Transcription factor specificity protein 1 modulates TGFβ1/Smad signaling to negatively regulate SIGIRR expression by human M1 macrophages stimulated with substance P.

Abstract: The stimuli inducing expression of single immunoglobulin IL-1-related receptor (SIGIRR) and the relevant regulatory mechanisms are not well defined. Transforming growth factor β1 (TGFβ1) delays internalization of neurokinin-1 receptor (NK1R) and subsequently enhances cellular signaling. This study investigated the effect of TGFβ1 on SIGIRR protein production by human M1 macrophages in response to stimulation with substance P (SP). SP caused upregulation of SIGIRR expression in a concentration-dependent manner, whereas aprepitant (an NK1R inhibitor) blunted this response. Silencing p38γMAPK or TAK-1 partially attenuated the response to SP stimulation, while TGFβ1/2/3 siRNA dramatically diminished it. SP induced much greater SIGIRR protein production than either lipopolysaccharide (a TLR4 agonist) or resiquimod (a TLR7/8 agonist). Unexpectedly, silencing of transcription factor specificity protein 1 (Sp1) led to significant upregulation of SIGIRR expression after SP stimulation, while KLF2 siRNA only partially enhanced it and Fli-1 siRNA reduced it. SP also upregulated TGFβ1 expression, along with a corresponding increase of SIGIRR protein, whereas silencing TGFβ1/2/3 blunted these responses. Sp1 siRNA or mithramycin (a gene-selective Sp1 inhibitor) significantly enhanced the expression of TGFβ1 and SIGIRR by macrophages after SP stimulation. Importantly, this effect of Sp1 siRNA on TGFβ1 and SIGIRR was blunted by siRNA for Smad2, Smad3, or Smad4, but not by TAK-1 siRNA. Next, we investigated the influence of transcription factor cross-talk on SIGIRR expression in response to SP. Co-transfection of macrophages with Sp1 siRNA and C/EBPβ or TIF1β siRNA attenuated the upregulation of SIGIRR by SP, while a combination of Sp1 siRNA and Fli-1 siRNA dramatically diminished it. In conclusion, TGFβ1 may be an intermediary between SP/NK1R activation and SIGIRR expression in Sp1 siRNA-transfected macrophages. In addition, Sp1 modulates TGFβ1/Smad signaling and negatively regulates SIGIRR protein production by macrophages after SP stimulation.

Yamaguchi|Rui|R| Sakamoto|Arisa|A| Yamaguchi|Reona|R| Haraguchi|Misa|M| Narahara|Shinji|S| Sugiuchi|Hiroyuki|H| Yamaguchi|Yasuo|Y|

D053773:Transforming Growth Factor beta1

Specificity protein 1
TGFβ1
SIGIRR
Neurokinin-1 receptor
Substance P


Identification of Novel Candidate Epitopes on SARS-CoV-2 Proteins for South America: A Review of HLA Frequencies by Country.

Abstract: Coronavirus disease (COVID-19), caused by the virus SARS-CoV-2, is already responsible for more than 4.3 million confirmed cases and 295,000 deaths worldwide as of May 15, 2020. Ongoing efforts to control the pandemic include the development of peptide-based vaccines and diagnostic tests. In these approaches, HLA allelic diversity plays a crucial role. Despite its importance, current knowledge of HLA allele frequencies in South America is very limited. In this study, we have performed a literature review of datasets reporting HLA frequencies of South American populations, available in scientific literature and/or in the Allele Frequency Net Database. This allowed us to enrich the current scenario with more than 12.8 million data points. As a result, we are presenting updated HLA allelic frequencies based on country, including 91 alleles that were previously thought to have frequencies either under 5% or of an unknown value. Using alleles with an updated frequency of at least ≥5% in any South American country, we predicted epitopes in SARS-CoV-2 proteins using NetMHCpan (I and II) and MHC flurry. Then, the best predicted epitopes (class-I and -II) were selected based on their binding to South American alleles (Coverage Score). Class II predicted epitopes were also filtered based on their three-dimensional exposure. We obtained 14 class-I and four class-II candidate epitopes with experimental evidence (reported in the Immune Epitope Database and Analysis Resource), having good coverage scores for South America. Additionally, we are presenting 13 HLA-I and 30 HLA-II novel candidate epitopes without experimental evidence, including 16 class-II candidates in highly exposed conserved areas of the NTD and RBD regions of the Spike protein. These novel candidates have even better coverage scores for South America than those with experimental evidence. Finally, we show that recent similar studies presenting candidate epitopes also predicted some of our candidates but discarded them in the selection process, resulting in candidates with suboptimal coverage for South America. In conclusion, the candidate epitopes presented provide valuable information for the development of epitope-based strategies against SARS-CoV-2, such as peptide vaccines and diagnostic tests. Additionally, the updated HLA allelic frequencies provide a better representation of South America and may impact different immunogenetic studies.

Requena|David|D|
Médico|Aldhair|A|
Chacón|Ruy D|RD|
Ramírez|Manuel|M|
Marín-Sánchez|Obert|O|

D000483:Alleles
D000595:Amino Acid Sequence
D000073640:Betacoronavirus
D000086382:COVID-19
D000086663:COVID-19 Vaccines
D018352:Coronavirus Infections
D018984:Epitopes, T-Lymphocyte
D005787:Gene Frequency
D014644:Genetic Variation
D006680:HLA Antigens
D006801:Humans
D058873:Pandemics
D011024:Pneumonia, Viral
D000086402:SARS-CoV-2
D013020:South America
D022223:Vaccines, Subunit
D014759:Viral Envelope Proteins
D014765:Viral Vaccines

epitope
SARS-CoV-2
South America
HLA
COVID-19
allele frequency
literature review
immunoinformatics


Social and cultural construction processes involved in HPV vaccine hesitancy among Chinese women: a qualitative study.

Abstract:
BACKGROUND
HPV vaccine is a prophylactic vaccine to prevent HPV infections. Recommended by the World Health Organization, this vaccine is clinically proven to be one of the most effective preventive measures against the prevalence of cervical cancer and other HPV-associated cancers and chronic genital conditions. However, its uptake rate among women in Hong Kong is insignificant-only approximately 2.9% adolescent girls and 9.7% female university students received HPV vaccination in 2014. With the notion of Critical Medical Anthropology, we aimed to identify if different influential factors, ranging from individual, societal, and cultural, are involved in the decision-making process of whether to receive HPV vaccination.

METHODS
We adopted a qualitative approach and conducted in-depth individual semistructured interviews with 40 women in Hong Kong between May and August 2017.

RESULTS
We noted that the following factors intertwined to influence the decision-making process: perceptions of HPV and HPV vaccine; perceived worthiness of HPV vaccines, which was in turn influenced by vaccine cost, marriage plans, and experiences of sexual activities; history of experiencing gynecological conditions, stigma associated with HPV vaccination, acquisition of information on HPV vaccines, distrust on HPV vaccines, and absence of preventive care in the healthcare practice.

CONCLUSIONS
HPV vaccination is promoted in a manner that is "feminized" and "moralized" under the patriarchal value system, further imposing the burden of disease on women, and leading to health inequality of women in pursuing the vaccination as a preventive health behaviour as a result. We believe that this ultimately results in an incomplete understanding of HPV, consequently influencing the decision-making process. The "mixed-economy" medical system adopting capitalist logic also molds a weak doctor-patient relationship, leading to distrust in private practice medical system, which affects the accessibility of information regarding HPV vaccination for participants to make the decision.

D007722:Health Knowledge, Attitudes, Practice

HPV vaccination
Vaccine hesitancy
Chinese
Women
Decision making process
Human papillomavirus


Urinary tract infection caused by extended-spectrum β-lactamase-producing bacteria: Risk factors and antibiotic resistance.

Abstract:
BACKGROUND
The aim of this study was to investigate the risk factors for acquisition of extended spectrum β-lactamase (ESBL)-producing bacteria in community-acquired urinary tract infection (UTI) and to evaluate their antimicrobial resistance.

METHODS
The medical records of hospitalized children were retrospectively evaluated. Children with ESBL-producing bacteria UTI were matched with controls with non-ESBL-producing bacteria UTI of the same age and gender.

RESULTS
A total of 243 patients with community-acquired UTI in a 5 year period were evaluated, of whom 46% had UTI caused by ESBL bacteria. Seventy-seven cases were matched with 77 controls. There were no significant differences in the clinical presentation between the two groups apart from a longer hospital stay in the ESBL group (9.1 ± 5.5 days vs 8.0 ± 4.4 days, P = 0.013). Significant potential risk factors for ESBL-UTI were previous use of antibiotics in the last 3 months, previous hospitalization in the last 3 months, history of recurrent UTI, and presence of renal anomalies. On logistic regression analysis, history of previous hospitalization in the last 3 months (OR, 3.83; 95%CI: 1.49-9.84) was identified as an independent significant risk factor for ESBL-UTI. There was a significantly higher resistance to amoxicillin-clavulanate, amikacin, gentamycin and quinolones in the ESBL group compared with the control group.

CONCLUSION
Recognizing the risk factors for ESBL-UTI helps to identify the high-risk cases and enables proper management.

extended spectrum β-lactamase-producing bacteria


Generation of Large Fragment Knock-In Mouse Models by Microinjecting into 2-Cell Stage Embryos.

Abstract: Large fragment knock-in mouse models such as reporters and conditional mutant mice are important models for biological research. Here we describe 2-cell (2C)-homologous recombination (HR)-CRISPR, a highly efficient method to generate large fragment knock-in mouse models by CRISPR-based genome engineering. Using this method, knock-in founders can be generated routinely in a time frame of about two months with high germline transmission efficiency. 2C-HR-CRISPR will significantly promote the advancement of basic and translational research using genetic mouse models.

Knock-in
2-Cell stage
CRISPR-Cas9
Homologous recombination


Anti-biofouling conducting polymer nanoparticles as a label-free optical contrast agent for high resolution subsurface biomedical imaging.

Abstract: Optical coherence tomography (OCT) is a modern high resolution subsurface medical imaging technique. Herein we describe: (i) the synthesis of a thiophene-functionalized oligo(ethylene glycol) methacrylate (OEGMA)-based statistical copolymer, denoted poly(2TMOI-OEGMA); (ii) the preparation of sterically-stabilized polypyrrole (PPy) nanoparticles of approximately 60 nm diameter; (iii) the evaluation of these nanoparticles as a NIR-absorbing optical contrast agent for high-resolution OCT imaging. We show that poly(2TMOI-OEGMA)-stabilized PPy nanoparticles exhibit similar optical properties to poly(vinyl alcohol) (PVA)-stabilized PPy nanoparticles of comparable size prepared using commercially available PVA. Spectroscopic measurements and Mie calculations indicate that both types of PPy nanoparticles strongly absorb NIR radiation above 1000 nm, suggesting their potential use as OCT contrast agents. In vitro OCT studies indicate that both types of PPy nanoparticles reduce NIR backscattering within homogeneous intralipid tissue phantoms, offering almost identical contrast performance in this medium. However, PVA-stabilized PPy nanoparticles became colloidally unstable when dispersed in physiological buffer and immersed in a solid biotissue phantom and hence failed to generate a strong contrast effect. In contrast, the poly(2TMOI-OEGMA)-stabilized PPy nanoparticles remained well-dispersed and hence exhibited a strong rapid onset contrast effect within the biotissue phantom under identical physiological conditions. Ex vivo studies performed on excised chicken and porcine skin tissue demonstrated that topical administration of a low concentration of poly(2TMOI-OEGMA)-stabilized PPy nanoparticles rapidly enhances OCT image contrast in both cases, allowing key tissue features to be readily identified.

Au|Kin Man|KM|
Lu|Zenghai|Z|
Matcher|Stephen J|SJ|
Armes|Steven P|SP|

Conducting polymer nanoparticles
Optical contrast agent
Optical coherence tomography
Protein–nanoparticle interactions
Subsurface imaging


Impact of military on biofuels consumption and GHG emissions: the evidence from G7 countries.

Abstract: It was aimed to test the relation among the greenhouse gases emissions, economic growth, biofuels consumption, and militarization in G7 countries during the 1985-2015 period by Pedroni 1995 and panel Johansen tests and two long-run estimators-dynamic OLS and fully modified OLS. Long-run estimators found that economic growth and militarization have statistically significant positive impact on CO2 emission of G7 countries. Furthermore, the panel causality tests were applied: Dumitrescu and Hurlin (Econ Model 29(4):1450-1460, 2012) and panel Granger causality. These tests determined the causal relationship between the variables. The results of this paper implied that economic growth and biofuels consumption depend on militarization, and economic growth and militarization are granger causes of the greenhouse gases emissions.

D056804:Biofuels
D002245:Carbon Dioxide
D019049:Developed Countries
D057217:Economic Development
D017752:Greenhouse Effect
D000074382:Greenhouse Gases
D008889:Military Personnel

Biofuels
GHG emissions
Militarization
Panel causality
Panel cointegration


Risk patterns among college youth: identification and implications for prevention and treatment.

Abstract:
PURPOSE
This study identified underlying subgroups among college students in terms of lifestyle characteristics and health risk behaviors and then investigated how demographic factors were associated with the underlying risk patterns to bolster health promotion efforts and interventions.

METHOD
College students (N = 996) enrolled at Indiana University during 2009-2010 participated in a multidimensional online survey. Latent class analysis was used to identify underlying risk patterns based on seven lifestyle and health behaviors, including frequent alcohol use, binge drinking, smoking, low physical activity, low vegetable intake, low fruit intake, and poor sleep.

RESULTS
Four distinct risk behavior patterns were identified for both males and females including a "healthy" class, "low substance use but poor other health behaviors" class, "high substance use" (males)/"high alcohol use" (females) class, and a risk class characterized by elevated probability of all seven indicators. The highest risk class included 34% of the males and 22% of the females; they tended to be older or in more advanced undergraduate classes. Among males, compared with the "healthy" class, the "high substance use" class was more likely to contain non-Hispanic White students and students in advanced classes. Among females, the "low substance use but poor other health behaviors" class was associated with racial/ethnic minority status and lower levels of parental education.

CONCLUSIONS
Our data suggest that risky health behaviors may tend to cluster in some students and that health promotion techniques might effectively be targeted to identifiable student subgroups.

Luo|Juhua|J| Agley|Jon|J| Hendryx|Michael|M| Gassman|Ruth|R| Lohrmann|David|D|

risk patterns
college youth
latent class analysis
health behaviors
risk factors


The goal trumps the means: Highlighting goals is more beneficial than highlighting means in means-end training.

Abstract: Means-end actions are an early-emerging form of problem-solving. These actions require initiating initial behaviors with a goal in mind. In this study, we explored the origins of 8-monthold infants' means-end action production using a cloth-pulling training paradigm. We examined whether highlighting the goal (toy) or the means (cloth) was more valuable for learning to perform a well-organized means-end action. Infants were given the opportunity to both practice cloth-pulling and view modeling of the action performed by an adult throughout the session. Infants either saw the same toy or the same cloth in successive trials so that the goal or means were highlighted prior to modeling of the action. All infants improved throughout the session regardless of which aspect of the event was highlighted. Beyond this general improvement, repetition of goals supported more rapid learning and more sustained learning than did repetition of means. These findings provide novel evidence that, at the origins of means-end action production, emphasizing the goal that structures an action facilitates the learning of new meansend actions.

Gerson|Sarah A|SA|
Woodward|Amanda L|AL|

goals
means-end actions
problem-solving
cognitive development
infant cognition


The effect of dye-sensitized solar cell based on the composite layer by anodic TiO2 nanotubes.

Abstract: TiO2 nanotube arrays are very attractive for dye-sensitized solar cells (DSSCs) owing to their superior charge percolation and slower charge recombination. Highly ordered, vertically aligned TiO2 nanotube arrays have been fabricated by a three-step anodization process. Although the use of a one-dimensional structure provides an enhanced photoelectrical performance, the smaller surface area reduces the adsorption of dye on the TiO2 surface. To overcome this problem, we investigated the effect of DSSCs constructed with a multilayer photoelectrode made of TiO2 nanoparticles and TiO2 nanotube arrays. We fabricated the novel multilayer photoelectrode via a layer-by-layer assembly process and thoroughly investigated the effect of various structures on the sample efficiency. The DSSC with a four-layer photoelectrode exhibited a maximum conversion efficiency of 7.22% because of effective electron transport and enhanced adsorption of dye on the TiO2 surface.

Yang|Jun Hyuk|JH|
Kim|Kyung Hwan|KH|
Bark|Chung Wung|CW|
Choi|Hyung Wook|HW|

Composite layer
TiO2 nanotube array
DSSCs
Photoelectrode
Anodic oxidation


Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2.

Abstract: Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis.

Gong|Fu-Han|FH| Long|Li|L| Yang|Yong-Sheng|YS| Shen|De-Hong|DH| Zhang|Yu-Song|YS| Wang|Xue-Sheng|XS| Zhang|Xue-Ping|XP| Xiao|Xiao-Qiang|XQ|


Risk and Protective Factors Affecting Sexual Risk Behavior Among School-Aged Adolescents in Fiji, Kiribati, Samoa, and Vanuatu.

Abstract: There are limited studies on the prevalence and correlates of sexual risk behavior among adolescents in Pacific Island countries. In order to inform public sexual and reproductive health interventions, the aim of this study was to assess the prevalence and correlates of various sexual risk behaviors among in-school adolescents in 4 Pacific Island countries using data from the Global School-Based Health Survey. In a cross-sectional study, 6792 school-going adolescents (49.7% boys and 50.3% girls; 13-16 years old) from Fiji, Kiribati, Samoa, and Vanuatu were surveyed with a self-administered questionnaire. Overall, 18.9% of students reported to ever had sex (ranging from 12.9% in Vanuatu to 57.5% in Samoa), and of those sexually active, 38.0% had an early sexual debut (<14 years), 38.1% had 2 or more sexual partners during their lifetime, 39.5% had not used a condom at last sex, 50.9% had not used birth control at last sex, and 77.8% engaged in sexually risky behavior using a composite measure. Multivariate logistic regression found that male sex, older age, tobacco use, alcohol use, mental distress, having no close friends, and truancy were associated with several of 5 or all 5 sexual risk behaviors. Sexual and reproductive health promotion programs are indicated to address the high risk of sexually transmitted infection, HIV, and pregnancy in this adolescent population.

protective factors
Fiji
Kiribati
Samoa
Vanuatu
Global School-Based Health Survey
mental distress
sexual behavior
substance use


Multiscale Distribution Entropy and t-Distributed Stochastic Neighbor Embedding-Based Fault Diagnosis of Rolling Bearings.

Abstract: As a nonlinear dynamic method for complexity measurement of time series, multiscale entropy (MSE) has been successfully applied to fault diagnosis of rolling bearings. However, the MSE algorithm is sensitive to the predetermined parameters and depends heavily on the length of the time series and MSE may yield an inaccurate estimation of entropy or undefined entropy when the length of time series is too short. To improve the robustness of complexity measurement for short time series, a novel nonlinear parameter named multiscale distribution entropy (MDE) was proposed and employed to extract the nonlinear complexity features from vibration signals of rolling bearing in this paper. Combining with t-distributed stochastic neighbor embedding (t-SNE) for feature dimension reduction and Kriging-variable predictive models based class discrimination (KVPMCD) for automatic identification, a new intelligent fault diagnosis method for rolling bearings was proposed. Finally, the proposed approach was applied to analyze the experimental data of rolling bearings and the results indicated that the proposed method could distinguish the different fault categories of rolling bearings effectively.

Tu|Deyu|D| Zheng|Jinde|J|0000-0001-5735-4916 Jiang|Zhanwei|Z| Pan|Haiyang|H|


Impact of Sports Activity on Medium-Term Clinical and Radiological Outcome after Reverse Shoulder Arthroplasty in Cuff Deficient Arthropathy; An Institutional Register-Based Analysis.

Abstract: There is a lack of consensus on what physicians can recommend and what patients can expect concerning sports activity after reverse shoulder arthroplasty (RSA). The purpose of this retrospective register-based observational study was to investigate the association between participation in sports or physical activity involving the upper extremity and 5-year clinical and radiological outcomes for primary RSA patients. We screened the institutional arthroplasty registry for patients reporting the type and level of sports postoperatively after primary, unilateral RSA due to rotator cuff deficiency. One hundred thirty-eight patients with clinical and radiological outcomes documented at a minimum 5-year follow-up were divided into three groups comprising those who participated regularly in: sports mainly involving the upper extremity (sports upper extremities, SUE, n = 49), sports mainly involving the lower extremities (sports lower extremities, SLE, n = 21), and those who did not participate in sports at all (no sports, NS, n = 68). The participants had a mean age of 72 years (standard deviation (SD) 8) and were overall predominantly female patients (62%). Primary clinical outcomes included the Constant Score (CS) and Shoulder Pain and Disability Index (SPADI). Secondary radiographs were analyzed for radiolucent lines (RLL), signs of glenoid or humeral prosthesis loosening, bone resorption, bone formation, and scapular notching. A total number of 8 senior surgeons were involved in treatment of patients, and two types of prosthesis were used. The SUE group had non-significantly higher mean scores for CS (75 points) and SPADI (88 points) compared to SLE (71 and 78 points, respectively) and NS patients (66 and 78 points, respectively) (p ≥ 0.286). The incidence of RLL around the humeral diaphysis was higher in NS compared to SUE patients (32% versus 12%, respectively) (p = 0.025); all other radiological parameters were similar between the groups. There were no cases of loosening in the SUE group that led to revision surgery. Patients engaging in sports activities involving the upper extremity show similarly good functional scores 5 years post-RSA as the other groups, without additional signs of implant loosening as a result of increased shoulder use.

Endell|David|D|0000-0001-7869-5621 Audigé|Laurent|L|0000-0003-3962-3996 Grob|Alexandra|A| Schwyzer|Hans-Kaspar|HK| Glanzmann|Michael|M| Marzel|Alex|A| Scheibel|Markus|M|

sports
radiological outcomes
reverse shoulder arthroplasty
shoulder surgery


Effects of periodontal treatment on the medical status of patients with type 2 diabetes mellitus: a pilot study.

Abstract:
BACKGROUND
Studies have demonstrated that periodontal disease is associated with the development of systemic complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this pilot study was to investigate which markers among various systemic disease parameters are affected by periodontal treatment in patients with T2DM.

METHODS
Twelve patients with T2DM were given oral hygiene instructions and subsequent subgingival scaling and root planing. The periodontal status was recorded, and blood and urine samples were taken to measure various parameters of glucose control and systemic status at baseline and 1 month following the periodontal treatment. Serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay.

RESULTS
After the periodontal treatment, the glycated hemoglobin value was significantly improved. The levels of urinary N-acetyl-β-D-glucosaminidase and albumin, which are markers of renal dysfunction, also decreased significantly after treatment. Among the parameters measured in serum, the γ-glutamyl transpeptidase level, which is usually interpreted as a marker of liver dysfunction, was significantly reduced. The serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were also significantly reduced by periodontal treatment.

CONCLUSION
Within the limitations of this pilot study, periodontal treatment may be effective not only in improving metabolic control, but also in reducing the risk of diabetic kidney and liver disease in patients with T2DM.

Hayashi|Joichiro|J| Hasegawa|Akihiko|A| Hayashi|Kohei|K| Suzuki|Takafumi|T| Ishii|Makiko|M| Otsuka|Hideharu|H| Yatabe|Kazuhiro|K| Goto|Seiichi|S| Tatsumi|Junichi|J| Shin|Kitetsu|K|

Periodontal treatment
Type 2 diabetes mellitus
Glycated hemoglobin
Urinary N-acetyl-β-D-glucosaminidase
γ-glutamyl transpeptidase


Transcriptome analysis reveals the effect of high-grain pelleted and non-pelleted diets on ruminal epithelium of Hu-lamb.

Abstract: High-grain non-pelleted (HG) and high-grain pelleted (HP) diets are becoming prevalent for ruminant feeding in intensive farms. However, rare information is about their effect on sheep and the comparison between these two kinds of diets. The current study investigated how HG and HP diets affected the transcriptome profiles of rumen epithelium in Hu-lamb. Fifteen male Hu-lambs were assigned randomly to three groups (n = 5 for each group). Lambs in the control (CON), HG, and HP groups were fed with low-grain non-pelleted diet (30% grain), HG diet (70% grain), and HP diet (70% grain), respectively, for 42 days. All these lambs were slaughtered to collect ruminal epithelium samples for transcriptome analysis. Results showed both HG and HP diets obviously changed the transcriptome profiles, and 192, 319, and three differentially expressed genes (DEGs) were identified for CON_HG, CON_HP, and HG_HP comparisons, respectively. Clusters of orthologous group functional classification of CON_HG and CON_HP DEG datasets both showed the enrichments of DEGs in pathways involved in protein biogenesis and modification as well as energy production and conversion. Kyoto encyclopedia of genes and genomes pathway analysis of CON_HG and CON_HP DEG datasets both displayed the enrichments of DEGs in ribosome and oxidative phosphorylation. Almost all these DEGs involved in translation and ribosomal structure and biogenesis as well as oxidative phosphorylation were downregulated in the HG and HP groups compared to the CON group. Furthermore, CON_HP comparison demonstrated more DEGs related to these two pathways than CON_HG comparison. In conclusion, both HG and HP diets inhibited energy production and conversion as well as protein synthesis and modification in ruminal epithelium. HP diet showed lower growth benefits, induced severer rumen acidosis, and more seriously inhibited energy production and protein synthesis as compared to HG diet.

Xue|Y|Y|
Yin|Y|Y|
Trabi|E B|EB|
Xie|F|F|
Lin|L|L|
Mao|S|S|

Sheep
Energy production
Ribosome
Oxidative phosphorylation
Protein synthesis


Prevalence of Asymptomatic Microalbuminuria in HIV Positive Children in India.

Abstract:
OBJECTIVE
To study the prevalence of covert or early renal involvement among human immunodeficiency virus (HIV) positive children.

METHODS
A cross-sectional observational study was carried out on 250 HIV positive children (2-18 y) on follow-up in a tertiary care hospital from January 2014 through June 2015. Those who met the study criteria were evaluated for microalbuminuria and glomerular and tubular dysfunctions.

RESULTS
Fifty-one out of two hundred fifty (20%) children were found to have microalbuminuria though none had any other evidence of renal dysfunction. The incidence of microalbuminuria in children on Anti Retroviral Therapy (ART) and those not on ART was 20% and 21% respectively. Neither was there any difference in those with a CD4 count ≤500/cu mm compared with those with counts >500/cu mm. However, the overall CD4 counts were significantly lower in children with microalbuminuria.

CONCLUSIONS
Microalbuminuria was detected in 20% of asymptomatic HIV positive children suggesting early glomerular dysfunction and need for regular screening and follow-up.

Microalbuminuria
HIV positive children
HIVAN


Postoperative Risk Factors and Outcome of Patients With Liver Transplantation Who Were Admitted to Pediatric Intensive Care Unit: A 10-Year Single-Center Review in China.

Abstract:
INTRODUCTION
The aim of this study was to present our 10-year experience of pediatric intensive care unit (PICU) management with pediatric liver recipients and to understand the importance of close interdisciplinary cooperation in 2 hospitals.

METHODS
A retrospective chart review study was performed according to our hospital's medical records and the pediatric liver transplant database of Renji hospital.

RESULTS
A total of 767 patients received liver transplantation (LT) performed in Renji hospital between October 2006 and December 2016, of which 97 of them were admitted to PICU in our center for various complications developed after transplantation. 8.8% (16/208) and 14.4% (81/559) of patients were transferred to PICU in stages I and II, respectively, and was comparable in the 2 stages (P = .017). The majority of patients was late postoperative children (median 185 post-LT days) in stage I. More patients were transferred to PICU directly in stage II. PICU admitted more younger (median 8.2 months) and early postoperative patients in stage II. The median length of PICU stay was 11.0 (6.0-20.5) days. The median length of mechanical ventilation was 5.0 (0.0-12.0) days. The most frequent complications were pulmonary complications (52 [53.6%] patients), surgical complications (22 [22.7%] patients), sepsis (7 [7.2%]), and other miscellaneous complications (16 [16.5%] patients). The overall 28-day PICU mortality was 25.8% (n = 25) and 64.0% (n = 16) of the deaths happened in the early postoperative period. There was significant difference concerning mortality in children with surgical complications and medical problems (54.5% [12/22] vs 17.3% [13/75], P = .001). Multivariate analysis by regression showed that the pediatric risk of mortality III score was the only independent prognostic factor (P = .031).

CONCLUSIONS
Multiple complications occur in children with LT. Although challenging, interdisciplinary cooperation between different hospitals is an effective mean to enable children to maximize the benefit gained from LT in China.

risk factor
pediatric intensive care unit
interdisciplinary cooperation
PRISM III score
child
orthotopic liver transplantation


Thyroid eye disease survey: An anonymous web-based survey in the Indian subcontinent.

Abstract:
Purpose
To evaluate the current practice patterns in the treatment of thyroid eye disease (TED) in Indian subcontinent through a web-based survey of members of Oculoplastics Association of India (OPAI).

Methods
This was an online web-based questionnaire survey disseminated via monkeysurvey.com to all ratified active members of OPAI between May 1, 2016 and June 30, 2016. Questions encompassed the background, training, region, and experience of oculoplastic surgeons along with the management protocol of TED.

Results
Of the 435 emails sent to OPAI members, 9 bounced and 180 (42.3%) responded within the study period. A large majority (96%) of respondents were oculoplastic surgeons practicing in India and the remaining practiced within South-East Asia. Two-thirds of respondents were oculoplastic surgeons with less than 10 years of clinical experience; 82% were fellowship trained in Oculoplasty. Almost all (99%) favored a multidisciplinary management of TED. A large majority routinely grade the severity (89%) and activity (87%) of disease before management. While corticosteroid remained the treatment of choice, 54% preferred immune-modulators as the second-line of therapy for recalcitrant TED. Three-quarters did not use orbital radiotherapy as a management modality in active TED owing to concerns over its efficacy and/or safety.

Conclusion
The survey gives useful insights to the practice patterns of TED management in Indian subcontinent. Multidisciplinary approach and grading of disease severity and activity were the rule rather than exception among OPAI members. Immune modulation was the preferred steroid-sparing agent in recalcitrant disease. Orbital radiotherapy was an uncommon treatment choice.

Pradhan|Anuradha|A|
Ganguly|Anasua|A|
Naik|Milind N|MN|
Nair|Akshay Gopinathan|AG|
Desai|Savari|S|
Rath|Suryasnata|S|

thyroid eye disease
survey
India
orbital decompression


A novel approach to earlobe reconstruction using the V to Y advancement flap.

Abstract:
BACKGROUND
The V to Y advancement flap offers an excellent option for reconstructing defects of the lobule and adjacent structures of the external ear. We demonstrate its utility for small defects of the earlobe including those extending to the antitragal and conchal bowl regions. To our knowledge use of this technique for earlobe reconstruction has not been reported.

METHODS
A review of the literature was performed on the use of the V to Y flap for earlobe reconstruction. We then described its use in reconstructing lobular defects in 6 patients. All patients had a non-melanoma skin cancer involving the earlobe. All surgeries were performed under local anesthetic at a tertiary care centre in Halifax, Canada. Defects ranged in size from 1.0 to 1.4 cm. All defects were reconstructed with only a V to Y advancement flap. Patient photographs were taken intra-operatively and post-operatively. For all patients, satisfaction of the final aesthetic result was assessed on a 10 point scale in follow-up at 6 months.

RESULTS
A review of the literature did not reveal any reports of the V to Y flap used in isolation for lobular reconstruction. At our centre from 2018 to 2020, this method was well tolerated under local anesthetic in 6 patients with non-melanoma skin cancers of the earlobe. All patients reported an aesthetically satisfying result at 6 months with scores ranging between 8 and 10. Scarring in all cases was minimal.

CONCLUSION
The V to Y advancement flap is a simple technique for reconstructing small defects of the lobule. This method is technically straight-forward, poses minimal risk to the patient, and in our experience, yields a favourable cosmetic outcome.

Flap
Ear
Aesthetics
Ear auricles
Reconstructive surgical procedures
Skin neoplasms
Surgical


Complete sequences of the mitochondrial DNA of the Grateloupia filicina (Rhodophyta).

Abstract: In this study, we sequenced and analyzed the complete mitogenome of Grateloupia filicina (Lamouroux) C. Agardh. The complete G. filicina mitogenome was 29,274-bp long, containing 51 genes, including 24 protein-coding genes, 1 intron, 2 rRNA genes, 24 tRNA genes, and 1 unidentified open reading frame. Twenty-one of the 24 (87.5%) protein-coding genes ended with the stop codon TAA, whereas 3 (12.5%) ended with TAG. All the protein-coding genes in G. filicina used the start codon ATG. Phylogenetic analysis revealed that G. filicina clustered with G. taiwanensis. The complete mitochondrial genome sequence provided here would be useful for understanding the evolution of Grateloupia further.

Li|Yue|Y|
Meinita|Maria Dyah Nur|MDN|
Liu|Tao|T|
Chi|Shan|S|
Yin|Hongxin|H|

Grateloupia filicina
phylogenetic analysis
Mitochondrial genome


Measurements of Microstructural, Chemical, Optical, and Electrical Properties of Silicon-Oxygen-Nitrogen Films Prepared by Plasma-Enhanced Atomic Layer Deposition.

Abstract: In this study, silicon nitride (SiNx) thin films with different oxygen concentration (i.e., SiON film) were precisely deposited by plasma enhanced atomic layer deposition on Si (100) substrates. Thus, the effect of oxygen concentration on film properties is able to be comparatively studied and various valuable results are obtained. In detail, x-ray reflectivity, x-ray photoelectron spectroscopy, atomic force microscopy, and spectroscopic ellipsometry are used to systematically characterize the microstructural, optical, and electrical properties of SiON film. The experimental results indicate that the surface roughness increases from 0.13 to 0.2 nm as the oxygen concentration decreases. The refractive index of the SiON film reveals an increase from 1.55 to 1.86 with decreasing oxygen concentration. Accordingly, the band-gap energy of these films determined by oxygen 1s-peak analysis decreases from 6.2 to 4.8 eV. Moreover, the I-V tests demonstrate that the film exhibits lower leakage current and better insulation for higher oxygen concentration in film. These results indicate that oxygen affects microstructural, optical, and electrical properties of the prepared SiNx film.

Ma|Hong-Ping|HP|0000-0003-4175-5437
Lu|Hong-Liang|HL|0000-0003-2398-720X
Yang|Jia-He|JH|
Li|Xiao-Xi|XX|
Wang|Tao|T|
Huang|Wei|W|
Yuan|Guang-Jie|GJ|
Komarov|Fadei F|FF|
Zhang|David Wei|DW|

silicon nitride
plasma enhanced atomic layer deposition
optical properties
oxygen contamination
silicon oxynitride


Structured and Modular Training Pathway for Robot-assisted Radical Prostatectomy (RARP): Validation of the RARP Assessment Score and Learning Curve Assessment.

Abstract:
BACKGROUND
Use of robot-assisted radical prostatectomy (RARP) for prostate cancer is increasing. Structured surgical training and objective assessment are critical for outcomes.

OBJECTIVE
To develop and validate a modular training and assessment pathway via Healthcare Failure Mode and Effect Analysis (HFMEA) for trainees undertaking RARP and evaluate learning curves (LCs) for procedural steps.

DESIGN, SETTING, AND PARTICIPANTS
This multi-institutional (Europe, Australia, and United States) observational prospective study used HFMEA to identify the high-risk steps of RARP. A specialist focus group enabled validation. Fifteen trainees who underwent European Association of Urology robotic surgery curriculum training performed RARP and were assessed by mentors using the tool developed. Results produced LCs for each step. A plateau above score 4 indicated competence.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
We used a modular training and assessment tool (RARP Assessment Score) to evaluate technical skills. LCs were constructed. Multivariable Kruskal-Wallis, Mann-Whitney U, and κ coefficient analyses were used.

RESULTS AND LIMITATIONS
Five surgeons were observed for 42 console hours to map steps of RARP. HFMEA identified 84 failure modes and 46 potential causes with a hazard score ≥8. Content validation created the RARP Assessment Score: 17 stages and 41 steps. The RARP Assessment Score was acceptable (56.67%), feasible (96.67%), and had educational impact (100%). Fifteen robotic surgery trainees were assessed for 8 mo. In 426 RARP cases (range: 4-79), all procedural steps were attempted by trainees. Trainees were assessed with the RARP Assessment Score by their expert mentors, and LCs for individual steps were plotted. LCs demonstrated plateaus for anterior bladder neck transection (16 cases), posterior bladder neck transection (18 cases), posterior dissection (9 cases), dissection of prostatic pedicle and seminal vesicles (15 cases), and anastomosis (17 cases). Other steps did not plateau during data collection.

CONCLUSIONS
The RARP Assessment Score based on HFMEA methodology identified critical steps for focused RARP training and assessed surgeons. LCs demonstrate the experience necessary to reach a level of competence in technical skills to protect patients.

PATIENT SUMMARY
We developed a safety and assessment tool to gauge the technical skills of surgeons performing robot-assisted radical prostatectomy. Improvement was monitored, and measures of progress can be used in future to guide mentors when training surgeons to operate safely.

Lovegrove|Catherine|C|
Novara|Giacomo|G|
Mottrie|Alex|A|
Guru|Khurshid A|KA|
Brown|Matthew|M|
Challacombe|Ben|B|
Popert|Richard|R|
Raza|Johar|J|
Van der Poel|Henk|H|
Peabody|James|J|
Dasgupta|Prokar|P|
Ahmed|Kamran|K|

Training
Robot-assisted radical prostatectomy
Assessment
Learning curve
Patient safety


The orally active pterocarpanquinone LQB-118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress.

Abstract:
BACKGROUND
The targeted induction of reactive oxygen species (ROS) is a developing mechanism for cancer therapy. LQB-118 is a pterocarpanquinone and ROS-inducing agent with proven antineoplastic activity. Here, LQB-118 efficacy and mechanism of activity, were examined in Prostate Cancer (PCa) cell and tumor models.

METHODS
PC3, LNCaP, and LAPC4 PCa cells were applied. Dicoumarol treatment was used to inhibit quinone reductase activity. N-acetylcysteine (NAC) was applied as a ROS scavenger. ROS production was quantified by H2 DCFDA flow cytometry. LQB-118 treated cells were evaluated for changes in lipid peroxidation, viability, and apoptosis. Treatment-induced gene expression was measured by RT-qPCR and Western Blot. SOD1 knockdown was achieved with siRNA or miRNA mimic transfection. MicroRNA specificity was determined by 3'UTR reporter assay. Oral LQB-118 treatment (10 mg/kg/day) efficacy was determined in athymic male nude mice bearing subcutaneous PC3 xenograft tumors.

RESULTS
LQB-118 treatment triggered PCa cell death and apoptosis. Therapeutic activity was at least partially dependent upon quinone reduction and ROS generation. LQB-118 treatment caused an increase in cellular ROS and lipid peroxidation. Treated cells exhibited elevated levels of NQO1, Nrf2, and SOD1. The miRNAs miR-206, miR-1, and miR-101 targeted and reduced SOD1 expression. The knockdown of SOD1, by siRNA or miRNA, enhanced LQB-118 cytotoxicity. Orally administered LQB-118 treatment significantly reduced the growth of established PCa xenograft tumors.

CONCLUSION
LQB-118 is a developing and orally active pterocarpanquinone agent that effectively kills PCa cells through quinone reduction and ROS generation. The inhibition SOD1 expression enhances LQB-118 activity, presumably by impairing the cellular antioxidant response.


Inhibition of Mammalian Glycoprotein YKL-40: IDENTIFICATION OF THE PHYSIOLOGICAL LIGAND.

Abstract: YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin's physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles such as mediating cellular receptors and cell adhesion and migration. Here, we consider the feasibility of polysaccharides, including cello-oligosaccharides, hyaluronan, heparan sulfate, heparin, and chondroitin sulfate, and collagen-like peptides as physiological ligands for YKL-40. We use molecular dynamics simulations to resolve the molecular level recognition mechanisms and calculate the free energy of binding the hypothesized ligands to YKL-40, addressing thermodynamic preference relative to chito-oligosaccharides. Our results suggest that chitohexaose and hyaluronan preferentially bind to YKL-40 over collagen, and hyaluronan is likely the preferred physiological ligand, because the negatively charged hyaluronan shows enhanced affinity for YKL-40 over neutral chitohexaose. Collagen binds in two locations at the YKL-40 surface, potentially related to a role in fibrillar formation. Finally, heparin non-specifically binds at the YKL-40 surface, as predicted from structural studies. Overall, YKL-40 likely binds many natural ligands in vivo, but its concurrence with physical maladies may be related to associated increases in hyaluronan.

lectin
thermodynamics
chitinase
glycosaminoglycan
glycoside hydrolase
molecular modeling


Plant oils: From chemical composition to encapsulated form use.

Abstract: The last decade has witnessed a burgeoning global movement towards essential and vegetable oils in the food, agriculture, pharmaceutical, cosmetic, and textile industries thanks to their natural and safe status, broad acceptance by consumers, and versatile functional properties. However, efforts to develop new therapy or functional agents based on plant oils have met with challenges of limited stability and/or reduced efficacy. As a result, there has been increased research interest in the encapsulation of plant oils, whereby the nanocarriers serve as barrier between plant oils and the environment and control oil release leading to improved efficacy, reduced toxicity and enhanced patient compliance and convenience. In this review, special concern has been addressed to the encapsulation of essential and vegetable oils in three types of nanocarriers: polymeric nanoparticles, liposomes and solid lipid nanoparticles. First, the chemical composition of essential and vegetable oils was handled. Moreover, we gather together the research findings reported by the literature regarding the different techniques used to generate these nanocarriers with their significant findings. Finally, differences and similarities between these nanocarriers are discussed, along with current and future applications that are warranted by their structures and properties.

Lammari|Narimane|N|
Louaer|Ouahida|O|
Meniai|Abdeslam Hassen|AH|
Fessi|Hatem|H|
Elaissari|Abdelhamid|A|

Encapsulation
Vegetable oil
Polymeric nanoparticle
Liposome
Solid lipid nanoparticle
Essential oil


Association between cardiac troponin I concentrations and electrocardiographic abnormalities in dogs with blunt trauma.

Abstract:
OBJECTIVE
To determine whether a normal cardiac troponin I (cTnI) concentration and normal ECG on entry rule out the development of a clinically significant cardiac arrhythmia (CSCA, defined as an arrhythmia requiring anti-arrhythmic treatment) in dogs that have sustained blunt trauma.

DESIGN
Prospective, observational study. Client-owned dogs were enrolled between January 2015 and November 2016.

SETTING
University teaching hospital.

ANIMALS
Forty-seven client-owned dogs with a history of witnessed or suspected blunt trauma within 24 hours prior to presentation to the hospital.

INTERVENTIONS
On admission to the emergency service, dogs had a standard 3-lead ECG and cTnI concentration (using a veterinary point-of-care device* ) performed. Animal Trauma Triage (ATT) scores, Modified Glasgow Coma Scale (MGCS), and the details regarding the nature and timing of the injury were recorded. The patients were monitored in the ICU for a minimum of 24 hours on continuous ECG telemetry. Cardiac rhythm was monitored every hour, and any abnormalities were noted. The need for anti-arrhythmic therapy was recorded. There were no treatment interventions.

MEASUREMENTS AND MAIN RESULTS
Five of 47 dogs (10.6%) developed a CSCA during hospitalization after sustaining blunt trauma. A normal entry ECG and normal cardiac troponin concentration on entry had a 100% negative predictive value (NPV) for ruling out the development of a CSCA, although a normal cardiac troponin concentration alone also had an NPV of 100%. A normal entry ECG had an NPV of 95.3%. The prognosis for survival to discharge was 89.4% in this study population (42/47 dogs).

CONCLUSIONS
In dogs with blunt trauma, an entry cTnI concentration or a combination of cTnI and ECG on entry may be useful in determining which patients are at a higher risk for the development of CSCA during the first 12 to 24 hours after the trauma.

arrhythmias
biomarkers
canine
myocardial injury
traumatic myocarditis


Confining nano-sized platinum in nitrogen doped ordered mesoporous carbon: An effective approach toward efficient and robust hydrogen evolution electrocatalyst.

Abstract: Despite recent progress in the development of earth abundant electrochemical catalyst for hydrogen evolution reaction (HER), Pt based materials still stand as the state of the art HER catalyst. Due to the high cost of Pt, it is desirable to increase the utilization efficiency of Pt in practical HER process to a realize cost effective hydrogen production. Herein, we repot a novel nitrogen doped ordered mesoporous carbon supported Pt (Pt@NOMC-A) catalyst with a low Pt loading of 7.2 wt% and show that the synergy between Pt nanoparticles and carbon support, as well as the physical confinement offered by the carbon support enhance the electrochemical performance of the novel catalyst. Pt@NOMC-A exhibits a low HER overpotential comparable with commercial 20 wt% Pt/C catalyst under acidic, neutral and alkaline condition. Furthermore, Pt@NOMC-A shows a superior electrochemical stability under working conditions suppressing that of commercial Pt/C catalyst.

Yin|Yaqing|Y| Liu|Tingting|T| Liu|Dan|D| Wang|Zhao|Z| Deng|Qibo|Q| Qu|Deyu|D| Xie|Zhizhong|Z| Tang|Haolin|H| Li|Junsheng|J|

Nitrogen doped
Ordered mesoporous carbon
Hydrogen evolution reaction
Pt catalyst


Unravelling the prostate-specific antigen controversy: a West of Scotland perspective.

Abstract:
BACKGROUND
The use of serum prostate-specific antigen (PSA) as a screening tool for prostate cancer in asymptomatic men is hugely controversial in the light of randomised controlled trials failing to demonstrate a benefit without risk of significant overtreatment. However, PSA can be used as a tool to risk assess disease progression in men with lower urinary tract symptoms suggestive of benign prostatic enlargement (LUTS/BPE). The aim of this study was to canvas the opinions of West of Scotland Urologists regarding the use of PSA in both symptomatic and asymptomatic patients.

METHODS
A questionnaire-based survey was sent to all the Consultants and Trainees in the West of Scotland.

RESULTS
Survey response rate was 45% (47/105). In patients <70 years, 93% would perform a PSA testing in patients symptomatic of LUTS/BPE, but only 17% would offer PSA screening to asymptomatic patients. In patients >70 years, only 48% of urologists would perform a PSA if patients were symptomatic and none would offer PSA screening. In terms of self-testing, 59% of urologists would have a PSA test if symptomatic and 31% of urologists would have PSA screening.

CONCLUSIONS
This study highlights significant variability in the use of PSA for both asymptomatic and symptomatic men. Despite a lack of evidence, PSA screening is still offered to asymptomatic men. Further randomised studies are required to determine the utility of PSA-based screening algorithms for prostate cancer detection.

Zafar|Nauman|N|
Miller|Steve|S|
Leburn|Vicki|V|
Qureshi|Khaver N|KN|
Rajan|Prabhakar|P|

D055088:Early Detection of Cancer
D006801:Humans
D059411:Lower Urinary Tract Symptoms
D008297:Male
D008403:Mass Screening
D008875:Middle Aged
D017430:Prostate-Specific Antigen
D011471:Prostatic Neoplasms
D018570:Risk Assessment
D012606:Scotland
D011795:Surveys and Questionnaires
D014572:Urology

Prostate-specific Antigen
prostate cancer guidelines
prostate cancer screening
prostate cancer treatment


Identification of differentially expressed lncRNAs as potential plasma biomarkers for active tuberculosis.

Abstract:
BACKGROUND
Tuberculosis, one of the deadliest infectious diseases worldwide, is difficult to diagnose. As long noncoding RNAs (lncRNAs) were demonstrated to be promising biomarkers, we aimed to identify lncRNAs in plasma as potential biomarkers for tuberculosis.

METHODS
We analyzed a GEO dataset (GSE94907) to identify the differential lncRNAs in serum exosomes between active tuberculosis (ATB) patients and healthy controls. To search for promising candidates that can be used for tuberculosis diagnosis, we excluded low-abundance lncRNAs using a cutoff value of FPKM >5. Four lncRNAs were selected for validation using real-time quantitative PCR in 69 ATB patients and 69 healthy individuals. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of these lncRNAs for ATB.

RESULTS
Integrated analysis of the GEO dataset and NONCODE database identified nine dysregulated lncRNAs in ATB patient serum exosomes. Compared with the heathy controls, NONHSAT101518.2, NONHSAT067134.2, NONHSAT148822.1 and NONHSAT078957.2 were significantly downregulated in ATB patient plasma. ROC curve analysis suggests that these four lncRNAs can discriminate ATB from healthy individuals with high specificity and sensitivity.

CONCLUSION
We identified four differentially expressed lncRNAs in ATB patient plasma that can be used as potential diagnostic biomarkers of ATB.

Fang|Yalun|Y| Zhao|Jingjie|J| Wang|Xiaoyan|X| Wang|Xinfeng|X| Wang|Li|L| Liu|Ling|L| Liu|Junli|J| Gao|Meng|M| Yuan|Chao|C|

Plasma
Biomarker
Active tuberculosis
Long noncoding RNA


Application of Biomimetic Cell-Derived Nanoparticles with Mannose Modification as a Novel Vaccine Delivery Platform against Teleost Fish Viral Disease.

Abstract: Although cell membrane-coated nanoparticles are widely used as a promising nanodelivery platform, a few studies reported their application in developing the teleost nanovaccine delivery system. Here, we present a biomimetic vaccine delivery platform by encapsulating chitosan-loaded DNA vaccine with teleost erythrocytes membrane modified by mannose. The developed CS-G@M-M nanovaccine delivery platform shows good biocompatibility in vivo and in vitro. With further modification of mannose moiety, the constructed CS-G@M-M showed enhanced uptake by antigen-presenting cells (APCs) and increased accumulation of CS-G@M-M in immune tissues including spleen, kidney, and hindgut. Critically, using a quantitative real-time polymerase chain reaction (qRT-PCR) assay, increased mRNA levels of immune-related genes were detected in spleen and hindgut of vaccinated fish. Moreover, through enzyme-linked immunosorbent assay (ELISA), we found that the levels of CD80/86, TNF-α, IgM, and IgZ in spleen and hindgut were significantly increased. To evaluate the immunoprotection efficacy of the constructed nanovaccine, spring viremia of carp virus (SVCV), a rhabdovirus of worldwide importance that requires notification within 48 h to the International Office of Epizootics once detected, was used as a model for virus challenge. We carried out three challenge tests on 3rd, 21st, and 70th days post vaccination, respectively. Notably, CS-G@M-M nanovaccine showed durability of immunoprotection efficacy that could protect zebrafish from SVCV challenge. This work presents a novel design of smart teleost erythrocytes membrane-coated nanoparticles, which are inherently biocompatible, promising for eliciting robust adaptive immune responses in preventing fish viral diseases.

Zhang|Chen|C| Zhang|Peng-Qi|PQ| Guo|Sheng|S| Chen|Guo|G| Zhao|Zhao|Z| Wang|Gao-Xue|GX| Zhu|Bin|B|0000-0001-5702-524X

mannose modification
biomimetic vaccine
erythrocytes membrane
zebrafish
antigen presentation


Evaluation of viral contamination in a baculovirus expression system.

Abstract: Insect expression systems based on baculovirus are widely used for generating recombinant proteins. Here, the infectivity of baculoviruses under the physiological stresses of 'freeze-thaw' and sonication and the baculoviral contamination of recombinant proteins after protein purification were evaluated. Our findings suggest that Nonidet P-40 (NP-40) treatment of baculoviruses completely abolishes their infectivity and that recombinant proteins purified with affinity beads do not include infectious baculoviruses. We therefore suggest that baculovirus is completely inactivated by NP-40 treatment and that recombinant proteins are unlikely to be contaminated with infectious baculoviruses after their affinity purification.

Ono|Chikako|C| Hirano|Junki|J| Okamoto|Toru|T| Matsuura|Yoshiharu|Y|


Face processing in autism: Reduced integration of cross-feature dynamics.

Abstract: Characteristic problems with social interaction have prompted considerable interest in the face processing of individuals with Autism Spectrum Disorder (ASD). Studies suggest that reduced integration of information from disparate facial regions likely contributes to difficulties recognizing static faces in this population. Recent work also indicates that observers with ASD have problems using patterns of facial motion to judge identity and gender, and may be less able to derive global motion percepts. These findings raise the possibility that feature integration deficits also impact the perception of moving faces. To test this hypothesis, we examined whether observers with ASD exhibit susceptibility to a new dynamic face illusion, thought to index integration of moving facial features. When typical observers view eye-opening and -closing in the presence of asynchronous mouth-opening and -closing, the concurrent mouth movements induce a strong illusory slowing of the eye transitions. However, we find that observers with ASD are not susceptible to this illusion, suggestive of weaker integration of cross-feature dynamics. Nevertheless, observers with ASD and typical controls were equally able to detect the physical differences between comparison eye transitions. Importantly, this confirms that observers with ASD were able to fixate the eye-region, indicating that the striking group difference has a perceptual, not attentional origin. The clarity of the present results contrasts starkly with the modest effect sizes and equivocal findings seen throughout the literature on static face perception in ASD. We speculate that differences in the perception of facial motion may be a more reliable feature of this condition.

Autism spectrum disorder
Facial motion
Face perception
Cross-feature integration
Dynamic elements


The role of MHC genes in contagious cancer: the story of Tasmanian devils.

Abstract: The Tasmanian devil, a marsupial species endemic to the island of Tasmania, harbours two contagious cancers, Devil Facial Tumour 1 (DFT1) and Devil Facial Tumour 2 (DFT2). These cancers pass between individuals in the population via the direct transfer of tumour cells, resulting in the growth of large tumours around the face and neck of affected animals. While these cancers are rare, a contagious cancer also exists in dogs and five contagious cancers circulate in bivalves. The ability of tumour cells to emerge and transmit in mammals is surprising as these cells are an allograft and should be rejected due to incompatibility between Major Histocompatibility Complex (MHC) genes. As such, considerable research has focused on understanding how DFT1 cells evade the host immune system with particular reference to MHC molecules. This review evaluates the role that MHC class I expression and genotype plays in allowing DFT1 to circumvent histocompatibility barriers in Tasmanian devils. We also examine recent research that suggests that Tasmanian devils can mount an immune response to DFT1 and may form the basis of a protective vaccine against the tumour.

MHC
Contagious cancer
Vaccine
Devil Facial Tumour Disease
MHC downregulation


Epidemiological aspects of suicide attempts among Moroccan children.

Abstract: Suicidal behavior among children has significantly increased in Morocco. We conducted a study on the epidemiological aspect to propose a treatment strategy. Descriptive retrospective study over a period of 3 years (April 2012-April 2015) involving children who visited pediatric medical emergencies of the Children Hospital of Rabat after an autolysis attempt. We observed epidemiological parameters, history, social and family context, the means used, the presumed cause, clinical manifestation, and the management. 66 patients were identified. A female predominance was found (sex =15). The average age was 13 years old. This was a first episode in 97% of cases. Psychiatric history was found in 6 patients. The causes of suicide attempt were unidentified in 65%. The most frequent cause was family conflict (35%). The most frequent method was pharmaceutical drug ingestion (54.4%). Children were asymptomatic (57.6%). Neurological manifestations (30%) were most frequent. Digestive symptoms (12%) and hemodynamic (3%) were also discovered. Patients were hospitalized in a general pediatric service 92.4% of the times, admitted to intensive care 4.5% of the times, and two patients refused to be hospitalized. The treatment consisted of gastric lavage (18%) supplemented by symptomatic measures. The outcome was favorable in 95.4% of cases. We recorded 2 deaths by rat poison poisoning. All patients were advised in writing after leaving to follow up with a psychological treatment. Suicide attempts are the result of an ill being, mostly among children living in a family with conflict. Upstream treatment is essential to identify children at risk. Additionally, a psychiatric care in hospital is essential to avoid recurrences.

Mekaoui|Nour|N|
Karboubi|Lamiae|L|
Ouadghiri|Fatima Zahra|FZ|
Dakhama|Badr Sououd Benjelloun|BS|


Fabrication of Photocontrolled Surfaces for Oil/Water Separation through Sulfur(VI) Fluoride Exchange.

Abstract: Smart surfaces with controllable wettability have attracted substantial interest owing to the potential use of these materials for the separation of oil from oily water caused by frequent oil-spill accidents. Because there are few separation materials on the market that are capable of switching between hydrophobicity and hydrophilicity, this work reports an efficient and low-cost method to fabricate a photoresponsive membrane through the sulfur(VI) fluoride exchange reaction (SuFEx) between poly(4-vinylphenol sulfofluoridate) and (E)-1-(4-(tert-butoxy)phenyl)-2-(4-(trifluoromethoxy)phenyl)diazene. The resulting material displays switchable wettability between hydrophobic and hydrophilic states when subjected to ultraviolet or visible irradiation. This membrane can be recycled (greater than five times) and features superior efficiency (up to 97.9 %) for the separation of oils that have both higher and lower densities than water. This work is the first proof-of-concept application of SuFEx to fabricate functional materials for environmental remediation.

Zhu|Haiguang|H| Chen|Dongyun|D| Li|Najun|N| Xu|Qingfeng|Q| Li|Hua|H| He|Jinghui|J| Wang|Hua|H| Wu|Peng|P| Lu|Jianmei|J|

oil/water separation
smart surface
photoresponsive
membrane
exchange reaction
sulfur fluoride


Pro-angiogenic near infrared-responsive hydrogels for deliberate transgene expression.

Abstract:
CuS nanoparticles (CuSNP) are degradable, readily prepared, inexpensive to produce and efficiently cleared from the body. In this work, we explored the feasibility of CuSNP to function as degradable near infrared (NIR) nanotransducers within fibrin-based cellular scaffolds. To prepare NIR-responsive CuSNP hydrogels, fibrinogen was dissolved in cell culture medium and supplemented with aqueous dispersions of CuSNP. Fibrinogen polymerization was catalyzed by the addition of thrombin. In some experiments, HUVEC, C3H/10T1/2 or C3H/10T1/2-fLuc cells, that harbor a heat-activated and rapamycin-dependent gene switch for regulating the expression of firefly luciferase transgene, were incorporated to the sol phase of the hydrogel. For in vivo experiments, hydrogels were injected subcutaneously in the back of adult C3H/HeN mice. Upon NIR irradiation, CuSNP hydrogels allowed heat-inducible and rapamycin-dependent transgene expression in cells contained therein, in vitro and in vivo. C3H/10T1/2 cells cultured in CuSNP hydrogels increased metabolic activity, survival rate and fibrinolytic activity, which correlated with changes at the transcriptome level. Media conditioned by CuSNP hydrogels increased viability of HUVEC which formed pseudocapillary structures and remodeled protein matrix when entrapped within these hydrogels. After long-term implantation, the skin patches that covered the CuSNP hydrogels showed increased capillary density which was not detected in mice implanted with matrices lacking CuSNP. In summary, NIR-responsive scaffolds harboring CuSNP offer compelling features in the tissue engineering field, as degradable implants with enhanced integration capacity in host tissues that can provide remote controlled deployment of therapeutic gene products.

STATEMENT OF SIGNIFICANCE
Hydrogels composed of fibrin embedding copper sulfide nanoparticles (CuSNP) efficiently convert incident near infrared (NIR) energy into heat and can function as cellular scaffolding. NIR laser irradiation of CuSNP hydrogels can be employed to remotely induce spatiotemporal patterns of transgene expression in genetically engineered multipotent stem cells. CuSNP incorporation in hydrogel architecture accelerates the cell-mediated degradation of the fibrin matrix and induces pro-angiogenic responses that may facilitate the integration of these NIR-responsive scaffolds in host tissues. CuSNP hydrogels that harbor cells capable of controlled expression of therapeutic gene products may be well suited for tissue engineering as they are biodegradable, enhance implant vascularization and can be used to deploy growth factors in a desired spatiotemporal fashion.

Martín-Saavedra|Francisco|F| Escudero-Duch|Clara|C| Prieto|Martín|M| Sánchez-Casanova|Silvia|S| López|Daniel|D| Arruebo|Manuel|M| Voellmy|Richard|R| Santamaría|Jesús|J| Vilaboa|Nuria|N|

D061307:Human Umbilical Vein Endothelial Cells

Hydrogel
Scaffold
Copper
Angiogenesis
Gene therapy
Near-infrared


Melanocortin-4 receptor in subthalamic nucleus is involved in the modulation of nociception.

Abstract: Deep brain stimulation of the subthalamic nucleus (STN-DBS) stimulation produces significant improvement of overall pain related to Parkinson disease; however, the mechanisms underlying analgesic effects of STN-DBS are still unknown. This report describes direct neuroanatomical evidence for the central melanocortinergic-opioidergic circuits in the STN. We investigated melanocortin-4 receptor (MC4R) and mu-opioid receptor (MOR)-positive expression of the STN in MC4R-GFP transgenic mice using fluorescence immunohistochemical detection. Immunohistochemistry showed a large number of MC4R-GFP- and MOR-positive neurons within the STN region, and approximately 50% of MC4R-GFP-positive neurons coexpressed MOR. The results of this study showed direct neuroanatomical evidence for the central melanocortinergic-opioidergic signaling in the STN region. These findings contribute to the view of melanocortinergic-opioidergic circuits in the subthalamic nucleus as a reliable source of modulating of nociception with therapeutic potential for alleviating pain.

melanocortin-4 receptor
Subthalamic nucleus
nociception
mu-opioid receptor


Incidence of venous and arterial thromboembolic events reported in the tofacitinib rheumatoid arthritis, psoriasis and psoriatic arthritis development programmes and from real-world data.

Abstract:
OBJECTIVES
Tofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within.

METHODS
This post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years' exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed.

RESULTS
12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the all tofacitinib cohorts' average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09-0.27) and 0.15 (0.09-0.22)); PE (0.12 (0.06-0.22) and 0.13 (0.08-0.21)); ATE (0.32 (0.22-0.46) and 0.38 (0.28-0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00-0.36) and 0.06 (0.02-0.15)); PE (0.13 (0.02-0.47) and 0.09 (0.04-0.19)); ATE (0.52 (0.22-1.02) and 0.22 (0.13-0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00-0.28) and 0.13 (0.00-0.70)); PE (0.08 (0.00-0.43) and 0.00 (0.00-0.46)); ATE (0.31 (0.08-0.79) and 0.38 (0.08-1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database.

CONCLUSIONS
DVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32-0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13-0.41)).

Mease|Philip|P|0000-0002-6620-0457
Charles-Schoeman|Christina|C|
Cohen|Stanley|S|
Fallon|Lara|L|
Woolcott|John|J|
Yun|Huifeng|H|
Kremer|Joel|J|
Greenberg|Jeffrey|J|
Malley|Wendi|W|
Onofrei|Alina|A|
Kanik|Keith S|KS|
Graham|Daniela|D|
Wang|Cunshan|C|
Connell|Carol|C|
Valdez|Hernan|H|
Hauben|Manfred|M|
Hung|Eric|E|
Madsen|Ann|A|
Jones|Thomas V|TV|
Curtis|Jeffrey R|JR|0000-0002-8907-8976

rheumatoid arthritis
psoriatic arthritis
DMARDs (synthetic)


Importance of electrocardiographic markers in predicting cardiac events in children.

Abstract: ECG is a common diagnostic tool in medical practice. Sudden cardiac death (SCD) is a rare but devastating event. The most common cause of SCD in the young is a primary arrhythmic event, which is often produced by malignant ventricular arrhythmia. Several electrocardiographic markers for ventricular repolarization and depolarization have been proposed to predict this arrhythmic risk and SCD in children. Although many of these parameters can easily be used in clinical practice, some of them need specific techniques for interpretation. In this review, we summarized the current knowledge regarding the clinical importance and the ability of these ECG parameters to predict adverse cardiac events in the pediatric population.

children
sudden cardiac death
arrhythmia
repolarization
depolarization
electrocardiography


Incorporating a compact proton therapy unit into an existing National Cancer Institute-designated comprehensive cancer center.

Abstract: Proton beams offer specific dosimetric advantages for radiation therapy. Their depth-dose relationship is characterized by the Bragg peak beyond which no dose is deposited. The elimination of exit dose for passively scattered proton beams results in greatly reduced low and intermediate doses to distant uninvolved normal tissues, but little or no difference in conformality of higher prescription doses immediately surrounding the targeted tissue. This approach is highly desirable in certain clinical scenarios such as the treatment of pediatric patients with curable malignancies for whom protons will theoretically reduce the risk of treatment related late effects. However, typical proton facilities are too large to be well integrated into most existing urban cancer centers where space is at a premium. The use of a new compact proton facility can more feasibly be incorporated into existing medical center space. In addition, they are associated with much lower cost than the typical mega-facility. The smaller capacity of this type of proton facility is quite reasonable as long as this limited and relatively expensive technology is reserved for those patients who stand to benefit the most.

D054547:National Cancer Institute (U.S.)

proton beam
radiation therapy
Bragg peak
pediatric radiation oncology
proton center


Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents.

Abstract: Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.

porphyrins nanoformulation malaria micelles nanocapsules


McCune-Albright syndrome, a rare form of precocious puberty: Diagnosis, treatment, and follow-up.

Abstract:
INTRODUCTION
McCune-Albright syndrome (MAS) is a genetic disorder defined by fibrous dysplasia of bone, café-au-lait skin spots, and autonomous hyperfunction of one or more endocrine organs. MAS is caused by activating mutations of the GNAS1 gene. The most frequent type of endocrinopathy is gonadal endocrinopathy in the form of peripheral precocious puberty.

OBJECTIVE
To describe the clinical characteristics, laboratory and imaging tests at the time of diagnosis and over the course of the disease, focusing on the classical triad of MAS.

POPULATION AND METHODS
Observational, descriptive, retrospective clinical study of patients with MAS seen at the Department of Endocrinology of Hospital de Niños Ricardo Gutiérrez between 1974 and 2019.

RESULTS
Twelve girls are described, all of whom developed peripheral precocious puberty (PPP) secondary to functional ovarian cysts. Their age at presentation was early (2.6 ± 1.3 years). Gonadotropin levels were suppressed or in the prepubertal range with generally high estradiol levels. Ten girls had café-au-lait skin spots since birth. During the course of disease, polyostotic fibrous dysplasia was detected in all patients. The treatments used to reduce ovarian cyst recurrence and hyperestrogenism effects showed varied effectiveness.

CONCLUSIONS
In this series, the onset of PPP helped to make an early diagnosis of MAS and was difficult to treat. The course of disease showed persistent gonadal hyperfunction and worsening of bone injuries.

Gryngarten|Mirta|M|
Comar|Haydeé|H|
Arcari|Andrea|A|
Boulgourdjian|Elisabeth|E|
Escobar|María E|ME|
Domené|Horacio|H|

D019080:Cafe-au-Lait Spots
D005260:Female
D005359:Fibrous Dysplasia, Polyostotic
D005500:Follow-Up Studies
D006801:Humans
D009364:Neoplasm Recurrence, Local
D011629:Puberty, Precocious
D012189:Retrospective Studies

McCune-Albright syndrome
precocious puberty
fibrous dysplasia of bone


Upstream open reading frame with NOTCH2NLC GGC expansion generates polyglycine aggregates and disrupts nucleocytoplasmic transport: implications for polyglycine diseases.

Abstract: Neuronal intranuclear inclusion disease (NIID) is neurodegenerative disease characterized by widespread inclusions. Despite the identification of GGC repeat expansion in 5'UTR of NOTCH2NLC gene in adult-onset NIIDs, its pathogenic mechanism remains unclear. Gain-of-function poly-amino-acid proteins generated by unconventional translation have been revealed in nucleotide repeat expansion disorders, inspiring us to explore the possibility of unconventional translation in NIID. Here we demonstrated that NOTCH2NLC 5'UTR triggers the translation of a polyglycine (polyG)-containing protein, N2NLCpolyG. N2NLCpolyG accumulates in p62-positive inclusions in cultured cells, mouse models, and NIID patient tissues with NOTCH2NLC GGC expansion. Translation of N2NLCpolyG is initiated by an upstream open reading frame (uORF) embedding the GGC repeats. N2NLCpolyG tends to aggregate with the increase of GGC repeat units, and displays phase separation properties. N2NLCpolyG aggregation impairs nuclear lamina and nucleocytoplasmic transport but does not necessarily cause acute death on neuronal cells. Our study suggests a similarity of pathogenic mechanisms between NIID and another GGC-repeat disease, fragile X-associated tremor ataxia syndrome. These findings expand our knowledge of protein gain-of-function in NIID, and further highlight evidence for a novel spectrum of diseases caused by aberrant polyG protein aggregation, namely the polyG diseases.

Zhong|Shaoping|S| Lian|Yangye|Y| Luo|Wenyi|W| Luo|Rongkui|R| Wu|Xiaoling|X| Ji|Jun|J| Ji|Yuan|Y| Ding|Jing|J|0000-0001-5135-4210 Wang|Xin|X|

Upstream open reading frame
NOTCH2NLC
Polyglycine
Nucleocytoplasmic transport
Neuronal intranuclear inclusion disease
GGC repeat expansion


Cytokines, JAK-STAT Signaling and Radiation-Induced DNA Repair in Solid Tumors: Novel Opportunities for Radiation Therapy.

Abstract: A number of solid tumors are treated with radiation therapy (RT) as a curative modality. At the same time, for certain types of cancers the applicable doses of RT are not high enough to result in a successful eradication of cancer cells. This is often caused by limited pharmacological tools and strategies to selectively sensitize tumors to RT while simultaneously sparing normal tissues from RT. We present an outline of a novel strategy for RT sensitization of solid tumors utilizing Jak inhibitors. Here, recently published pre-clinical data are reviewed which demonstrate the promising role of Jak inhibition in sensitization of tumors to RT. A wide number of currently approved Jak inhibitors for non-malignant conditions are summarized including Jak inhibitors currently in clinical development. Finally, intersection between Jak/Stat and the levels of serum cytokines are presented and discussed as they relate to susceptibility to RT.

Hall|William A|WA|
Sabharwal|Lavannya|L|
Udhane|Vindhya|V|
Maranto|Cristina|C|
Nevalainen|Marja T|MT|


A rare case of congenital heart disease: anomalous origin of coronary artery from innominate artery with coronary fistula and truncus arteriosus.

Abstract: Anomalous origin of a single coronary artery arising from the innominate artery associated with coronary artery fistula and truncus arteriosus is extremely rare. We found this anomaly in a 16-month-old infant-girl who received Rastelli procedure during the operation. The three defects described above are rarely found together; indeed, such a case as ours may be the first reported in the literature.

Anomalous origin of coronary
coronary fistula
truncus arteriosus


New automated single-cell technique for segmentation and quantitation of lipid droplets.

Abstract: Lipid droplets are the major organelle for intracellular storage of triglycerides and cholesterol esters. Various methods have been attempted for automated quantitation of fluorescently stained lipid droplets using either thresholding or watershed methods. We find that thresholding methods deal poorly with clusters of lipid droplets, whereas watershed methods require a smoothing step that must be optimized to remove image noise. We describe here a novel three-stage hybrid method for automated segmentation and quantitation of lipid droplets. In this method, objects are initially identified by thresholding. They are then tested for circularity to distinguish single lipid droplets from clusters. Clusters are subjected to a secondary watershed segmentation. We provide a characterization of this method in simulated images. Additionally, we apply this method to images of fixed cells containing stained lipid droplets and GFP-tagged proteins to provide a proof-of-principle that this method can be used for colocalization studies. The circularity measure can additionally prove useful for the identification of inappropriate segmentation in an automated way; for example, of non-cellular material. We will make the programs and source code available to the community under the Gnu Public License. We believe this technique will be of interest to cell biologists for light microscopic studies of lipid droplet biology.

automated
segmentation
lipid droplet
watershed
digital image analysis
quality control


Hemiprosthesis for Femoral Neck Fractures in the Elderly: A Retrospective Study of 319 Patients.

Abstract:
BACKGROUND
In geriatric patients with Pauwels types II and III femoral neck fractures, hemiprosthesis is the therapy of choice.

OBJECTIVES
This study was conducted to analyze the results after cemented hemiprosthesis placement, the first year after surgery.

PATIENTS AND METHODS
This retrospective study was conducted on 319 patients over 70 years with displaced femoral neck fractures treated surgically at our hospital from 2007 to 2012. All medical information was available including retrospective posthospital discharge records as well as inpatient course and one-year mortality.

RESULTS
From a total of 319 patients, 78% (n = 249) were female and 22% (n = 70) were male, with the mean age of 83.6 years. Seventeen percent of the patients suffered from heart failure, 23% from diabetes, and 19% from renal insufficiency. Time to surgery averaged one day postinjury. Average operative time skin-to-skin was 50 minutes. Seventy-three percent of the patients could mobilize independently on discharge. Of the remaining patients, 2/3 had already lost independent mobilization prior to the fracture. Hospital mortality averaged 5% (national average in Germany: 8%), and 30-day and 90-day mortality rates were 5% and 15%, respectively. Within one year, 22% of the patients died (national average: 27%). Also, 14 patients were re-admitted, for contralateral prosthetic implantation (n = 7) or revision after the periprosthetic fracture (n = 5). Fifty-three percent of the patients were admitted to hospital during the year for other diseases (national average: 54%).

CONCLUSIONS
Hemiprosthesis placement for displaced femoral neck fractures is a common and safe procedure. Despite recent decreases in hospital mortality, the risk of death remains more than twice as high within one year than that for uninjured patients of the same age.

Hemiprosthesis
Geriatric
Femur Fracture
Trauma in Elderly


Identification of G2607A mutation in EGFR gene with a significative rate in Moroccan patients with Bladder Cancer.

Abstract: The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing. Our results showed the absence of mutations in the EGFR kinase domain in these exons in all analysed specimens. However, sequence analysis of the EGFR-TK domain, revealed the presence of (G2607A) polymorphism at exon 20. Statistical analysis showed significant difference in the frequencies of G2607A polymorphism between cancer cases and healthy controls (p=0.0001) and the frequencies of the GG and GA/AA genotypes among the cancer cases were 28% and 72%, respectively. Moreover, allelic frequencies of G2607A polymorphism showed significant difference between cancer cases and healthy controls (p=0.0025). Data analysis showed no significant association between G2607A polymorphism and patients' age, clinical stage and tumor grade (p > 0.05). However, a significant difference was found between this polymorphism and patients' sex that could be a sampling bias due to the very limited number of women with bladder cancer. Our findings highlight that, mutations in EGFR kinase domain is a rare event in bladder cancer, suggesting, that treatment of bladder cancer patients with TKI may not be effective. However, the EGFR G2607A polymorphism in exon 20 is frequent in bladder cancer cases and must be further explored for its relevance in the treatment of this disease.

El Hamdani|W|W|
Hadami|K|K|
Bensaid|M|M|
El Ahanidi|H|H|
Ameur|A|A|
Filali Maltouf|A|A|
Abbar|M|M|
Attaleb|M|M|
Albouzidi|A|A|
El Mzibri|M|M|

D020022:Genetic Predisposition to Disease

EGFR
Bladder Cancer
Polymorphism
Morocco.
Mutation analysis


How to design psychiatric facilities to foster positive social interaction - A systematic review.

Abstract: Psychiatric facilities are often criticised of being poorly designed which may contribute to violent incidents and patients' complaints of feeling bored and lacking meaningful interactions with peers and staff. There is a lack of understanding how to design environments for staff, patients and visitors to engage in positive social interactions (e.g. conversation, sharing, peer support). We conducted a systematic literature review on which architectural typologies and design solutions facilitate helpful social interactions between users of psychiatric facilities. Several interventions were identified such as choosing a community location; building smaller (up to 20 beds) homelike and well integrated facilities with single/double bedrooms and wide range of communal areas; provision of open nursing stations; ensuring good balance between private and shared spaces for patients and staff; and specific interior design interventions such as arranging furniture in small, flexible groupings, introduction of plants on wards, and installing private conversation booths. These interventions range from simple and non-costly to very complex ones. The evidence should inform the design of new hospitals and the retrofitting of existing ones.

D005160:Facility Design and Construction

Design
Facility
Social interaction
Review
Architecture
Psychiatric hospital


Mental Health Stigma Prevention: Pilot Testing a Novel, Language Arts Curriculum-Based Approach for Youth.

Abstract:
BACKGROUND
Researchers have emphasized the importance of integrating mental health education with academic curriculum. The focus of the current studies was Mental Health Matters (MHM), a mental health curriculum that is integrated with English language arts. It is taught by trained community member volunteers and aims to increase knowledge and decrease stigma toward individuals with mental health disorders.

METHODS
In Study 1, 142 sixth graders participated in MHM and completed pre- and postprogram measures of mental health knowledge, stigma, and program acceptability. Teachers also completed ratings of acceptability. Study 2 (N = 120 seventh graders) compared participants who had participated in MHM the previous year with those who had not using the same measures.

RESULTS
Sixth grade students and teachers rated the program as highly acceptable. Participants significantly increased their knowledge and decreased their levels of stigma. Seventh graders who had participated in MHM had significantly more mental health knowledge than peers who had not, but there were no differences in stigma.

CONCLUSIONS
The model appears to be acceptable to students and teachers. Future research is needed to assess the long-term effectiveness of integrating mental health education with other academic curriculum such as language arts or science.

Weisman|Hannah L|HL|0000-0001-6691-3628
Kia-Keating|Maryam|M|
Lippincott|Ann|A|
Taylor|Zachary|Z|
Zheng|Jimmy|J|

mental health
stigma
curriculum
child and adolescent health
school health instruction


Biochemical and blood gas alterations in buffalo (Bubalus bubalis) whole blood stored in CPDA-1 and CPD/SAG-M bags.

Abstract:
OBJECTIVE
The objective of this study was to evaluate the biochemical and blood gas alterations of whole blood of buffaloes that was stored in citrate-phosphate-dextrose with adenine (CPDA-1) and CPD/SAG-M blood bags for 42 days.

DESIGN
Prospective study.

INTERVENTIONS
Ten male buffaloes were used in this study. A total volume of 900 mL of blood was collected from each buffalo so that 450 mL was stored in CPDA-1 and 450 mL was stored in CPD/SAG-M bags at 2-6°C for 42 days. The stored blood was evaluated at 7 time points (D): D0 (immediately after blood collection) and 7 (D7), 14 (D14), 21 (D21), 28 (D28), 35 (D35), and 42 (D42) days after collection. Blood gas, biochemical, and microbiological parameters were monitored.

MEASUREMENTS AND MAIN RESULTS
The overall blood pH decreased from 6.997 ± 0.05 at D0 to 6.784 ± 0.09 at D42, differing from baseline from D14 onward (P < 0.05). There were increases in partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), lactate, and potassium (K) and decreases in the concentrations of sodium, bicarbonate, glucose, and pH (P < 0.05) during storage in both bags but no alterations in total protein concentration. Most of the variables were consistently similar between the 2 types of blood bags (P > 0.05) evaluated, with the exception of pCO2 , HCO3, cholesterol, and total protein, which had higher values in the CPDA-1 bag (P < 0.05). The K, pO2 , and lactate had the highest alterations during storage, with increases from baseline to D42 of 563%, 317%, and 169%, respectively.

CONCLUSION
In general, no significant changes of clinical importance were observed after storage of whole blood samples from buffaloes for 42 days in the 2 types of blood bags that are indicated for use with this species.

de Oliveira|Francisco Leonardo Costa|FLC|

buffaloes
pH
blood conservation
hemotherapy


Resveratrol Alleviates Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Mice by Mediating PI3K/Akt/VEGFA Pathway.

Abstract: Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon, and its incidence is on the rise worldwide. Resveratrol (RSV), a polyphenolic compound, was recently indicated to exert anti-inflammatory effects on UC. Consequently, the current study was conducted to investigate the mechanism of RSV on alleviating UC in mice by mediating intestinal microflora homeostasis. First, potential targets that RSV may regulate UC were screened using the TCMSP database. Next, mice were treated differently, specifically subjected to sham-operation and dextran sulfate sodium (DSS) induction, and then treated or untreated with RSV. Disease Activity Index (DAI) and Hematoxylin-Eosin (HE) staining were employed to analyze the pathological changes of mice colon. In addition, the expression patterns of inflammatory factors in spleen tissues were detected using ELISA, while the protein expression patterns of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), and vascular endothelial growth factor A (VEGFA) in colon tissues were determined by means of immunohistochemistry (IHC) and Western blot analysis. Moreover, changes in intestinal flora and metabolite diversity in UC were analyzed by metabonomics. It was found that RSV played inhibitory roles in the PI3K/Akt pathway in mice. Meanwhile, the administration of RSV induced downregulated the expressions of TNF-α, IFN-γ, IL-1β, IL-6, and IL-4. The six floras of Haemophilus and Veillonella were significantly enriched in UC, while Clostridium, Roseburia, Akkermansia, and Parabacteroides were found to be enriched in control samples. Lastly, it was noted that Akkermansia could regulate the intestinal flora structure of UC mice through triacylglycerol biosynthesis, glycerol phosphate shuttle, cardiolipin biosynthesis, and other metabolic pathways to improve UC in mice. Altogether, our findings indicate that RSV suppressed the activation of the PI3K/Akt pathway and reduced the VEGFA gene expression to alleviate UC in mice.

Zhu|Fang|F| Zheng|Jujia|J| Xu|Fang|F| Xi|Yiyuan|Y| Chen|Jun|J| Xu|Xiangwei|X|

resveratrol
ulcerative colitis
phosphoinositide 3-kinase
protein kinase B
vascular endothelial growth factor A


Mechanical Prosthetic Heart Valve Thrombosis in a Patient Receiving Rivaroxaban.

Abstract: Direct oral anticoagulants are not approved for use in patients with mechanical valves. When used to replace vitamin K antagonists, they may cause catastrophic consequences. The authors describe the case of a patient who, after discontinuation of warfarin and introduction of rivaroxaban, developed thrombosis of his mechanical mitral prosthesis.

Carvalho Silva|Daniela Marisa|DM|
Braga|Ana|A|
de Jesus|Ilídio|I|
Neves|José|J|

Prosthetic heart valve
Thrombosis
Rivaroxaban
Direct oral anticoagulants
Mechanical prosthesis


Excretion of necrotic hepatocellular carcinoma tissues into the biliary system after transcatheter arterial chemoembolization.

Abstract:
AIM
To evaluate the incidence and condition of necrotic tumor excretion into the biliary system in patients with hepatocellular carcinoma (HCC) >5 cm treated with conventional transcatheter arterial chemoembolization (TACE).

METHODS
Eighty-three patients who underwent TACE for newly developed HCC >5 cm without an intraductal tumor thrombus and were followed-up by computed tomography for longer than 6 months were eligible. According to the location, the maximum tumors were divided into central (in contact with the left or right hepatic duct, n = 39) or peripheral (not in contact with them, n = 44). When high-density material in the biliary system that was not seen on pretreatment computed tomography was identified, it was determined as excreted necrotic tumor tissue containing iodized oil. The incidence, interval between TACE and occurrence of the necrotic tumor excretion, and clinical course were evaluated.

RESULTS
Tumor excretion into the biliary system was identified in nine (10.8%) patients with a central tumor (mean diameter, 85.0 ± 29.6 mm) 28-433 days (mean, 219.3 ± 128.2) after the initial TACE. In one patient, the necrotic tumor cast caused cholangitis 1203 days after the initial TACE, and was endoscopically removed. Infection of the embolized tumor developed in two cases and percutaneous drainage was carried out 105 and 158 days later, respectively.

CONCLUSIONS
Excretion of necrotic tumors into the biliary system after TACE was not rare in patients with centrally located HCC >5 cm. The detached tumor rarely caused symptoms and the communication between the tumor and bile duct caused the infection of tumors.

Miyayama|Shiro|S| Yamashiro|Masashi|M| Nagai|Keiichi|K| Yokka|Akira|A| Yoshida|Miki|M| Sakuragawa|Naoko|N| Sanada|Taku|T| Notsumata|Kazuo|K|