How are compassion fatigue, burnout, and compassion satisfaction affected by quality of working life? Findings from a survey of mental health staff in Italy.

Abstract:
BACKGROUND
Quality of working life includes elements such as autonomy, trust, ergonomics, participation, job complexity, and work-life balance. The overarching aim of this study was to investigate if and how quality of working life affects Compassion Fatigue, Burnout, and Compassion Satisfaction among mental health practitioners.

METHODS
Staff working in three Italian Mental Health Departments completed the Professional Quality of Life Scale, measuring Compassion Fatigue, Burnout, and Compassion Satisfaction, and the Quality of Working Life Questionnaire. The latter was used to collect socio-demographics, occupational characteristics and 13 indicators of quality of working life. Multiple regressions controlling for other variables were undertaken to predict Compassion Fatigue, Burnout, and Compassion Satisfaction.

RESULTS
Four hundred questionnaires were completed. In bivariate analyses, experiencing more ergonomic problems, perceiving risks for the future, a higher impact of work on life, and lower levels of trust and of perceived quality of meetings were associated with poorer outcomes. Multivariate analysis showed that (a) ergonomic problems and impact of work on life predicted higher levels of both Compassion Fatigue and Burnout; (b) impact of life on work was associated with Compassion Fatigue and lower levels of trust and perceiving more risks for the future with Burnout only; (c) perceived quality of meetings, need of training, and perceiving no risks for the future predicted higher levels of Compassion Satisfaction.

CONCLUSIONS
In order to provide adequate mental health services, service providers need to give their employees adequate ergonomic conditions, giving special attention to time pressures. Building trustful relationships with management and within the teams is also crucial. Training and meetings are other important targets for potential improvement. Additionally, insecurity about the future should be addressed as it can affect both Burnout and Compassion Satisfaction. Finally, strategies to reduce possible work-life conflicts need to be considered.

Cetrano|Gaia|G| Tedeschi|Federico|F| Rabbi|Laura|L| Gosetti|Giorgio|G| Lora|Antonio|A| Lamonaca|Dario|D| Manthorpe|Jill|J| Amaddeo|Francesco|F|

Compassion fatigue
Burnout
Compassion satisfaction
Quality of working life
Mental health staff
Mental health services


Physical violence and violent threats reported by Aboriginal and Torres Strait Islander people with a disability: cross sectional evidence from a nationally representative survey.

Abstract:
BACKGROUND
A recent Royal Commission into the treatment of Australians living with disabilities has underscored the considerable exposure to violence and harm in this population. Yet, little is known about exposure to violence among Aboriginal and Torres Strait Islander people living with disabilities. The objective of this paper was to examine the prevalence, disability correlates and aspects of violence and threats reported by Aboriginal and Torres Strait Islander people living with disabilities.

METHODS
Data from the 2014-15 National Aboriginal and Torres Strait Islander Social Survey were used to measure physical violence, violent threats and disability. Multivariable logistic and ordinal logistic regression models adjusted for complex survey design were used to examine the association between measures of disability and exposure to violence and violent threats.

RESULTS
In 2014-15, 17% of Aboriginal and Torres Strait Islander people aged 15-64 with disability experienced an instance of physical violence compared with 13% of those with no disability. Approximately 22% of those with a profound or severe disability reported experiencing the threat of physical violence. After adjusting for a comprehensive set of confounding factors and accounting for complex survey design, presence of a disability was associated with a 1.5 odds increase in exposure to physical violence (OR = 1.54 p < 0.001), violence with harm (OR = 1.55 p < 0.001), more frequent experience of violence (OR = 1.55 p < 0.001) and a 2.1 odds increase (OR = 2.13 p < 0.001) in exposure to violent threats. Severity of disability, higher numbers of disabling conditions as well as specific disability types (e.g., psychological or intellectual) were associated with increased odds of both physical violence and threats beyond this level. Independent of these effects, removal from one's natural family was strongly associated with experiences of physical violence and violent threats. Aboriginal and Torres Strait Islander women, regardless of disability status, were more likely to report partner or family violence, whereas men were more likely to report violence from other known individuals.

CONCLUSION
Aboriginal and Torres Strait Islander people with disability are at heightened risk of physical violence and threats compared to Aboriginal and Torres Strait Islander people without disability, with increased exposure for people with multiple, severe or specific disabilities.

D044468:Native Hawaiian or Other Pacific Islander

Violence
Threats
Aboriginal and Torres Strait Islander
Disability


Opening of ATP-sensitive K(+) (KATP) channels enhance hydroxyl radical generation induced by MPP(+) in rat striatum.

Abstract: The present study examined whether opening of adenosine triphosphate (ATP) sensitive K(+) (KATP) channels can enhance 1-methyl-4-phenylpyridinium (MPP(+))-induced hydroxyl radical (OH) generation in rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5nmol/ml per min) was infused through a microdialysis probe to detect the generation of OH as reflected by the non-enzymatic formation of 2.3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) (5mM) enhanced generation of OH with concomitant increased efflux of dopamine (DA). Cromakalim (100μM), a KATP channel opener, through the microdialysis probe significantly increased both DA efflux and OH formation induced by MPP(+). Another KATP channel opener, nicorandil (1mM), also increased the level DA or DHBA, but these changes were not significant. However, in the presence of glibenclamide (10μM), a KATP channel antagonist, and the increase of MPP(+)-induced DA or DHBA were not observed. Cromakalim (10, 50 and 100μM) increased MPP(+)-induced DHBA formation in a concentration-dependent manner. However, the effects of cromakalim in the presence of glibenclamide were abolished. These results suggest that opening of KATP channels may cause OH generation by MPP(+).


Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology.

Abstract: The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.

electrophysiology
model membranes
conductive channels
impedance analysis
lipid bilayer electrostatics
membrane-particle interactions
soft capacitor


Two for one: surgical skills and CanMEDS roles--a combined course for surgical residents.

Abstract:
BACKGROUND
The purpose of this study was to develop a surgical skills program for first-year surgical residents by integrating the Canadian Medical Education Direction for Specialists (CanMEDS) roles.

METHODS
A 9-week course combining basic surgical skills and CanMEDS roles was developed and provided to 24 residents from the Departments of Surgery and Obstetrics and Gynecology at the University of Calgary. Sessions consisted of a pretest/posttest, teaching the surgical skills, supervised practice, posttest, and teaching CanMEDS roles.

RESULTS
The pretest scores indicated the residents' preparation and understanding of the session, which improved as the course progressed. The residents' satisfaction surveys graded on a scale from 1 to 5, syllabus content, syllabus effectiveness, teaching expectations, technical demonstrations, practice sessions, confidence gained, and bench model fidelity indicated a mean of 4.09 (standard deviation = 0.81) satisfaction with the new course. Similarly, preceptors' satisfaction surveys graded on a scale from 1 to 5 demonstrated a mean of 4.16 (standard deviation = 0.69) satisfaction.

CONCLUSIONS
Surgical skills and CanMEDS roles of communication, professionalism, collaborator and manager, can be taught simultaneously proving that this new teaching format can be feasible, effective, and logistically convenient, providing a satisfying experience for both residents and preceptors.

Ponton-Carss|Alicia C|AC|
Donnon|Tyrone|T|
Kortbeek|John B|JB|

surgical skills
communication
Professionalism
Professionalism
collaborator
manager
Interpersonal and Communication Skills
Medical Knowledge
Patient Care
curriculum
professional


Structural features of an acidic polysaccharide with the potential of promoting osteoblast differentiation from Lycium ruthenicum Murr.

Abstract: The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of Lycium ruthenicum, a traditional herb for treatment of postmenopausal metabolic disorders. Structural identification indicated that LRP-S2A, with a relative molecular weight of 2.65 × 106 Da and an uronic acid content of 41.8%, contained Rha, Ara, Gal, Glc and GlcA in a molar ratio of 1.00 : 2.07 : 0.57 : 2.59 : 4.33 and was composed of a backbone consisting of 6-O-Me-α-(1→4)-D-GlcpA, 2-O-acetyl-α-(1→4)-D-Glcp, α-(1→2,4)-L-Rhap, β-(1→3)-D-Galp andα-(1→3,5)-L-Araf, and some branches consisting of 6-O-Me-α-(1→4)-D-GlcpA and terminal α-L-Araf. These results suggested that LRP-S2A with the potential of promoting osteoblast differentiation was a new acidic polysaccharide.

Wang|Shu-Qi|SQ| Liu|Bing|B| Liu|Su|S| Xie|Song-Zi|SZ| Pan|Li-Hua|LH| Zha|Xue-Qiang|XQ| Li|Qiang-Ming|QM| Luo|Jian-Ping|JP|

acidic polysaccharide
osteoblast differentiation
Lycium ruthenicum Murr.
structure elucidation


Cytologic findings of hematologic malignancies in bronchoalveolar lavage fluid.

Abstract:
INTRODUCTION
Bronchoalveolar lavage (BAL) is often performed in leukemia and lymphoma patients with pulmonary infiltrates, mainly to rule out infection. However, malignant hematopoietic infiltrates are uncommon and a comprehensive cytologic study has not yet been performed.

MATERIALS AND METHODS
We retrospectively reviewed all BAL samples from our institution for the past 22 years (November 1992-October 2014).

RESULTS
There were 37 cases of hematologic malignancies identified on BAL specimens (21 female patients and 16 male patients, age 22-80 years). Eighteen patients (49%) had pneumonia-like symptoms at the time of initial diagnosis of their malignancy, including fever, dyspnea, respiratory distress/hypoxia, and cough. The biopsy-proven cases were 25 leukemia (12 acute myeloid leukemia, 6 acute promyelocytic leukemia, 2 acute monocytic leukemia, 2 acute myelomonocytic leukemia, 1 chronic myeloid leukemia in blast phase, 1 large granular leukemia, and 1 plasma cell leukemia), 11 lymphoma (8 diffuse large B-cell lymphoma, 1 mantle cell lymphoma, 1 natural killer/T-cell lymphoma, and 1 T-cell lymphoma), and 1 multiple myeloma. Chest X-ray findings included opacities, consolidation, and interstitial edema. Four patients had BAL specimens with concomitant microorganisms. Eighteen patients subsequently died (2 days to 4 years), 15 were alive (3 weeks to 8 years of follow-up), and 4 were lost to follow-up.

CONCLUSIONS
BAL is especially important in distinguishing inflammatory/infectious processes from neoplastic disorders because many patients with hematologic malignancies can have pneumonia-like symptoms as part of their initial disease presentation. Causative pathogens are identified in only a minority of malignant BAL specimens from these patients. Lung involvement in patients with hematologic malignancies carries a poor prognosis.

Murro|Diana|D|
Slade|Jamie Macagba|JM|
Gattuso|Paolo|P|

Cytology
Bronchoalveolar lavage
Leukemia
Lymphoma
Plasma cell myeloma


What's in a Name? Correlates of Ecstasy Users Knowing or Agreeing that Molly is Ecstasy/MDMA.

Abstract: Ecstasy (MDMA) has regained popularity in powder and crystalline form, known as Molly. However, it is unknown whether all Molly users are aware that Molly is ecstasy. A total of 1045 nightclub/festival-attending adults in New York City were surveyed about ecstasy/MDMA/Molly use in 2016. Users were asked if they agreed that "Molly is (or is supposed to be) ecstasy/MDMA." Of the 43.5% reporting lifetime use, 84.6% agreed that Molly is ecstasy, 9.5% disagreed, and 5.9% reported not knowing that Molly is ecstasy. Prevalence of use of other drugs (e.g., ketamine, opioids, methamphetamine, NBOMe, 2C series) was lowest among those not knowing that Molly is ecstasy, and highest among those not agreeing that Molly is ecstasy. Those not knowing that Molly is ecstasy were less likely to have used powder or crystal MDMA and less likely to have used in the past 12 months or to report intention to use again. Those disagreeing or not knowing that Molly is ecstasy were at over six times the odds of obtaining ecstasy from an unknown dealer, and those disagreeing were at four times higher odds of having suspected or found out that their ecstasy was adulterated. Results suggest that knowing or agreeing that Molly is ecstasy/MDMA can help indicate ecstasy-related risk.

ecstasy
MDMA
Drug knowledge
epidemiology


Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells.

Abstract: Human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) and embryonic stem cells, hold great promise for cell-based therapies, but safety concerns that complicate consideration for routine clinical use remain. Installing a "safety switch" based on the inducible caspase-9 (iCASP9) suicide gene system should offer added control over undesirable cell replication or activity. Previous studies utilized lentiviral vectors to integrate the iCASP9 system into T cells and iPSCs. This method results in random genomic insertion of the suicide switch and inefficient killing of the cells after the switch is "turned on" with a small molecule (eg, AP1903). To improve the safety and efficiency of the iCASP9 system for use in iPSC-based therapy, we precisely installed the system into a genomic safe harbor, the AAVS1 locus in the PPP1R12C gene. We then evaluated the efficiencies of different promoters to drive iCASP9 expression in human iPSCs. We report that the commonly used EF1α promoter is silenced in iPSCs, and that the endogenous promoter of the PPP1R12C gene is not strong enough to drive high levels of iCASP9 expression. However, the CAG promoter induces strong and stable iCASP9 expression in iPSCs, and activation of this system with AP1903 leads to rapid killing and complete elimination of iPSCs and their derivatives, including MSCs and chondrocytes, in vitro. Furthermore, iPSC-derived teratomas shrank dramatically or were completely eliminated after administration of AP1903 in mice. Our data suggest significant improvements on existing iCASP9 suicide switch technologies and may serve as a guide to other groups seeking to improve the safety of stem cell-based therapies.

Shi|Zhong-Dong|ZD|
Tchao|Jason|J|
Wu|Ling|L|
Carman|Aaron J|AJ|

suicide gene
safety switch
induced pluripotent stem cell
inducible caspase-9
genomic safe harbor
AAVS1 locus
CAG promoter
genome editing
stem cell therapy


Bayesian Source Attribution of Salmonella Typhimurium Isolates From Human Patients and Farm Animals in England and Wales.

Abstract: The purpose of the study was to apply a Bayesian source attribution model to England and Wales based data on Salmonella Typhimurium (ST) and monophasic variants (MST), using different subtyping approaches based on sequence data. The data consisted of laboratory confirmed human cases and mainly livestock samples collected from surveillance or monitoring schemes. Three different subtyping methods were used, 7-loci Multi-Locus Sequence Typing (MLST), Core-genome MLST, and Single Nucleotide Polymorphism distance, with the impact of varying the genetic distance over which isolates would be grouped together being varied for the latter two approaches. A Bayesian frequency matching method, known as the modified Hald method, was applied to the data from each of the subtyping approaches. Pigs were found to be the main contributor to human infection for ST/MST, with approximately 60% of human cases attributed to them, followed by other mammals (mostly horses) and cattle. It was found that the use of different clustering methods based on sequence data had minimal impact on the estimates of source attribution. However, there was an impact of genetic distance over which isolates were grouped: grouping isolates which were relatively closely related increased uncertainty but tended to have a better model fit.

Arnold|Mark|M|
Smith|Richard Piers|RP|
Tang|Yue|Y|
Guzinski|Jaromir|J|
Petrovska|Liljana|L|

source attribution
Salmonella Typhimurium
Bayesian modelling
SNP distance
core-genome multi locus sequence typing
multi locus sequence typing


Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion.

Abstract:
AIM
To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer (BCLC) early (A) and intermediate (B) stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).

METHODS
A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival (RFS) and overall survival (OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE.

RESULTS
Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/mL, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/mL, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/mL, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.

CONCLUSION
PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early- and intermediate-stage HCC patients with MVI.

Ye|Jia-Zhou|JZ| Chen|Jun-Ze|JZ| Li|Zi-Hui|ZH| Bai|Tao|T| Chen|Jie|J| Zhu|Shao-Liang|SL| Li|Le-Qun|LQ| Wu|Fei-Xiang|FX|

D000971:Antineoplastic Combined Chemotherapy Protocols

Postoperative adjuvant transcatheter arterial chemoembolization


Domains of Everyday Creativity and Personal Values.

Abstract: We examined the applicability of the hybrid model of creativity, which specifies distinct domains that all express an underlying general creativity factor, in data from representative samples from Central Russia and the North Caucasus (N = 2,046). Using multigroup confirmatory analysis, Study 1 supported the invariance of a model with the six unifactorial domains (i.e., crafts, visual arts, performance, theater, products for work, and machine graphics) at the first level and a general creativity factor at the second level. Study 2 examined socio-demographic characteristics and 19 basic values that might be associated with creative activity. The more modern Central Russian region scored higher on global creativity and on all 6 domains. Of the 4 higher order values in the Schwartz model, Openness to Change values correlated positively and Conservation values correlated negatively with global creativity and with creativity in most domains. Variation across domains in the specific values that predicted creativity revealed that creativity in each domain had some unique motivators. We draw on culture and social structure to explain differences between regions in the value motivators of creativity.

Lebedeva|Nadezdha|N|
Schwartz|Shalom H|SH|
Van De Vijver|Fons J R|FJR|
Plucker|Jonathan|J|
Bushina|Ekaterina|E|

values
hybrid model of creativity
Russia
North Caucasus
global creativity
cultural regions
domains of creativity


Botanical, Phytochemical, Anti-Microbial and Pharmaceutical Characteristics of Hawthorn (Crataegusmonogyna Jacq.), Rosaceae.

Abstract: Hawthorn (Crataegus monogyna Jacq.) is a wild edible fruit tree of the genus Crataegus, one of the most interesting genera of the Rosaceae family. This review is the first to consider, all together, the pharmaceutical, phytochemical, functional and therapeutic properties of C. monogyna based on numerous valuable secondary metabolites, including flavonoids, vitamin C, glycoside, anthocyanin, saponin, tannin and antioxidants. Previous reviews dealt with the properties of all species of the entire genera. We highlight the multi-therapeutic role that C. monogyna extracts could have in the treatment of different chronic and degenerative diseases, mainly focusing on flavonoids. In the first part of this comprehensive review, we describe the main botanical characteristics and summarize the studies which have been performed on the morphological and genetic characterization of the C. monogyna germplasm. In the second part, the key metabolites and their nutritional and pharmaceutical properties are described. This work could be an essential resource for promoting future therapeutic formulations based on this natural and potent bioactive plant extract.

phytochemical
pharmaceutical
Hawthorn
flavonoids
free radical scavenging


PPARα agonist WY-14,643 induces adipose atrophy and fails to blunt chronic ethanol-induced hepatic fat accumulation in mice lacking adipose FGFR1.

Abstract: Fibroblast growth factor 21 (FGF21) is mainly regulated by peroxisome proliferator-activated receptor α (PPARα) in liver. The PPARα-FGF21 axis protects against alcohol-related liver disease (ALD). FGF21 exerts its effect via FGF receptor 1 (FGFR1). However, liver specific FGFR1 abrogation had no effect on ALD. Adipose tissues highly express FGFR1. When adipocyte specific FGFR1 knockout (fgfr1adipoQ-cre) mice and corresponding normal control (fgfr1fl/fl) mice were fed with Lieber-DeCarli ethanol liquid diet for 3 weeks, liver triglyceride (TG) accumulation was increased in the fgfr1fl/fl mice to a greater extent than in the fgfr1adipoQ-cre mice. When PPARα agonist WY-14,643 was added in the liquid ethanol diet at 10 mg/L, the ethanol-induced liver TG accumulation was blunted in the fgfr1fl/fl mice but not in the fgfr1adipoQ-cre mice. There was no significant difference in WY-14,643-induced fatty acid oxidation, ethanol metabolism, and oxidative stress between the fgfr1fl/fl and fgfr1adipoQ-cre mice. Interestingly, adipose atrophy was induced by WY-14,643 in the fgfr1adipoQ-cre mice but not in the fgfr1fl/fl mice. Serum free fatty acid was also decreased by WY-14,643 in the fgfr1adipoQ-cre mice but not in the fgfr1fl/fl mice. These results suggest that WY-14,643 inhibits alcoholic fatty liver and regulates adipose tissue mass and fat mobilization from adipose tissues to liver in an adipocyte FGFR1-dependent manner.

Xu|Yunhui|Y|
Denning|Krista L|KL|
Lu|Yongke|Y|

D051496:Receptor, Fibroblast Growth Factor, Type 1


A new interpretation of nonpulmonary vein substrates of the left atrium in patients with atrial fibrillation.

Abstract:
Background
Substrate analysis of the left atrium in patients undergoing atrial fibrillation ablation has limitations when performed by means of simple bipolar acquisition.

Objective
To evaluate the incidence of low-voltage zones (LVZs) through maps constructed by means of various catheters: multipolar (MC), omnipolar (OC), and circular catheters (CMCs) with the 3D electro-anatomical systems (3d-S) CARTO3 and EnSite Precision.

Methods
To assess LVZs, we acquired maps by means of CMC and MC in the voltage range 0.05-0.5 mV in 70 consecutive patients in sinus rhythm. In the case of OC only, we made an intra-patient comparison of bipolar maps constructed by means of the along and across, and HD-Wave configurations of the EnSite 3d-S in the ranges of 0.05-0.5 and 0.5-1.0 mV. On the basis of this comparison, we chose the range that best identified LVZs as a set of different colors (SDC) compatible with patchy fibrosis (qualitative analysis). Subsequently, we detected the voltage values corresponding to purple and gray points, close to SDC, and the value inside corresponding to blue, green, and red colors, and we evaluated the color change in other voltage ranges. Finally, we performed a quantitative analysis of LVZs by applying the qualitative characteristics described above.

Results
On the basis of our settings, for OC, the optimal range identifying LVZs was 0.3-0.6 mV. OC revealed smaller LVZs than MC (P < .05 or P < .001), except in the lateral wall. No significant differences were observed between CMCs.

Conclusions
In our experience, OC does not present the limits of bipolar HD maps, though further studies are needed in order to confirm that 0.3-0.6 mV is the optimal voltage range within which to identify LVZs.

atrial fibrillation
3D mapping
ablation index
catheter ablation
lesion index


End-of-Life Planning Depends on Socio-Economic and Racial Background: Evidence from the US Health and Retirement Study (HRS).

Abstract:
CONTEXT
Americans express a strong preference for participating in decisions regarding their medical care, yet they are often unable to participate in decision-making regarding their end-of-life care.

OBJECTIVE
To examine determinants of end-of-life planning; including, the effect of an individual's ageing and dying process, health status and socio-economic and racial/ethnic background.

METHODS
US observational cohort study, using data from the Health and Retirement Study (1992 - 2014) including 37,494 individuals. Random-effects logistic regression analysis was used to examine the relationship between the presence of a living will and a range of individual time-varying characteristics, including time to death, and several time-invariant characteristics.

RESULTS
End-of-life planning depends on several patient characteristics and circumstances, with socio-economic and racial/ethnic background having the largest effects. The probability of having a living will rises sharply late in life, as we would expect, and is further modified by the patient's proximity to death. The dying process, exerts a stronger influence on end-of-life planning than does the aging.

CONCLUSIONS
Understanding differences that increase end-of-life planning is important to incentivize patients' participation. Advance planning should be encouraged and accessible to people of all ages as it is inevitable for the provision of patient-centered and cost-effective care.

Orlovic|Martina|M| Warraich|Haider|H| Wolf|Douglas|D| Mossialos|Elias|E|

End-of-life
End-of-life planning
Living will
Advance care planning


Oral and maxillofacial tumours in children and adolescents: Clinicopathologic audit of 75 cases in an academic medical centre, Sokoto, Northwest Nigeria.

Abstract:
Background
Maxillofacial tumours in children and adolescents have been documented worldwide; however, few studies were reported from Africa, especially sub-Saharan Africa. In Nigeria, most of the studies emanated from the Southwest region.

Aim
To present an audit of clinicopathologic features and treatment of orofacial tumours in children and adolescents in Sokoto, Northwest Nigeria.

Patients and Methods
Clinicopathologic records of the Departments of Dental and Maxillofacial Surgery, Paediatrics and Histopathology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria, were reviewed for all the oral and maxillofacial tumours managed in children <19 years from January 2011 to December 2015.

Results
Two hundred and twenty-two tumours were noted in all age groups during the study duration and 75 (33.8%) of these occurred in children and adolescents. A total of 45 (60%) males and thirty (40%) females constitute the patient population with a male to female ratio of 1.5:1. There are 32 (42.7%) benign tumours and 43 (57.3%) malignant tumours. Burkitt's lymphoma was the most common malignant tumour in 24 cases (55.8%), whereas pleomorphic adenoma was the most common benign soft tissue tumour in 4 cases (30.8%) and fibro-osseous lesions were the most common benign jaw tumours in 10 cases (52.6%). Chemotherapy alone was the treatment modality in 24 cases of malignant tumour whereas 13 cases had combination chemotherapy and irradiation.

Conclusions
Our findings established that oral and maxillofacial tumours in children and adolescents are quite common in Sokoto, Northwest region of Nigeria, particularly the malignant types. There is a need for improved universal healthcare insurance for all citizens to adequately manage these children effectively.

Taiwo|Abdurrazaq Olanrewaju|AO|
Braimah|Ramat Oyebunmi|RO|
Ibikunle|Adebayo Aremu|AA|
Obileye|Mutiat Feyisetan|MF|
Jiya|Nma Muhammed|NM|
Sahabi|Saddiku Malami|SM|
Jaja|Idris Kabiru|IK|

tumours
children
Adolescents
orofacial
Burkitt's lymphoma
pleomorphic adenoma
chemotherapy
chemoradiation


Validation of CanAssist Breast immunohistochemistry biomarkers on an automated platform and its applicability in tissue microarray.

Abstract: CanAssist Breast (CAB) is a prognostic test for early-stage hormone receptor-positive invasive breast cancer. The test involves performing immunohistochemical (IHC) analysis for five biomarkers, namely CD44, ABCC4, ABCC11, N-cadherin, and pan-cadherin. In addition to IHC grading information, three clinical features, i.e., tumor size, grade, and lymph node status, serve as input into the machine learning-based algorithm to generate the CAB risk score. CAB was developed and initially validated using manual IHC. This study's objectives included: i) automate CAB IHC on an autostainer and establish its performance equivalence with manual IHC ii) validate CAB test using samples in Tissue MicroArray (TMA) format. IHC for CAB biomarkers was standardized on Ventana BenchMark XT autostainer. Two IHC methods were compared for IHC gradings and corresponding CAB risk scores/risk categories. A concordance analysis was done using MedCalcTM software. The manual and automated IHC staining methods exhibited a high level of concordance on IHC gradings for 40 cases with an Intra-class Correlation Coefficient (ICC) of >0.85 for 4 of 5 biomarkers. 100% concordance was achieved in risk categorization (low- or high-risk), with very good agreement between the risk scores demonstrated by a kappa statistic of 0.83. TMA versus whole tissue section concordance was analyzed using 45 samples on an autostainer, and the data showed 92% concordance in terms of risk category. The results confirm the equivalence between manual and automated staining methods and demonstrate the utility of TMA as an acceptable format for CanAssist Breast testing.

Serkad|Chandra Prakash V|CPV|
Attuluri|Arun Kumar|AK|
Basavaraj|Chetana|C|
Adinarayan|Manjula|M|
Krishnamoorthy|Naveen|N|
Ananthamurthy|Savitha B|SB|
Mallikarjuna|Siraganahalli E|SE|
Bakre|Manjiri M|MM|

Breast cancer
machine learning
method comparison
prognosis
risk classifier


Comparative analysis of redox and inflammatory properties of pristine nanomaterials and commonly used semiconductor manufacturing nano-abrasives.

Abstract: Continued expansion of the nanotechnology industry has necessitated the self-assessment of manufacturing processes, specifically in regards to understanding the health related aspects following exposure to nanomaterials. There exists a growing concern over potential occupational exposure in the semiconductor industry where Al2O3, CeO2 and SiO2 nanoparticles are commonly featured as part of the chemical mechanical planarization (CMP) process. Chronic exposure to toxicants can result not only in acute cytotoxicity but also initiation of a chronic inflammatory state associated with diverse pathologies. In the current investigation, pristine nanoparticles and CMP slurry formulations of Al2O3, SiO2 and CeO2 were employed to assess their ability to induce cytotoxicity, inflammatory responses and reactive oxygen species in a mouse alveolar macrophage cell model. The pristine nanoparticles and slurries were not intrinsically cytotoxic and did not generate free radicals but were found to act as scavengers in the presence of an oxidant stimulant. Al2O3 and SiO2 nanoparticles increased levels of pro-inflammatory cytokines while pristine SiO2 nanoparticles induced generation of F2-Isoprostanes. In co-treatment studies, the pristine nanomaterials modulated the response to the inflammatory stimulant lipopolysaccharide. The studies have established that pristine nanoparticles and slurries do not impact the cells in a similar way indicating that they should not be used as slurry substitutes in toxicity evaluations. Further, we have defined how an alveolar cell line, which would likely be the first challenged upon nanomaterial aerosolization, responds to diverse mixtures of nanomaterials. Moreover, our findings reinforce the importance of using multiple analytic methods to define the redox state of the cell following exposure to commonly used industrial nanomaterials and toxicants.

Flaherty|Nicole L|NL|
Chandrasekaran|Akshaya|A|
del Pilar Sosa Peña|Maria|M|
Roth|Gary A|GA|
Brenner|Sara A|SA|
Begley|Thomas J|TJ|
Melendez|J Andrés|JA|

Nanoparticle
Chemical mechanical planarization
Slurry
Alveolar macrophage
Al(2)O(3)
CeO(2)
Inflammation
Redox activity
SiO(2)


Transflammation: How Innate Immune Activation and Free Radicals Drive Nuclear Reprogramming.

Abstract:
SIGNIFICANCE
Yamanaka and colleagues galvanized the field of stem cell biology and regenerative medicine by their generation of induced pluripotent stem cells. Evidence is emerging that activation of innate immune signaling is critical for efficient reprogramming to pluripotency and for the nuclear reprogramming occurring in transdifferentiation. Recent Advances: We have shown that innate immune signaling triggers a global change in the expression of epigenetic modifiers to enhance DNA accessibility. In this state of epigenetic plasticity, overexpression of lineage determination factors, and/or environmental cues and paracrine factors, can induce pluripotency, or can direct transdifferentiation to another somatic cell lineage. Accumulating evidence reveals that innate immune activation triggers the generation of reactive oxygen species and reactive nitrogen species, and that these free radicals are required for nuclear reprogramming to pluripotency or for transdifferentiation.

CRITICAL ISSUES
We have discovered a limb of innate immune signaling that regulates DNA accessibility, in part, by the action of free radicals to induce post-translational modification of epigenetic modifiers.

FUTURE DIRECTIONS
It is of scientific interest and clinical relevance to understand the mechanisms by which free radicals influence epigenetic plasticity, and how these mechanisms may be therapeutically modulated. Antioxid. Redox Signal. 00, 000-000.

Meng|Shu|S|
Chanda|Palas|P|
Thandavarayan|Rajarajan A|RA|
Cooke|John P|JP|

D000818:Animals
D054338:Cell Transdifferentiation
D065150:Cellular Reprogramming
D053595:Embryonic Stem Cells
D044127:Epigenesis, Genetic
D005609:Free Radicals
D006801:Humans
D007113:Immunity, Innate
D057026:Induced Pluripotent Stem Cells
D051379:Mice
D052247:Nitric Oxide Synthase Type II
D017382:Reactive Oxygen Species
D015398:Signal Transduction

transflammation
innate immunity
nuclear reprogramming
induced pluripotent stem cells
nitric oxide


Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung.

Abstract: Distal airway stem cells (DASCs) in the mouse lung can differentiate into bronchioles and alveoli. However, it remains unclear whether the same stem cells exist in the human lung. Here, we found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (∆Np63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually exclusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both ∆Np63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, ΔNp63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.

Tanaka|Yusuke|Y| Yamaguchi|Miki|M| Hirai|Sachie|S| Sumi|Toshiyuki|T| Tada|Makoto|M| Saito|Atsushi|A| Chiba|Hirofumi|H| Kojima|Takashi|T| Watanabe|Atsushi|A| Takahashi|Hiroki|H| Sakuma|Yuji|Y|

D018507:Gene Expression Regulation, Developmental

Lung
Distal airway stem cell (DASC)
∆Np63
3D culture
Thyroid transcription factor 1 (TTF-1)


Shiga toxin 2eB-transgenic lettuce vaccine is effective in protecting weaned piglets from edema disease caused by Shiga toxin-producing Escherichia coli infection.

Abstract: Porcine edema disease (ED) is a toxemia that is caused by enteric infection with Shiga toxin 2e (Stx2e)-producing Escherichia coli (STEC) and is associated with high mortality. Since ED occurs most frequently during the weaning period, preweaning vaccination of newborn piglets is required. We developed stx2eB-transgenic lettuce as an oral vaccine candidate against ED and examined its protective efficacy using a piglet STEC infection model. Two serially developed Stx2eB-lettuce strains, 2BN containing ingredient Stx2eB constituting a concentration level of 0.53 mg Stx2eB/g of powdered lettuce dry weight (DW) and 2BH containing ingredient Stx2eB constituting a concentration level of 2.3 mg of Stx2eB/g of powdered lettuce DW, were evaluated in three sequential experiments. Taken the results together, oral administration of Stx2eB-lettuce vaccine was suggested to relieve the pathogenic symptoms of ED in piglets challenged with virulent STEC strain. Our data suggested that Stx2eB-lettuce is a promising first oral vaccine candidate against ED.

Shiga toxin 2e-producing Escherichia coli


Neuroimmune Interactions in Inflammation and Acute Kidney Injury.

Abstract: Inflammation contributes to the pathogenesis of a wide variety of disorders including kidney diseases. Recent advances have shown that neural pathways are able to regulate immunity and inflammation. The cholinergic anti-inflammatory pathway (CAP) is a well-studied neural circuit involving the vagus nerve that is thought to contribute to the response to inflammatory disorders. Expression of receptors for neurotransmitters is found in some immune cells, including β2 adrenergic receptors on CD4 T cells and alpha 7 subunit of the nicotinic acetylcholine (ACh) receptor on macrophages. Once nerves are activated, neurotransmitters such as norepinephrine and ACh are released at nerve terminals, and the neurotransmitters can activate immune cells located in close proximity to the nerve terminals. Thus, vagus nerve stimulation induces activation of immune cells, leading to an anti-inflammatory response. Recent studies demonstrate a non-pharmacological organ protective effect of electrical nerve stimulation, pulsed ultrasound treatment, or optogenetic C1 neuron activation. These modalities are thought to activate the CAP and attenuate inflammation. In this review, we will focus on the current understanding of the mechanisms regarding neuroimmune interactions with a particular focus on inflammation associated with kidney disease.

Inoue|Tsuyoshi|T|
Tanaka|Shinji|S|
Okusa|Mark D|MD|

inflammation
kidney injury
immunity
vagus nerve
neuroimmunomodulation


Investigation and genome-wide association study for Fusarium crown rot resistance in Chinese common wheat.

Abstract:
BACKGROUND
Fusarium crown rot (FCR) is a severe and chronic disease in common wheat and is able to cause serious yield loss and health problems to human and livestock.

RESULTS
Here, 234 Chinese wheat cultivars were evaluated in four greenhouse experiments for FCR resistance and genome-wide association studies (GWAS) were performed using the wheat 660 K genotyping assay. The results indicated that most cultivars evaluated showed FCR disease index (DI) of 40-60, while some cultivars showed stably good FCR resistance (DI < 30). GWAS identified 286 SNPs to be significantly associated with FCR resistance, of which 266, 6 and 8 were distributed on chromosomes 6A, 6B and 6D, respectively. The significant SNPs on 6A were located in a 7.0-Mb region containing 51 annotated genes. On the other hand, QTL mapping using a bi-parental population derived from UC1110 and PI610750 detected three QTLs on chromosomes 6A (explaining 7.77-10.17% of phenotypic variation), 2D (7.15-9.29%) and 2A (5.24-6.92%). The 6A QTL in the UC1110/PI610750 population falls into the same chromosomal region as those detected from GWAS, demonstrating its importance in Chinese materials for FCR resistance.

CONCLUSION
This study could provide useful information for utilization of FCR-resistant wheat germplasm and further understanding of molecular and genetics basis of FCR resistance in common wheat.

Fusarium crown rot
GWAS
Disease index
QTL
Bread wheat


Declining early mortality after hip and knee arthroplasty.

Abstract:
BACKGROUND
We aimed to measure the period effect (change over time) in 30-day mortality after total hip arthroplasty (THA) and total knee arthroplasty (TKA) using data from the Australian Orthopaedic Association National Joint Replacement Registry.

METHODS
We performed an observational study using national registry data from all hospitals performing THA and TKA in Australia including people undergoing primary elective conventional THA and TKA for osteoarthritis from 2003 to 2017, inclusive. Data from the Australian Orthopaedic Association National Joint Replacement Registry, the National Death Index and the Australian Bureau of Statistics were used to generate unadjusted 30-day mortality, the incident rate ratio for mortality adjusted for age and gender, and the standardized mortality ratio at 30 days for each year separately.

RESULTS
For the years 2003 and 2017, respectively, for THA, the unadjusted 30-day mortality was 0.23% and 0.06%, and the standardized mortality ratio was 1.11 (95% CI: 0.73, 1.49) and 0.38 (95% CI: 0.16, 0.59). The incident rate ratio was significantly higher than the reference year (2017) from 2003 to 2010, and for 2012, 2013 and 2016, decreasing over time. For the years 2003 and 2017, respectively, for TKA, the unadjusted 30-day mortality was 0.17% and 0.08%, and the standardized mortality ratio was 0.84 (95% CI: 0.55, 1.13) and 0.61 (95% CI: 0.38, 0.83). The incident rate ratio was significantly higher than the reference year (2017) from 2003 to 2009 inclusive, decreasing over time.

CONCLUSIONS
Thirty-day mortality after THA and TKA declined from 2003 to 2017. This may be due to improvements in intra-operative and post-operative patient management.

Harris|Ian A|IA|0000-0003-0887-7627
Hatton|Alesha|A|
de Steiger|Richard|R|
Lewis|Peter|P|
Graves|Stephen|S|

mortality
arthroplasty
orthopaedic surgery


Evaluation of Antimicrobial Activity of Buforin I and Nisin and Synergistic Effect of the Combination of them as a Novel Antimicrobial Preservative.

Abstract: One of the most effective methods for increasing the antimicrobial activity of a substance is to combine it with one or more other antimicrobial agents. The aim of the present study was to evaluate the antimicrobial effect of buforin I and nisin alone and investigate the synergistic action of these compounds against the most important food spoilage microorganisms in clouding B. subtilis, S. epidermidis, L. innocua, E. coli, S. Enteritidis, A. oryzae, R. glutinis and G. candidum. The results of MIC and MBC/MFC examinations showed that buforin I had higher antimicrobial activity than nisin on all the microbial strains used in this study (p≤0.5). E.coli was the most resistant to both antimicrobial agents, while Listeria innocua and Staphylococcus epidermidis were the most sensitive to nisin and buforin I, respectively. The results of synergistic interaction between buforin I and nisin indicated that the combination of buforin I and nisin on B. subtilis, S. epidermidis and A. oryzae showed synergistic effect, while it had no effect on S. Enteritidis and Geotrichum candidum. The combination of buforin I and nisin showed partial synergistic effect on Listeria innocua, Escherichia coli, Rhodotorula glutinis. Assessment of viability of the microorganisms under the antimicrobial agents alone and in combination with each other at MICs and FICs indicated that use of these antimicrobial agents in combination enhances antimicrobial activity at lower concentrations of both agents. The present study investigated the antimicrobial properties of buforin I against food spoilage microorganisms for the first time and suggests that its use alone or in combination with nisin may provide a clear horizon for the application of antimicrobial peptides as natural preservatives. Thus, the combination of antimicrobial peptides and traditional antimicrobial food preservative could be a promising option for the prevention of contamination, spoilage, and infestation of food and beverage products.

Roshanak|Sahar|S|
Shahidi|Fakhri|F|
Tabatabaei Yazdi|Farideh|F|
Javadmanesh|Ali|A|
Movaffagh|Jebraeil|J|

Antimicrobial effects, Synergistic effects, Buforin I, Nisin


Development of an immune-related prognostic index associated with osteosarcoma.

Abstract: Tumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.

Yin|Chao-Dong|CD| Hou|Ying-Lan|YL| Liu|Xiao-Ren|XR| He|Yu-Sheng|YS| Wang|Xin-Ping|XP| Li|Cheng-Jie|CJ| Tan|Xiao-Hong|XH| Liu|Jun|J|

D015972:Gene Expression Regulation, Neoplastic

prognostic index
Osteosarcoma
tumor immunity


Qualitative study of barriers to clinical trial retention in adults with recently diagnosed type 1 diabetes.

Abstract:
OBJECTIVES
Regular physical exercise may preserve β cell function in newly diagnosed adults with type 1 diabetes (T1D). However, clinical trials to test this theory require the recruitment and retention of adults with new-onset T1D, which can be challenging. We sought to determine the overall experiences of newly diagnosed adults with T1D in an exercise study, to understand issues that influence the retention of trial participants in such studies.

DESIGN
Qualitative methodology using individual face-to-face (n=6) and telephone interviews (n=14). Interview transcripts were thematically analysed using the framework method.

SETTING
The study took place at five participating UK hospitals.

PARTICIPANTS
Twenty participants, aged 19-55 years, in the Exercise for Type 1 Diabetes study were interviewed to explore their study experiences and identify motivators and deterrents towards the study. Participants in control and intervention arms were interviewed, as were people with T1D who had completed (n=16) and withdrawn (n=4).

RESULTS
Participants revealed barriers and facilitators to retention; the majority were generalisable to clinical trials of people with newly diagnosed T1D. Coming to terms with a diagnosis of T1D, lack of time, work pressures, level of health professional support, volume, clarity and consistency of information and feedback and a desire for knowledge about their condition were all cited as influencing factors to trial retention.

CONCLUSIONS
To our knowledge, this is the first qualitative study to examine the experience of being involved in an exercise trial by people with T1D. Findings suggest appointments could be shorter, available outside of working hours and planned longer in advance; study information should be clear, consistent and in electronic and paper formats; questionnaires need minimising; healthcare support and feedback needs providing regularly; thought is required around how to support non-exercising arm participants. These considerations may improve participant retention rates in new-onset T1D studies.

clinical trials
trial retention
type 1 diabetes
exercise
participants
physical activity


Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl-α-d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB.

Abstract: Mucopolysaccharidosis IIIB is caused by a marked decrease in N-acetyl-α-d-glucosaminidase (NAGLU) enzyme activity, which leads to the accumulation of heparan sulfate in key organs, progressive brain atrophy, and neurocognitive decline. In this open-label study, 11 eligible patients aged 2 to <12 years (developmental age ≥ 1 year) were sequentially allocated to recombinant human NAGLU enzyme (SBC-103) in 3 staggered- and escalating-dose groups (0.3 mg/kg [n = 3], 1.0 mg/kg [n = 4], or 3.0 mg/kg [n = 4]) by intravenous infusion every 2 weeks for 24 weeks, followed by a 4-week interruption (Part A), treatment at 1.0 and/or 3.0 mg/kg every 2 weeks starting at week 28 (Part B), and treatment at 5.0 or 10.0 mg/kg every 2 weeks (Part C) for approximately 2 total years in the study. The primary objective of the study was safety and tolerability evaluation; secondary objectives included evaluation of SBC-103 effects on total heparan sulfate levels in cerebrospinal fluid (CSF), brain structural magnetic resonance imaging (cortical gray matter volume), and neurocognitive status (age equivalent/developmental quotient). During the study, 13 treatment-emergent serious adverse events (SAEs) occurred in 3 patients; 32 infusion-associated reactions (IARs) occurred in 8 patients. Most AEs were mild and intravenous treatment with SBC-103 was well tolerated. Mean (SD) changes from baseline at 52 weeks in Part C for the 5.0 and 10.0 mg/kg doses, respectively, were: -4.7% (8.3) and - 4.7% (14.7) for heparan sulfate levels in CSF, -8.1% (3.5) and - 10.3% (9.4) for cortical gray matter volume, +2.3 (6.9) points and +1.0 (9.2) points in cognitive age equivalent and -8.9 (10.2) points and -14.4 (9.2) points in developmental quotient. In summary, SBC-103 was generally well tolerated. Changes in heparan sulfate levels in CSF were small and were not maintained from earlier study time points, there was no clear evidence overall of clinically meaningful improvement in neurocognitive function at the higher doses investigated, and no dose-dependent effects were observed.

Whitley|Chester B|CB|
Vijay|Suresh|S|
Yao|Bert|B|
Pineda|Mercé|M|
Parker|Geoff J M|GJM|
Rojas-Caro|Sandra|S|
Zhang|Xiaoping|X|
Dai|Yang|Y|
Cinar|Amy|A|
Bubb|Gillian|G|
Patki|Kiran C|KC|
Escolar|Maria L|ML|

D064420:Drug-Related Side Effects and Adverse Reactions

SBC-103
Mucopolysaccharidosis
Heparan sulfate
Enzyme replacement therapy
Lysosomal storage disease
Sanfilippo syndrome


Electrochemical Mechanism of Tellurium Reduction in Alkaline Medium.

Abstract: A systematic electrochemical study was conducted to investigate the reduction of tellurium (Te) in alkaline solutions. The effect of various parameters, including tellurite ion concentration, applied potential, and pH was investigated by both linear sweep voltammograms (LSVs) and electrochemical quartz crystal microbalance (EQCM). EQCM was essential to understand the reduction of Te(0) to soluble   (-I) or Te2-(-II). The Tafel slopes for two Te reduction reactions [i.e., Te(IV) to Te(0) and Te(0) to Te(-I)] indicated that the electrochemical reduction of Te is strongly dependent on solution pH, whereas it is independent of the concentration of   . At relatively weaker alkaline solutions (i.e., pH ≤ 12.5), the discharge of   was determined to be the rate-limiting step during the reduction of Te(IV) to Te(0). For the reduction of Te(0) to Te(-I), the reaction follows a four-step reaction, which consisted of two discharge and two electrochemical reactions. The second discharge reaction was the rate-limiting step when pH ≤12.5 with the Tafel slope of 120 mV/decade. At a higher pH of 14.7, the Tafel slope was shifted to be 40 mV/decade, which indicated that the rate-limiting step was altered to the second electrochemical reaction. Te(0) deposits were found either on the surface of an electrode or in the solution depending on pH due to the different rate-limiting reactions, revealing that pH was a key parameter to dictate the morphology of the Te(0) deposits in alkaline media.

Wu|Tingjun|T|
Kim|Jiwon|J|
Myung|Nosang V|NV|

tellurium reduction
LSV
EQCM
Tafel slopes
alkaline bath
electrochemical kinetics


Model-based analyses reveal insular population diversification and cryptic frog species in the Ischnocnema parva complex in the Atlantic forest of Brazil.

Abstract: The Atlantic Forest (AF) of Brazil has long been recognized as a biodiversity conservation hotspot. Despite decades of studies the species inventory of this biome continues to increase with the discovery of cryptic diversity and the description of new species. Different diversification mechanisms have been proposed to explain the diversity in the region, including models of forest dynamics, barriers to gene flow and dispersal. Also, sea level change is thought to have influenced coastal diversification and isolated populations on continental islands. However, the timing and mode of diversification of insular populations in the AF region were rarely investigated. Here, we analyze the phylogeography and species diversity of the small-sized direct-developing frog Ischnocnema parva. These frogs are independent from water bodies but dependent on forest cover and high humidity, and provide good models to understand forest dynamics and insular diversification. Our analysis was based on DNA sequences for one mitochondrial and four nuclear genes of 71 samples from 18 localities including two islands, São Sebastião, municipality of Ilhabela, and Mar Virado, municipality of Ubatuba, both in the state of São Paulo. We use molecular taxonomic methods to show that I. parva is composed of six independently evolving lineages, with the nominal I. parva likely endemic to the type locality. The time-calibrated species tree shows that these lineages have diverged in the Pliocene and Pleistocene, suggesting the persistence of micro-refuges of forest in the AF. For the two insular populations we used approximate Bayesian computation to test different diversification hypotheses. Our findings support isolation with migration for São Sebastião population, with ∼1Mya divergence time, and isolation without migration for Mar Virado population, with ∼13Kya divergence time, suggesting a combination of different processes for diversification on AF islands.

Gehara|Marcelo|M|
Barth|Adriane|A|
Oliveira|Eliana Faria de|EF|
Costa|Marco Antonio|MA|
Haddad|Célio Fernando Baptista|CFB|
Vences|Miguel|M|

Cryptic diversity
Insular diversification
ABC
Amphibia
Brachycephalidae
Species delimitation


REFINE: a randomized trial comparing cyclosporine A and tacrolimus on fibrosis after liver transplantation for hepatitis C.

Abstract: REFINE was a 12-month, prospective, open-label study in 356 patients receiving de novo liver transplantation for hepatitis C virus (HCV) cirrhosis, randomized to cyclosporine A (CsA) or tacrolimus with (i) no steroids, IL-2 receptor antibody induction and mycophenolic acid, or (ii) slow steroid tapering. The primary analysis population based on availability of liver biopsies comprised 165 patients (88 CsA, 77 tacrolimus). There was no difference in the primary endpoint, fibrosis stage ≥2 at 12 months, which occurred in 63/88 CsA-treated patients (71.6%) and 52/77 tacrolimus-treated patients (67.5%) (odds ratio [OR] 1.11; 95% CI 0.56, 2.21; p = 0.759). Similarly, no significant between-group difference occurred at month 24 (OR 1.15; 95% CI 0.47, 2.80; p = 0.767). Among steroid-free patients, fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 (7/37 [18.9%] vs. 16/38 [42.1%]; p = 0.029). HCV viral load was similar in both the tacrolimus- and CsA-treated cohorts. Mean blood glucose was significantly higher with tacrolimus from day 15 onward. Biopsy-proven acute rejection, graft loss and death were similar. These results showed no differences in posttransplant HCV-induced liver fibrosis between patients treated with CsA or tacrolimus in steroid-containing regimens, whereas CsA in steroid-free protocols was associated with reduced severity of fibrosis progression at 1 year posttransplant.

Levy|G|G|
Villamil|F G|FG|
Nevens|F|F|
Metselaar|H J|HJ|
Clavien|P-A|PA|
Klintmalm|G|G|
Jones|R|R|
Migliaccio|M|M|
Prestele|H|H|
Orsenigo|R|R|
|||

fibrosis
liver transplantation
cirrhosis
cyclosporine A (CsA)
Calcineurin inhibitor
clinical research/practice
hepatology
immunosuppressant


Discontinued anxiolytic drugs (2009 - 2014).

Abstract:
INTRODUCTION
Anxiety is a complex psychiatric disorder with an unknown aetiology and involving several neurotransmitter systems. These constraints have meant that researchers have looked to develop drugs, which target a variety of molecular targets, with the aim of creating safer and more effective anxiolytic drugs. Apart from the 'traditional' GABAergic and serotonergic systems, the endocannabinoid, opioidergic, glutamatergic, neurokinin, and even cholinergic systems have been (and are being) considered as preferred targets for prospective new drugs.

AREAS COVERED
This review presents candidate drugs that were investigated for the treatment of anxiety-spectrum disorders and then discontinued between the 2009 and 2014 period.

EXPERT OPINION
Despite the large variety of molecular targets, and the considerable financial and R&D resources dedicated to finding treatment solutions for anxiety-spectrum disorders, a great number of candidates have failed to reach the market. Indeed, there is still an unmet need for more effective anxiolytics that give patients a better quality of life. Although there are inherent problems with psychiatric drug development, it is thought that repurposed drugs may provide some benefit in the future.

D000818:Animals
D014151:Anti-Anxiety Agents
D001008:Anxiety Disorders
D015195:Drug Design
D015507:Drugs, Investigational
D006801:Humans
D058990:Molecular Targeted Therapy
D017211:Treatment Failure

serotonin and norepinephrine reuptake inhibitor


[Formula: see text]Official Position of the American Academy of Clinical Neuropsychology (AACN): Guidelines for Practicum Training in Clinical Neuropsychology.

Abstract: Practical experience is central to the education and training of neuropsychologists, beginning in graduate school and extending through postdoctoral fellowship. However, historically, little attention has been given to the structure and requirements of practicum training in clinical neuropsychology. A working group of senior-level neuropsychologists, as well as a current postdoctoral fellow, all from a diverse range of settings (The AACN Practicum Guidelines Workgroup), was formed to propose guidelines for practicum training in clinical neuropsychology. The Workgroup reviewed relevant literature and sought input from professional organizations involved in education and training in neuropsychology. The proposed guidelines provide a definition of practicum training in clinical neuropsychology, detail entry and exit criteria across competencies relevant to practicum training in clinical neuropsychology, and discuss the relationship between doctoral training programs and practicum training sites. The proposed guidelines also provide a methodology for competency-based evaluation of clinical neuropsychology practicum trainees and outline characteristics and features that are integral to an effective training environment. Although the guidelines discussed below may not be implemented in their entirety across all clinical neuropsychology practicum training sites, they are consistent with the latest developments in competency-based education.

Nelson|Aaron P|AP|
Roper|Brad L|BL|
Slomine|Beth S|BS|
Morrison|Chris|C|
Greher|Michael R|MR|
Janusz|Jennifer|J|
Larson|Jennifer C|JC|
Meadows|Mary-Ellen|ME|
Ready|Rebecca E|RE|
Rivera Mindt|Monica|M|
Whiteside|Doug M|DM|
Willment|Kim|K|
Wodushek|Thomas R|TR|

Guidelines
Practicum
Training
Clinical neuropsychology.
Competencies


Alterations of neocortical pyramidal neurons: turning points in the genesis of mental retardation.

Abstract: Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions.

apoptosis
calcium spikes
dendrites
dendritic spines
fetal alcohol spectrum disorders


Comment on the paper "Improving Poor Man's Kramers-Kronig analysis and Kramers-Kronig constrained variational analysis".

Abstract: The title paper [Spectrochim. Acta A213 (2019): 391-396] reports an improvement of the "Poor Man's Kramers-Kronig analysis" and of the "Kramers-Kronig constrained variational analysis" thanks to an ad hoc modification of some analytical formulas existing in the literature. This ad hoc modification is not based on mathematical grounds. In this comment we show that no ad hoc modification is required but a correction of the analytical formula used by the authors of the title paper [Spectrochim. Acta A213 (2019): 391-396].

Rousseau|Emmanuel|E| Izard|Nicolas|N| Bantignies|Jean-Louis|JL| Felbacq|Didier|D|

Kramers–Kronig relations
Poor Man’s Kramers–Kronig analysis


Devil in the details? Developmental dyslexia and visual long-term memory for details.

Abstract: Cognitive theories on causes of developmental dyslexia can be divided into language-specific and general accounts. While the former assume that words are special in that associated processing problems are rooted in language-related cognition (e.g., phonology) deficits, the latter propose that dyslexia is rather rooted in a general impairment of cognitive (e.g., visual and/or auditory) processing streams. In the present study, we examined to what extent dyslexia (typically characterized by poor orthographic representations) may be associated with a general deficit in visual long-term memory (LTM) for details. We compared object- and detail-related visual LTM performance (and phonological skills) between dyslexic primary school children and IQ-, age-, and gender-matched controls. The results revealed that while the overall amount of LTM errors was comparable between groups, dyslexic children exhibited a greater portion of detail-related errors. The results suggest that not only phonological, but also general visual resolution deficits in LTM may play an important role in developmental dyslexia.

Huestegge|Lynn|L|
Rohrßen|Julia|J|
van Ermingen-Marbach|Muna|M|
Pape-Neumann|Julia|J|
Heim|Stefan|S|

orthographic representations
visual resolution deficit
language and word processing
memory errors
phonology and reading
picture processing


Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

Abstract: Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

Necrotizing fasciitis
Medical malpractice
Clinical forensic medicine
Forensic pathology
LRINEC score


Extreme Anatomy: Gear for the Pioneer.

Abstract: This special issue of The Anatomical Record explores extravagant adaptions that vertebrates have evolved from their base groups to survive in the most challenging environments. The special issue stems from a symposium entitled "Extreme Anatomy: Living beyond the edge," which was held April 23, 2017, at the annual meeting of the American Association of Anatomists, (now called the American Association for Anatomy), in Chicago, IL. In part 1 of this issue, we encounter fossorial mammals and cave-dwelling fish and salamanders that have reduced visual systems accompanied by a variety of mechanosensory adaptations. In rivers and seas, teeth may not suffice in the pursuit of prey: aquatic vertebrates are adorned with armor or weaponry or elaborate keratinous sieves. As vertebrates exploit a great diversity of niches, selection has favored a dizzying array of specialized sensory and locomotor adaptions for deep diving, rapid flight, and navigation through dark and complex settings. Each special adaptation, some seemingly quite "extreme" deviations from an original Bauplan, becomes a tool for a pioneer-like diversification of vertebrates. Anat Rec, 2019. © 2019 American Association for Anatomy.

D003247:Conservation of Natural Resources

adaptation aquatic bipedality evolutionary tetrapod


Effects of oxygen plasma treatment on interfacial shear strength and post-peak residual strength of a PLGA fiber-reinforced brushite cement.

Abstract: Biodegradable calcium phosphate cements (CPCs) are promising materials for minimally invasive treatment of bone defects. However, CPCs have low mechanical strength and fracture toughness. One approach to overcome these limitations is the modification of the CPC with reinforcing fibers. The matrix-fiber interfacial shear strength (ISS) is pivotal for the biomechanical properties of fiber-reinforced CPCs. The aim of the current study was to control the ISS between a brushite-forming CPC and degradable PLGA fibers by oxygen plasma treatment and to analyze the impact of the ISS alterations on its bulk mechanical properties. The ISS between CPC matrix and PLGA fibers, tested in a single-fiber pull-out test, increased up to 2.3-fold to max. 3.22±0.92MPa after fiber oxygen plasma treatment (100-300W, 1-10min), likely due to altered surface chemistry and morphology of the fibers. This ISS increase led to more efficient crack bridging and a subsequent increase of the post-peak residual strength at biomechanically relevant, moderate strains (up to 1%). At the same time, the work of fracture significantly decreased, possibly due to an increased proportion of fractured fibers unable to further absorb energy by frictional sliding. Flexural strength and flexural modulus were not affected by the oxygen plasma treatment. This study shows for the first time that the matrix-fiber ISS and some of the resulting mechanical properties of fiber-reinforced CPCs can be improved by chemical modifications such as oxygen plasma treatment, generating the possibility of avoiding catastrophic failures at the implant site and thus enhancing the applicability of biodegradable CPCs for the treatment of (load-bearing) bone defects.

Maenz|Stefan|S|
Hennig|Max|M|
Mühlstädt|Mike|M|
Kunisch|Elke|E|
Bungartz|Matthias|M|
Brinkmann|Olaf|O|
Bossert|Jörg|J|
Kinne|Raimund W|RW|
Jandt|Klaus D|KD|

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

Plasma treatment
Interfacial shear strength
Calcium phosphate cement
Mechanical properties
Fiber reinforcement


The interaction of Hsc70 protein with fibrillar α-Synuclein and its therapeutic potential in Parkinson's disease.

Abstract: We recently described the effect of the constitutively expressed chaperone, Hsc70 protein, on α‑Synuclein aggregation, a phenomenon associated with Parkinson disease. In vitro, Hsc70 binds to soluble α‑Syn and slows down its assembly into fibrils. Hsc70 also binds fibrillar α‑Syn, 5-fold tighter than soluble α‑Syn. This interaction reduces the cytotoxicity associated with naked α‑Syn fibrils. Herein, we discuss the feasibility of engineering a "minichaperone" which could be used against α‑Syn assembly propagation in Parkinson disease: taking what is necessary and sufficient within Hsc70 to protect against the damaging repercussions of high molecular weight α‑Syn species' passage from one neuron to another in the brain.

Hsc70
chaperones
Parkinson’s disease
alpha synuclein
heat shock protein


Antihyperglycemic and in vivo antioxidative activity evaluation of Cinnamomum bejolghota (Buch.-Ham.) in streptozotocin induced diabetic rats: an ethnomedicinal plant in Assam.

Abstract:
OBJECTIVE
To evaluate the antihyperglycemic property of Cinnamomum bejolghota (Buch.-Ham.) on streptozotocin induced type-2 diabetic rats.

METHODS
Oral glucose tolerance test level was measured at 0, 30, 60, 90 and 120 min after the administration of extract. The extract was orally administered once daily at two dose levels of 250 and 500 mg/kg for 15 d. The effect of methanolic extract of Cinnamomum bejolghota (MECB) on the divergence of body weights, blood glucose levels and the biochemical parameters viz., total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, aspartate transaminase, alanine transaminase, alkaline phosphatase were measured in an autoanalyzer. Histopathology of pancreas and in vivo antioxidative status was studied.

RESULTS
A significant increase in bodyweights and rapid decrease in hyperglycemic peak was experiential in animals treated with MECB. After 15 d treatment the total cholesterol, TG, low density lipoprotein level decreased and high density cholesterol level increased significantly. MECB reduced the levels of the elevated marker enzymes aspartate transaminase, alanine transaminase and alkaline phosphatase. MECB reduced the lipid peroxidation and improved the level of catalase and glutathione in liver. Histopathological studies of pancreas in diabetic and treated groups substantiate the cytoprotective action of extract.

CONCLUSIONS
It can be evident from the research work that Cinnamomum bejolghota (Buch.-Ham.) has potent antihyperglycemic activity and supports the in vivo antioxidative status.

Gogoi|Barnali|B|
Kakoti|Bibhuti Bhusan|BB|
Borah|Sudarshana|S|
Borah|Nilutpal Sharma|NS|

Antioxidant
Cinnamomum bejolghota
Histopathology
Anti-hyperglycemic


Nanoplasmonic chitosan nanofibers as effective SERS substrate for detection of small molecules.

Abstract: The use of surface enhanced Raman spectroscopy (SERS) is limited by low reproducibility and uniformity of the response. Solving these problems can turn the laboratory use of SERS into real-world application. In this regard, soft SERS-active substrates can enable portable instrumentation and reduce costs in the fabrication of SERS-based sensors. Here, plasmonic free-standing films made of biocompatible chitosan nanofibers and gold nanoparticles are engineered by a simple protocol varying the concentration of chloroauric acid. The concentration and distribution of gold nanoparticles in films are controlled in a predictable way, and SERS spectra for the standard 2-naphthalenethiol with concentration less than 10(-15) M are acquired in a reproducible way. The statistical analysis reveals a relatively high and locally uniform performance of SERS with an enhancement factor of 2 × 10(5) for 86% of the points on the imaged area of the SERS substrate. Potential SERS detection of small molecules, both Rhodamine 6G and d-Glucose, in the micromolar range is demonstrated.

Severyukhina|Alexandra N|AN|
Parakhonskiy|Bogdan V|BV|
Prikhozhdenko|Ekaterina S|ES|
Gorin|Dmitry A|DA|
Sukhorukov|Gleb B|GB|
Möhwald|Helmuth|H|
Yashchenok|Alexey M|AM|

chitosan nanofibers
SERS
gold nanoparticles
Rhodamine 6G
d-Glucose


How to diagnose and treat post-stroke seizures and epilepsy.

Abstract: Stroke is one of the commonest causes of seizures and epilepsy, mainly among the elderly and adults. This seminar paper aims to provide an updated overview of post-stroke seizures and post-stroke epilepsy (PSE) and offers clinical guidance to anyone involved in the treatment of patients with seizures and stroke. The distinction between acute symptomatic seizures occurring within seven days from stroke (early seizures) and unprovoked seizures occurring afterwards (late seizures) is crucial regarding their different risks of recurrence. A single late post-stroke seizure carries a risk of recurrence as high as 71.5% (95% confidence interval: 59.7-81.9) at ten years and is diagnostic of PSE. Several clinical and stroke characteristics are associated with increased risk of post-stroke seizures and PSE. So far, there is no evidence supporting the administration of antiepileptic drugs as primary prevention, and evidence regarding their use in PSE is scarce.

Zelano|Johan|J| Holtkamp|Martin|M| Agarwal|Nivedita|N| Lattanzi|Simona|S| Trinka|Eugen|E| Brigo|Francesco|F|

post-stroke seizures
post-stroke epilepsy
treatment
intracerebral haemorrhage
ischaemic stroke


Large-scale profiling of the proteome and dual transcriptome in Nile tilapia (Oreochromis niloticus) challenged with low- and high-virulence strains of Streptococcus agalactiae.

Abstract: Streptococcus agalactiae is a common pathogen in aquatic animals, especially tilapia, that hinders aquaculture development and leads to serious economic losses. Previously, a S. agalactiae strain named HN016 was identified from infected tilapia, and the attenuated strain YM001 was subsequently obtained by continuous passaging in Tryptic Soy Broth (TSB) medium. YM001 has been demonstrated as a safe vaccine for S. agalactiae infection in tilapia. To understand the molecular bases of the virulence of these two strains, we performed proteomic and transcriptomic analysis to reveal the protein and gene expression changes in the liver and intestine during the infection process. HN016 significantly decreased the contents of white blood cells (WBCs), neutrophils (NEUs), red blood cells (RBCs) and hematocrit (HCT) and increased the levels of total protein (TP), albumin (ALB) and globulin (GLO), while no such significant differences were observed when comparing the control with YM001. During the infection process, pathogenic peptidoglycan hydrolase, CSPA and membrane proteins were significantly differentially expressed between YM001 and HN016. Furthermore, both proteome and transcriptome data showed that the complement and coagulation cascades pathway and the antigen processing and presentation pathway were stimulated in the liver and intestine, respectively, by YM001 infection compared to HN016 infection. The interaction network analysis of key virulence genes from pathogens suggested that CSPA, as a key node, affects the expression of DOLPP1, MIPEP, PA2G4, OCIAD1, G3BP1 and CLIC5 with a positive correlation. The present evidence suggests that during the infection process, CSPA was the key genes contributing to low virulence in YM001.

Zhou|Yi|Y| Liu|Yu|Y| Luo|Yongju|Y| Zhong|Huan|H| Huang|Ting|T| Liang|Wanwen|W| Xiao|Jun|J| Wu|Wende|W| Li|Liping|L| Chen|Ming|M|

Proteome
Transcriptome
Tilapia
Streptococcus agalactiae
Virulence
Cold shock protein


Investigation of ice-assisted sonication on the microstructure and chemical quality of Ganoderma lucidum spores.

Abstract: Ganoderma lucidum spores (GLS) are well known for disease treatment and vitality enhancement, and have been shown to contain a variety of bioactive components, such as polysaccharides and triterpenes. However, the resilient bilayer sporoderm structure of GLS restricts the release of bioactive components and limits its complete pharmacological effects. The current study was aimed to improve the quality of GLS by means of a customized sonication technique, particularly, the effect of sonication processing parameters on GLS-breaking efficiencies was investigated. Significant morphological changes, such as cracked, fractured, and disintegrated GLS were observed using scanning electron microscopy (SEM) after sonication treatment. The performance for breaking GLS sporoderm was obtained at ultrasonic power density of 23.7 W/cm(2) , duty cycle 100%, and 90-min processing time. Through the combination of sonication in an ice bath, sporoderm breaking efficiency can be further increased from 45% to almost 75%. FTIR analysis revealed an increase in bioactive components of polysaccharide, protein, and fatty acid from the sonication processed GLS when compared to ground spores available commercially. The current results indicated that the ice bath combined sonication method is more effective in delivering GLS ingredients and could be an economic technique for the production of high-quality broken sporoderm GLS.

Zhao|Ding|D| Chang|Ming-Wei|MW| Li|Jing-Song|JS| Suen|William|W| Huang|Jie|J|

D017550:Spectroscopy, Fourier Transform Infrared

Ganoderma lucidum
Ganoderma lucidum spore
mushroom
sporoderm-breaking ratio
ultrasound


miRNA-101 inhibits ovarian cancer cells proliferation and invasion by down-regulating expression of SOCS-2.

Abstract:
OBJECTIVE
To investigate the expression of miRNA-101 in normal and malignant ovarian tissues and cells as well as its impact on the proliferation and invasion of human ovarian cancer H08910 and SKOV3 cell lines.

METHODS
Real time polymerase chain reaction (RT-PCR) was employed to detect the miR-101 and SOCS-2 expression in 20 separate ovarian cancer tissues and para-carcinoma tissues, human ovarian cancer cells (H08910 and SKOV3) and normal human ovarian epithelial cells (HUM-CELL-0088). After H08910 and SKOV3 ovarian cancer cells were respectively transfected with miR-NC (H08910/NC and SKOV3/NC) and miR-101 (H08910/miR-101 and SKOV3/miR-101), Western Blot was employed to detect the SOCS-2 expression in transfected cells. CCK-8 and clone formation and Transwell assays were employed to determine the proliferation and invasion ability of wild type and transfected ovarian cancer cells.

RESULTS
The expression of miR-101 in ovarian cancer tissues and cells was significantly lower than that in para-carcinoma tissues (t=19.12, P=0.002) and normal human ovarian epithelial cells (HUM-CELL-0088) (F=14.37, P=0.000), respectively. In contrast, the SOCS-2 expression in ovarian cancer tissues and cells was significantly higher than that in para-carcinoma tissues (t=25.03, P=0.000) and HUM-CELL-0088 cells (F=14.9, P=0.000) by Western Blotting analysis, respectively. Compared with wild type and empty vector transfected cells, the expression of SOCS-2 was significantly decreased in miR-101 transfected H08910 (t=10.9, P=0.001) and SKOV3 cells (t=21.03, P=0.000). The results of CCK-8, clone formation and Transwell assays revealed that the proliferation and invasion ability of ovarian cancer cells was markedly inhibited by the transfection of miR-101.

CONCLUSION
MiR-101 was validated to be reduced and SOCS-2 expression increased in ovarian cancer tissues and cells. The over expression of miR-101 can remarkably reduce the in vitro proliferation and invasion ability of ovarian cancer cells through the down-regulation of SOCS-2.


The Extended Community-Level Effects of Genetic Variation in Foliar Wax Chemistry in the Forest Tree Eucalyptus globulus.

Abstract: Genetic variation in foundation trees can influence dependent communities, but little is known about the mechanisms driving these extended genetic effects. We studied the potential chemical drivers of genetic variation in the dependent foliar community of the focal tree Eucalyptus globulus. We focus on the role of cuticular waxes and compare the effects to that of the terpenes, a well-studied group of secondary compounds known to be bioactive in eucalypts. The canopy community was quantified based on the abundance of thirty-nine distinctive arthropod and fungal symptoms on foliar samples collected from canopies of 246 progeny from 13 E. globulus sub-races grown in a common garden trial. Cuticular waxes and foliar terpenes were quantified using gas chromatography - mass spectrometry (GC-MC). A total of 4 of the 13 quantified waxes and 7 of the 16 quantified terpenes were significantly associated with the dependent foliar community. Variation in waxes explained 22.9% of the community variation among sub-races, which was equivalent to that explained by terpenes. In combination, waxes and terpenes explained 35% of the genetic variation among sub-races. Only a small proportion of wax and terpene compounds showing statistically significant differences among sub-races were implicated in community level effects. The few significant waxes have previously shown evidence of divergent selection in E. globulus, which signals that adaptive variation in phenotypic traits may have extended effects. While highlighting the role of the understudied cuticular waxes, this study demonstrates the complexity of factors likely to lead to community genetic effects in foundation trees.

Eucalyptus globulus
Foundation trees
Foliar terpenes
Community genetics
Cuticular wax compounds
Extended phenotype


Menopause guideline appraisal and algorithm development for premature ovarian insufficiency.

Abstract:
OBJECTIVES
Clinical practice guidelines (CPGs) are systematically developed statements that guide clinicians to provide appropriate healthcare. The aims of this study were: 1) to systematically evaluate the quality of menopause management CPGs; 2) to identify menopause topics included in the CPGs; 3) to summarize the recommendations regarding either early menopause (EM) or premature ovarian insufficiency (POI) provided by high-scoring CPGs; and 4) to develop EM/POI management algorithms.

STUDY DESIGN
A systematic search for CPGs published between 2012 and 2017 was conducted using Medline, Embase, All EBM, CPG databases and medical websites. Appraisal was conducted by 4 independent reviewers using the Appraisal of Guidelines for Research & Evaluation II instrument (AGREE II). Inter-rater reliability was calculated using the intraclass correlation coefficient. Recommendations regarding EM/POI were extracted from high-scoring CPGs and translated into a management algorithm, which was refined on the basis of feedback from expert clinicians.

RESULTS
The systematic search yielded 22 CPGs for review. Only 2 were assessed as high quality, with 10 average and 10 considered low quality. Scope and purpose (73% ± 15%) and clarity of presentation (78% ± 15%) achieved the highest mean scores, while applicability scored the lowest (23% ± 18%). Inter-rater agreement was 0.74 (good) to 0.91 (very good). The most comprehensive CPGs were those developed by the National Institute for Health and Care Excellence (NICE), the International Menopause Society (IMS) and the European Menopause and Andropause Society (EMAS).

CONCLUSIONS
Most menopause CPGs are poor to average quality and there is variation between them in EM/POI management recommendations. EM/POI management algorithms were developed from high-scoring CPGs.

Yeganeh|Ladan|L|
Boyle|Jacqueline A|JA|
Wood|Anna|A|
Teede|Helena|H|
Vincent|Amanda J|AJ|

Menopause
Premature ovarian insufficiency
Clinical practice guidelines
AGREE II
Menopausal hormone therapy


Immunological biomarkers identifying natalizumab-treated multiple sclerosis patients at risk of progressive multifocal leukoencephalopathy.

Abstract: Natalizumab-induced progressive multifocal leukoencephalopathy appears to be unleashed by complex interactions between viral and immunological host factors leading the latent form of JC virus to become pathogenic. Positive anti-JC virus antibody status, prior use of immunosuppressants, and increasing duration of natalizumab treatment have been proposed as risk factors for progressive multifocal leukoencephalopathy in multiple sclerosis patients, but while they may help to identify the most appropriate patients for natalizumab, their use have some limitations. Therefore, a large body of studies is ongoing to identify alternative, reliable immunological markers capable to improve the safety and efficacy of therapy, and to guide tailored clinical decisions.

Serana|Federico|F|
Chiarini|Marco|M|
Sottini|Alessandra|A|
Bertoli|Diego|D|
Giustini|Viviana|V|
Tessitore|Marion Vaglio|MV|
Caimi|Luigi|L|
Capra|Ruggero|R|
Imberti|Luisa|L|

K-deleting recombination excision circles


Transient Type 1 Brugada Pattern without Ongoing Fever during COVID-19 Pneumonia.

Abstract:
Patients with COVID-19 pneumonia can develop heart problems and may also may be susceptible to proarrhythmia, virus-related issues such as fever, stress, electrolyte disturbance and adverse effects from the use of antiviral drugs. We report a transient Brugada-like ECG pattern without ongoing fever in a 57-year-old man, admitted with a diagnosis of COVID-19 pneumonia, who did not have syncope or a family history of sudden cardiac death.

LEARNING POINTS
Patients with COVID-19 pneumonia can develop heart problems.A transient Brugada-like ECG pattern was observed in a non-febrile COVID-19 patient.SARS-CoV-2 may have a direct effect on myocardial ion channels.

Pasqualetto|Maria Cristina|MC|
Corrado|Andrea|A|
Secco|Eleonora|E|
Graceffa|Fabio|F|
Rigo|Fausto|F|

Brugada pattern
fever
COVID-19
myocardial ion channels


COVID-19 among the inhabitants of the slums in the city of Buenos Aires: a population-based study.

Abstract:
OBJECTIVE
To summarise the unfolding of the COVID-19 epidemic among slum dwellers and different social strata in the city of Buenos Aires during the first 20 weeks after the first reported case.

DESIGN
Observational study using a time-series analysis. Natural experiment in a big city.

SETTING
Population of the city of Buenos Aires and the integrated health reporting system records of positive RT-PCR for COVID-19 tests.

PARTICIPANTS
Records from the Argentine Integrated Health Reporting System for all persons with suspected and RT-PCR-confirmed diagnosis of COVID-19 between 31 January and 14 July 2020.

OUTCOMES
To estimate the effects of living in a slum on the standardised incidence rate of COVID-19, corrected Poisson regression models were used. Additionally, the impact of socioeconomic status was performed using an ecological analysis at the community level.

RESULTS
A total of 114 052 people were tested for symptoms related with COVID-19. Of these, 39 039 (34.2%) were RT-PCR positive. The incidence rates for COVID-19 towards the end of the 20th week were 160 (155 to 165) per 100 000 people among the inhabitants who did not reside in the slums (n=2 841 997) and 708 (674 to 642) among slums dwellers (n=233 749). Compared with the better-off socioeconomic quintile (1.00), there was a linear gradient on incidence rates: 1.36 (1.25 to 1.46), 1.61 (1.49 to 1.74), 1.86 (1.72 to 2.01), 2.94 (2.74 to 3.16) from Q2 to Q5, respectively. Slum dwellers were associated with an incidence rate of 14.3 (13.4 to 15.4).

CONCLUSIONS
The distribution of the epidemic is socially conditioned. Slum dwellers are at a much higher risk than the rest of the community. Slum dwellers should not be considered just another risk category but an entirely different reality that requires policies tailored to their needs.

Macchia|Alejandro|A|0000-0002-5424-5009
Ferrante|Daniel|D|
Battistella|Gabriel|G|
Mariani|Javier|J|
González Bernaldo de Quirós|Fernán|F|

D000087123:COVID-19 Nucleic Acid Testing


Study on the Utilization of Iron Tailings in Ultra-High-Performance Concrete: Fresh Properties and Compressive Behaviors.

Abstract: In this paper iron tailing sand (TS) are used as aggerate to develop ultra high-performance concrete (UHPC). The mix proportion of UHPC is designed and TS were added by 25%, 50%, 75% and 100% (wt.%, i.e., weight percentage) to replace natural river sand. Firstly, the influence of TS on the slurry behavior was carried out. The experimental result indicates that with the continuously increasing content of TS, the workability of slurry decreases, while the air content increases. Considering the workability, the optimal replacing dosage of TS should be less than 50%. Then, tests for the hardened specimens were taken. The compressive behavior and micro-porosity deteriorate with increasing content of TS, and the compressive strength had a positive linear relationship with the workability, which indicated that the decline the compressive behavior is mainly due to the loss of flowability. Finally, autogenous shrinkages of UHPC with different TS dosage were also tested. At the same time, the micro-structure of specimens was discussed, which was deteriorate with the increasing dosage of TS. Therefore, comprehensively considering the compressive behavior, micro-structure and shrinkage behavior, as much as 50% of the aggregate could be replaced by TS when developing UHPC.

Zhao|Yunqi|Y| Gu|Xiaowei|X| Qiu|Jingping|J| Zhang|Weifeng|W| Li|Xiaohui|X|

ultra high-performance concrete (UHPC)
workability
autogenous shrinkage
micro-structure
iron ore tailings


Optimizing Care for Adults with Congenital Heart Disease: Results of a Conjoint Analysis Based on a Nationwide Sample of Patients Included in the German National Register.

Abstract: (1) Background: Congenital heart disease (CHD) requires lifelong specialized care. Failure to follow up and gaps in care are common in this group and lead to increased morbidity/mortality. We evaluated patients' perceived needs and expectations regarding specialized care using state-of-the-art statistical and market research techniques based on a nationwide sample of CHD patients. (2) Methods: A random sample of adults with CHD registered in the German National Register for Congenital Heart Defects were invited to answer an adaptive online questionnaire based on the conjoint analysis (CA) technique. CA determines the relative importance of various aspects of health care provision and allows individuals to trade between characteristics, thus recognizing limited resources. (3) Results: 637 patients participated (mean age 33.8 ± 12.6 years; 55.6% female; disease complexity: simple defect 12.6%, moderate complexity 40.3%, complex CHD 40.2%) in the analysis. Patients assigned the highest relative importance to aspects of patient-physician communication, physician qualifications, waiting time, medical care, and medical equipment. Comfort-related aspects such as driving time or hotel aspects of care received much lower scores. We identified four well-defined clusters of patients with differing expectation patterns: (i) time sensitive patients; (ii) excellence seeking patients; (iii) continuity seekers, and (iv) support seeking patients. (4) Conclusions: Adult CHD patients rank effective patient-physician interaction and communication as the most important factors. As we identified significant heterogeneity between CHD patients, centers should cater for individual preferences and integrate individual needs into treatment plans to prevent failure to follow up and ensure patient compliance.

Lammers|Astrid E|AE|
Helm|Paul C|PC|0000-0002-1868-4266
Bauer|Ulrike M|UM|
van Huelsen|Ann-Kathrin|AK|
Schneider|Helmut|H|
Baumgartner|Helmut|H|
Diller|Gerhard-Paul|GP|

conjoint analysis
adult congenital heart disease
healthcare provision
registry
survey


Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America.

Abstract:
BACKGROUND
little is known about the forecasting of new variants of SARS-COV-2 in North America and the interaction of variants with vaccine-derived neutralizing antibodies.

METHODS
the affinity scores of the spike receptor-binding domain (S-RBD) of B.1.1.7, B. 1.351, B.1.617, and P.1 variants in interaction with the neutralizing antibody (CV30 isolated from a patient), and human angiotensin-converting enzyme 2 (hACE2) receptor were predicted using the template-based computational modeling. From the Nextstrain global database, we identified prevalent mutations of S-RBD of SARS-CoV-2 from December 2019 to April 2021. Pre- and post-vaccination time series forecasting models were developed based on the prediction of neutralizing antibody affinity scores for S-RBD of the variants.

RESULTS
the proportion of the B.1.1.7 variant in North America is growing rapidly, but the rate will reduce due to high affinity (~90%) to the neutralizing antibody once herd immunity is reached. Currently, the rates of isolation of B. 1.351, B.1.617, and P.1 variants are slowly increasing in North America. Herd immunity is able to relatively control these variants due to their low affinity (~70%) to the neutralizing antibody. The S-RBD of B.1.617 has a 110% increased affinity score to the human angiotensin-converting enzyme 2 (hACE2) in comparison to the wild-type structure, making it highly infectious.

CONCLUSION
The newly emerged B.1.351, B.1.617, and P.1 variants escape from vaccine-induced neutralizing immunity and continue circulating in North America in post- herd immunity era. Our study strongly suggests that a third dose of vaccine is urgently needed to cover novel variants with affinity scores (equal or less than 70%) to eliminate developing viral mutations and reduce transmission rates.