of ER stress in a time dependent manner. We have taken gain-in and loss-of functional approaches to characterize Bag5 protein function in cardiomyocytes. Adenoviral mediated expression of Bag5 significantly decreased cell death as well as improved cellular viability in ER stress. Along with this, ER stress-induced CHOP protein expression is significantly decreased in cells that overexpress Bag5. Conversely, we found that siRNA-mediated knockdown of Bag5 caused cell death, increased cytotoxicity, and decreased cellular viability in cardiomyocytes. Mechanistically, we found that Bag5 protein expression is significantly increased in the ER during ER stress and that this in turn modulates GRP78 protein stability and reduces ER stress. This study suggests that Bag5 is an important regulator of ER function and so could be exploited as a tool to improve cardiomyocyte function under stress conditions. J. Cell. Biochem. 117: 1813-1821, 2016. © 2016 Wiley Periodicals, Inc.

Gupta|Manish K|MK|
Tahrir|Farzaneh G|FG|
Knezevic|Tijana|T|
White|Martyn K|MK|
Gordon|Jennifer|J|
Cheung|Joseph Y|JY|
Khalili|Kamel|K|
Feldman|Arthur M|AM|

D048868:Adaptor Proteins, Signal Transducing


Nocardiosis in Immunocompromised Patients on Alternative Pneumocystis Prophylaxis.

Abstract: Prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) prevents Pneumocystis jirovecii pneumonia and nocardiosis in immunocompromised patients but sometimes is avoided because of purported allergies or side effects. Of 25 immunocompromised patients receiving alternative prophylaxis in whom nocardiosis developed, 16 subsequently tolerated TMP/SMX treatment. Clinicians should consider TMP/SMX allergy evaluation and rechallenging to assess patient tolerance.

Puing|Alfredo G|AG|
Epstein|David J|DJ|
Banaei|Niaz|N|
Subramanian|Aruna K|AK|
Liu|Anne Y|AY|

D006801:Humans
D016867:Immunocompromised Host
D009617:Nocardia Infections
D011010:Pneumocystis
D045363:Pneumocystis carinii
D011020:Pneumonia, Pneumocystis
D012189:Retrospective Studies

immunocompromised
trimethoprim/sulfamethoxazole
Pneumocystis jirovecii
Nocardia
bacteria
drug allergy
fungi
respiratory infections
sulfa


A study of enhanced performance of VUV/UV process for the degradation of micropollutants from contaminated water.

Abstract: VUV/UV is a chemical-free and straightforward solution for the degradation of emerging contaminants from water sources. The objective of this work was to investigate the feasibility of VUV/UV advanced oxidation process for the effective degradation of a target micropollutant, atrazine, under continuous flow operation of 0.5-6.5L/min. To provide an in-depth understanding of process, a comprehensive computational fluid dynamics (CFD) model, incorporating flow hydrodynamics, 185nm VUV and 254nm UV radiation propagation along with a complete kinetic scheme, was developed and validated experimentally. The experimental degradation rates and CFD predicted values showed great consistency with less than 2.9% average absolute relative deviation (AARD). Utilizing the verified model, energy-efficiency of the VUV/UV process under a wide range of reactor configurations was assessed in terms of electrical energy-per-order (EEO), OH concentration as well as delivered UV and VUV dose distributions. Thereby, the extent of mixing and circulation zones was found as key parameter controlling the treatment economy and energy-efficiency of the VUV/UV process. Utilizing a CFD-driven baffle design strategy, an improved VUV/UV process with up to 72% reduction in the total electrical energy requirement of atrazine degradation was introduced and verified experimentally.

D001280:Atrazine
D017076:Computer-Aided Design
D057446:Hydrodynamics
D017665:Hydroxyl Radical
D010084:Oxidation-Reduction
D014466:Ultraviolet Rays
D014865:Waste Disposal, Fluid
D014874:Water Pollutants, Chemical
D014876:Water Pollution

Contaminants of emerging concerns (CECs)


A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle.

Abstract: Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

Mackinder|Luke C M|LC|
Meyer|Moritz T|MT|
Mettler-Altmann|Tabea|T|
Chen|Vivian K|VK|
Mitchell|Madeline C|MC|
Caspari|Oliver|O|
Freeman Rosenzweig|Elizabeth S|ES|
Pallesen|Leif|L|
Reeves|Gregory|G|
Itakura|Alan|A|
Roth|Robyn|R|
Sommer|Frederik|F|
Geimer|Stefan|S|
Mühlhaus|Timo|T|
Schroda|Michael|M|
Goodenough|Ursula|U|
Stitt|Mark|M|
Griffiths|Howard|H|
Jonikas|Martin C|MC|

Rubisco
carbon fixation
pyrenoid
Chlamydomonas reinhardtii
CO2-concentrating mechanism


The genetic workup for structural congenital heart disease.

Abstract: Congenital heart disease (CHD) is the most prevalent birth defect and is the result of multiple etiologies including genetic and environmental causes. This article reviews the genetic workup for structural CHD in the clinical setting, beginning with CHD epidemiology and etiology and then moving to genetic testing, clinical evaluation, and genetic counseling. An algorithm is presented as a guide to genetic test selection, and available tests are explained with their respective advantages and limitations. Finally, future advances are discussed. As this review focuses on structural heart disease, isolated cardiomyopathies, inherited primary arrhythmia syndromes and aortopathies are not discussed.

genetics
congenital heart disease
genetic testing
genetic counseling


Outcomes of simultaneous pancreas and kidney transplants based on preemptive transplant compared to those who were on dialysis before transplant - a retrospective study.

Abstract: Among kidney transplant recipients, the duration of pretransplant dialysis is significantly associated with worse post-transplant outcomes. However, data on the outcomes of preemptive simultaneous pancreas and kidney (SPK) are limited. We analyzed primary SPK recipients transplanted between January 2000 and December 2017. Patients were divided into two groups based on pretransplant dialysis history of preemptive versus non-preemptive. Patient and survival of grafts were outcomes of interest. Of the 644 recipients, 174 (27%) were preemptive and 470 (73%) were not. Most of the baseline characteristics were similar between the groups. In the univariable analysis, the non-preemptive transplant was associated with 54% increased risk for kidney death-censored graft failure (DCGF; HR: 1.54; 95% CI: 1.01-2.35; P = 0.05). There was a 29% increased risk after adjustment for confounding factors (HR: 1.29; 95% CI: 0.83-2.02; P = 0.26), although this association was not statistically significant. Similarly, there was a 16% increased risk of pancreas DCGF in univariable analysis and 1% after adjustment, which was also not statistically significant. When outcomes were based on the duration of pretransplant dialysis, the duration was not associated with either patient survival or survival of either graft in K-M analysis. In SPK recipients, with pretransplant dialysis history, there was a tendency toward inferior graft survival, mainly for the kidney more than the pancreas.

Parajuli|Sandesh|S|0000-0003-1667-7465
Swanson|Kurtis J|KJ|
Patel|Ravi|R|
Astor|Brad C|BC|0000-0002-0876-0069
Aziz|Fahad|F|0000-0001-8230-3889
Garg|Neetika|N|
Mohamed|Maha|M|
Al-Qaoud|Talal|T|
Redfield|Robert|R|
Djamali|Arjang|A|0000-0001-7675-6128
Kaufman|Dixon|D|
Odorico|Jon|J|
Mandelbrot|Didier A|DA|

D006085:Graft Survival
D006801:Humans
D016030:Kidney Transplantation
D010179:Pancreas
D016035:Pancreas Transplantation
D006435:Renal Dialysis
D012189:Retrospective Studies
D016896:Treatment Outcome

patient survival
graft survival
pancreas kidney transplant


The conformational analysis of push-pull enaminones using Fourier transform IR and NMR spectroscopy, and quantum chemical calculations. V. α-Methyl-, fluorine-β-N,N-dimethylaminovinyl trifluoromethyl ketones.

Abstract: IR Fourier spectra of two enaminoketones with general formula F3CCOCRCHN(CH3)2, R=F (DMTFBN); R=CH3, (DMTMBN) were studied in various pure solvents. For comparison results of earlier investigated enaminoketone R=H (DMTBN) was also presented. On the basis of NMR and IR spectra it was shown that enaminoketones DMTBN, DMTFBN and DMTMBN presented in solutions as equilibrium of two conformers, (E-s-Z)⇌(E-s-E) (for DMTFBN these conformers are denoted as (Z-s-Z) and (Z-s-E), respectively). DFT calculations were carried out to evaluate relative energy and dipole moment of each spatial form. It was shown that 'closed-ring' complex formation between (E-s-Z) and (E-s-E) conformers of DMTBN accounts for discrepancies between DFT calculations of conformer relative energies and experimentally evaluated enthalpies of (E-s-Z)⇌(E-s-E) equilibrium. In α-substituted DMTFBN and DMTMBN, where formation of 'closed-ring' complex was impossible we did not observe such discrepancies. For both (E-s-Z) and (E-s-E) conformers of the DMTBN and DMTMBN the main influence on the ν̃(CO) vibrations has the solvent's hydrogen bond donor (HBD) acidity, whereas for the DMTFBN an influence of the solvent's polarity/polarizability dominated.

Vdovenko|Sergey I|SI|
Gerus|Igor I|II|
Zhuk|Yuri I|YI|
Kukhar|Valery P|VP|
Röschenthaler|Gerd-Volker|GV|

D017550:Spectroscopy, Fourier Transform Infrared

Conformational analysis
Enaminoketones
DFT calculations
NMR and IR-spectra


Predictors and mediators of outcome in cognitive behavioral therapy for chronic pain: the contributions of psychological flexibility.

Abstract: There is now a consensus in the literature that future improvements in outcomes obtained from cognitive behavioral therapy (CBT) for chronic pain will require research to identify patient and treatment variables that help explain outcomes. The first aim of this study was to assess whether pre-treatment scores on measures of psychological (in)flexibility, acceptance, committed action, cognitive (de)fusion, and values-based action predict outcomes in a multidisciplinary, multicomponent, group-based CBT program for adults with chronic pain. The second aim was to assess whether change scores on these same measures mediate outcomes in the treatment program. Participants were 232 people attending treatment for chronic pain. Of the psychological flexibility measures, only pre-treatment scores on the psychological inflexibility scale predicted outcomes; higher scores on this measure were associated with worse outcomes. However, change scores on each of the psychological flexibility measures separately mediated outcomes. The efficacy of CBT for chronic pain may be improved with a greater focus on methods that increase psychological flexibility.

Åkerblom|Sophia|S|0000-0002-9220-3176
Perrin|Sean|S|
Rivano Fischer|Marcelo|M|
McCracken|Lance M|LM|

Predictor
Mediator
Cognitive behavioral therapy
Chronic pain
Psychological flexibility


Unruptured Pseudoaneurysm of the Mitral Aortic Intervalvular Fibrosa.

Abstract: A 38-year-old female with a history of primary mitral regurgitation experienced shortness of breath even at rest 4 months previously. Cardiac computed tomography showed a large unruptured aneurysm arising from the mitral-aortic intervalvular fibrosa adjacent to the anterior mitral leaflet. The patient passed away because the pseudoaneurysm ruptured into the pericardium. (Level of Difficulty: Beginner.).

Dang|Garima|G|
Basapure|Rohit|R|
Hira|Priya|P|
Bandyopadhyay|Dhrubajyoti|D|
Dey|Amit Kumar|AK|

aortic
mitral regurgitation
CT, computed tomography
MR, mitral regurgitation
NYHA, New York Heart Association
TTE, transthoracic echocardiogram
echocardiography
imaging