Comorbidity of posttraumatic stress disorder with alcohol dependence among US adults: results from National Epidemiological Survey on Alcohol and Related Conditions.

Abstract:
BACKGROUND
Despite the high rates of comorbidity of post-traumatic stress disorder (PTSD) and alcohol dependence (AD) in clinical and epidemiological samples, little is known about the prevalence, clinical presentation, course, risk factors and patterns of treatment-seeking of co-occurring PTSD-AD among the general population.

METHODS
The sample included respondents of the Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Weighted means, frequencies and odds ratios (ORs) of sociodemographic correlates, prevalence of psychiatric disorders and rates of treatment-seeking were computed.

RESULTS
In the general population, the lifetime prevalence of PTSD only, AD only and PTSD-AD was 4.83%, 13.66% and 1.59%, respectively. Individuals with comorbid PTSD-AD were more likely than those with PTSD or AD only to have suffered childhood adversities and had higher rates of Axis I and II disorders and suicide attempts. They also met more PTSD diagnostic criteria, had earlier onset of PTSD and were more likely to use drugs and alcohol to relieve their PTSD symptoms than those with PTSD only; they also met more AD diagnostic criteria than those with AD only and had greater disability. Individuals with PTSD-AD had higher rates of treatment seeking for AD than those with AD only, but similar rates than those with PTSD only.

CONCLUSION
PTSD-AD is associated with high levels of severity across a broad range of domains even compared with individuals with PTSD or AD only, yet treatment-seeking rates are very low. There is a need to improve treatment access and outcomes for individuals with PTSD-AD.

Blanco|Carlos|C| Xu|Yang|Y| Brady|Kathleen|K| Pérez-Fuentes|Gabriela|G| Okuda|Mayumi|M| Wang|Shuai|S|

Comorbidity
Alcohol dependence
Post-traumatic stress disorder (PTSD)
NESARC
Substance use disorders


Quantitative material decomposition using linear iterative near-field phase retrieval (LIPR) dual-energy X-ray imaging.

Abstract: This paper expands the LIPR formalism to achieve quantitative material thickness decomposition. Propagation-based phase contrast X-ray imaging with subsequent phase retrieval has been shown to improve the signal-to-noise ratio (SNR) by factors of up to hundreds compared to conventional X-ray imaging. This is a key step in biomedical imaging, where radiation exposure must be kept low without compromising the SNR. However, for a satisfactory phase retrieval from a single measurement, assumptions must be made about the object investigated. To avoid such assumptions, we use two measurements collected at the same propagation distance but at different X-ray energies. Phase retrieval is then performed by incorporating the Alvarez-Macovski (AM) model, which models the X-ray interactions as being comprised of distinct photoelectric and Compton scattering components. We present the first application of dual-energy phase retrieval with the AM model to monochromatic experimental X-ray projections at two different energy for obtaining split X-ray interactions. Our phase retrieval method allows us to separate the object investigated into the projected thicknesses of two known materials. Our phase retrieval output leads to no visible loss in spatial resolution while the SNR improves by factors of 2 to 10. This corresponds to a possible X-ray dose reduction by a factor of 4 to 100, under the Poisson noise assumption.

Li|Heyang Thomas|HT|0000-0001-9794-5075
Schaff|Florian|F|
Croton|Linda|L|
Morgan|Kaye S|KS|0000-0001-6997-7977
Kitchen|Marcus J|MJ|

phase retrieval
Dual-energy
phase contrast X-ray imaging
atomic number
density
iterative reconstruction


Relationship between motivational style and glycemic control in Jordanian patients with type 2 diabetes mellitus.

Abstract:
BACKGROUND
Although, there is increased recognition of the importance of blood glucose control and diabetes education in type 2 diabetes mellitus (T2DM), the relationship between motivation and long term outcomes, glycemic control, are lacking. The primary aims of the present study were to: (i) describe the motivational style of Jordanian patients with T2DM regarding self-care management, taking medications, and self-monitoring of blood glucose (SMBG), as well as following therapeutic dietary instructions and exercising regularly; and b) examine the significance of these factors in predicting glycemic control.

METHODS
A package including a treatment self-regulation questionnaire concerning diabetes, was administered to a convenience sample of 110 patients with T2DM. In addition, the most recent HbA1c results were extracted from the patients' medical records.

RESULTS
Fifty-eight patients (52.7 %) reported being intrinsically motivated with regard to taking medication and regular SMBG, whereas half the participants (50 %) were intrinsically motivated to follow therapeutic dietary instructions and regular exercise. Patients who were intrinsically motivated were 8.3-fold more likely (95 % confidence interval [CI] 1.44-47.86) to have glycemic control than those reporting extrinsic motivation. In addition, those who were intrinsically motivated to follow therapeutic dietary instructions and exercise regularly were 10.50-fold more likely (95 % CI 2.50-48.78) times more likely to report glycemic control than those reporting extrinsic motivation.

CONCLUSION
Interventional strategies should focus on promoting intrinsic motivation in order to enhance glycemic control.

Al-Hassan|Mousa A|MA|
Al-Akour|Nemeh A|NA|
Aburas|Motaz Mohammad|MM|

motivational style
glycemic control
type 2 diabetes
Jordan


Clear aligner orthodontic treatment: Angle Society of Europe consensus viewpoint.

Abstract: Orthodontics has witnessed not only an exponential rise in demand from adult patients but accompanying this, the emergence of alternate aesthetic treatment options to the more traditional fixed labial appliance. The concept of using clear aligners as a means of achieving tooth movement has increased in popularity among both patients and clinicians alike. However, the question over best research evidence as to their clinical effectiveness to treat a range of malocclusion traits remains elusive and controversial among the profession.In an attempt to offer the profession some clear guidance, The Angle Society of Europe reviewed and discussed the current published evidence (2005-2018) on their clinical use, during the annual meeting in January 2020, to help formulate a consensus viewpoint on the clinical applications.

clear aligners
adult orthodontics
evidence-based dentistry


The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma.

Abstract:
INTRODUCTION
The prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis.

MATERIALS AND METHODS
Patients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables.

RESULTS
Increased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability.

CONCLUSION
Our findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.

Hou|Tao|T| Guo|Tianhui|T| Nie|Runcong|R| Hong|Dongchun|D| Zhou|Zhiwei|Z| Zhang|Xing|X| Liang|Yao|Y|

Soft tissue sarcoma
SII
Hs-mGPS
Survival
Prognostic factors


Perceptual responses: Clinical versus practical blood flow restriction resistance exercise.

Abstract: The purpose of the current investigation was to compare the acute perceptual responses during low-load resistance exercise (RE) with clinical blood flow restriction (cBFR-RE) and practical blood flow restriction (pBFR-RE), and during conventional low- (LL-RE) and high-load resistance exercise (HL-RE), to determine if these responses differed between young males and females. Twenty-nine participants (14 males: 23.6±2.7years, 25.3±3.1kg/m2 and 15 females: 20.3±1.6years, 23.4±1.9kg/m2) completed the following exercise conditions in a randomized design: 1) cBFR-RE, 2) pBFR-RE, 3) HL-RE, and 4) LL-RE. Low-load conditions consisted of 30-15-15-15 repetitions of two-leg press (LP) and knee extension (KE) exercises with 30% one-repetition maximum (1-RM), and HL-RE consisted of 3 sets of 10 repetitions at 80% 1-RM, all with 60s rest intervals. Ratings of perceived exertion (RPE) and discomfort were assessed before exercise and immediately following each set. RPE was significantly higher in HL-RE compared to all low-load conditions for both exercises after each set (all p<0.05). cBFR-RE resulted in significantly greater RPE than pBFR-RE and LL-RE for both exercises for sets 1-4 for LP and sets 2-3 for KE (all p<0.05). Levels of discomfort were similar between cBFR-RE and HL-RE, which tended to be significantly higher than pBFR-RE and LL-RE (p<0.05). Men reported significantly greater RPE than women following sets 2-4 during KE with cBFR-RE and sets 2 and 3 during KE for HL-RE (all p<0.05). Males also reported significantly greater discomfort than women following sets 2-4 for KE LL-RE (p<0.05). Altogether, these data suggest that pBFR-RE may provide a more favorable BFR condition based on perceptual responses and that perceptual responses may differ between sexes across varying resistance exercise conditions.

Miller|Ryan M|RM|
Galletti|Bianca A R|BAR|
Koziol|Karolina J|KJ|
Freitas|Eduardo D S|EDS|
Heishman|Aaron D|AD|
Black|Christopher D|CD|
Larson|Daniel J|DJ|
Bemben|Debra A|DA|
Bemben|Michael G|MG|

Perceived exertion
RPE
Discomfort
Kaatsu
Pain
Sex differences


Proteomic Evaluation of the Comorbidity-Inflammation Paradigm in Heart Failure With Preserved Ejection Fraction: Results From the PROMIS-HFpEF Study.

Abstract:
BACKGROUND
A systemic proinflammatory state has been hypothesized to mediate the association between comorbidities and abnormal cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). We conducted a proteomic analysis to investigate this paradigm.

METHODS
In 228 patients with HFpEF from the multicenter PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction), 248 unique circulating proteins were quantified by a multiplex immunoassay (Olink) and used to recapitulate systemic inflammation. In a deductive approach, we performed principal component analysis to summarize 47 proteins known a priori to be involved in inflammation. In an inductive approach, we performed unbiased weighted coexpression network analyses of all 248 proteins to identify clusters of proteins that overrepresented inflammatory pathways. We defined comorbidity burden as the sum of 8 common HFpEF comorbidities. We used multivariable linear regression and statistical mediation analyses to determine whether and to what extent inflammation mediates the association of comorbidity burden with abnormal cardiac structure/function in HFpEF. We also externally validated our findings in an independent cohort of 117 HFpEF cases and 30 comorbidity controls without heart failure.

RESULTS
Comorbidity burden was associated with abnormal cardiac structure/function and with principal components/clusters of inflammation proteins. Systemic inflammation was also associated with increased mitral E velocity, E/e' ratio, and tricuspid regurgitation velocity; and worse right ventricular function (tricuspid annular plane systolic excursion and right ventricular free wall strain). Inflammation mediated the association between comorbidity burden and mitral E velocity (proportion mediated 19%-35%), E/e' ratio (18%-29%), tricuspid regurgitation velocity (27%-41%), and tricuspid annular plane systolic excursion (13%) (P<0.05 for all), but not right ventricular free wall strain. TNFR1 (tumor necrosis factor receptor 1), UPAR (urokinase plasminogen activator receptor), IGFBP7 (insulin-like growth factor binding protein 7), and GDF-15 (growth differentiation factor-15) were the top individual proteins that mediated the relationship between comorbidity burden and echocardiographic parameters. In the validation cohort, inflammation was upregulated in HFpEF cases versus controls, and the most prominent inflammation protein cluster identified in PROMIS-HFpEF was also present in HFpEF cases (but not controls) in the validation cohort.

CONCLUSIONS
Proteins involved in inflammation form a conserved network in HFpEF across 2 independent cohorts and may mediate the association between comorbidity burden and echocardiographic indicators of worse hemodynamics and right ventricular dysfunction. These findings support the comorbidity-inflammation paradigm in HFpEF.

Sanders-van Wijk|Sandra|S|
Tromp|Jasper|J|
Beussink-Nelson|Lauren|L|
Hage|Camilla|C|
Svedlund|Sara|S|
Saraste|Antti|A|
Swat|Stanley A|SA|
Sanchez|Cynthia|C|
Njoroge|Joyce|J|
Tan|Ru-San|RS|
Fermer|Maria Lagerström|ML|
Gan|Li-Ming|LM|
Lund|Lars H|LH|
Lam|Carolyn S P|CSP|
Shah|Sanjiv J|SJ|

heart failure
comorbidity
analysis
inflammation
biomarkers
echocardiography


Synthesis, Phase Behavior and Computational Simulations of a Pyridyl-Based Liquid Crystal System.

Abstract: A homologous set of liquid crystalline materials (Tn) bearing Schiff base/ester linkages were prepared and investigated via experimental and theoretical techniques. Terminal flexible groups of different chain lengths were connected to the end of phenylbenzoate unit while the other end of molecules was attached to the heterocyclic pyridine moiety. The molecular structures of the designed molecules were evaluated by FT-IR, NMR spectroscopic analyses, whereas their mesomorphic properties were investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). They all exhibited dimorphic properties with the exception of the members having the shortest and longest terminal flexible chains (n = 6 and 16), which were monomorphic. The T16 derivative was further found possessing purely smectic A (SmA) mesophase while others have their lengths covered by nematic (N) phase. Moreover, the computational evaluation of the azomethine derivatives was carried out using a DFT approach. The polarity of the investigated derivatives was predicted to be appreciably sensitive to the size of the system. Furthermore, the Frontier molecular orbitals analysis revealed various distributions of electron clouds at HOMO and LUMO levels.

Alamro|Fowzia S|FS|
Ahmed|Hoda A|HA|0000-0003-3966-7024
Popoola|Saheed A|SA|0000-0002-3906-0380
Aboelnaga|Asmaa|A|

schiff base/ester
computational DFT calculations
mesophase behavior
pyridyl based liquid crystals


We need to talk: an observational study of the impact of electronic medical record implementation on hospital communication.

Abstract:
BACKGROUND
Increasing attention is being given to the importance of communication in the delivery of high-quality healthcare. We sought to determine whether communication improved in a hospital setting following the introduction of an electronic medical record (EMR).

METHODS
This pre-post cohort design enrolled 75 patient-nurse-physician triads prior to the introduction of EMR, and 123 triads after the introduction of EMR. Nurses and patients reported whether they communicated with the physician that day. Patients, nurses and physicians answered several questions about the plan of care for the day. Responses were scored for degree of agreement and compared between pre-EMR and post-EMR cohorts. The primary outcome was Total Agreement Score, calculated as the sum of the agreement responses. Chart review was performed to determine patients' actual length of stay.

RESULTS
Although there was no difference between the frequency of nurses reporting communication with physicians before and after EMR, face-to-face communication was significantly reduced (67% vs 51%, p=0.03). Total Agreement Score was significantly lower after the implementation of EMR (p=0.03). Additionally, fewer patients accurately predicted their expected length of stay after EMR (34% vs 26%, p=0.001).

CONCLUSIONS
The implementation of EMR was associated with a decrease in face-to-face communication between physicians and nurses, and worsened overall agreement about the plan of care.

Taylor|Stephanie Parks|SP|
Ledford|Robert|R|
Palmer|Victoria|V|
Abel|Erika|E|

D015331:Cohort Studies
D003142:Communication
D057286:Electronic Health Records
D005431:Florida
D006785:Hospitals, University
D006801:Humans
D007400:Interprofessional Relations
D007407:Interviews as Topic
D007902:Length of Stay
D009723:Nurse-Patient Relations
D010347:Patient Care Planning
D010820:Physicians

Electronic medical record
communication
interdisciplinary communication
physician-nurse communication


Novel spontaneous myelodysplastic syndrome mouse model.

Abstract:
Background
Myelodysplastic syndrome (MDS) is a group of disorders involving hemopoietic dysfunction leading to leukemia. Although recently progress has been made in identifying underlying genetic mutations, many questions still remain. Animal models of MDS have been produced by introduction of specific mutations. However, there is no spontaneous mouse model of MDS, and an animal model to simulate natural MDS pathogenesis is urgently needed.

Methods
In characterizing the genetically diverse mouse strains of the Collaborative Cross (CC) we observed that one, designated JUN, had abnormal hematological traits. This strain was thus further analyzed for phenotypic and pathological identification, comparing the changes in each cell population in peripheral blood and in bone marrow.

Results
In a specific-pathogen free environment, mice of the JUN strain are relatively thin, with healthy appearance. However, in a conventional environment, they become lethargic, develop wrinkled yellow hair, have loose and light stools, and are prone to infections. We found that the mice were cytopenic, which was due to abnormal differentiation of multipotent bone marrow progenitor cells. These are common characteristics of MDS.

Conclusions
A mouse strain, JUN, was found displaying spontaneous myelodysplastic syndrome. This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models. JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Li|Weisha|W|0000-0002-1370-6067 Cao|Lin|L| Li|Mengyuan|M| Yang|Xingjiu|X| Zhang|Wenlong|W| Song|Zhiqi|Z| Wang|Xinpei|X| Zhang|Lingyan|L| Morahan|Grant|G| Qin|Chuan|C| Gao|Ran|R|

myelodysplastic syndrome (MDS)
spontaneous mouse model
The Collaborative Cross Mice


Substrate preferences of long-chain acyl-CoA synthetase and diacylglycerol acyltransferase contribute to enrichment of flax seed oil with α-linolenic acid.

Abstract: Seed oil from flax (Linum usitatissimum) is enriched in α-linolenic acid (ALA; 18:3Δ9 ), but the biochemical processes underlying the enrichment of flax seed oil with this polyunsaturated fatty acid are not fully elucidated. Here, a potential process involving the catalytic actions of long-chain acyl-CoA synthetase (LACS) and diacylglycerol acyltransferase (DGAT) is proposed for ALA enrichment in triacylglycerol (TAG). LACS catalyzes the ATP-dependent activation of free fatty acid to form acyl-CoA, which in turn may serve as an acyl-donor in the DGAT-catalyzed reaction leading to TAG. To test this hypothesis, flax LACS and DGAT cDNAs were functionally expressed in Saccharomyces cerevisiae strains to probe their possible involvement in the enrichment of TAG with ALA. Among the identified flax LACSs, LuLACS8A exhibited significantly enhanced specificity for ALA over oleic acid (18:1Δ9 ) or linoleic acid (18:2Δ9 ). Enhanced α-linolenoyl-CoA specificity was also observed in the enzymatic assay of flax DGAT2 (LuDGAT2-3), which displayed ∼20 times increased preference toward α-linolenoyl-CoA over oleoyl-CoA. Moreover, when LuLACS8A and LuDGAT2-3 were co-expressed in yeast, both in vitro and in vivo experiments indicated that the ALA-containing TAG enrichment process was operative between LuLACS8A- and LuDGAT2-3-catalyzed reactions. Overall, the results support the hypothesis that the cooperation between the reactions catalyzed by LACS8 and DGAT2 may represent a route to enrich ALA production in the flax seed oil.

Xu|Yang|Y|
Holic|Roman|R|
Li|Darren|D|
Pan|Xue|X|
Mietkiewska|Elzbieta|E|
Chen|Guanqun|G|0000-0001-5790-3903
Ozga|Jocelyn|J|
Weselake|Randall J|RJ|

Linum usitatissimum
polyunsaturated fatty acids
LACS
DGAT
Saccharomyces cerevisiae
seed oil biosynthesis


Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model.

Abstract: Cholestatic liver diseases can progress to end-stage liver disease and reduce patients' quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.

heme oxygenase-1
cholestatic liver disease
oxidative stress
apoptosis
inflammation
fibrosis


Nicotinamide Effectively Suppresses Fusarium Head Blight in Wheat Plants.

Abstract: Pyridine nucleotides such as a nicotinamide adenine dinucleotide (NAD) are known as plant defense activators. We previously reported that nicotinamide mononucleotide (NMN) enhanced disease resistance against fungal pathogen Fusarium graminearum in barley and Arabidopsis. In this study, we reveal that the pretreatment of nicotinamide (NIM), which does not contain nucleotides, effectively suppresses disease development of Fusarium Head Blight (FHB) in wheat plants. Correspondingly, deoxynivalenol (DON) mycotoxin accumulation was also significantly decreased by NIM pretreatment. A metabolome analysis showed that several antioxidant and antifungal compounds such as trigonelline were significantly accumulated in the NIM-pretreated spikes after inoculation of F. graminearum. In addition, some metabolites involved in the DNA hypomethylation were accumulated in the NIM-pretreated spikes. On the other hand, fungal metabolites DON and ergosterol peroxide were significantly reduced by the NIM pretreatment. Since NIM is relative stable and inexpensive compared with NMN and NAD, it may be more useful for the control of symptoms of FHB and DON accumulation in wheat and other crops.

nicotinamide
fusarium head blight
pyridine nucleotide
metabolomics
antifungal compound
DNA hypomethylation
trichothecene mycotoxin


Influence of pregnancy on long-term durability of allografts in right ventricular outflow tract.

Abstract:
BACKGROUND
There is very limited published evidence about the influence of pregnancy on allograft durability in right ventricular outflow tract position. We present the first study using mixed and joint modeling.

METHODS
This retrospective study compared clinical and valve related outcomes of all consecutive female hospital survivors in their fertile life phase (18-50 years) based on pregnancy. Serial echocardiographic measurements of pulmonary gradient and regurgitation were analyzed for their association with valve replacement using joint models for longitudinal and time-to-event data. Occurrence of first pregnancy was included as a time-dependent intermediate event in both the longitudinal and survival analyses of the joint model to assess its impact on the hemodynamic and clinical outcome.

RESULTS
In total, 196 consecutive women in their fertile life-phase with an allograft were included. Complete information of 176 (90%) allografts in 165 women was available, including 1395 echocardiograms. Of these women, 51 (30.9%) women had 84 completed pregnancies at an average age of 29.1 ± 3.9 (SD) years; 8.1 ± 6.1 years since allograft implantation. Tetralogy of Fallot was the most common diagnosis in both groups. After a mean follow-up of 15.2 years (range 0.1-30), 7 (13.7%) parous women underwent valve replacement versus 20 (17.5%) nulliparous women. During this follow-up, the mean allograft gradient in parous (24.2 mm Hg) and nulliparous (21.0 mm Hg) women was comparable (P = .225). A 1-mm Hg increase in pulmonary gradient increased the instantaneous risk of pulmonary valve replacement (PVR) by a ratio of 1.051 (P < .001), regardless of pregnancy. Similarly, development of moderate or severe regurgitation increased the risk of PVR (P = .038), regardless of pregnancy. Pregnancy was not associated with a change in the allograft gradient (P = .258), regurgitation grade (P = .774), or hazard of PVR (P = .796) during follow-up.

CONCLUSIONS
Pregnancy is not associated with impaired allograft durability in women with good cardiac health.

Romeo|Jamie L R|JLR|
Papageorgiou|Grigorios|G|
Takkenberg|Johanna J M|JJM|
Roos-Hesselink|Jolien W|JW|
van Leeuwen|Wouter J|WJ|
Cornette|Jerome M J|JMJ|
Rizopoulos|Dimitris|D|
Bogers|Ad J J C|AJJC|
Mokhles|M Mostafa|MM|

D019918:Heart Valve Prosthesis Implantation

pregnancy
allograft
right ventricular outflow tract
congenital heart disease


The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma.

Abstract:
BACKGROUND
We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines.

METHODS
A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of "stemness"-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)-related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers.

RESULTS
Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p<.05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p<.05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394).

CONCLUSIONS
The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of "stemness"- and EMT-related markers, and decreased survival.

Lee|Yangkyu|Y|
Park|Hyunjin|H|
Lee|Hyejung|H|
Cho|Jai Young|JY|
Yoon|Yoo-Seok|YS|
Choi|Young-Rok|YR|
Han|Ho-Seong|HS|
Jang|Eun Sun|ES|
Kim|Jin-Wook|JW|
Jeong|Sook-Hyang|SH|
Ahn|Soomin|S|
Kim|Haeryoung|H|

Gross classification
Prognosis
Carcinoma, hepatocellular


A Comparison of Lower Eyelid Retraction in Normal Individuals with Positive versus Negative Orbital Vector.

Abstract:
PURPOSE
The present study aimed to compare lower eyelid retraction (LER) in individuals with a positive orbital vector with that of individuals with a negative orbital vector.

MATERIALS AND METHODS
This cross-sectional study was conducted on 123 normal individuals including 64 men and 59 women aged 20-80 years. After the individuals underwent Hertel exophthalmometry, two side-view and front-view photos were taken using a camera. The orbital vector angle and the extent of scleral show were then measured in millimeter, using the Photoshop software. Eventually, the recorded data were analyzed through statistical software.

RESULTS
The findings of this study showed that LER has a significant correlation with orbital vector angle and the extent of proptosis (P < 0.05). The mean value of orbital vector angle in individuals without LER was 9.76°, while this figure was calculated to be - 13.65° in individuals with LER. The mean protrusion value based on Hertel exophthalmometry was 14.08 mm in individuals without LER and 16.27 mm in individuals with LER. The extent of scleral show had a significant correlation with proptosis and orbital vector angle (P = 0.01), with a mean value of - 0.41 mm in individuals without LER and 0.94 mm in participants with LER.

CONCLUSIONS
The prevalence of LER and scleral show is positively correlated with the extent of proptosis and negatively correlated with orbital vector angle.

Rajabi|Mohammad Taher|MT|
Malmir|Minoo|M|
Mahmoudzadeh|Raziyeh|R|
Salabati|Mirataollah|M|
Tabatabaie|Seyed Ziaeddin|SZ|
Rajabi|Mohammad Bagher|MB|
Hosseini|Seyedeh Simindokht|SS|

lower eyelid retraction
Hertel exophthalmometry
scleral show
proptosis


Enantio- and Diastereoselective Synthesis of Hydroxy Bis(boronates) via Cu-Catalyzed Tandem Borylation/1,2-Addition.

Abstract: Catalytic enantioselective synthesis of 1-hydroxy-2,3-bisboronate esters through multicomponent borylation/1,2-addition is reported. Catalyst and substrates are readily available, form both a C-B and C-C bond, and generate up to three contiguous stereocenters. The reaction is tolerant of aryl, vinyl, and alkyl aldehydes and ketones in up to 95% yield, >20:1 dr, and 99:1 er. Intramolecular additions to aldehydes and ketones result in stereodivergent processes. The hydroxy bis(boronate) ester products are amenable to site-selective chemical elaboration.

Green|Jacob C|JC|
Joannou|Matthew V|MV|
Murray|Stephanie A|SA|
Zanghi|Joseph M|JM|
Meek|Simon J|SJ|


Age-Dependent Increase in Soldier Pheromone of the Termite Reticulitermes speratus.

Abstract: Pheromone communication helps maintaining the sophisticated colony organization in social insects. In the termite Reticulitermes speratus, there are two functionally distinct soldier groups: royal guards and entrance guards. Royal guards protect kings and queens in the innermost part of the nest, whereas entrance guards prevent predators from intruding into the nest at the periphery. A recent study revealed that younger and older soldiers work as royal and entrance guards, respectively. This age-dependent distribution is thought to help workers to recognize where in the nest they are located. However, it is not known whether workers can discriminate the age of soldiers. Here, we show that the abundance of soldier pheromone changes with age and that workers discriminate a soldier's age by recognizing the pheromone abundance. Gas chromatography-mass spectrometry analysis revealed that the chemical profiles of extracts in three soldier groups of different ages (newly differentiated, royal guard, and entrance guard soldiers) are markedly different. Entrance guard soldiers have the most soldier pheromone among the three age classes. Furthermore, our bioassays suggested that the worker's movement from chamber to chamber is inhibited only when a soldier with less soldier pheromone is located at the chamber entrance. These results suggest that the soldier pheromone functions as a soldier age indicator and that workers change their behavior depending on the age of the soldier defending the chamber entrance. This study contributes to our understanding of the relationship between aging and pheromone communication in social insects.

Soldier
Pheromone
Termite
Social Insects
Aging
Terpene


Does dexmedetomidine provide cardioprotection in coronary artery bypass grafting with cardiopulmonary bypass? A pilot study.

Abstract:
OBJECTIVE
The purpose of this pilot study was to evaluate whether dexmedetomidine has a cardioprotective effect during coronary artery bypass graft surgery with cardiopulmonary bypass (CPB).

DESIGN
A prospective, double-blind, randomized controlled trial.

SETTING
A university hospital.

PARTICIPANTS
Thirty-eight patients undergoing coronary artery bypass graft surgery.

INTERVENTIONS
Patients were randomized into 2 groups: dexmedetomidine and placebo groups. In the dexmedetomidine group, dexmedetomidine infusion was started by a loading dose of 0.5 μg/kg/10 min, followed by a continuous infusion of 0.5 μg/kg/h. The placebo group received the same volume of saline. Measurements of central venous pressure, mean pulmonary artery pressure (MPAP) and cardiac index were performed before and after dexmedetomidine loading dose and 2, 24 and 48 hours after CPB. Simultaneously, arterial blood was sampled for CK-MB, cardiac troponin T, and N-terminal probrain natriuretic peptide.

MEASUREMENTS AND MAIN RESULTS
CK-MB, cardiac troponin T and N-terminal probrain natriuretic peptide values were elevated in the periods after CPB in both groups (p<0.05) and there were no statistically significant differences between groups. MPAP was decreased in the dexmedetomidine group at the 2nd, 24th and 48th hour after CPB (p<0.001, p<0.001, p = 0.002, respectively). Higher cardiac index values were seen earlier in the dexmedetomidine group than in the placebo group (p< 0.05).

CONCLUSIONS
Myocardial damage was not reduced by administration of 0.5 μg/kg loading dose and 0.5 μg/kg/h infusion of dexmedetomidine. However MPAP tended to be lower in the dexmedetomidine group. Large-scale clinical outcome studies are indicated to confirm the effect of dexmedetomidine.

Tosun|Zeynep|Z|
Baktir|Mehmet|M|
Kahraman|Husnu Cemal|HC|
Baskol|Gulden|G|
Guler|Gulen|G|
Boyaci|Adem|A|

dexmedetomidine
coronary artery bypass grafting
cardiopulmonary bypass
cardioprotective effect


State of the Art Review: Physical Activity and Older Adults.

Abstract: Physical activity is an important component of a healthy lifestyle for all adults and especially for older adults. Using information from the updated 2008 Physical Activity Guidelines, 3 dimensions of physical activity are identified for older adults. These include increasing aerobic activity, increasing muscle-strengthening activity, and reducing sedentary or sitting behavior. Although the overall goal of the physical activity recommendations is to prevent chronic diseases and conditions from developing, many older adults are already affected. Therefore, suggested types of physical activity are described for specific diseases and conditions that are designed to mediate the condition or prevent additional disability. Finally, barriers to participation in physical activity specific to older adults are described, and possible solutions offered. Encouraging older adults to continue or even start a physical activity program can result in major health benefits for these individuals.

Macera|Caroline A|CA|
Cavanaugh|Alyson|A|
Bellettiere|John|J|

physical activity
older adults
chronic disease
barriers
muscle strengthening
sedentary behavior


De novo and pre-existing atrial fibrillation in acute coronary syndromes: impact on prognosis and cardiovascular events in long-term follow-up.

Abstract:
AIMS
The aim of the study was to compare in-hospital and long-term prognosis in patients with acute coronary syndromes (ACS) and de novo vs. pre-existing atrial fibrillation (AF). Atrial fibrillation increases the risk of serious adverse events including death in patients with ACS. However, it is unclear whether de novo and pre-existing AF portend a different risk.

METHODS AND RESULTS
We analysed the incidence, clinical characteristics, and in-hospital and long-term outcomes in patients with AF and ACS based on combined data from Polish Registry of Acute Coronary Syndrome (PL-ACS) (n = 581 843) and SILICARD (n = 852 063) databases. Atrial fibrillation at admission was diagnosed in of 6.16% patients [de novo: 1129 (2.46%); pre-existing: 1691 (3.7%)]. Groups were compared (N = 1023 vs. 1023) after matching for relevant clinical factors. De novo and pre-existing AF differed in in-hospital diuretic (52% vs. 58%; P = 0.008) and aldosterone inhibitor (27.5% vs. 32.5%; P = 0.02) use, Thrombolysis In Myocardial Infarction (TIMI) flow before percutaneous coronary intervention (P = 0.016), and diuretic (52.1% vs. 58%; P = 0.008) and oral anticoagulant (27.5% vs. 32.5%; P = 0.018) use at discharge. In-hospital mortality in the de novo AF group was significantly higher (13.1% vs. 8.31%; P = 0.0005). Post-discharge 12-month survival was similar between groups (14.5% vs. 15.3%, P = 0.63). Long-term re-hospitalization due to heart failure (22.7% vs. 17.2%; P < 0.005) and medical contact due to AF (48.4% vs. 26.1%, P < 0.0001) rates were higher in the group with pre-existing AF, without the difference of stroke or myocardial infarction occurrence.

CONCLUSION
De novo AF accounts for 40% of all AF cases in ACS patients and is an unfavourable in-hospital prognostic factor. The occurrence of de novo AF during ACS should require special attention and caution in the treatment of these patients.

Buchta|Piotr|P|0000-0001-8725-000X
Kalarus|Zbigniew|Z|
Mizia-Stec|Katarzyna|K|
Myrda|Krzysztof|K|
Skrzypek|Michał|M|
Ga Sior|Mariusz|M|

Acute coronary syndromes
Prognosis
De novo atrial fibrillation


Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization.

Abstract: The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 23×31 factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2 ± 2.6) nm and average Zeta potential of (-36.5 ± 0.9) mV, and exhibiting a polydispersity index of 0.206 ± 0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10-12 m2 s-1) as those published by other authors since, typically, diffusion coefficients for molecules range from 10-10 to 10-7 m2 s-1, but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10-12 m2 s-1.

Glasser|Cássia A|CA|
Vila|Marta M D C|MM|
Pereira|Júlio C|JC|
Chaud|Marco V|MV|
Oliveira Júnior|José M|JM|
Tubino|Matthieu|M|
Balcão|Victor M|VM|

infrared spectrophotometry with Fourier transform


The meaning ascribed to wheeled mobility devices by individuals who use wheelchairs and scooters: a metasynthesis.

Abstract:
PURPOSE
To synthesize qualitative study findings on the meaning ascribed to wheelchairs and wheeled mobility devices (WMD) by WMD users.

METHOD
Bibliographic databases were systematically searched up to January 2015 to identify relevant papers. Reviewers selected studies, assessed methodological quality and thematically synthesized findings using a metasynthesis process described by Thomas and Harden (2008).

RESULTS
Twenty articles were included. Four descriptive themes emerged: physical environment interaction; sociocultural experiences; participation in activities and occupations; and WMD-self relationship. WMD use was found to be a complex experience that can fluctuate through interaction with aspects of the environment and opportunities for participation. The analytic theme, dynamic duality of WMD experience, addressed the simultaneous enabling and disabling aspects of WMD use.

CONCLUSIONS
Metasyntheses enable researchers to gain a deeper understanding of issues by examining findings across studies. Findings of this study provide a framework for understanding the complexity of WMD use. The framework has practical applications for clinicians and users of WMD in understanding the experience of WMD to be neither singular nor static. Implications for Rehabilitation The meaning of wheeled mobility device (WMD) use is dynamically influenced by the environment and opportunities afforded for occupational and social participation. A duality of experiences can emerge for WMD users, where wheeled mobility use can be at the same time positive and negative, based on the interaction with the environment. Clinicians need to determine the meaning that each individual user ascribes to the WMD, and to consider how that meaning may change over time. By understanding the meaning ascribed to WMD use by individuals, clinicians can be better prepared to work with the WMD users to address negative reinforcers of the experience in physical and sociocultural environments as well as highlighting the positive experiences.

Ripat|Jacquie|J|
Verdonck|Michele|M|
Carter|Roger Jaffrey|RJ|

D006233:Disabled Persons
D011211:Electric Power Supplies
D004779:Environment Design
D006801:Humans
D007398:Interpersonal Relations
D009790:Occupations
D036301:Qualitative Research
D011788:Quality of Life
D058992:Social Participation
D012959:Socioeconomic Factors
D014910:Wheelchairs

Qualitative research
assistive technology
literature review
powered mobility


Regulation of the Synthesis and Secretion of the Iron Chelator Cyclodipeptide Pulcherriminic Acid in Bacillus licheniformis.

Abstract: The cyclodipeptide pulcherriminic acid synthesized by Bacillus licheniformis is an iron chelator that antagonizes certain pathogens by removing iron from the environment. But since the insoluble iron-pulcherriminic acid complex cannot act as an iron carrier as siderophores do, excessive synthesized pulcherriminic acid causes iron starvation for the producer cells. At present, the regulation of pulcherriminic acid synthesis and the mechanism by which B. licheniformis strikes a balance between biocontrol and self-protection from excessive iron removal remain unclear. This study provides insights into the regulatory network and explains the mechanism of pulcherriminic acid biosynthesis. The yvmC-cypX synthetic gene cluster was directly negatively regulated by three regulators: AbrB, YvnA, and YvmB. Within the regulatory network, YvnA expression was repressed not only by AbrB but also by iron-limiting environments, while YvmB expression was repressed by YvnA. The transporter gene yvmA is repressed by YvmB and is required for pulcherriminic acid secretion. The biosynthesis window is determined by the combined concentration of the three regulators in an iron-rich environment. Under iron-limiting conditions, cells close the pulcherriminic acid synthesis pathway by downregulating YvnA expression.IMPORTANCE The cyclodipeptides are widespread in nature and exhibit a broad variety of biological and pharmacological activities. The cyclodipeptide scaffold is synthesized by nonribosomal peptide synthetases (NRPSs) and cyclodipeptide synthases (CDPSs). At present, it is clear that CDPSs use aminoacyl tRNAs as substrates to synthesize the two peptide bonds, and the pulcherriminic acid synthase YvmC is a member of the eight identified CDPSs. However, little is known about the regulation of cyclodipeptide synthesis and secretion. In this study, we show that AbrB, which is considered to be the main regulator of NRPS-dependent pathways, is also involved in the regulation of CDPS genes. However, AbrB is not the decisive factor for pulcherriminic acid synthesis, as the expression of YvnA determines the fate of pulcherriminic acid synthesis. With this information on how CDPS gene transcription is regulated, a clearer understanding of cyclodipeptide synthesis can be developed for B. licheniformis Similar approaches may be used to augment our knowledge on CDPSs in other bacteria.

Wang|Dong|D| Zhan|Yangyang|Y| Cai|Dongbo|D| Li|Xiaoyun|X| Wang|Qin|Q| Chen|Shouwen|S|

D015964:Gene Expression Regulation, Bacterial

cyclodipeptide
pulcherriminic acid
Bacillus licheniformis
AbrB
iron depletion


Drug repositioning in cancer: The current situation in Japan.

Abstract: Cancer is a leading cause of death worldwide, and the incidence continues to increase. Despite major research aimed at discovering and developing novel and effective anticancer drugs, oncology drug development is a lengthy and costly process, with high attrition rates. Drug repositioning (DR, also referred to as drug repurposing), the process of finding new uses for approved noncancer drugs, has been gaining popularity in the past decade. DR has become a powerful alternative strategy for discovering and developing novel anticancer drug candidates from the existing approved drug space. Indeed, the availability of several large established libraries of clinical drugs and rapid advances in disease biology, genomics/transcriptomics/proteomics and bioinformatics has accelerated the pace of activity-based, literature-based and in silico DR, thereby improving safety and reducing costs. However, DR still faces financial obstacles in clinical trials, which could limit its practical use in the clinic. Here, we provide a brief review of DR in cancer and discuss difficulties in the development of DR for clinical use. Furthermore, we introduce some promising DR candidates for anticancer therapy in Japan.

drug repositioning
cancer
Japan
clinical trial
intellectual property


Long-term mortality in patients with ST-segment elevation myocardial infarction is associated with anti-citrullinated protein antibodies.

Abstract:
BACKGROUND
Cardiovascular (CV) mortality is higher in patients with rheumatoid arthritis (RA), in particular when anti-citrullinated protein antibodies (ACPA) are present. Recently, ACPA have also been described in a cohort of patients without RA, but with coronary artery disease (CAD). It is however unknown if ACPA can consistently be found in patients with CAD, and if ACPA are associated with mortality in these patients. The purpose of this study was to assess the relationship between ACPA and long-term outcomes including mortality in patients with ST-elevation myocardial infarction (STEMI) without RA.

METHODS
All patients with STEMI from the MISSION! Intervention Study were analyzed. Patients with RA were excluded. The association between ACPA (anti-CCP3) at baseline and 10year mortality and re-infarction was investigated.

RESULTS
In total, 29 (11%) of 275 included patients were ACPA-positive, substantiating the previous description of ACPA in CAD patients. Increased cumulative cardiac mortality was observed in ACPA-positive patients in comparison with ACPA-negative patients. Moreover, after correction for other associated factors, ACPA-positivity was associated with long-term mortality (HR 3.1 [CI 1.4-7.1] p-value=0.01) and long-term combined endpoint of re-infarction and death (HR 2.4 [1.2-4.6] p-value=0.01).

CONCLUSION
In STEMI patients without RA, the presence of ACPA is independently associated with long-term mortality and the combined endpoint of re-infarction and death. ACPA in patients with and without RA might act as an independent pro-atherogenic factor.

Hermans|Maaike P J|MPJ|
van der Velden|Daniel|D|
Montero Cabezas|José M|JM|
Putter|Hein|H|
Huizinga|Tom W J|TWJ|
Kuiper|Johan|J|
Toes|Rene E M|REM|
Schalij|Martin J|MJ|
Wouter Jukema|J|J|
van der Woude|Diane|D|

D000072657:ST Elevation Myocardial Infarction


OPTN/SRTR 2015 Annual Data Report: Lung.

Abstract: In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years.

Valapour|M|M|
Skeans|M A|MA|
Smith|J M|JM|
Edwards|L B|LB|
Cherikh|W S|WS|
Uccellini|K|K|
Israni|A K|AK|
Snyder|J J|JJ|
Kasiske|B L|BL|

D000847:Annual Reports as Topic
D006085:Graft Survival
D006801:Humans
D007166:Immunosuppressive Agents
D016040:Lung Transplantation
D040841:Resource Allocation
D014019:Tissue Donors
D009927:Tissue and Organ Procurement
D016896:Treatment Outcome
D014481:United States
D014850:Waiting Lists

lung transplant
lung allocation score
End-stage lung disease
organ allocation
transplant outcomes


Beneficial Effects of Scutellaria baicalensis on Penile Erection in Streptozotocin-Induced Diabetic Rats.

Abstract: We have reported that ethanol extracts of the root from Scutellaria baicalensis Georgi (ESB) relax cavernous smooth muscles via the NO/cGMP system and Ca[Formula: see text]-sensitive K[Formula: see text] channels in the rabbit corpus cavernosum. In the present study, erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrical stimulation of the cavernous nerve. The ICP/MAP ratio was dose-dependently increased by the treatment of ESB in normal SD rats ([Formula: see text]). To investigate the beneficial effect of ESB on erectile dysfunction in a diabetic animal model, male SD rats were injected with streptozotocin (60[Formula: see text]mg/kg) and then 300[Formula: see text]mg/kg/day ESB was administered daily for eight weeks. In our in vivo study, administration of ESB in STZ rats significantly increased the ICP, ICP/MAP ratio, area under the curve (AUC), as well as the cavernous cGMP levels. Morphometric analyses showed that ESB administration increased both smooth muscle volume and the regular arrangement of collagen fibers compared to the STZ group. The protein expression levels of endothelial nitric oxide synthase (eNOS) and SM [Formula: see text]-actin from penile tissues were also significantly increased in the ESB-treated rats. Taken together, these results suggest that ESB ameliorates penile erectile dysfunction via the activation of the NO/cGMP pathways of the penile corpus cavernosum in a streptozotocin-induced diabetic rat model.

Li|Xiang|X|
Lee|Yun Jung|YJ|
Kim|Hye Yoom|HY|
Tan|Rui|R|
Park|Min Cheol|MC|
Kang|Dae Gill|DG|
Lee|Ho Sub|HS|

Scutellaria baicalensis
Penile Erection
Diabetes
NO/cGMP
Corpus Cavernosum


Brain Abscess Complicating a Traumatic Intracerebral Hemorrhagic Contusion.

Abstract: A 63-year-old right-handed man was admitted to our hospital after sustaining a traumatic right-sided subdural hematoma, subarachnoid hemorrhage, and temporal lobe hemorrhagic contusion. He was managed non-operatively and discharged without any neurologic deficits. Two weeks later he presented with worsening headaches and altered sensorium. Imaging studies showed that the patient had developed a cerebral abscess at the site of his intracerebral hemorrhage. The abscess was surgically resected, and the patient was treated with antibiotics with complete resolution of symptoms. This case illustrates the importance of timely recognition of a rare complication of intracranial hemorrhage, and the utility of MR spectroscopy.

brain abscess
imaging
central nervous system infections
nervous system
techniques
trauma


Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials.

Abstract:
BACKGROUND
Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI).

METHODS
A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy.

RESULTS
Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control.

CONCLUSIONS
In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.

Xu|Jia-Ying|JY| Liu|Dai|D| Zhong|Yang|Y| Huang|Rong-Chong|RC|

D045164:Mesenchymal Stem Cell Transplantation

D016032:Randomized Controlled Trials as Topic

Cells
Meta-analysis
Bone marrow-derived cells (BMCs)
Acute myocardial infarction (AMI)
Cell therapy


Long-term exposure to ambient nitrogen dioxide and ozone modifies systematic low-grade inflammation: The CHCN-BTH study.

Abstract: The potential effect of long-term exposure to ambient air pollutants on low-grade systematic inflammation has seldom been evaluated taking indoor air pollution and self-protection behaviors on smog days into account. A total of 24,346 participants at baseline were included to conduct a cross-sectional study. The annual (2016) average pollutant concentrations were assessed by air monitoring stations for PM2.5, PM10, SO2, NO2, O3 and CO. Associations between annual ambient air pollution and low-grade systematic inflammation (hsCRP>3 mg/L) were estimated by generalized linear mixed models. Stratification analysis was also performed based on demographic characteristics, health-related behaviors and disease status. Annual ambient NO2 and O3 were all associated with low-grade systematic inflammation in single-pollutant models after adjusting for age, sex, blood lipids, blood pressure, lifestyle risk factors, cooking fuel, heating fuel and habits during smog days (NO2 per 10 μg/m3: OR = 1.057, P = 0.018; O3 per 10 μg/m3: OR = 0.953, P = 0.012). The 2-year and 3-year ozone concentrations were consistently associated with lower systematic inflammation (2-year O3 per 10 μg/m3: OR = 0.959, P = 0.004; 3-year O3 per 10 μg/m3: OR = 0.961, P = 0.014). In two-pollutant models, the estimated effects of annual NO2 and O3 on low-grade systematic inflammation remained stable. The effect size of annual pollutants on inflammation increased in participants without air-purifier usage (NO2 per 10 μg/m3: OR = 1.079, P = 0.009; O3 per 10 μg/m3: OR = 0.925, P = 0.001), while the association was null in the air-purifier usage group. Thus, long-term exposure to ambient NO2 and O3 was associated with low-grade systemic inflammation, and the results were generally stable after sensitivity analysis. The usage of air purifiers on smog days can modify the association between gaseous pollutants and systematic inflammation.

Liu|Kuo|K| Cao|Han|H| Li|Bingxiao|B| Guo|Chunyue|C| Zhao|Wei|W| Han|Xiaoyan|X| Zhang|Han|H| Wang|Zhengfang|Z| Tang|Naijun|N| Niu|Kaijun|K| Pan|Li|L| He|Huijing|H| Cui|Ze|Z| Sun|Jixin|J| Shan|Guangliang|G| Zhang|Ling|L|

Nitrogen dioxide
Ozone
Low-grade systematic inflammation
Long-term gaseous pollutant


Coming face to face with implicit bias, microagressions, and macroaggressions: Understanding the influence of structural racism and misogyny on physician wellness.

Abstract: Implicit bias, microaggressions, and macroaggressions have a negative impact on physician and trainee wellness. In this article, we describe how structural racism, misogyny, and other social constructs have shaped the medical landscape. Increasing awareness in medical education, patient care, and research can help to dismantle the effects.

Richards|Regina D|RD|
Wohlauer|Max V|MV|

D007722:Health Knowledge, Attitudes, Practice

Implicit bias
Macroaggressions
Microaggressions
Diversity
Equity
Inclusion


Interaction of folate - Linked silica nanoparticles with HeLa cells: Analysis and investigation the effect of polymer length.

Abstract: This work is a continuance to our previous findings on silica nanoparticles (NPs) modified with diamine polymer, carboxymethyl-β-cyclodextrin (CM-β-CD) and folic acid (FA), respectively. When four different polymer lengths (D230, D400, D2000 and D4000) were analyzed, the release rate of anticancer agents was inversely related to the polymer length while the cell toxicity was directly related to the length. We investigate here the effect of polymer length on the extent of cellular interaction with HeLa cells. The mean particle size, the polydispersity (PD) and the zeta potential of the NPs were measured using dynamic light scattering (DLS), the quantitative analysis of the extent of NPs' interaction was studied using fluorescence microscopy and transmission electron microscopy (TEM) was used to qualitatively visualize them. The particle size increased by increasing the polymer length, the PD values were within the acceptable ranges (0.3-0.5) and the zeta potential was in the range of (-16 to -20 mV). A direct relation was observed between the fluorescence intensity and the length. All modified NPs were capable of entering the cells, however a greater number of NPs with long polymers was observed compared to short polymers. Thus, the direct relation of polymer length to the cell toxicity is due to the release rate behavior and the enhanced interaction of NPs which possess long polymers.

Silica nanoparticles
HeLa cells
Polymer length
Fluorescence intensity
TEM images


In Vitro Metabolite Formation in Human Hepatocytes and Cardiomyocytes and Metabolism and Tissue Distribution in Monkeys of the 2'-C-Methylguanosine Prodrug BMS-986094.

Abstract: BMS-986094, a 2'-C-methylguanosine prodrug for the treatment of chronic hepatitis C virus infection, was withdrawn from phase 2 clinical trials because of unexpected cardiac and renal toxicities. To better understand these toxicities, the in vitro metabolism of BMS-986094 in human hepatocytes (HHs) and human cardiomyocytes (HCMs) and the measurement of BMS-986094 and selected metabolites in monkey plasma and tissues were assessed. BMS-986094 was extensively metabolized by HHs and HCMs, resulting in more efficient formation and accumulation of the active triphosphorylated metabolite, INX-09114, and less efficient efflux of metabolites in HCMs. The predominant metabolism pathway (hydrolysis) in HHs and HCMs was not associated with the formation of reactive metabolites or oxidative stress. In cynomolgus monkeys dosed with BMS-986094 of 15 or 30 mg/kg/d for 3 weeks, the nucleoside metabolite M2 was the major plasma analyte (66%-68% of the combined area under the curve). INX-09114 was the highest drug-related species in the heart and kidney (2,610-4,280 ng/mL [males]; ∼2-420× the concentration of other analytes). Other analytes increased dose dependently, with BMS-986094 highest in diaphragm (≤4,400 ng/mL) followed by M2 in liver and kidney (≤1,360 ng/mL), and M7 and M8 in other tissues (≤124 ng/mL). Three weeks after the last dose, INX-09114 remained high in the heart and kidney (≤1,870 ng/mL), with low M2 (≤37 ng/mL) in plasma and tissues. Persistent high concentrations of INX-09114 in the heart and kidney appeared to correlate with toxicities in these tissues in monkeys.

Li|Wenying|W|
Trouba|Kevin J|KJ|
Ma|Li|L|
Kwagh|Jae|J|
Storck|Christopher|C|
Zhu|Yongxin|Y|
Flint|Oliver|O|
Humphreys|William G|WG|
Wang|Jian|J|
Liu|Ang|A|
Wang|Bonnie|B|
Graziano|Michael J|MJ|
Davies|Marc H|MH|
Sanderson|Thomas P|TP|

metabolite HCV NS5b cardiotoxicity nucleotide


Stem cells from human amniotic fluid exert immunoregulatory function via secreted indoleamine 2,3-dioxygenase1.

Abstract: Although human amniotic fluid does contain different populations of foetal-derived stem cells, scanty information is available on the stemness and the potential immunomodulatory activity of in vitro expanded, amniotic fluid stem cells. By means of a methodology unrequiring immune selection, we isolated and characterized different stem cell types from second-trimester human amniotic fluid samples (human amniotic fluid stem cells, HASCs). Of those populations, one was characterized by a fast doubling time, and cells were thus designated as fHASCs. Cells maintained their original phenotype under prolonged in vitro passaging, and they were able to originate embryoid bodies. Moreover, fHASCs exhibited regulatory properties when treated with interferon (IFN)-γ, including induction of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). On coculture with human peripheral blood mononuclear cells, IFN-γ-treated fHASCs caused significantly decreased T-cell proliferation and increased frequency in CD4(+)  CD25(+)  FOXP3(+) regulatory T cells. Both effects required an intact IDO1 function and were cell contact-independent. An unprecedented finding in our study was that purified vesicles from IFN-γ-treated fHASCs abundantly expressed the functional IDO1 protein, and those vesicles were endowed with an fHASC-like regulatory function. In vivo, fHASCs were capable of immunoregulatory function, promoting allograft survival in a mouse model of allogeneic skin transplantation. This was concurrent with the expansion of CD4(+)  CD25(+)  Foxp3(+) T cells in graft-draining lymph nodes from recipient mice. Thus fHASCs, or vesicles thereof, may represent a novel opportunity for immunoregulatory maneuvers both in vitro and in vivo.

Romani|Rita|R|
Pirisinu|Irene|I|
Calvitti|Mario|M|
Pallotta|Maria Teresa|MT|
Gargaro|Marco|M|
Bistoni|Giovanni|G|
Vacca|Carmine|C|
Di Michele|Alessandro|A|
Orabona|Ciriana|C|
Rosati|Jessica|J|
Pirro|Matteo|M|
Giovagnoli|Stefano|S|
Matino|Davide|D|
Prontera|Paolo|P|
Rosi|Gabriella|G|
Grohmann|Ursula|U|
Talesa|Vincenzo N|VN|
Donti|Emilio|E|
Puccetti|Paolo|P|
Fallarino|Francesca|F|

T cells
cell culture
cloning
immunosuppression
lymphocytes
pluripotent stem cells


Cellular senescence in dental pulp stem cells.

Abstract:
OBJECTIVE
This short review summarizes our current knowledge about dental stem cell aging and about possible targets for the regulation of cellular senescence.

DESIGN
A literature search was performed using a combination of keywords, e.g., stem cells, replicative senescence, differentiation potential, dental pulp, dental follicle and periodontal ligament.

RESULTS
Previous studies have shown that cellular senescence occurs while the proliferation of dental stem cells. Moreover, the differentiation potential was significantly decreased in senescent stem cells and senescent cells secrete also factors that are harmful to the adjacent tissue cells. Moreover, many targets for the regulation of cellular senescence are considered; for example pathways related to the nutrient sensing such as the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway.

CONCLUSIONS
The regulation of cellular senescence will play a crucial role in the clinical use of stem cells. However, there is no cell culture protocol available that prevents dental stem cell senescence. Therefore, more knowledge about molecular processes in stem cells is needed before and after the induction of senescence.

D000091162:AMP-Activated Protein Kinase Kinases

Cellular senescence
Dental pulp stem cells
AMPK
Odontogenic differentiation
SIRT


Engineering a Humanised Niche to Support Human Haematopoiesis in Mice: Novel Opportunities in Modelling Cancer.

Abstract: Despite the bone marrow microenvironment being widely recognised as a key player in cancer research, the current animal models that represent a human haematopoietic system lack the contribution of the humanised marrow microenvironment. Here we describe a murine model that relies on the combination of an orthotopic humanised tissue-engineered bone construct (ohTEBC) with patient-specific bone marrow (BM) cells to create a humanised bone marrow (hBM) niche capable of supporting the engraftment of human haematopoietic cells. Results showed that this model supports the engraftment of human CD34+ cells from a healthy BM with human haematopoietic cells migrating into the mouse BM, human BM compartment, spleen and peripheral blood. We compared these results with the engraftment capacity of human CD34+ cells obtained from patients with multiple myeloma (MM). We demonstrated that CD34+ cells derived from a diseased BM had a reduced engraftment potential compared to healthy patients and that a higher cell dose is required to achieve engraftment of human haematopoietic cells in peripheral blood. Finally, we observed that hematopoietic cells obtained from the mobilised peripheral blood of patients yields a higher number of CD34+, overcoming this problem. In conclusion, this humanised mouse model has potential as a unique and patient-specific pre-clinical platform for the study of tumour-microenvironment interactions, including human bone and haematopoietic cells, and could, in the future, serve as a drug testing platform.

bone marrow
multiple myeloma
humanised mouse model
CD34+ haematopoietic stem cell
tissue engineering
tumour microenvironment


Intraoperative vertebral artery angiography to guide c1-2 transarticular screw fixation in a patient with athetoid cerebral palsy.

Abstract: We present a case of an athetoid cerebral palsy with quadriparesis caused by kyphotic deformity of the cervical spine, severe spinal stenosis at the cervicomedullary junction, and atlantoaxial instability. The patient improved after the first surgery, which included a C1 total laminectomy and C-arm guided righ side unilateral C1-2 transarticular screw fixation. C1-2 fixation was not performed on the other side because of an aberrant and dominant vertebral artery (VA). Eight months after the first operation, the patient required revision surgery for persistent neck pain and screw malposition. We used intraoperative VA angiography with simultaneous fluoroscopy for precise image guidance during bilateral C1-2 transarticular screw fixation. Intraoperative VA angiography allowed the accurate insertion of screws, and can therefore be used to avoid VA injury during C1-2 transarticular screw fixation in comorbid patients with atlantoaxial deformities.

Chung|Jong Chul|JC|
Jung|Sung Sam|SS|
Park|Ki Seok|KS|
Ha|Ho Gyun|HG|

Vertebral artery
Transarticular screw fixation
Athetoid cerebral palsy
Atlantoaxial instability
Intraoperative angiography


Postmenopausal labial agglutination mimics urinary incontinence and hidden vaginal lesion.

Abstract: Labial agglutination has rarely been reported in postmenopausal women and its treatment has been based on experience with prepubertal girls. We describe an 83-year-old woman who presented with labial agglutination and severe urinary incontinence. She had been treated intermittently with a topical estrogen cream for 3 years, but her symptoms persisted. Surgery was performed and her urinary incontinence was instantly resolved. Incidental vaginal low-grade squamous intraepithelial neoplasia was noted. Later, the lesion progressed and was confirmed to be condyloma acuminata. No recurrence of labial agglutination was noted 3 months after the surgery. We emphasize that surgical intervention should be the first consideration for labial agglutination with urinary symptoms in postmenopausal women. This case also highlights that surgery can not only resolve patients' symptoms early, but can also enable access to the region for essential gynecologic procedures.

D065310:Squamous Intraepithelial Lesions of the Cervix

labial agglutination
urinary incontinence
labial fusion
urinary dysfunction


Risk factors for pulmonary complications after posterior spinal instrumentation and fusion in the treatment of congenital scoliosis: a case-control study.

Abstract:
BACKGROUND
Although surgery prevents the progression of deformity and maintains the overall balance of the spine in congenital scoliosis (CS) patients, it is associated with a high risk of perioperative complications. Pulmonary complication is one of the most common complications. This retrospective study aimed to investigate the risk factors for pulmonary complications in CS patients after posterior spinal instrumentation and fusion.

METHODS
Analysis of consecutive patients who underwent posterior spinal instrumentation and fusion for congenital scoliosis was performed. Preoperative clinical data, intraoperative variables, and perioperative radiographic parameters were collected to analyze the risk factors for pulmonary complications. Patients were separated into groups with and without postoperative pulmonary complications. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of pulmonary complications.

RESULTS
Three hundred and twenty-three CS patients were included. Forty-five (13.9%) patients developed postoperative pulmonary complications, which included pleural effusion in 34 (75.6%) cases, pneumonia in 24 (53.3%) cases, pneumothorax in 3 (6.7%) cases, atelectasis in 4 (8.9%) cases, pulmonary edema in 2 (4.4%) cases, respiratory failure in 2 (4.4%) cases, and prolonged mechanical ventilation in 4 (8.9%) cases. The independent risk factors for development of pulmonary complications included age (Odds ratio (OR) = 1.088, P = 0.038), reoperation (OR = 5.150, P = 0.012), preoperative pulmonary disease (OR = 10.504, P = 0.004), correction rate (OR = 1.088, P = 0.001), middle thoracic screw-setting (OR = 12.690, P = 0.043), and thoracoplasty (OR = 5.802, P = 0.001). The area under the receiver operating characteristic (ROC) curve based on predicted probability of the logistic regression was 0.903.

CONCLUSIONS
Age, reoperation, preoperative pulmonary disease, correction rate, middle thoracic screw-setting, and thoracoplasty were independent risk factors for pulmonary complications after posterior spinal instrumentation and fusion in CS patients.

Wu|Lei|L| Zhang|Xi-Nuo|XN| Wang|Yun-Sheng|YS| Liu|Yu-Zeng|YZ| Hai|Yong|Y|

Posterior spinal instrumentation and fusion


The impact of lymphopenia during chemoradiotherapy using photons or protons on the clinical outcomes of esophageal cancer patients.

Abstract: We assessed the development of lymphopenia during concurrent chemoradiotherapy (CRT) using X-ray versus proton beams and the impact on survival in patients with esophageal cancer. Among patients with esophageal cancer who were administered concurrent CRT with a curative intent at our institute from 2014 to 2018, 69 (15 receiving X-ray radiotherapy (XRT) and 54 receiving proton beam therapy [PBT]) who underwent weekly blood testing during treatment were enrolled. The absolute lymphocyte counts (ALC) at 1, 5 and 6 weeks were significantly higher in the patients who received PBT than in those who received XRT (p = 0.002, p = 0.006 and p = 0.009, respectively), and a similar trend in the neutrophil-to-lymphocyte ratio (NLR) was observed (p = 0.003 at 5 weeks). The 2-year overall survival (OS) and progression-free survival (PFS) rates tended to be higher in the patients who maintained an ALC ≥200 compared with those who did not (p = 0.083 and p = 0.053, respectively), and similar trends were observed in the NLR (p = 0.061 and p = 0.038, respectively). Dose-volume analysis revealed significant correlations between volumes of the thoracic bones irradiated by 5-50 Gy and minimum ALCs and maximum NLR. These findings suggested that PBT prevented the development of lymphopenia during CRT by reducing the irradiated volume of the thoracic bone, and the maintained lymphocyte count is possibly one of the early predictors for survival in patients with esophageal cancer.

Sumiya|Taisuke|T| Ishikawa|Hitoshi|H| Hiroshima|Yuichi|Y| Nakamura|Masatoshi|M| Murakami|Motohiro|M| Mizumoto|Masashi|M| Okumura|Toshiyuki|T| Sakurai|Hideyuki|H|

lymphopenia
esophageal cancer
chemoradiotherapy (CRT)
proton beam therapy (PBT)


Contactless Inductive Bubble Detection in a Liquid Metal Flow.

Abstract: The detection of bubbles in liquid metals is important for many technical applications. The opaqueness and the high temperature of liquid metals set high demands on the measurement system. The high electrical conductivity of the liquid metal can be exploited for contactless methods based on electromagnetic induction. We will present a measurement system which consists of one excitation coil and a pickup coil system on the opposite sides of the pipe. With this sensor we were able to detect bubbles in a sodium flow inside a stainless steel pipe and bubbles in a column filled with a liquid Gallium alloy.

Gundrum|Thomas|T| Büttner|Philipp|P| Dekdouk|Bachir|B| Peyton|Anthony|A| Wondrak|Thomas|T| Galindo|Vladimir|V| Eckert|Sven|S|

bubble detection
liquid metal
contactless inductive measurements
two phase flow
void fraction


Lysosome-Targeted and Fluorescence-Turned "On" Cytotoxicity Induced by Alkaline Phosphatase-Triggered Self-Assembly.

Abstract: Selectively inducing lysosomal membrane permeabilization (LMP) is a promising strategy for cancer therapy. But integrating alkaline phosphatase (ALP)-instructed self-assembly and lysosome-targeting to induce LMP for selective killing of cancer cells was not reported. Herein, a pyrene-peptide conjugate Py-Phe-Phe-Glu-Tyr(H2 PO3 )-Gly-lyso (Py-Yp-Lyso) is rationally designed and demonstrated for its lysosome-targeting cytotoxicity on cancer cells, together with its pyrene (Py) excimer fluorescence turning "on" at 480 nm. In vitro results showed that, Py-Yp-Lyso is efficiently dephosphorylated by ALP to yield Py-Phe-Phe-Glu-Tyr-Gly-lyso (Py-Y-Lyso) which self-assembles into nanofibers. Cell experiments verified that, after being taken up by HeLa cells, the excimer fluorescence of Py-Yp-Lyso assemblies has turned "on" and the assemblies specifically target the lysosomes, inducing LMP and ultimate cancer cell death. In vivo experiments indicated that Py-Yp-Lyso has the highest inhibition effect on HeLa tumors among the four compounds studied. This is anticipated for applying Py-Yp-Lyso to treat cancers in the clinic in the future.

lysosome-targeting
cytotoxicity
self-assembly
excimer fluorescence
nanofibers


Robust Traffic Light and Arrow Detection Using Digital Map with Spatial Prior Information for Automated Driving.

Abstract: Traffic light recognition is an indispensable elemental technology for automated driving in urban areas. In this study, we propose an algorithm that recognizes traffic lights and arrow lights by image processing using the digital map and precise vehicle pose which is estimated by a localization module. The use of a digital map allows the determination of a region-of-interest in an image to reduce the computational cost and false detection. In addition, this study develops an algorithm to recognize arrow lights using relative positions of traffic lights, and the arrow light is used as prior spatial information. This allows for the recognition of distant arrow lights that are difficult for humans to see clearly. Experiments were conducted to evaluate the recognition performance of the proposed method and to verify if it matches the performance required for automated driving. Quantitative evaluations indicate that the proposed method achieved 91.8% and 56.7% of the average f-value for traffic lights and arrow lights, respectively. It was confirmed that the arrow-light detection could recognize small arrow objects even if their size was smaller than 10 pixels. The verification experiments indicate that the performance of the proposed method meets the necessary requirements for smooth acceleration or deceleration at intersections in automated driving.

Yoneda|Keisuke|K|0000-0002-3247-7001 Kuramoto|Akisuke|A| Suganuma|Naoki|N| Asaka|Toru|T| Aldibaja|Mohammad|M| Yanase|Ryo|R|

image processing
intelligent transportation system
traffic light detection


How the Cervical Microbiota Contributes to Cervical Cancer Risk in Sub-Saharan Africa.

Abstract: Despite ongoing efforts, sub-Saharan Africa faces a higher cervical cancer burden than anywhere else in the world. Besides HPV infection, definitive factors of cervical cancer are still unclear. Particular states of the cervicovaginal microbiota and viral infections are associated with increased cervical cancer risk. Notably, HIV infection, which is prevalent in sub-Saharan Africa, greatly increases risk of cervicovaginal dysbiosis and cervical cancer. To better understand and address cervical cancer in sub-Saharan Africa, a better knowledge of the regional cervicovaginal microbiome is required This review establishes current knowledge of HPV, HIV, cervicovaginal infections, and the cervicovaginal microbiota in sub-Saharan Africa. Because population statistics are not available for the region, estimates are derived from smaller cohort studies. Microbiota associated with cervical inflammation have been found to be especially prevalent in sub-Saharan Africa, and to associate with increased cervical cancer risk. In addition to high prevalence and diversity of HIV and HPV, intracellular bacterial infections such as Chlamydia, Gonorrhea, and Mycoplasma hominis are much more common than in regions with a low burden of cervical cancer. This suggests the prevalence of cervical cancer in sub-Saharan Africa may be partially attributed to increased cervical inflammation resulting from higher likelihood of cervical infection and/or microbial dysbiosis.

Klein|Cameron|C|
Kahesa|Crispin|C|
Mwaiselage|Julius|J|
West|John T|JT|
Wood|Charles|C|
Angeletti|Peter C|PC|

cervical cancer
sub-saharan Africa
HPV
HIV
microbiome


Source-specific sewage pollution detection in urban river waters using pharmaceuticals and personal care products as molecular indicators.

Abstract: Source-specific elucidation of domestic sewage pollution caused by various effluent sources in an urban river water, as conducted for this study, demands knowledge of the relation between concentrations of pharmaceuticals and personal care products (PPCPs) as molecular indicators (caffeine, carbamazepine, triclosan) and water quality concentrations of total nitrogen (T-N) and total phosphorous (T-P). River water and wastewater samples from the Asahikawa River Basin in northern Japan were analyzed using derivatization-gas chromatography/mass spectrometry. Caffeine, used as an indicator of domestic sewage in the Asahikawa River Basin, was more ubiquitous than either carbamazepine or triclosan (92-100 %). Its concentration was higher than any target compound used to assess the basin: <4.4-370 ng/L for caffeine, <0.6-3.9 ng/L for carbamazepine, and <1.1-13 ng/L for triclosan. Higher caffeine concentrations detected in wastewater effluents and the strongly positive mutual linear correlation between caffeine and T-N or T-P (R 2 > 0.759) reflect the contribution of septic tank system effluents to the lower Asahikawa River Basin. Results of relative molecular indicators in combination with different molecular indicators (caffeine/carbamazepine and triclosan/carbamazepine) and cluster analysis better reflect the contribution of sewage than results obtained using concentrations of respective molecular indicators and cluster analysis. Relative molecular indicators used with water quality parameters (e.g., caffeine/T-N ratio) in this study provide results more clearly, relatively, and quantitatively than results obtained using molecular indicators alone. Moreover, the caffeine/T-N ratio reflects variations of caffeine flux from effluent sources. These results suggest strongly relative molecular indicators are also useful indicators, reflecting differences in spatial contributions of domestic sources for PPCPs in urban areas.

Sewage pollution
Urban river water
Molecular indicator
PPCPs
Total nitrogen
Aerobic septic tank systems
Emerging contaminants


Unveiling novel interactions of histone chaperone Asf1 linked to TREX-2 factors Sus1 and Thp1.

Abstract: Anti-silencing function 1 (Asf1) is a conserved key eukaryotic histone H3/H4 chaperone that participates in a variety of DNA and chromatin-related processes. These include the assembly and disassembly of histones H3 and H4 from chromatin during replication, transcription, and DNA repair. In addition, Asf1 is required for H3K56 acetylation activity dependent on histone acetyltransferase Rtt109. Thus, Asf1 impacts on many aspects of DNA metabolism. To gain insights into the functional links of Asf1 with other cellular machineries, we employed mass spectrometry coupled to tandem affinity purification (TAP) to investigate novel physical interactions of Asf1. Under different TAP-MS analysis conditions, we describe a new repertoire of Asf1 physical interactions and novel Asf1 post-translational modifications as ubiquitination, methylation and acetylation that open up new ways to regulate Asf1 functions. Asf1 co-purifies with several subunits of the TREX-2, SAGA complexes, and with nucleoporins Nup2, Nup60, and Nup57, which are all involved in transcription coupled to mRNA export in eukaryotes. Reciprocally, Thp1 and Sus1 interact with Asf1. Albeit mRNA export and GAL1 transcription are not affected in asf1Δ a strong genetic interaction exists between ASF1 and SUS1. Notably, supporting a functional link between Asf1 and TREX-2, both Sus1 and Thp1 affect the levels of Asf1-dependent histone H3K56 acetylation and histone H3 and H4 incorporation onto chromatin. Additionally, we provide evidence for a role of Asf1 in histone H2B ubiquitination. This work proposes a functional link between Asf1 and TREX-2 components in histone metabolism at the vicinity of the nuclear pore complex.

Pamblanco|Mercè|M|
Oliete-Calvo|Paula|P|
García-Oliver|Encar|E|
Luz Valero|M|M|
Sanchez del Pino|Manuel M|MM|
Rodríguez-Navarro|Susana|S|

D015966:Gene Expression Regulation, Fungal

histones
TREX-2
Sus1
SAGA
(5-10) yAsf1
TAP-MS strategy
yeast


Antibody Pull-Down Experiments in Fission Yeast.

Abstract: Proteins act as executors for almost all kinds of cellular processes. The majority of proteins achieve their proper functions through interacting with other proteins. Knowing the binding partners of a protein is instrumental for understanding its function. The antibody pull-down method is a powerful and common approach to detect protein-protein interactions. Here, an antibody pull-down protocol is described for detecting protein-protein interactions in fission yeast Schizosaccharomyces pombe.

Antibody
Pull-down
Fission yeast
Protein-protein interaction
Schizosaccharomyces pombe
Co-immunoprecipitation
In vivo


How accurate is the Pearson r-from-Z approximation? A Monte Carlo simulation study.

Abstract: The Pearson r-from-Z approximation estimates the sample correlation (as an effect size measure) from the ratio of two quantities: the standard normal deviate equivalent (Z-score) corresponding to a one-tailed p-value divided by the square root of the total (pooled) sample size. The formula has utility in meta-analytic work when reports of research contain minimal statistical information. Although simple to implement, the accuracy of the Pearson r-from-Z approximation has not been empirically evaluated. To address this omission, we performed a series of Monte Carlo simulations. Results indicated that in some cases the formula did accurately estimate the sample correlation. However, when sample size was very small (N = 10) and effect sizes were small to small-moderate (ds of 0.1 and 0.3), the Pearson r-from-Z approximation was very inaccurate. Detailed figures that provide guidance as to when the Pearson r-from-Z formula will likely yield valid inferences are presented.

Pearson r-from-Z
Monte Carlo simulation
correlation
effect size
meta-analysis


Performance and mechanisms of sulfadiazine removal using persulfate activated by Fe3O4@CuOx hollow spheres.

Abstract: A Fe-Cu bimetal catalyst (FCHS) was synthesized by depositing Fe3O4 on the shell of CuOx hollow spheres, which were prepared via a soft template method. Several characterization methods, including XRD, SEM-EDS&mapping, TEM, FTIR, and XPS, were used to reveal the morphology and surface properties of FCHS. The characterization results demonstrated that the double-shell hollow structure is formed with a dense coating of Fe3O4 nanoparticles on the surface of CuOx hollow spheres. FCHS can exhibit excellent catalytic activity to degrade sulfadiazine (SDZ) with the oxidant of persulfate (PS). The optimal SDZ removal performance was explored by adjusting reaction parameters, including catalyst dosage, oxidant dosage, and solution pH. The SDZ removal efficiency in the FCHS + PS system could reach 95% at the optimal reaction condition ([catalyst]0 = 0.2 g/L, [PS]0 = 2 mM, pH = 7.0) with 5 mg/L of SDZ. Meanwhile, the degradation efficiency decreased with the coexistence of phosphate or carbonate anions. According to the results of radicals scavenging experiments and the electron paramagnetic resonance analysis, the radicals of SO4·-, O2·- and ·OH generated in the FCHS + PS system contribute to the degradation of SDZ. Moreover, the results of XPS revealed that the solid-state charge-transfer redox couple of Fe(III)/Fe(II) and Cu(I)/Cu(II) can promote the activation of PS. It means that the cooperation effect between Cu oxides and Fe oxides in the double-shell structure is beneficial to the catalytic degradation of SDZ. Furthermore, four possible pathways for SDZ degradation were proposed according to the analysis of intermediate products detected by the LCMS-IT-TOF.

Liu|Ting|T| Wu|Kun|K| Wang|Meng|M| Jing|Chunyang|C| Chen|Yuanyuan|Y| Yang|Shengjiong|S| Jin|Pengkang|P|

Sulfadiazine
Persulfate
Hollow spheres
Degradation mechanism
Fe–Cu oxides


Association of antidiabetic medications targeting the glucagon-like peptide 1 pathway and heart failure events in patients with diabetes.

Abstract:
BACKGROUND
Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors (GLP-1 agents) may be protective in heart failure (HF). We set out to determine whether GLP-1 agent use is associated with HF risk in diabetics.

METHODS AND RESULTS
In this retrospective cohort study of members of a large health system, we identified >19,000 adult diabetics from January 1, 2000, to July 1, 2012. GLP-1 agent users were matched 1:2 to control subjects with the use of propensity matching based on age, race, sex, coronary disease, HF, diabetes duration, and number of antidiabetic medications. The association of GLP-1 agents with time to HF hospitalization was tested with multivariable Cox regression. All-cause hospitalization and mortality were secondary end points. We identified 1,426 users of GLP-1 agents and 2,798 control subjects. Both were similar except for angiotensin-converting enzyme inhibitors/angiotensin receptor blocker use, number of antidiabetic medications, and age. There were 199 hospitalizations, of which 128 were for HF, and 114 deaths. GLP-1 agents were associated with reduced risk of HF hospitalization (adjusted hazard ratio [aHR] 0.51, 95% confidence interval [CI] 0.34-0.77; P = .002), all-cause hospitalization (aHR 0.54, 95% CI 0.38-0.74; P = .001), and death (aHR 0.31, 95% CI 0.18-0.53; P = .001).

CONCLUSIONS
GLP-1 agents may reduce the risk of HF events in diabetics.

Velez|Mauricio|M|
Peterson|Edward L|EL|
Wells|Karen|K|
Swadia|Tanmay|T|
Sabbah|Hani N|HN|
Williams|L Keoki|LK|
Lanfear|David E|DE|

heart failure
DPP-4 inhibitor
GLP-1 agonist
outcomes


Impact of Alprazolam on Comorbid Pain and Knee Functions in Total Knee Arthroplasty Patients Diagnosed with Anxiety and Depression.

Abstract:
PURPOSE
Studies report 19-33% postoperative moderate-severe pain and dissatisfaction in uncomplicated total knee arthroplasty (TKA), even after 1 year. High rates of undiagnosed depression and anxiety may have a strong impact on these unfavourable outcomes. Here we aimed to investigate the efficacy of alprazolam on postoperative analgesic use and knee functions.

METHODS
Seventy-six patients with a mean age of 65 ± 9.3 years (range 46-80) diagnosed with mild-moderate anxiety or depression according to the Hamilton anxiety scale (HAS) and Beck Depression Inventory (BDI) that underwent TKA were evaluated in the study. Group 1 patients were subjected to alprazolam treatment in addition to an analgesic/antiinflammatory drug, whereas Group 2 consisted of patients receiving only the standard postoperative pain management protocol. Visual analog scale (VAS) and postoperative analgesic use (g/day) were calculated to evaluate the magnitude of pain experienced. Preoperative and postoperative knee functions were assessed from the patients' Knee Society Score and Knee Society Functional Score records.

RESULTS
A positive correlation was found between the preoperative HAS, BDI, and total postoperative analgesic use in both groups. Although the decrease in VAS was significant in both groups, postoperative analgesic need (4.25 ± 0.30 g) in Group 1 was less compared to Group 2 (4.81 ± 0.41 g) (p=0.01). The mean change in postoperative (1 month) Knee Society Score and Knee Society Functional Score were also significantly improved in Group1 compared to Group 2.

CONCLUSION
Alprazolam can reduce postoperative analgesic use and improve knee functions by reducing the pain threshold, and enhancing overall mood via its antidepressive and anxiolytic properties in patients undergoing TKA diagnosed with mild-moderate anxiety/depression.

Yılmaz|Barış|B|
Kömür|Baran|B|
Aktaş|Erdem|E|
Sonnur Yılmaz|Firdes|F|
Çopuroğlu|Cem|C|
Özcan|Mert|M|
Çiftdemir|Mert|M|
Çopuroğlu|Elif|E|

Alprazolam
comorbid pain
anxiety
depression
total knee arthroplasty.


Response of the antioxidant enzymes of the erythrocyte and alterations in the serum biomarkers in rats following oral administration of nanoparticles.

Abstract: In this study, Al2O3, CuO and TiO2 nanoparticles (NPs) were administered to mature female rats (Rattus norvegicus var. albinos) via oral gavage (0, 0.5, 5, 50mg/kg b.w./day) for 14days to investigate their effects on 14 serum biomarkers and 4 antioxidant enzyme (catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase) activities in the erythrocyte. Data showed that Al2O3 did not cause any significant (P>0.05) change in the parameters, except few cases, while CuO and TiO2 caused significant alterations in antioxidant system parameters of the erythrocytes. Activities of catalase and superoxide dismutase significantly decreased in CuO and TiO2 administered rats. Oppositely, glutathione peroxidase activity increased in CuO and TiO2 administered rats. There were no significant alterations in the activity of glutathione S-transferase in the erythrocytes. Levels of glucose, cholesterol, bilirubin, triglyceride, triiodothyronine (T3), estradiol, prolactin and immunoglobulin M (IgM) in the serum altered after some of NP administrations, whereas cortisol, protein, creatinine, blood urea nitrogen (BUN), thyroxine (T4) and immunoglobulin G (IgG) levels in the serum did not change significantly after any of NP administration. There were outstanding increases in the levels of bilirubin and prolactin and decreases in the levels of triglyceride and estradiol. The present study demonstrated that the antioxidant enzymes in the erythrocyte were generally affected from copper and titanium NPs, while aluminium and copper NPs caused more significant alterations in serum biomarkers.

Canli|Esin G|EG|
Atli|Gülüzar|G|
Canli|Mustafa|M|

D015971:Gene Expression Regulation, Enzymologic

Antioxidant Erythrocyte Serum Rat Nanoparticle Metal


Evaluating the Quality of Experience Performance Metric for UAV-Based Networks.

Abstract: In this work, we consider a UAV-assisted cell in a single user scenario. We consider the Quality of Experience (QoE) performance metric calculating it as a function of the packet loss ratio. In order to acquire this metric, a radio-channel emulation system was developed and tested under different conditions. The system consists of two independent blocks, separately emulating connections between the User Equipment (UE) and unmanned aerial vehicle (UAV) and between the UAV and Base station (BS). In order to estimate scenario usage constraints, an analytical model was developed. The results show that, in the described scenario, cell coverage can be enhanced with minimal impact on QoE.

QoE
emulation
UAV
5G
6G
aerial base station
flying network