Impact of the prevalence of different pathogens on the performance of sampling plans in lettuce products.

Abstract: Prevalence and concentration of Listeria monocytogenes, Salmonella spp. and enteric pathogenic viruses (namely Hepatitis A-HAV, and noroviruses genogroup I-NoVGI and genogroup II-NoVGII) were determined in raw and RTE lettuce from a Spanish processing premise. Fifteen samplings were made from September 2010 to February 2012 (n=600 samples). Sampling strategies for pathogen detection were suggested by the characterization of the uncertainty in prevalence associated with the performance of two-class attributes sampling plans (c=0). A probabilistic model was run (1000 iterations) using a Bayesian approach with a conjugate beta distribution considering the impact of taking different number of samples on the proportion of positive samples and lots (within- and between-lot prevalence). No enumeration results were obtained for the pathogens tested. Presence of L. monocytogenes and NoVGII in RTE lettuce (10%) and NoVGI and NoVGII in unprocessed lettuce (10%) was obtained in the tested lots during cold season. Results evidenced that, as the number of samples increased, the probability of rejecting a contaminated lot became higher, yielding right-skewed distributions with values close to 1. According to our results, 25 samples would result in 80% of rejected lots, while 95% confidence level would be reached with n>100. However, although those levels would imply a unrealistic high number of samples making the application of the sampling plan unfeasible, these results might be useful for food operators and risk managers to know the underlying distributions of microbial contamination together with potential control measures to be applied to assure a safer production of minimally processed vegetables.

Pérez-Rodríguez|Fernando|F| González-García|Patricia|P| Valero|Antonio|A| Hernández|Marta|M| Rodríguez-Lázaro|David|D|

Food-borne pathogens
Leafy green
Microbial testing
Predictive microbiology
Virus


Motion-invariant SRT treatment detection from direct M-scan OCT imaging.

Abstract:
PURPOSE
Selective retina therapy (SRT) is a laser treatment targeting specific posterior retinal layers. It is focused on inducing damage to the retinal pigment epithelium (RPE), while sparing other retinal tissue compared to traditional photocoagulation. However, the targeted RPE layer is invisible with most imaging modalities and induced SRT lesions cannot be monitored. In this work, imaging scans acquired from an experimental setup that couples the SRT laser beam with an optical coherence tomography (OCT) beam are analyzed in order to evaluate the treatment as they occur.

METHODS
We isolated a small part of the time-resolved scan corresponding to the end of the treatment, for which we have microscopic evidence of the SRT outcome. We then use a convolutional neural network to correspond each scan to the treatment result. We explore which aspects of the scan convey more valuable information for a robust therapy evaluation. By only using this adequately small part, we can achieve an online estimation, while being resilient to eye movement.

RESULTS
The available dataset consists of time- resolved OCT scans of 98 ex vivo porcine eyes, treated with different energy levels. The proposed method yields high performance in the task of predicting whether the applied energy was adequate for SRT treatment, by focusing on the immediate OCT signal acquired during treatment time.

CONCLUSIONS
We propose a strategy toward online noninvasive SRT treatment assessment, able to provide a satisfying evaluation of a treatment status, that therefore could be used for the planning of the treatment continuation.

Selective retina Therapy
Computer assisted intervention
Online dosimetry
Time-resolved OCT


Electroacupuncture accelerates the delayed intestinal transit in POI by suppressing M1 like muscularis macrophages and IL6 secretion.

Abstract:
BACKGROUND
Electroacupuncture (EA) at ST-36 could accelerate the delayed gastrointestinal (GI) motility in many GI motility dysfunction models, but the definite effect and mechanisms are unclear. In this study, we intended to investigate the effects of EA on intestinal manipulation (IM) mice model and involved mechanisms.

METHODS
Male C57BL/6 mice were randomized into five groups: normal control, intestinal manipulation (IM), IM with sham EA (SEA), IM with high-frequency EA (HEA), and IM with low-frequency EA (LEA). The GI transit was evaluated. The infiltration of muscularis macrophages (MMφ) and its phenotype were analyzed with flow cytometry. Magnetic-activated cell sorting was applied to isolate MMφ, and the relationship between the MMφ and interstitial cells of Cajal (ICCs) was further investigated.

RESULTS
(1) Compared with the IM group, HEA and LEA attenuated the delayed intestinal transit. (2) Both the HEA and LEA obviously reduced the MMφ and suppressed the M1 activation of the MMφ in the ileum. (3) EA restored the disrupted ICC networks through inhibiting the release of IL6 by the MMφ.

CONCLUSION
(1) Electroacupuncture at acupoint ST-36 could accelerate the delayed intestinal transit in the IM murine model by restoring the ICC networks. (2) EA protected the ICCs through reducing the MMφ, inhibiting its M1 polarization and its IL6 secretion.

electroacupuncture
IL6
MMφ
ICCs
M1 activation


Secular Trends in the Incidence of and Mortality Due to Alzheimer's Disease and Other Forms of Dementia in China From 1990 to 2019: An Age-Period-Cohort Study and Joinpoint Analysis.

Abstract:
Background
The number of individuals with dementia is increasing, which negatively affects families, communities, and health care systems worldwide. The changes in the incidence of and mortality due to Alzheimer's disease and other forms of dementia at the national level in China have remained unknown over the past three decades.

Methods
Following the general analytical strategy used in the Global Burden of Disease Study (GBD) 2019, the age- and sex-specific incidence and mortality rates for dementia in China were analyzed. Trends in the incidence of and mortality due to dementia from 1990 to 2019 were assessed by joinpoint regression analysis. The effects of age, period and cohort on the incidence of and mortality due to dementia were estimated by an age-period-cohort model.

Results
The age-standardized incidence and mortality rates per 100,000 population were 103.83 (95% UI, 87.93-118.87) and 23.32 (95% UI, 5.66-61.31), respectively, for dementia in 2019. From 1990 to 2019, a significant average annual percentage change (AAPC) in the age-standardized incidence rate was observed in both males [0.49% (95% CI, 0.43-0.55%)] and females [0.31% (95% CI, 0.24-0.38%)], and the age-standardized mortality rate significantly increased in males [0.42% (95% CI, 0.31-0.53%)]. The population aged 55-59 years had the highest AAPC in the incidence of dementia [0.87% (95% CI, 0.81-0.93%)]. The age effect showed that the relative risks (RRs) of incident dementia and dementia-associated mortality increased with age among males and females, and individuals aged 60 years and older had significantly higher RRs. The RR of incident dementia increased with time, and the RR started to substantially increase in 2009. The cohort effect showed that the incidence decreased in successive birth cohorts.

Conclusion
Alzheimer's disease and other forms of dementia continue to become more common among males and females in China, and the associated mortality rate in males significantly increased from 1990 to 2019. Early interventions should be implemented to reduce the burden of dementia on individuals at high risk in China.

incidence
dementia
China
Alzheimer’s disease
epidemiology


Food sovereignty, food security and health equity: a meta-narrative mapping exercise.

Abstract: There has been growing policy interest in social justice issues related to both health and food. We sought to understand the state of knowledge on relationships between health equity--i.e. health inequalities that are socially produced--and food systems, where the concepts of 'food security' and 'food sovereignty' are prominent. We undertook exploratory scoping and mapping stages of a 'meta-narrative synthesis' on pathways from global food systems to health equity outcomes. The review was oriented by a conceptual framework delineating eight pathways to health (in)equity through the food system: 1--Multi-Scalar Environmental, Social Context; 2--Occupational Exposures; 3--Environmental Change; 4--Traditional Livelihoods, Cultural Continuity; 5--Intake of Contaminants; 6--Nutrition; 7--Social Determinants of Health and 8--Political, Economic and Regulatory context. The terms 'food security' and 'food sovereignty' were, respectively, paired with a series of health equity-related terms. Combinations of health equity and food security (1414 citations) greatly outnumbered pairings with food sovereignty (18 citations). Prominent crosscutting themes that were observed included climate change, biotechnology, gender, racialization, indigeneity, poverty, citizenship and HIV as well as institutional barriers to reducing health inequities in the food system. The literature indicates that food sovereignty-based approaches to health in specific contexts, such as advancing healthy school food systems, promoting soil fertility, gender equity and nutrition, and addressing structural racism, can complement the longer-term socio-political restructuring processes that health equity requires. Our conceptual model offers a useful starting point for identifying interventions with strong potential to promote health equity. A research agenda to explore project-based interventions in the food system along these pathways can support the identification of ways to strengthen both food sovereignty and health equity.

Weiler|Anelyse M|AM|
Hergesheimer|Chris|C|
Brisbois|Ben|B|
Wittman|Hannah|H|
Yassi|Annalee|A|
Spiegel|Jerry M|JM|

D005523:Food Supply
D000069576:Health Equity
D006801:Humans
D012935:Social Justice
D012959:Socioeconomic Factors

food sovereignty
Food security
health equity
meta-narrative
social justice
social determinants


USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B.

Abstract: Decreased expression of the USP44 deubiquitinase has been associated with global increases in H2Bub1 levels during mouse embryonic stem cell (mESC) differentiation. However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin is not known. We identified USP44 as an integral subunit of the nuclear receptor co-repressor (N-CoR) complex. USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N-CoR complex. Chromatin immunoprecipitation (ChIP) experiments confirmed that USP44 recruitment reduces H2Bub1 levels at N-CoR target loci. Furthermore, high expression of USP44 correlates with reduced levels of H2Bub1 in the breast cancer cell line MDA-MB-231. Depletion of either USP44 or TBL1XR1 impairs the invasiveness of MDA-MB-231 cells in vitro and causes an increase of global H2Bub1 levels. Our findings indicate that USP44 contributes to N-CoR functions in regulating gene expression and is required for efficient invasiveness of triple-negative breast cancer cells.

Lan|Xianjiang|X|
Atanassov|Boyko S|BS|
Li|Wenqian|W|
Zhang|Ying|Y|
Florens|Laurence|L|
Mohan|Ryan D|RD|
Galardy|Paul J|PJ|
Washburn|Michael P|MP|
Workman|Jerry L|JL|
Dent|Sharon Y R|SYR|

D018160:Receptors, Cytoplasmic and Nuclear

USP44
N-CoR
breast cancer
H2B ubiquitination
transcription


BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide.

Abstract: Like thapsigargin, which is undergoing clinical trials, trilobolide is a natural product with promising anticancer and anti-inflammatory properties. Similar to thapsigargin, it has limited aqueous solubility that strongly reduces its potential medicinal applications. The targeted delivery of hydrophobic drugs can be achieved using liposome-based carriers. Therefore, we designed a traceable liposomal drug delivery system for trilobolide. The fluorescent green-emitting dye BODIPY, cholesterol and trilobolide were used to create construct 6. The liposomes were composed of dipalmitoyl-3-trimethylammoniumpropane and phosphatidylethanolamine. The whole system was characterized by atomic force microscopy, the average size of the liposomes was 150 nm in width and 30 nm in height. We evaluated the biological activity of construct 6 and its liposomal formulation, both of which showed immunomodulatory properties in primary rat macrophages. The uptake and intracellular distribution of construct 6 and its liposomal formulation was monitored by means of live-cell fluorescence microscopy in two cancer cell lines. The encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in theranostic applications.

Škorpilová|Ludmila|L|
Rimpelová|Silvie|S|
Jurášek|Michal|M|
Buděšínský|Miloš|M|
Lokajová|Jana|J|
Effenberg|Roman|R|
Slepička|Petr|P|
Ruml|Tomáš|T|
Kmoníčková|Eva|E|
Drašar|Pavel B|PB|
Wimmer|Zdeněk|Z|

liposomes
sesquiterpene lactone trilobolide
drug delivery
BODIPY conjugates
cancer targeting
natural compounds


Human intestinal sarcocystosis in Iran: there but not seen.

Abstract: Human sarcocystosis is a rare infection caused by the genus Sarcocystis who human serve as definitive (intestinal form of infection) host or intermediate (extraintestinal form) host for some various Sarcocystis species. The detection of Sarcocystis oocysts/sporocysts in the feces usually incidentally and is achieved by microscopic examination of the fresh or preserved specimens. To rule out any parasitological etiology among 23,875 (aged 2 months to 95 years) apparently immunocompetent Iranian individuals (from October of 2010 to June of 2016) with abdominal discomforts referred to several teaching hospitals and local clinical laboratories in Fars Province, Iran, their fecal samples were examined using light microscopy. Most pathogenic parasite-positive and doubtful samples were sent to the Intestinal Protozoology Laboratories of Fasa and Shiraz Universities of Medical Sciences to further examination to detect probable co-infection with other underdiagnose parasitoses. In addition to the common protozoal and helminthic infections, during the course of examining stool specimens using direct smear mixed with saline or iodine mounts and by formalin-ethyl acetate techniques, four cases of intestinal Sarcocystis infection as only or concurrently infected with other parasites were found. The present paper presents cases of human intestinal Sarcocystis infection in Iran. Since Sarcocystis are small in size and usually rare in stool, they often go unnoticed. It should be noted that stool smears must be examined with great care to avoid misinterpretation of Sarcocystis infections in microscopic examinations. To the best of our knowledge, co-infection of intestinal sarcocystosis and other principal parasitoses in stool investigations has not been reported earlier.

Agholi|Mahmoud|M|
Taghadosi|Zahra|Z|
Mehrabani|Davood|D|
Zahabiun|Farzaneh|F|
Sharafi|Zahra|Z|
Motazedian|Mohammad Hossein|MH|
Hatam|Gholam Reza|GR|
Naderi Shahabadi|Shahrbanou|S|

Human
Intestinal sarcocystosis
Iran
Sarcocystis
Sporocyst


Innovation design of medical equipment based on TRIZ.

Abstract:
BACKGROUND
Medical equipment is closely related to personal health and safety, and this can be of concern to the equipment user. Furthermore, there is much competition among medical equipment manufacturers. Innovative design is the key to success for those enterprises.

OBJECTIVE
The design of medical equipment usually covers vastly different domains of knowledge. The application of modern design methodology in medical equipment and technology invention is an urgent requirement.

METHODS
TRIZ (Russian abbreviation of what can be translated as `theory of inventive problem solving') was born in Russia, which contain some problem-solving methods developed by patent analysis around the world, including Conflict Matrix, Substance Field Analysis, Standard Solution, Effects, etc. TRIZ is an inventive methodology for problems solving.

RESULTS
As an Engineering example, infusion system is analyzed and re-designed by TRIZ. The innovative idea is generated to liberate the caretaker from the infusion bag watching out. The research in this paper shows the process of the application of TRIZ in medical device inventions.

CONCLUSION
It is proved that TRIZ is an inventive methodology for problems solving and can be used widely in medical device development.

Gao|Changqing|C| Guo|Leiming|L| Gao|Fenglan|F| Yang|Bo|B|

D000465:Algorithms
D017076:Computer-Aided Design
D004867:Equipment Design
D006801:Humans
D007262:Infusions, Intravenous
D008962:Models, Theoretical
D011340:Problem Solving

Innovation design
medical equipment
TRIZ


Effect of adjunctive ranitidine for antipsychotic-induced weight gain: A systematic review of randomized placebo-controlled trials.

Abstract: This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, non-randomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m2) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective and safe option for reducing antipsychotic-induced weight gain and improving negative symptoms in patients with schizophrenia. Larger RCTs are warranted to confirm these findings. Trial registration PROSPERO: CRD42016039735.

Gu|Xiao-Jing|XJ|
Chen|Rui|R|
Sun|Chen-Hui|CH|
Zheng|Wei|W|
Yang|Xin-Hu|XH|
Wang|Shi-Bin|SB|
Ungvari|Gabor S|GS|
Ng|Chee H|CH|
Golenkov|Andrei|A|
Lok|Grace K I|GKI|
Li|Lu|L|
Chow|Ines H I|IHI|
Wang|Fei|F|
Xiang|Yu-Tao|YT|

D016032:Randomized Controlled Trials as Topic

ranitidine
weight gain
meta-analysis
Schizophrenia
negative symptom
antipsychotics


Human adipose tissue microvascular endothelial cells secrete PPARγ ligands and regulate adipose tissue lipid uptake.

Abstract: Human adipose cells cannot secrete endogenous PPARγ ligands and are dependent on unknown exogenous sources. We postulated that the adipose tissue microvascular endothelial cells (aMVECs) cross-talk with the adipose cells for fatty acid (FA) transport and storage and also may secrete PPARγ ligands. We isolated aMVECs from human subcutaneous adipose tissue and showed that in these cells, but not in (pre)adipocytes from the same donors, exogenous FAs increased cellular PPARγ activation and markedly increased FA transport and the transporters FABP4 and CD36. Importantly, aMVECs only accumulated small lipid droplets and could not be differentiated to adipose cells and are not adipose precursor cells. FA exchange between aMVECs and adipose cells was bidirectional, and FA-induced PPARγ activation in aMVECs was dependent on functional adipose triglyceride lipase (ATGL) protein while deleting hormone-sensitive lipase in aMVECs had no effect. aMVECs also released lipids to the medium, which activated PPARγ in reporter cells as well as in adipose cells in coculture experiments, and this positive cross-talk was also dependent on functional ATGL in aMVECs. In sum, aMVECs are highly specialized endothelial cells, cannot be differentiated to adipose cells, are adapted to regulating lipid transport and secreting lipids that activate PPARγ, and thus, regulate adipose cell function.

Gogg|Silvia|S| Nerstedt|Annika|A| Boren|Jan|J| Smith|Ulf|U|

Adipose tissue
endothelial cells
Cell Biology


Predicting the switchable screw sense in fluorene-based polymers.

Abstract: A chirality-switching free-energy landscape was reconstructed on a 43-mer of poly(9,9-dioctylfluoren-2,7-diyl) (PDOF). The simulations were conducted on amorphous silica surface as well as in the vacuum phase for a single chain or for a group of sixteen chains. The achiral-to-chiral transition occurs only on amorphous silica (activation free-energy 35 kcal mol(-1) ), where the enantiomeric (homochiral) basins are detected. This was supported by the experiments where effective chirality induction to PDOF using circularly polarized light (CPL) was attained only for a film deposited on a quartz glass and not for a solution or a suspension. These results indicate that interactions of PDOF with amorphous silica play a crucial role in chirality switching. Importance of chain assembling was also indicated. Theoretical ECD spectra of the enantiomeric basins containing a 51 helix reproduce the experimental spectra.

polymers
chirality induction
chiral switches
helical structures
molecular dynamics


Use of dipeptidyl peptidase-4 inhibitors and the risk of arthralgia: Population-based cohort and nested case-control studies.

Abstract:
PURPOSE
The objective of this study was to investigate the association between the administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case-control study designs.

METHODS
Using Taiwan's National Health Insurance Research Database, we identified patients who were newly prescribed with DPP-4 inhibitors, thiazolidinediones (TZDs), or acarbose between 1 March 2009 and 31 December 2012. The exposure of studied drugs was categorized into five exclusive categories: DPP-4 inhibitor, TZD, acarbose, combined use, or non-use, and assessed in a time-varying manner. Time-dependent Cox proportional hazard models were used to estimate the association between DPP-4 inhibitors and the risk of arthralgia. Particularly, we tested the impact of different cumulative duration, timing, and individual substance of DPP-4 inhibitors use on risk of arthralgia. A corresponding nested case-control study using conditional logistic regression was conducted to verify this association.

RESULTS
An increased risk of arthralgia was observed during the first year after initiating DPP-4 inhibitors (adjusted Hazard Ratio = 1.35; 95% confidence interval [CI], 1.04-1.75) but the risk declined with cumulative use. This duration-response relation was not found in TZDs use and acarbose use. In the nested case-control study, there was a slightly increased risk of arthralgia (aOR = 1.08; 95% CI, 1.04-1.12) associated with current DPP-4 inhibitor use.

CONCLUSION
A relatively higher risk of arthralgia was associated with the initial administration of DPP-4 inhibitors, however, the risk declined among long-term users.

Wang|Chen-Yu|CY| Fu|Shau-Huai|SH| Yang|Rong-Sen|RS| Hsiao|Fei-Yuan|FY|0000-0003-1660-9120

dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors)


Effective Tacrolimus Treatment for Patients with Non-Severe Aplastic Anemia That is Refractory/Intolerant to Cyclosporine A: A Retrospective Study.

Abstract:
Background
For symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) may be an option if these patients do not respond or become tolerant to cyclosporine A (CsA).

Methods
We enrolled 101 NSAA patients who were refractory or intolerant to CsA with no chance of HSCT or ATG treatment and treated these patients with tacrolimus for at least 6 months, with follow-up for at least one year.

Results
The overall response rate (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%), and the median time to optimal response was 6 (3～10) months. Thirty-two (31.7%) cases had elevated creatinine levels. Eight (7.9%) cases had elevations in AST/ALT. A total of 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12 ng/mL, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cell levels pre-FK treatment were much lower than those of healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004) but increased significantly after FK treatment (3.7±0.6% vs 7.1±0.8%, P=0.0039).

Conclusion
Our data suggest that tacrolimus is a salvage treatment for patients with NSAA that is refractory or intolerant to CsA.

Du|Yali|Y| Huang|Yuzhou|Y| Zhou|Wenzhe|W| Liu|Xinjian|X| Chen|Fangfei|F|0000-0002-7127-1495 Yang|Chen|C| Chen|Miao|M| Ruan|Jing|J|0000-0001-9775-6186 Han|Bing|B|

tacrolimus
non-severe aplastic anemia
cyclosporine A


Monitoring human genotoxicity risk associated to urban and industrial Buenos Aires air pollution exposure.

Abstract: The quality of life in large megacities is directly affected by its air quality. In urban environments, suspended particles from anthropogenic origin is one of the main air contaminants identified as highly genotoxic, mutagenic, or carcinogenic. Atmospheric monitoring is therefore imperative, and bioassays to detect the effects of genotoxic agents give usually excellent results. Analysis of micronucleus (MN) in exfoliated oral mucosa cells is a sensitive non-invasive method for monitoring genetic damage in human populations. The first aim of this study was to analyze and characterize levels of volatile organic compounds (VOCs), particulate matter (PM), and polycyclic aromatic hydrocarbons (PAHs) in two areas from Buenos Aires: La Plata city, an urban (U) area and Ensenada, an industrial (I) area. Secondly, we evaluated the possible health risk of its inhabitants through a simple genotoxic assay on exfoliated oral mucosa cells. Whole blood cell count and nuclear abnormalities frequencies were evaluated in the exfoliated oral mucosa cells from urban and industrial inhabitants. Smoking habit represented a significant factor increasing MN percentage while, age did not increase the production of any of the nuclear aberrations assayed (micronuclei, binucleated, karyorrhexis) when the inhabitants from the urban and the industrial areas were compared. In addition, changes in MN and binucleated cell percentages in males and females were found to be area-dependent. We suggest that regardless PM concentration, PM-specific characteristics (size, shape, chemical elements, etc.) and VOCs levels could be responsible for the different harmful genotoxic effects seen in the two areas. Although this is a preliminary study, our results allowed to recognize that individuals living in both the urban and the industrial areas could be considered susceptible groups and should periodically undergo biological monitoring and appropriate care.

Genotoxicity
Air pollution
Urban environment
Micronucleus
Industrial environment


Skeletal Muscle Loss during Tyrosine Kinase Inhibitor Treatment for Advanced Hepatocellular Carcinoma Patients.

Abstract:
Introduction
The measurement of body composition such as the skeletal muscle index (SMI) has been reported to be useful for predicting prognosis in hepatocellular carcinoma (HCC). In this study, we analyzed skeletal muscle change during sorafenib and lenvatinib therapy and the association between SMI and prognosis.

Methods
A total of 67 patients with advanced HCC and Child-Pugh grade A status treated with tyrosine kinase inhibitors (TKIs) at Hiroshima University between September 2009 and December 2018 were enrolled in this retrospective cohort study. Patients underwent computed tomography (CT) imaging before starting sorafenib treatment and 1-3 months after treatment initiation.

Results
In all patients, the median SMI was 45.3 cm2/m2 before TKI treatment and 42.1 cm2/m2 after treatment; 54 of 67 (80.6%) patients experienced SMI loss. The median ΔSMI was -1.5 cm2/m2/months, and no difference in ΔSMI was observed between patients receiving sorafenib and lenvatinib. No significant differences were observed in median ΔSMI between patients with and without progressive disease (-2.35 and -1.1 cm2/m2/months, respectively), albumin-bilirubin grade 1 and 2 group disease (-1.7 and -1.5 cm2/m2/months, respectively), and relative dose intensity ≤80 and >80 (-1.8 and -1.2 cm2/m2/months, respectively).

Conclusion
This report demonstrated that patients receiving TKI treatment experienced a significant loss of skeletal muscle mass regardless of disease progression, hepatic reserve, or which TKI (sorafenib or lenvatinib) they received.

Uchikawa|Shinsuke|S| Kawaoka|Tomokazu|T| Namba|Maiko|M| Kodama|Kenichiro|K| Ohya|Kazuki|K| Morio|Kei|K| Nakahara|Takashi|T| Murakami|Eisuke|E| Tsuge|Masataka|M| Hiramatsu|Akira|A| Imamura|Michio|M| Takahashi|Shoichi|S| Chayama|Kazuaki|K| Aikata|Hiroshi|H|

Skeletal muscle
Tyrosine kinase inhibitor
Hepatocellular carcinoma
Sorafenib
Lenvatinib


Talking with text: communication in therapist-led, live chat cancer support groups.

Abstract: CancerChatCanada is a pan-Canadian initiative with a mandate to make professionally led cancer support groups available to more people in Canada. Although online support groups are becoming increasingly popular, little is known about therapist-led, synchronous groups using live chat. The purpose of this study was to generate a rich descriptive account of communication experiences in CancerChatCanada groups and to gain an understanding of processes associated with previously-reported benefits. We used interpretive description to analyze interview segments from 102 patients, survivors and family caregivers who participated in CancerChatCanada groups between 2007 and 2011. The analysis yielded four inter-related process themes (Reaching Out From Home, Feeling Safe, Emotional Release, and Talking With Text) and one outcome theme (Resonance and Kinship). The findings extend previous research about text-only online support groups and provide novel insights into features of facilitated, live chat communication that are valued by group members.

Stephen|Joanne|J| Collie|Kate|K| McLeod|Deborah|D| Rojubally|Adina|A| Fergus|Karen|K| Speca|Michael|M| Turner|Jill|J| Taylor-Brown|Jill|J| Sellick|Scott|S| Burrus|Kimberly|K| Elramly|Mai|M|

Communication
Live chat
Cancer
Canada
Online support groups
Therapist led


Andean Sacha Inchi (Plukenetia Volubilis L.) Leaf-Mediated Synthesis of Cu2O Nanoparticles: A Low-Cost Approach.

Abstract: In this work, Andean sacha inchi (Plukenetia volubilis L.) leaves were used to prepare monodispersed cuprous oxide (Cu2O) nanoparticles under heating. Visual color changes and UV-visible spectroscopy of colloidal nanoparticles showed λmax at 255 nm, revealing the formation of copper oxide nanoparticles. Transmission electron microscopy and dynamic light scattering analysis indicated that the prepared nanoparticles were spherical with an average size of 6-10 nm. The semi-crystalline nature and Cu2O phase of as-prepared nanoparticles were examined by X-ray diffraction. Fourier-transform infrared spectroscopy confirmed the presence of polyphenols, alkaloids and sugar in the sacha inchi leaf, allowing the formation of Cu2O nanoparticles from Cu2+. Additionally, as-synthesized Cu2O nanoparticles exhibited good photocatalytic degradation activity against methylene blue (>78%, 150 min) with rate constant 0.0219106 min-1. The results suggested that the adopted method is low-cost, simple, ecofriendly and highly selective for the synthesis of small Cu2O nanoparticles and may be used as a nanocatalyst in the future in the efficient treatment of organic pollutants in water.

Kumar|Brajesh|B| Smita|Kumari|K| Debut|Alexis|A| Cumbal|Luis|L|

plukenetia volubilis
Cu2O nanoparticles
XRD
catalysis
green synthesis


Use of Thiopurines During Conception and Pregnancy Is Not Associated With Adverse Pregnancy Outcomes or Health of Infants at One Year in a Prospective Study.

Abstract:
BACKGROUND & AIMS
Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, which makes it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children.

METHODS
We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016. Patients were counseled before pregnancy and seen bimonthly during pregnancy. We collected and analyzed data on medication use, as well as lifestyle and clinical factors, during conception and pregnancy. Pregnancy outcomes (live birth, spontaneous abortion, elective abortion, and stillbirth), birth outcomes (gestational age, birth weight, and congenital abnormalities), and health outcomes of infants 1 year after birth were compared between women who did and did not use a thiopurine during conception and pregnancy. In addition, health outcomes of infants 1 year after birth were compared with infants born to mothers without IBD from the same geographic region.

RESULTS
Our study comprised 309 women with confirmed IBD (216 with Crohn's disease, 85 with ulcerative colitis, and 8 with IBD unclassified). During the study period, 311 pregnancies of 232 women resulted in a live birth; a thiopurine was used during 108 pregnancies (35%). After correction for diagnosis, fertility treatment, and disease activity, there was no association between thiopurine use and spontaneous abortions. Birth outcomes were similar between women who did and did not use a thiopurine. Among infants 1 year of age, there were no differences in median growth, number of infections, allergies, adverse reactions to vaccinations, or chronic diseases between those born to women who did and did not use a thiopurine or between women with and without IBD.

CONCLUSIONS
In this prospective cohort study, we found no association between maternal thiopurine use during pregnancy and increased spontaneous abortions, adverse birth outcomes, or adverse health outcomes of infants 1 year after birth.

Kanis|Shannon L|SL|
de Lima-Karagiannis|Alison|A|
de Boer|Nanne K H|NKH|
van der Woude|C Janneke|CJ|

Infant
Drug
Immunomodulators
Neonate
Risk
Side Effect


Nitrogen-Doped Graphene on Transition Metal Substrates as Efficient Bifunctional Catalysts for Oxygen Reduction and Oxygen Evolution Reactions.

Abstract: Composites of transition metal and carbon-based materials are promising bifunctional catalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), and are widely used in rechargeable metal-air batteries. However, the mechanism of their enhanced bicatalytic activities remains elusive. Herein, we construct N-doped graphene supported by Co(111) and Fe(110) substrates as bifunctional catalysts for ORR and OER in alkaline media. First-principles calculations show that these heterostructures possess a large number of active sites for ORR and OER with overpotentials comparable to those of noble metal benchmark catalysts. The catalytic activity is modulated by the coupling strength between graphene and the metal substrates, as well as the charge distribution in the graphitic sheet, which is delicately mediated by N dopants. These theoretical results uncover the key parameters that govern the bicatalytic properties of hybrid materials and help prescribe the principles for designing multifunctional electrocatalysts of high performance.

graphene
transition metal
oxygen reduction
oxygen evolution
overpotential
rechargeable metal−air battery


Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients.

Abstract: VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200-0.927; P=0.031, respectively). Patients with the variant genotype of rs9582036 and rs9554320 had a shorter median PFS. No significant association of both SNPs with sunitinib PFS or OS was detected in either the SUTOX or SOGUG cohort. After the combination of all available data into a meta-analysis, the association of both SNPs with sunitinib PFS or OS did not achieve the threshold for statistical significance. Our findings suggest that, although VEGFR1 rs9582036 and rs9554320 are involved in sunitinib therapy outcome, its clinical use as biomarkers for prediction of sunitinib outcome in mRCC patients is limited, due to inconsistent findings when analyzing all existing studies together.

Liu|Xiaoyan|X|
Swen|Jesse J|JJ|
Boven|Epie|E|
Castellano|Daniel|D|
Gelderblom|Hans|H|
Mathijssen|Ron H J|RH|
Rodríguez-Antona|Cristina|C|
García-Donas|Jesus|J|
Rini|Brian I|BI|
Guchelaar|Henk-Jan|HJ|

D040281:Vascular Endothelial Growth Factor Receptor-1

meta-analysis
VEGFR1
sunitinib
metastatic renal cell carcinoma
validation study


Differential Psychological Factors Associated With Unnecessary Dental Avoidance and Attendance Behavior During the Early COVID-19 Epidemic.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 is challenging the dental community to an unprecedented degree. Knowledge of the increased risk of infection in dental settings has been disseminated to the public and guidelines have been formulated to assist dental attendance decision-making. However, dental attendance behaviors incompatible with treatment need is not uncommon in clinical settings. Important gaps remain in the knowledge about how psychological factors are affecting dental attendance behaviors during the COVID-19 epidemic. In this cross-sectional study, a questionnaire survey was performed during February and March 2020. A total of 342 and 294 dental patients who attended and avoided dental visits, respectively, were included. The participants were classified into four groups based on dental attendance behavior and emergent/urgent dental treatment need. Bivariate analysis was performed to investigate factors associated with dental attendance. Multivariable logistic regression based on principal component scores was performed to identify major psychological constructs associated with unnecessary dental avoidance and attendance. Among all the factors explored, inability to wear masks during dental treatment (P < 0.001; effect size: 0.32) was most closely associated with the overall pattern of dental attendance among participants. Multivariable regression suggested that unnecessary dental avoidance was associated with perceived risk of infection in general and in dental settings (odds ratio [95% CI]: 0.62 [0.53, 0.72]; p < 0.001), perceived impact of COVID-19 and dental problems on general health (0.79 [0.65, 0.97]; 0.021), and personal traits such as trust and anxiety (0.77 [0.61, 0.98]; 0.038). Unnecessary dental attendance was associated with optimism toward the epidemic (1.68 [1.42, 2.01]; <0.001) and trust (1.39 [1.13, 1.74]; 0.002). Multidisciplinary efforts involving dental and medical professionals as well as psychologists are warranted to promote more widespread adoption, among the general public, of dental attendance behaviors compatible with dental treatment need during the COVID-19 epidemic.

Wen|Yi Feng|YF|
Fang|Peng|P|
Peng|Jia-Xi|JX|
Wu|Shengjun|S|
Liu|Xufeng|X|
Dong|Qian Qian|QQ|

dental avoidance
COVID-19 epidemic
dental attendance
dental emergency
psychological characteristics


Social class and mental health: testing exploitation as a relational determinant of depression.

Abstract: This study tests whether social class exploitation operates as a relational mechanism that generates mental health inequalities in the nursing home industry. We ask, does social class exploitation (i.e., the acquisition of economic benefits from the labor of those who are dominated) have a systematic and predictable impact on depression among nursing assistants? Using cross-sectional data from 868 nursing assistants employed in 50 nursing homes in three U.S. states, we measure social class exploitation as "ownership type" (private for-profit, private not-for-profit, and public) and "managerial domination" (labor relations violations, perceptions of labor-management conflict). Depression is assessed using the original and revised versions of the Center for Epidemiologic Studies Depression Scale (CES-D and CESD-R). Using two-level logistic regressions, we find that private for-profit ownership and higher managerial domination are predictive of depression among nursing assistants even after adjustment for potential confounders and mediators. Our findings confirm the theoretical and empirical value of applying a social class approach to understanding how mental health inequalities are generated through exploitative mechanisms. Ownership type and managerial domination appear to affect depression through social relations that generate mental health inequalities through the process of acquiring profits, controlling production, supervising and monitoring labor, and enforcing disciplinary sanctions.

Muntaner|Carles|C|
Ng|Edwin|E|
Prins|Seth J|SJ|
Bones-Rocha|Katia|K|
Espelt|Albert|A|
Chung|Haejoo|H|

mental health
exploitation
depression
nursing assistant
work organization


Evidence of a tomato spotted wilt virus resistance-breaking strain originated through natural reassortment between two evolutionary-distinct isolates.

Abstract: A Tsw resistance-breaking tomato spotted wilt virus field isolate (TSWV-p331) found in northern Italy originated via reassortment from two evolutionary distinct TSWV strains, as revealed by recombination and phylogenetic analysis. Compared to the closest isolate present in the database, p331 NSs protein carries an unusually high number of amino acid substitutions, but no differences in the nucleocapsid protein. Despite these substitutions, p331 NSs is a potent silencing suppressor. As shown by phylogenetic analyses of TSWV nucleocapsid sequences collected over fifteen years, one likely p331 parental lineage has never been detected in northern Italy, allowing speculations on the origin of TSWV-p331.

Margaria|P|P| Ciuffo|M|M| Rosa|C|C| Turina|M|M|

D060467:Disease Resistance
D019143:Evolution, Molecular
D016679:Genome, Viral
D010802:Phylogeny
D010935:Plant Diseases
D012367:RNA, Viral
D016865:Reassortant Viruses
D011995:Recombination, Genetic
D017865:Tospovirus

Reassortment
Silencing suppressor
Phylogeny
Tospovirus


Quality of Work Life, Nurses' Intention to Leave the Profession, and Nurses Leaving the Profession: A One-Year Prospective Survey.

Abstract:
PURPOSE
To examine the associations among quality of work life, nurses' intention to leave the profession, and nurses leaving the profession.

DESIGN
A prospective study design was used.

METHODS
Participants were 1,283 hospital nurses with a purposive sampling in Taiwan. The self-reported questionnaire consisted of three questionnaires: the Chinese version of the Quality of Nursing Work Life scale, an intention-to-leave profession questionnaire, and a demographic questionnaire. Records of nurses leaving the profession were surveyed 1 year later. Data were analyzed by descriptive statistics and inferential statistics.

FINDINGS
As many as 720 nurses (56.1%) had tendencies to leave their profession. However, only 31 nurses (2.5%) left their profession 1 year later. Nurses' intention to leave the profession mediated the relationship between the milieu of respect and autonomy, quality of work life, and nurses leaving the profession.

CONCLUSIONS
The milieu of respect and autonomy describing the quality of work life predicts the nurses' intention to leave the profession, and together these predict nurses leaving the profession.

CLINICAL RELEVANCE
This study illustrates that nurse managers could provide effective interventions to ameliorate the milieu of respect and autonomy aspect of quality of work life to prevent nurses from leaving their profession.

Lee|Ya-Wen|YW|
Dai|Yu-Tzu|YT|
Chang|Mei Yeh|MY|
Chang|Yue-Cune|YC|
Yao|Kaiping Grace|KG|
Liu|Mei-Chun|MC|

quality of work life
Intention to leave the profession
leaving the profession
mediator


Leaving safety to visit a feeding site: is it optimal to hesitate while exposed?

Abstract: Animals living in complex environments experience differing risks of predation depending upon their location within the landscape. An animal could reduce the risk it experiences by remaining in a refuge site, but it may need to emerge from its refuge and enter more dangerous sites for feeding and other activities. Here, I consider the actions of an animal choosing to travel a short distance between a safe refuge and a dangerous foraging site, such as a bird leaving cover to visit a feeder. Although much work has been conducted examining the choice between a refuge and a foraging site when faced with a trade-off between starvation and predation risk, the work presented here is the first to consider the travel behaviour between these locations. Using state-dependent stochastic dynamic programming, I illustrate that there are several forms of optimal behaviour that can emerge. In some situations, the animal should choose to travel without stopping between sites, but in other cases, it is optimal for the animal to travel hesitantly towards the food, and to stop its travel at a point before it reaches the refuge. I discuss how this hesitant 'dawdling' behaviour may be optimal, and suggest further work to test these predictions.

refuges
travelling
feeders
distance to cover
optimal foraging
starvation/predation trade-off


Infection by and genotype characteristics of Enterocytozoon bieneusi in HIV/AIDS patients from Guangxi Zhuang autonomous region, China.

Abstract:
BACKGROUND
Enterocytozoon bieneusi has been increasingly reported to infect humans and various mammals. Microsporidia cause diarrhea in HIV-infected patients worldwide. PCR amplification and sequencing based on the internal transcribed spacer region have been used to describe the genotypes of E. bieneusi and transmission of microsporidiosis.

METHODS
In this study, we examined E. bieneusi infection and genotypes in HIV-positive patients in Guangxi, China. Stool specimens were collected from 285 HIV-positive patients and 303 HIV-negative individuals. E. bieneusi genotypes were characterized using nested PCR and sequencing.

RESULTS
Thirty-three (11.58%) HIV-positive patients were infected with microsporidia, and no infection was found in the 303 healthy controls. Three new genotypes were identified and named as GX25, GX456, and GX458; four known genotypes, PigEBITS7, Type IV/K, D, and Ebpc, were also identified. Our data showed that the positive rate for microsporidia was significantly higher in the rural patients than in the other occupation groups. In addition, the positive rate for microsporidia was significantly higher in the patients who drink unboiled water than in those with other drinking water sources.

CONCLUSIONS
Our results will provide baseline data for preventing and controlling E. bieneusi infection in HIV/AIDS patients. Further studies are required to clarify the epidemiology and potential sources of microsporidia. Our study showed that microsporidium infection occurs in the HIV/AIDS patients in Guangxi, China.

Liu|Hua|H| Jiang|Zhihua|Z| Yuan|Zhongying|Z| Yin|Jianhai|J| Wang|Zunfu|Z| Yu|Bingxue|B| Zhou|Dongsheng|D| Shen|Yujuan|Y| Cao|Jianping|J|

Genotype
Enterocytozoon bieneusi
HIV/AIDS
Risk factors


Exploring the Hydrogen-Induced Amorphization and Hydrogen Storage Reversibility of Y(Sc)0.95Ni2 Laves Phase Compounds.

Abstract: Rare-earth-based AB2-type compounds with Laves phase structure are readily subject to hydrogen-induced amorphization and disproportionation upon hydrogenation. In this work, we conducted the Sc alloying on Y0.95Ni2 to improve its hydrogen storage properties. The results show that the amorphization degree of Y0.95Ni2 deepens with the increasing hydrogenation time, pressure, and temperature. The Y(Sc)0.95Ni2 ternary compounds show a significant improvement in reversibility and dehydriding thermodynamics due to the reduced atomic radius ratio RA/RB and cell volume. Hydrogen-induced amorphization is fully eliminated in the Y0.25Sc0.7Ni2. The Y0.25Sc0.7Ni2 delivers a reversible hydrogen storage capacity of 0.94 wt.% and the dissociation pressure of 0.095 MPa at the minimum dehydrogenation temperature of 100 °C.

hydrogen-induced amorphization
reversibility
Sc substitution
hydrogen storage alloys


Methionine oxidation in α-synuclein inhibits its propensity for ordered secondary structure.

Abstract: α-Synuclein (AS) is an intrinsically disordered protein highly expressed in dopaminergic neurons. Its amyloid aggregates are the major component of Lewy bodies, a hallmark of Parkinson's disease (PD). AS is particularly exposed to oxidation of its methionine residues, both in vivo and in vitro Oxidative stress has been implicated in PD and oxidized α-synuclein has been shown to assemble into soluble, toxic oligomers, rather than amyloid fibrils. However, the structural effects of methionine oxidation are still poorly understood. In this work, oxidized AS was obtained by prolonged incubations with dopamine (DA) or epigallocatechin-3-gallate (EGCG), two inhibitors of AS aggregation, indicating that EGCG promotes the same final oxidation product as DA. The conformational transitions of the oxidized and non-oxidized protein were monitored by complementary biophysical techniques, including MS, ion mobility (IM), CD, and FTIR spectroscopy assays. Although the two variants displayed very similar structures under conditions that stabilize highly disordered or highly ordered states, differences emerged in the intermediate points of transitions induced by organic solvents, such as trifluoroethanol (TFE) and methanol (MeOH), indicating a lower propensity of the oxidized protein for forming either α- or β-type secondary structures. Furthermore, oxidized AS displayed restricted secondary-structure transitions in response to dehydration and slightly amplified tertiary-structure transitions induced by ligand binding. This difference in susceptibility to induced folding could explain the loss of fibrillation potential observed for oxidized AS. Finally, site-specific oxidation kinetics point out a minor delay in Met-127 modification, likely due to the effects of AS intrinsic structure.

methionine oxidation
amyloid
dopamine
epigallocatechin-3-gallate
ion mobility (IM)
Fourier transform IR (FTIR)
circular dichroism (CD)
mass spectrometry (MS)
neurodegenerative disease
α-synuclein (α-synuclein)


Lamellar ichthyosis with rickets.

Abstract: Lamellar ichthyosis (LI) is a rare genetic disorder with autosomal recessive inheritance. It is equally seen in both sexes and usually manifests at birth. The child presents as a collodion baby. The erythema is minimal or absent; but when present, it is maximum on the face. The scaling is generalized, accentuated on lower extremities and flexural areas. Rickets is a condition in which there is softening of bones leading to fractures and deformities. It is caused by vitamin D deficiency & lack of adequate calcium in diet. Children, 6 to 24 months of age, are at a higher risk due to rapidly growing bones. The association between various types of ichthyoses and rickets is well documented. We report a case of lamellar ichthyosis with rickets in a 14-year-old girl from our part of the world.

Lamellar ichthyosis
Rickets
Vitamin D deficiency


Liver transcriptome sequencing and de novo annotation of the large yellow croaker (Larimichthy crocea) under heat and cold stress.

Abstract: Large yellow croaker is an economically important marine fish in China. To understand the molecular mechanisms of this fish under temperature stress, liver transcriptomes of large yellow croakers undergoing heat and cold stress were investigated. The results showed that 130,246 contigs from cold stressed fish (CS), 109,203 contigs from control fish (NS) and 98,569 contigs from heat stressed fish (HS) were obtained from the liver transcriptomes with de novo analysis, respectively. And in total, 9467 (6113 up-regulated and 3364 down-regulated), 5350 (2185 up-regulated and 3165 down-regulated), 10,622 (3146 up-regulated and 7477 down-regulated) significantly differentially expressed genes were identified in CS-NS, HS-NS, and HS-CS, respectively. Pathway enrichment analysis showed that many pathways including those of energy metabolism and metabolic pathways were affected after temperature stress. Further qPCR analysis also confirmed that the expression levels of genes coding for key enzymes in metabolic pathways were dramatically changed.

Liver transcriptome
Large yellow croaker
Cold stress
Heat stress


Multi-Frequency Resonance Behaviour of a Si FractalNEMS Resonator.

Abstract: Novel Si-based nanosize mechanical resonator has been top-down fabricated. The shapeof the resonating body has been numerically derived and consists of seven star-polygons that forma fractal structure. The actual resonator is defined by focused ion-beam implantation on a SOIwafer where its 18 vertices are clamped to nanopillars. The structure is suspended over a 10 mtrench and has width of 12 m. Its thickness of 0.040 m is defined by the fabrication process andprescribes Young's modulus of 76 GPa which is significantly lower than the value of the bulk material.The resonator is excited by the bottom Si-layer and the interferometric characterisation confirmsbroadband frequency response with quality factors of over 800 for several peaks between 2 MHzand 16 MHz. COMSOL FEM software has been used to vary material properties and residual stressin order to fit the eigenfrequencies of the model with the resonance peaks detected experimentally.Further use of the model shows how the symmetry of the device affects the frequency spectrum.Also, by using the FEM model, the possibility for an electrical read out of the device was tested. Theexperimental measurements and simulations proved that the device can resonate at many differentexcitation frequencies allowing multiple operational bands. The size, and the power needed foractuation are comparable with the ones of single beam resonator while the fractal structure allowsmuch larger area for functionalisation.

fractal structure
NEMS
broadband frequency spectrum
nanoresonator
nonlinearity
piezoresistivity
self-similarity


Genomic Characterizations of Clade III Lineage of Candida auris, California, USA.

Abstract: Candida auris is an emerging multidrug-resistant yeast. We describe an ongoing C. auris outbreak that began in October 2019 in Los Angeles, California, USA. We used genomic analysis to determine that isolates from 5 of 6 patients belonged to clade III; 4 isolates were closely related.

Price|Travis K|TK|
Mirasol|Ruel|R|
Ward|Kevin W|KW|
Dayo|Ayrton J|AJ|
Hilt|Evann E|EE|
Chandrasekaran|Sukantha|S|
Garner|Omai B|OB|
de St Maurice|Annabelle|A|
Yang|Shangxin|S|

genomic characterization
clade III
Candida
Candida auris
California
yeast
outbreak
Los Angeles
United States
antimicrobial resistance
fungal infections
fungi


Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer.

Abstract:
BACKGROUND
Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation.

METHODS
The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF < 50% or > 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS.

RESULTS
A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5-16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p < 0.001) after adjusting for age, stage, grade, ER, node status and TIC.

CONCLUSIONS
Treatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.

Sardesai|Sagar|S|
Sukumar|Jasmine|J|
Kassem|Mahmoud|M|
Palettas|Marilly|M|
Stephens|Julie|J|
Morgan|Evan|E|
Addison|Daniel|D|
Baliga|Ragavendra|R|
Stover|Daniel G|DG|
VanDeusen|Jeffrey|J|
Williams|Nicole|N|
Cherian|Mathew|M|
Lustberg|Maryam|M|
Wesolowski|Robert|R|
Ramaswamy|Bhuvaneswari|B|

Trastuzumab
Breast cancer
Cardio-oncology
Chemotherapy
HER2


Patterns of alveolar macrophage activation upon attenuated and virulent African swine fever viruses in vitro.

Abstract: The pattern of porcine alveolar macrophage (AM) activation upon classical stimuli of two strains of African swine fever (ASF) viruses, an attenuated ASFV-BA71V and virulent ASFV-Georgia2007 were investigated. In an in vitro experiment ASFV-Georgia2007-infected AM showed M1 polarization pattern different from the one induced by classical stimuli. Altered morphology, appearance of binuclear cells, decreased synthesis of IFN-alpha as well as IFN-epsilon was observed compared with attenuated ASFV-BA71V, and decreased synthesis of IFN-omega compared with intact cells. However, CD68 level did not significantly differ between alveolar macrophage populations infected by ASFV-Georgia2007 and control group, while both LPS/IFN-gamma stimulation and non-pathogenic ASFV-BA71V virus increased the level of CD68 soluble receptor. AM infection with ASFV-Georgia2007 resulted in remarkable DNA proliferation whereas LPS/IFN-gamma and ASFV-BA71V induced less expressed DNA proliferation in activated cells. The higher value of nitric oxide was obvious in the cells infected with ASFV-BA71V, compared to ASFV-Georgia2007 and LPS/IFN-gamma activated cells. In conclusion, pattern of activation of alveolar macrophages induced by ASFV-Georgia2007 virus differs from the one expressed in LPS/IFN-gamma- and ASFV-BA71V-activated cells. ASFV-BA71V and LPS/IFN-gamma share similar antiviral response of porcine AM. Therefore we assume that wild type virulent ASFV can partially down regulate antiviral response of AM and conclude that evolutionary decrease of virulence in ASFV is related to alterations of control of the host cell antiviral response.

Tatoyan|Marina R|MR|
Izmailyan|Roza A|RA|
Semerjyan|Anna B|AB|
Karalyan|Naira Yu|NY|
Sahakyan|Carmen T|CT|
Mkrtchyan|Gayane L|GL|
Ghazaryan|Hovsep K|HK|
Arzumanyan|Hranush H|HH|
Semerjyan|Zara B|ZB|
Karalova|Elena M|EM|
Karalyan|Zaven A|ZA|

Alveolar macrophage activation
M1 polarization
African swine fever virus


Prevalence and correlates of stress and burnout among U.S. healthcare workers during the COVID-19 pandemic: A national cross-sectional survey study.

Abstract:
Background
COVID-19 has put extraordinary stress on healthcare workers. Few studies have evaluated stress by worker role, or focused on experiences of women and people of color.

Methods
The "Coping with COVID" survey assessed US healthcare worker stress. A stress summary score (SSS) incorporated stress, fear of exposure, anxiety/depression and workload (Omega 0.78). Differences from mean were expressed as Cohen's d Effect Sizes (ESs). Regression analyses tested associations with stress and burnout.

Findings
Between May 28 and October 1, 2020, 20,947 healthcare workers responded from 42 organizations (median response rate 20%, Interquartile range 7% to 35%). Sixty one percent reported fear of exposure or transmission, 38% reported anxiety/depression, 43% suffered work overload, and 49% had burnout. Stress scores were highest among nursing assistants, medical assistants, and social workers (small to moderate ESs, p < 0.001), inpatient vs outpatient workers (small ES, p < 0.001), women vs men (small ES, p < 0.001), and in Black and Latinx workers vs Whites (small ESs, p < 0.001). Fear of exposure was prevalent among nursing assistants and Black and Latinx workers, while housekeepers and Black and Latinx workers most often experienced enhanced meaning and purpose. In multilevel models, odds of burnout were 40% lower in those feeling valued by their organizations (odds ratio 0.60, 95% CIs [0.58, 0.63], p< 0.001).

Interpretation
Stress is higher among nursing assistants, medical assistants, social workers, inpatient workers, women and persons of color, is related to workload and mental health, and is lower when feeling valued.

Prasad|Kriti|K|
McLoughlin|Colleen|C|
Stillman|Martin|M|
Poplau|Sara|S|
Goelz|Elizabeth|E|
Taylor|Sam|S|
Nankivil|Nancy|N|
Brown|Roger|R|
Linzer|Mark|M|
Cappelucci|Kyra|K|
Barbouche|Michael|M|
Sinsky|Christine A|CA|

Burnout
COVID-19
Nursing
Mental health
Allied health professionals
Occupational stress


Research objectives to fill knowledge gaps in African swine fever virus survival in the environment and carcasses, which could improve the control of African swine fever virus in wild boar populations.

Abstract: The European Commission requested that EFSA provide study designs for the investigation of four research domains according to major gaps in knowledge identified by EFSA in a report published in 2019: i) the patterns of seasonality of African Swine Fever (ASF) in wild boar and domestic pigs in the EU; ii) the epidemiology of ASF in wild boar; iii) survival of ASF virus (ASFV) in the environment and iv) transmission of ASFV by vectors. In this Scientific Opinion, the third research domain on ASFV survival is addressed. Nine research objectives were proposed by the working group and broader ASF expert networks, such as ASF stop, ENETWILD, VectorNet, AHAW network and the AHAW Panel Experts. Of the nine research objectives, only one was prioritised and elaborated into a general protocol/study design research proposal, pertaining ASFV survival in feed and bedding. To investigate the survival of ASFV in feed, bedding and roughage, laboratory survival studies are proposed. To investigate possible risk mitigation measures, proof-of-concept approaches should be investigated.

|||
Nielsen|Søren Saxmose|SS|
Alvarez|Julio|J|
Bicout|Dominique Joseph|DJ|
Calistri|Paolo|P|
Depner|Klaus|K|
Drewe|Julian Ashley|JA|
Garin-Bastuji|Bruno|B|
Gonzales Rojas|Jose Luis|JL|
Schmidt|Christian|C|
Herskin|Mette|M|
Michel|Virginie|V|
Pasquali|Paolo|P|
Roberts|Helen Claire|HC|
Sihvonen|Liisa Helena|LH|
Spoolder|Hans|H|
Stahl|Karl|K|
Velarde|Antonio|A|
Winckler|Christoph|C|
Blome|Sandra|S|
Boklund|Anette|A|
Bøtner|Anette|A|
Dhollander|Sofie|S|
Rapagnà|Cristina|C|
Van der Stede|Yves|Y|
Miranda Chueca|Miguel Angel|MA|

African swine fever virus
survival
carcasses
wild boar
domestic pigs and management
risk factor


Proximity-Driven Site-Specific and Covalent Labeling of Proteins with a TexasRed Fluorophore Reacting (ReacTR) Peptide Tag.

Abstract: It is of vital importance to visualize proteins in living cells noninvasively in order to elucidate their functions. Here, we describe a fast, efficient, and one-step covalent protein labeling method utilizing a small peptide tag called TR512, which was previously engineered to bind to TexasRed fluorophore by phage display. To covalently label proteins with TexasRed fluorophore, proteins of interest (POI) were fused to a reactive TR512 (ReacTR) tag carrying two cysteine residues. Upon addition of TexasRed fluorophore conjugated to N-α-chloroacetamide, a cysteine group of the ReacTR tag rapidly reacts with the electrophilic N-α-chloroacetamide group due to the proximity effect by forming a covalent bond between the fluorophore and ReacTR tag. Our approach uses a small peptide tag and a small-molecule fluorophore for labeling; thereby minimal perturbation on the function and dynamics of the POI is expected.

TexasRed
Fluorophore
Peptide tags
Protein labeling
TR512
Fluorescence microscopy
Fluorette
Live-cell imaging
Protein imaging


A Putative Mitochondrial Iron Transporter MrsA in Aspergillus fumigatus Plays Important Roles in Azole-, Oxidative Stress Responses and Virulence.

Abstract: Iron is an essential nutrient and enzyme co-factor required for a wide range of cellular processes, especially for the function of mitochondria. For the opportunistic fungal pathogen Aspergillus fumigatus, the ability to obtain iron is required for growth and virulence during the infection process. However, knowledge of how mitochondria are involved in iron regulation is still limited. Here, we show that a mitochondrial iron transporter, MrsA, a homolog of yeast Mrs4p, is critical for adaptation to iron-limited or iron-excess conditions in A. fumigatus. Deletion of mrsA leads to disruption of iron homeostasis with a decreased sreA expression, resulted in activated reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA). Furthermore, deletion of mrsA induces hypersusceptibility to azole and oxidative stresses. An assay for cellular ROS content in ΔmrsA combined with rescue from the mrsA-defective phenotype by the antioxidant reagent L-ascorbic acid indicates that the increased sensitivity of ΔmrsA to the azole itraconazole and to oxidative stress is mainly the result of abnormal ROS accumulation. Moreover, site-directed mutation experiments verified that three conserved histidine residues related to iron transport in MrsA are required for responses to oxidative and azole stresses. Importantly, ΔmrsA causes significant attenuation of virulence in an immunocompromised murine model of aspergillosis. Collectively, our results show that the putative mitochondrial iron transporter MrsA plays important roles in azole- and oxidative-stress responses and virulence by regulating the balance of cellular iron in A. fumigatus.

Long|Nanbiao|N| Xu|Xiaoling|X| Qian|Hui|H| Zhang|Shizhu|S| Lu|Ling|L|

mitochondrial iron transporter
Aspergillus fumigatus
oxidative stresses
iron homeostasis
ROS
histidine residues
azole stresses


New digital tool to facilitate subcutaneous insulin therapy orders: an inpatient insulin dose calculator.

Abstract:
BACKGROUND
Inpatient hyperglycemia is associated with adverse outcomes in hospitalized patients, with or without known diabetes. The adherence to American College of Endocrinology and American Diabetes Association guidelines recommendations for inpatient glycemic control is still poor, probably because of their complexity and fear of hypoglycemia.

OBJECTIVE
To create software system that can assist health care providers and hospitalists to manage the insulin therapy orders and turn them into a less complicated issue.

METHODS
A software system was idealized and developed, according to recommendations of major consensus and medical literature.

RESULTS
HTML software was developed to be readily accessed from a workstation, tablet or smartphone. Standard initial daily total dose of insulin was 0.4 units/kg and could be modified by distinct factors, such as chronological age, renal and liver function, and high dose corticosteroids use. Insulin therapy consisted of basal, prandial and correction insulin according to nutritional support, glycemic control and outpatient treatment for diabetes. Human insulin or insulin analogues could be options for insulin therapy. Sensitivity factor was based on 1800 Rule for rapid-acting insulin and the 1500 Rule for short-acting insulin. Insulin-naïve patients with initial BG level less than 250 mg/dL were considered to have an initial step-wise approach with prandial and correction insulin. The calculator system has allowed insulin dose readjustments periodically, according to daily average blood glucose measurements.

CONCLUSION
We developed software that can be a useful tool for all public hospitals, where generally human insulin is the only available.

Insulin
Hyperglycemia
Hospitalization
Diabetes mellitus


Role of aromatic amino acids in amyloid self-assembly.

Abstract: Amyloids are proteins of a cross-β structure found as deposits in several diseases and also in normal tissues (nails, spider net, silk). Aromatic amino acids are frequently found in amyloid deposits. Although they are not indispensable, aromatic amino acids, phenylalanine, tyrosine and tryptophan, enhance significantly the kinetics of formation and thermodynamic stability, while tape or ribbon-like morphology is represented in systems with experimentally detected π-π interactions between aromatic rings. Analysis of geometries and energies of the amyloid PDB structures indicate the prevalence of aromatic-nonaromatic interactions and confirm that aromatic-aromatic interactions are not crucial for the amyloid formation.

Stanković|Ivana M|IM|
Niu|Shuqiang|S|
Hall|Michael B|MB|
Zarić|Snežana D|SD|

D057927:Hydrophobic and Hydrophilic Interactions

Aromatic amino acids
Amyloids
Self-assembly


An Easy-to-Implement Protocol for Preparing Postnatal Ventral Mesencephalic Cultures.

Abstract: Postnatally derived cultures of ventral mesencephalic neurons offer several crucial advantages over embryonic ventral mesencephalic cultures, including a higher content of TH-positive cells and the ability to derive cells from the substantia nigra, which contains the neurons most vulnerable to Parkinson's disease. On the other hand, these cultures are more challenging to produce consistently. Here, we provide an easy-to-implement protocol for culturing postnatal ventral mesencephalic cells from the substantia nigra (SN) and the ventral tegmental area using commercially available media, dishes, and general lab equipment, avoiding extensive material and equipment purchases. The protocol can be completed in about 5 h and provides ventral midbrain neuron cultures on cortex glia feeder layers in three weeks' time. The protocol uses an optimized protease digestion, tissue storage in Hibernate A during dissection and purification of neurons on an OptiPrep density gradient.

Lautenschläger|Janin|J|
Mosharov|Eugene V|EV|
Kanter|Ellen|E|
Sulzer|David|D|
Kaminski Schierle|Gabriele S|GS|

protocol
ventral mesencephalic neurons
substantia nigra
ventral tegmental area
Parkinson’s disease
dopaminergic neurons
postnatal neuron cultures
postnatal neurons


Most of qualitative dietary changes observed one year post-bariatric surgery can be achieved with a preoperative dietary intervention.

Abstract:
BACKGROUND AND OBJECTIVES
Bariatric surgery (BS) leads to several changes in nutritional habits that can be attributed to different mechanisms. Some of these changes could be achievable with a preoperative nutritional intervention. The objective was to evaluate dietary modifications during the preoperative and postoperative periods of BS.

METHODS
Prospective observational study of patients who underwent BS between 2010 and 2014 at the Hospital del Mar; 60 consecutive patients were included. Food consumption was measured by a validated food-frequency questionnaire at inclusion in the bariatric surgery program, after preoperative nutritional intervention, and one year after surgery. Generalized estimating equation models were used to assess differences in food group intake during follow up.

RESULTS
Energy intake significantly decreased from inclusion to 1 year of surgery (p=0.003). After the preoperative intervention and prior to surgery, there was an increase in intake of nuts, vegetables, poultry and rabbit, fruit, fish and skimmed milk products and a decrease in bread, soft drinks and pastry. At one year post-surgery, a continued decrease in the consumption of bread and soft drinks and an increase in nuts was observed (linear non-quadratic trend). Consumption of fruit, pastry, fish and skimmed milk products remained stable showing a linear and quadratic trend. Vegetables and poultry and rabbit increased in the preoperative period and decreased after surgery, showing a quadratic but not linear trend.

CONCLUSIONS
a preoperative nutritional intervention in morbidly obese patients can associate favorable dietary changes that are mostly maintained one year after bariatric surgery.

Benaiges|David|D|
Parri|Alejandra|A|
Subirana|Isaac|I|
Pedro-Botet|Juan|J|
Villatoro|Montserrat|M|
Ramon|Jose M|JM|
Climent|Elisenda|E|
Flores Le Roux|Juana A|JA|
Goday|Alberto|A|

Preoperative
Bariatric surgery
Food groups
Cirugía bariátrica
Dietary intake
Grupos de alimentos
Ingesta dietética
Micronutrientes
Micronutrients


Machine Learning-Based Classification of Lignocellulosic Biomass from Pyrolysis-Molecular Beam Mass Spectrometry Data.

Abstract: High-throughput analysis of biomass is necessary to ensure consistent and uniform feedstocks for agricultural and bioenergy applications and is needed to inform genomics and systems biology models. Pyrolysis followed by mass spectrometry such as molecular beam mass spectrometry (py-MBMS) analyses are becoming increasingly popular for the rapid analysis of biomass cell wall composition and typically require the use of different data analysis tools depending on the need and application. Here, the authors report the py-MBMS analysis of several types of lignocellulosic biomass to gain an understanding of spectral patterns and variation with associated biomass composition and use machine learning approaches to classify, differentiate, and predict biomass types on the basis of py-MBMS spectra. Py-MBMS spectra were also corrected for instrumental variance using generalized linear modeling (GLM) based on the use of select ions relative abundances as spike-in controls. Machine learning classification algorithms e.g., random forest, k-nearest neighbor, decision tree, Gaussian Naïve Bayes, gradient boosting, and multilayer perceptron classifiers were used. The k-nearest neighbors (k-NN) classifier generally performed the best for classifications using raw spectral data, and the decision tree classifier performed the worst. After normalization of spectra to account for instrumental variance, all the classifiers had comparable and generally acceptable performance for predicting the biomass types, although the k-NN and decision tree classifiers were not as accurate for prediction of specific sample types. Gaussian Naïve Bayes (GNB) and extreme gradient boosting (XGB) classifiers performed better than the k-NN and the decision tree classifiers for the prediction of biomass mixtures. The data analysis workflow reported here could be applied and extended for comparison of biomass samples of varying types, species, phenotypes, and/or genotypes or subjected to different treatments, environments, etc. to further elucidate the sources of spectral variance, patterns, and to infer compositional information based on spectral analysis, particularly for analysis of data without a priori knowledge of the feedstock composition or identity.

Nag|Ambarish|A|
Gerritsen|Alida|A|
Doeppke|Crissa|C|
Harman-Ware|Anne E|AE|

pyrolysis
molecular beam mass spectrometry
classifiers
random forest
decision tree
Gaussian Naïve Bayes
gradient boosting
multilayer perceptron
biomass analysis


Recognition and management of bladder bowel dysfunction in children with autism spectrum disorder.

Abstract: Children with autism spectrum disorder (ASD) with rigidities, anxiety or sensory preferences may establish a pattern of holding urine and stool, which places them at high risk of developing bladder bowel dysfunction (BBD). BBD, despite being common, is often unrecognised in children with ASD. With this case report of a 7-year-old girl with ASD presenting with acute retention of urine, we attempt to understand the underlying factors which may contribute to the association between BBD and ASD. Literature review indicates a complex interplay of factors such as brain connectivity changes, maturational delay of bladder function, cognitive rigidities and psychosocial stressors in children with ASD may possibly trigger events which predispose some of them to develop BBD. Simple strategies such as parental education, maintaining a bladder bowel diary and treatment of constipation may result in resolution of symptoms.

Raturi|Shilpee|S|
Li|Fay Xiangzhen|FX|
Wong|Chui Mae|CM|


Response to Novel Drugs before and after Allogeneic Stem Cell Transplantation in Patients with Relapsed Multiple Myeloma.

Abstract: Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.

López-Corral|Lucia|L|
Caballero-Velázquez|Teresa|T|
López-Godino|Oriana|O|
Rosiñol|Laura|L|
Pérez-Vicente|Sabina|S|
Fernandez-Avilés|Francesc|F|
Krsnik|Isabel|I|
Morillo|Daniel|D|
Heras|Inmaculada|I|
Morgades|Mireia|M|
Rifon|Jose J|JJ|
Sampol|Antonia|A|
Iniesta|Francisca|F|
Ocio|Enrique-María|EM|
Martin|Jesús|J|
Rovira|Montserrat|M|
Cabero|Martín|M|
Castilla-Llorente|Cristina|C|
Ribera|Josep-María|JM|
Torres-Juan|Marta|M|
Moraleda|Jose María|JM|
Martinez|Carmen|C|
Vázquez|Alejandro|A|
Gutierrez|Gonzalo|G|
Caballero|Dolores|D|
San Miguel|Jesús F|JF|
Mateos|María-Victoria|MV|
Pérez-Simón|Jose Antonio|JA|

D018380:Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation


A phase I study of the effect of repeated oral doses of pantoprazole on the pharmacokinetics of a single dose of fedratinib in healthy male subjects.

Abstract:
PURPOSE
Fedratinib, an oral, selective Janus kinase 2 inhibitor with activity against both wild-type and mutant Janus kinase 2, has pH-dependent solubility, with free solubility at pH 1. Concomitant administration of drugs that reduce gastric acid secretion, such as pantoprazole, may decrease the absorption of fedratinib and affect patient outcomes. The aim of this study was to evaluate the impact of 7-day repeated 40-mg doses of pantoprazole on the pharmacokinetic (PK) properties of a single 500-mg dose of fedratinib in healthy male subjects.

METHODS
In this phase I, single-center, open-label, two-period, two-treatment, fixed-sequence crossover study, healthy male subjects were administered a single dose of fedratinib 500 mg on day 1 in Period 1, followed by pantoprazole 40 mg daily for 7 days (day 1 to day 7) and a single dose of fedratinib 500 mg on day 7 in Period 2. After the discontinuation of nine subjects due to vomiting, the protocol was amended to provide ondansetron as antiemetic prophylaxis to an additional ten enrolled subjects.

RESULTS
Twenty-six subjects were included. Repeated doses of pantoprazole 40 mg resulted in clinically insignificant increases in fedratinib exposure. Maximum plasma concentration increased by 1.09-fold and area under the plasma concentration-time curve from time 0 to infinity increased by 1.15-fold. All treatment-emergent adverse events were mild or moderate, except for one instance of neutropenia, which was considered unrelated to study intervention.

CONCLUSION
Coadministration with pantoprazole did not have clinically meaningful effects on fedratinib PK. No new or unexpected safety signals were observed with fedratinib.

Ogasawara|Ken|K| Vince|Bradley|B| Xu|Christine|C| Zhang|Meng|M| Palmisano|Maria|M| Krishna|Gopal|G|

Pantoprazole
Pharmacokinetics
Fedratinib
Bioavailability
Healthy subjects
Proton pump inhibitors


Hand Motion Analysis Illustrates Differences When Drilling Cadaveric and Printed Temporal Bone.

Abstract:
OBJECTIVE
Temporal bone simulation is now commonly used to augment cadaveric education. Assessment of these tools is ongoing, with haptic modeling illustrating dissimilar motion patterns compared to cadaveric opportunities. This has the potential to result in maladaptive skill development. It is hypothesized that trainee drill motion patterns during printed model dissection may likewise demonstrate dissimilar hand motion patterns.

METHODS
Resident surgeons dissected 3D-printed temporal bones generated from microCT data and cadaveric simulations. A magnetic position tracking system (TrakSTAR Ascension, Yarraville, Australia) captured drill position and orientation. Skill assessment included cortical mastoidectomy, thinning procedures (sigmoid sinus, dural plate, posterior canal wall) and facial recess development. Dissection was performed by 8 trainees (n = 5 < PGY3 > n = 3) using k-cos metrics to analyze drill strokes within position recordings. K-cos metrics define strokes by change in direction, providing metrics for stroke duration, curvature, and length.

RESULTS
T-tests between models showed no significant difference in drill stroke frequency (cadaveric = 1.36/s, printed = 1.50/s, P < .40) but demonstrate significantly shorter duration (cadaveric = 0.37 s, printed = 0.16 s, P < .01) and a higher percentage of curved strokes (cadaveric = 31, printed = 67, P < .01) employed in printed bone dissection. Junior staff used a higher number of short strokes (junior = 0.54, senior = 0.38, P < .01) and higher percentage of curved strokes (junior = 35%, senior = 21%, P < .01).

CONCLUSIONS
Significant differences in hand motions were present between simulations, however the significance is unclear. This may indicate that printed bone is not best positioned to be the principal training schema.


HIF2α-arginase axis is essential for the development of pulmonary hypertension.

Abstract: Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension. The rise in right ventricular systolic pressure (RVSP) normally observed following chronic hypoxic exposure was absent in mice with pulmonary endothelial HIF-2α deletion. The RVSP of mice lacking HIF-2α in pulmonary endothelium after exposure to hypoxia was not significantly different from normoxic WT mice and much lower than the RVSP values seen in WT littermate controls and mice with pulmonary endothelial deletion of HIF-1α exposed to hypoxia. Endothelial HIF-2α deletion also protected mice from hypoxia remodeling. Pulmonary endothelial deletion of arginase-1, a downstream target of HIF-2α, likewise attenuated many of the pathophysiological symptoms associated with hypoxic pulmonary hypertension. We propose a mechanism whereby chronic hypoxia enhances HIF-2α stability, which causes increased arginase expression and dysregulates normal vascular NO homeostasis. These data offer new insight into the role of pulmonary endothelial HIF-2α in regulating the pulmonary vascular response to hypoxia.

Cowburn|Andrew S|AS|
Crosby|Alexi|A|
Macias|David|D|
Branco|Cristina|C|
Colaço|Renato D D R|RD|
Southwood|Mark|M|
Toshner|Mark|M|
Crotty Alexander|Laura E|LE|
Morrell|Nicholas W|NW|
Chilvers|Edwin R|ER|
Johnson|Randall S|RS|

D051792:Basic Helix-Loop-Helix Transcription Factors

D051795:Hypoxia-Inducible Factor 1, alpha Subunit


Comparative analysis of monoaminergic cerebrospinal fluid-contacting cells in Osteichthyes (bony vertebrates).

Abstract: Cerebrospinal fluid-contacting (CSF-c) cells containing monoamines such as dopamine (DA) and serotonin (5-HT) occur in the periventricular zones of the hypothalamic region of most vertebrates except for placental mammals. Here we compare the organization of the CSF-c cells in chicken, Xenopus, and zebrafish, by analyzing the expression of synthetic enzymes of DA and 5-HT, respectively, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), and draw an evolutionary scenario for this cell population. Due to the lack of TH immunoreactivity in this region, the hypothalamic CSF-c cells have been thought to take up DA from the ventricle instead of synthesizing it. We demonstrate that a second TH gene (TH2) is expressed in the CSF-c cells of all the three species, suggesting that these cells do indeed synthetize DA. Furthermore, we found that many CSF-c cells coexpress TH2 and TPH1 and contain both DA and 5-HT, a dual neurotransmitter phenotype hitherto undescribed in the brain of any vertebrate. The similarities of CSF-c cells in chicken, Xenopus, and zebrafish suggest that these characteristics are inherited from the common ancestor of the Osteichthyes. A significant difference between tetrapods and teleosts is that teleosts possess an additional CSF-c cell population around the posterior recess (PR) that has emerged in specific groups of Actinopterygii. Our comparative analysis reveals that the hypothalamus in mammals and teleosts has evolved in a divergent manner: placental mammals have lost the monoaminergic CSF-c cells, while teleosts have increased their relative number.

monoamine
dopamine
serotonin
ventricle
hypothalamus
CSF-contacting cells
RRID: AB_10000240
RRID: AB_2201528
RRID: AB_221448
RRID: AB_2314334
RRID: AB_2314655
RRID: AB_477522
RRID: AB_87181
RRID: AB_94865
evolution
paraventricular organ


Prognostic nutrition index as a predictor of coronary artery aneurysm in Kawasaki Disease.

Abstract:
BACKGROUND
Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet.

METHOD
This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients.

RESULT
Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%.

CONCLUSION
PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness.

Tai|I-Hsin|IH|
Wu|Pei-Lin|PL|
Guo|Mindy Ming-Huey|MM|
Lee|Jessica|J|
Chu|Chi-Hsiang|CH|
Hsieh|Kai-Sheng|KS|
Kuo|Ho-Chang|HC|0000-0002-3295-2984

D009080:Mucocutaneous Lymph Node Syndrome

Prognostic nutrition index
Coronary artery aneurysm
Kawasaki Disease
Albumin
Lymphocyte


HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

Abstract:
BACKGROUND
There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).

METHODS
Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.

RESULTS
We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201).

CONCLUSIONS
We suggest potential mechanisms to optimize these compounds and their future clinical implementation.


Infant mortality in white-faced capuchins: The impact of alpha male replacements.

Abstract: Infanticide is common in the context of alpha male replacements (AMR), particularly in groups where alpha males experience high reproductive skew and the infants are unlikely to be related to a new alpha male. We examined the relationship between the rate of infant mortality, infant age, and the occurrence and type of AMR in white-faced capuchin monkeys (Cebus capucinus imitator) of the Santa Rosa population in Sector Santa Rosa, Área de Conservación Guanacaste. Specifically, we investigated how the source of the new alpha male (coresident or extragroup) and relative aggression level during AMRs influenced infant mortality in this species. Between 1986 and 2015, we recorded 221 births in five study groups. Infants present at the time of an AMR, or born within 5.5 months following an AMR (i.e., conceived prior to AMR), experienced significantly higher mortality than those born during periods of group stability. Infant age was a significant predictor of infant survival, with the probability of surviving increasing by 0.4% for each additional day older an infant was at the time of the AMR. Infant mortality rates did not differ between AMRs by coresident males and extragroup males, possibly because the degree of relatedness between infants and new alphas did not significantly differ between coresident and extragroup AMRs. Infant mortality rates did not differ significantly between aggressive AMRs and more peaceful AMRs. Our results are consistent with predictions derived from the sexual selection hypothesis (SSH) of infanticide and suggest that future studies examine the role of testosterone as an underlying proximate mechanism for the aggression leading to this behavior. We argue that the sexual selection and generalized aggression hypotheses (GAH) of infanticide are best considered as different levels of analysis rather than competing hypotheses.

Brasington|Lauren F|LF|
Wikberg|Eva C|EC|
Kawamura|Shoji|S|
Fedigan|Linda M|LM|
Jack|Katharine M|KM|

capuchin
alpha male replacements
infanticide
coresident males
male aggression


Prognosis of anal canal adenocarcinoma versus lower rectal adenocarcinoma in Japan: a propensity score matching study.

Abstract:
PURPOSE
Anal canal adenocarcinoma (AC) is rare and its surgical outcomes and prognostic factors (PFs) are not well understood. The aim of this retrospective study was to identify the characteristics and PFs of AC, using population-based data in Japan.

METHODS
Patients with AC (n = 390) or lower rectal adenocarcinoma (LR) (n = 12,477) diagnosed between1991 and 2006 were enrolled in this study. We compared the clinical- and patient-related factors of the two diseases and then examined propensity score matching, overall survival (OS), and PFs.

RESULTS
AC tended to develop more often in women and in patients of advanced age. Macroscopically, AC was of an unclassified type and microscopically, it was of high-grade histological types such as mucinous adenocarcinoma, poorly differentiated adenocarcinoma (por), or signet-ring cell carcinoma (sig), with a high frequency of inguinal node metastasis (P < 0.05). The 5 year OS rates were 56.9% for AC and 67.9% for LR (P = 0.002). The PFs of AC were a high-grade histological type (por/sig), T, N, and M.

CONCLUSIONS
AC has a significantly worse prognosis than LR. Moreover, the AC lymph node metastatic sites for AC, especially the inguinal nodes, are different from those for LR.

Anal canal adenocarcinoma
Lower rectal adenocarcinoma
Propensity score matching
Overall survival
Inguinal node


Life events, social support, coping strategies, and quality of life in attempted suicide: A case-control study.

Abstract:
BACKGROUND
Though deliberate self-harm encompasses a wide variety of medical and social disciplines some of the important psychosocial variable such as life events, social support, coping strategies, and quality of life have not yet been explored in depth in India.

AIMS
The aim was to analyze and compare the type and severity of life events, coping strategies, social support, and quality of life of suicide attempters versus matched normal controls, and to identify the risk factors leading to suicide.

MATERIALS AND METHODS
A total of 50 consecutive suicide attempters were compared with same number of age, sex, and martial status matched healthy controls using Presumptive Stressful Life Events Scale, Social Support Questionnaire, AECOM Coping Style Scale, and WHO QOL-Bref.

RESULTS
Attempters experienced significantly more life events especially untoward events whereas the control group experienced more desirable and impersonal life events. Social support, positive coping, and of QOL were significantly lower in attempters. Among all risk factors desirable life events, good education, and good social support were protective against suicide.

CONCLUSION
Suicide attempters were differentiated from healthy controls based on more stressful life events, lower social support, less healthy coping, and poor QOL. Positive life events, good education, and good social support were protective factors against suicide. However, it is difficult to pinpoint a single factor responsible for suicidal behavior. It is the complex interplay of various interrelated factors and the resultant buffering effect, which is protecting the individual against deliberate self-harm.

life events
social support
Coping
quality of life
deliberate self harm