Analgesic purchases among older adults - a population-based study.

Abstract:
BACKGROUND
Pain is a frequent and inevitable factor affecting the quality of life among older people. Several studies have highlighted the ineffectiveness of treating chronic pain among the aged population, and little is known about the prevalence of analgesics administration among community-dwelling older adults. The objective was to examine older adults' prescription analgesic purchases in relation to SF-36 pain in a population-based setting.

METHODS
One thousand four hundred twenty community-dwelling citizens aged 62-86 years self-reported SF-36 bodily pain (pain intensity and pain-related interference) scores for the previous 4 weeks. The Social Insurance Institution of Finland register data on analgesic purchases for 6 months prior to and 6 months after the questionnaire data collection were considered. Special interest was focused on factors related to opioid purchases.

RESULTS
Of all participants, 84% had purchased prescription analgesics during 1 year. NSAIDs were most frequently purchased (77%), while 41% had purchased paracetamol, 32% opioids, 17% gabapentinoids, and 7% tricyclic antidepressants. Age made no marked difference in purchasing prevalence. The number of morbidities was independently associated with analgesic purchases in all subjects and metabolic syndrome also with opioid purchases in subjects who had not reported any pain.

DISCUSSION
Substantial NSAID and opioid purchases emerged. The importance of proper pain assessment and individual deliberation in terms of analgesic contraindications and pain quality, as well as non-pharmacological pain management, need to be highlighted in order to optimize older adults' pain management.


Penicillin G as a novel chiral selector in capillary electrophoresis.

Abstract: The penicillin sub-class of β-lactam antibiotics has not been examined for its enantiodiscriminating abilities in capillary electrophoresis (CE) until date. The present work was therefore designed to evaluate penicillin G potassium salt (PenG) as an ion-pair chiral selector (CS) using CE for its several attributes, namely, high solubility in water and lower alcohols, structure allowing multiple interactions with analytes and cost-effectiveness. Systematic experiments were performed to investigate the effect of composition of background electrolyte, applied voltage and capillary temperature on chiral separation. Baseline resolutions of enantiomers of five basic chiral drugs (namely, darifenacin, citalopram, sertraline, propranolol and metoprolol) were attained using a background electrolyte composed of water:methanol (90:10, v/v) and consisting of 10.7 or 16.1mM CS at 20°C using an applied voltage of 5kV.

Penicillin G
Penicillin G
Chiral selector
Chiral selector
Capillary electrophoresis
PenG
CS
darifenacin
propranolol
metoprolol
methanol
CIT
DAR
Enantioseparation
METO
MeCN
MeOH
PRO
SERT
acetonitrile
chiral selector
citalopram hydrobromide
penicillin G
sertraline hydrochloride

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


Cross-resistance to prosulfocarb and triallate in pyroxasulfone-resistant Lolium rigidum.

Abstract:
BACKGROUND
Plants can rapidly evolve resistance to herbicide in response to repeated selection. This study focuses on cross-resistance patterns observed in Lolium rigidum following pyroxasulfone recurrent selection.

RESULTS
The parental MR (multiresistant) population following four generations of pyroxasulfone recurrent selection evolved cross-resistance to prosulfocarb and triallate. At the recommended label rate of prosulfocarb or triallate (2000 g ha(-1) ), the progeny selected four times with pyroxasulfone (MR4) displayed 58 and 35% plant survival respectively. One additional cycle of prosulfocarb selection increased the resistance level to both prosulfocarb and triallate in the population MR4-P1. Prosulfocarb resistance is yet to be reported in L. rigidum field populations.

CONCLUSIONS
This study suggests that L. rigidum plants can rapidly evolve cross-resistance to several wheat-selective herbicides under recurrent selection of a single mode of action. Weed populations displaying broad-spectrum cross-resistance to several herbicide modes of action are increasing in frequency in intensive world agriculture. Proactive and integrated measures for resistance management need to be developed globally on appropriate herbicide use in crop rotations.

prosulfocarb
triallate
pyroxasulfone
evolution
herbicide resistance
plant adaptation
population genetics


Vitamin D3 in children with allergic asthma in clinical practice.

Abstract: Asthma is a chronic inflammatory disorder; type 2 inflammation is the most common asthma endotype in childhood. T regulatory cells are functionally and allergen-specifically defective in allergic patients. Vitamin D3 exerts many functions on immune system, mainly concerning T regulatory function. Asthma control is the goal of the asthma treatment. We aimed to stratified a group of 76 consecutive children (50 males, 26 females, mean age 10.4 + 2.2 years) with allergic asthma and visited for the first time at a third-level paediatric clinic during a 3-month period, considering the Vitamin D3 serum levels. The three Vitamin D3 classes were not able to discriminate significant difference for all the parameters considered. In conclusion, Vitamin D3 serum assessment seems to be scarcely useful to pheno/endotyping allergic asthmatic children in clinical practice.

Vitamin D3
asthma
clinical practice
asthma control


Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques.

Abstract: Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern.

Sundman|Mark H|MH|
Hall|Eric E|EE|
Chen|Nan-Kuei|NK|

head trauma
neurodegenerative disease
TBI
Alzheimer’s disease (AD)
Amyotrophic Lateral Sclerosis (ALS)
Chronic Traumatic Encephalopathy (CTE)
Diffusion Tensor Imaging
Magnetic Resonance Imaging
Parkinson’s disease (PD)
Positron Emission Tomography (PET)
Resting State Functional Connectivity
retrospective TBI screening


Awareness of obstetric warning signs in Ecuador: a cross-sectional study.

Abstract:
OBJECTIVE
In Ecuador, the reported maternal death rate was 45.71 per 100,000 live births in 2013. This may be partly due to a lack of maternal knowledge of obstetric warning signs during pregnancy, delivery and the post-partum period. This study sought to evaluate awareness of obstetric warning signs among pregnant women in relation to individual demographic and area-level socio-economic indicators.

STUDY DESIGN
We conducted a cross-sectional analysis of data collected by Ecuador's Ministry of Health at the conclusion of a national maternal health campaign (2014-2015). A nationally representative sample of 3435 pregnant women from the nine administrative zones completed surveys regarding basic demographics and their awareness of obstetric warning signs.

METHODS
We defined eight obstetrical warning signs according to the literature and Ecuadorian practice that could occur during pregnancy, delivery and the post-partum period (severe headache, strong abdominal ache, bleeding or presence of malodorous secretion, rupture of the amniotic sac, high fever, abnormal presentation of the baby, decrease in baby's movements and delayed labour). A woman was considered 'aware' if she recognised at least four of the eight warning signs and stated she would seek immediate healthcare at their presentation. For each administrative zone, four socio-economic indicators (poverty, illiteracy, unemployment and subemployment) were obtained from the National Institute of Statistics and Census. Correlates of awareness of the obstetric warning signs were evaluated using hierarchical logistic models clustered by the administrative zone.

RESULTS
Nationally, 86.9% of women were 'aware' of obstetric warning signs. After adjustment for age, socio-economic indicators and clustering, indigenous participants were 59% less likely to be aware of obstetric warning signs than mestizos (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.28-0.59). For every 1% increase in area poverty, participants had a 5% decreased likelihood of being aware of obstetric warning signs (OR = 0.95, 95% CI = 0.93-0.96), adjusting for age, ethnicity and other socio-economic indicators. The most effective source of campaign information about obstetric warning signs was personal communication with a healthcare professional, as opposed to mass media advertisements (OR = 1.90, 95% CI = 1.34-2.71).

CONCLUSIONS
A majority of Ecuadorian pregnant and post-partum women are aware of obstetric warning signs. Indigenous ethnicity and area-level poverty are associated with a lack of awareness. Personal communication with a healthcare professional was the most effective source of information. These findings have implications for improvement of maternal awareness of warning signs.

Bustamante|G|G|
Mantilla|B|B|
Cabrera-Barona|P|P|
Barragán|E|E|
Soria|S|S|
Quizhpe|E|E|
Jiménez Aguilar|A P|AP|
Hinojosa Trujillo|M H|MH|
Wang|E|E|
Grunauer|M|M|

D007722:Health Knowledge, Attitudes, Practice

Awareness
Warning signs
Ecuador
Maternal mortality
Pregnant mothers
Socio-economic factors


Transcriptional Control and mRNA Capping by the GDP Polyribonucleotidyltransferase Domain of the Rabies Virus Large Protein.

Abstract: Rabies virus (RABV) is a causative agent of a fatal neurological disease in humans and animals. The large (L) protein of RABV is a multifunctional RNA-dependent RNA polymerase, which is one of the most attractive targets for developing antiviral agents. A remarkable homology of the RABV L protein to a counterpart in vesicular stomatitis virus, a well-characterized rhabdovirus, suggests that it catalyzes mRNA processing reactions, such as 5'-capping, cap methylation, and 3'-polyadenylation, in addition to RNA synthesis. Recent breakthroughs in developing in vitro RNA synthesis and capping systems with a recombinant form of the RABV L protein have led to significant progress in our understanding of the molecular mechanisms of RABV RNA biogenesis. This review summarizes functions of RABV replication proteins in transcription and replication, and highlights new insights into roles of an unconventional mRNA capping enzyme, namely GDP polyribonucleotidyltransferase, domain of the RABV L protein in mRNA capping and transcription initiation.

transcription
mRNA capping
GDP polyribonucleotidyltransferase
rabies virus
L protein
de novo initiation


"I feel like death on legs": COVID-19 isolation and mental health.

Abstract: This study investigates the personal and collective responses to COVID-19, as it is described in British personal stories and newspaper reports from Britain and Sri Lanka and examines the social and economic impact of the pandemic on different societies. Although some studies have been done on the impact of COVID-19, none of these studies have focused specifically on the impact the coronavirus has had on different societies because of the global lockdown and restrictions on people's movements. This study attempts to address this gap in the literature by focusing on how the language used in a corpus of personal stories and newspaper reports collected over a span of one month, reveal the impact of COVID-19 on two societies by investigating how self-isolation and lockdown is leading to mental health breakdown in individuals and affecting wider social and economic collapse. The data was analysed using corpus linguistics methodology such as keyword analysis using AntConc (Anthony, 2019) and Linguistic Inquiry and Word Count (LIWC) (Pennebaker Conglomerates, 2015). The findings from LIWC shows that the enforced self-isolation is leading to mental health breakdown. The analysis of the news reports show that Britain's priorities are centred on the economy whereas Sri Lankan newspapers focus on educating people about the severity of COVID-19.


Consumers' Concerns and Perceptions of Farm Animal Welfare.

Abstract: In this paper, we explore the evolution of consumers' perceptions and concerns about the effects that intensification of production systems could have on the welfare of farm animals. Despite the differences in definitions of animal welfare that make perceptions about this complex subject extremely variable, there is a growing perception that farm animal welfare should be protected and improved. There is an increasing appreciation of animal welfare parameters over other quality attributes, and animal-friendly products are considered healthier, safer, tastier, more hygienic, authentic, environmentally friendly, and traditional by many consumers. The willingness to pay for the increases in price that higher levels of farm animal welfare could produce could be promoted by means of adequate information about management and housing conditions of the different farming species. Welfare-friendly products that are properly labeled with clear information provided by an internationally accepted, transparent, and traceable monitoring system will increase consumers' confidence in the food chain participants. Both consumers and citizens have the opportunity to improve the welfare of millions of farmed animals now and in the future, consumers by assuming their responsibility at the buying point, purchasing welfare-friendly products, and citizens by driving legislation to achieve some minimum standard of welfare conditions that could meet animals' needs.

Alonso|Marta E|ME|
González-Montaña|José R|JR|
Lomillos|Juan M|JM|

consumer
concerns
perceptions
farming
animal welfare


Antidepressant effect of BE360, a new selective estrogen receptor modulator, activated via CREB/BDNF, Bcl-2 signaling pathways in ovariectomized mice.

Abstract: We have previously reported that the carborane compound BE360, a novel selective estrogen receptor modulator, has a therapeutic potential against dementia. This study aimed to explore the effects and underlying mechanisms of BE360 on depression-like behaviors in ovariectomized (OVX) mice subjected to subchronic stress, which are postmenopausal depression models. BE360 was subcutaneously administrated using a mini-osmotic pump, for 2 weeks. Depression-like behaviors were evaluated using the forced swimming test. Neurogenesis in the hippocampal dentate gyrus (DG) was measured by analyzing cells expressing doublecortin (DCX) following 5-bromo-2'-deoxyuridine (BrdU) uptake. The levels of phosphorylated cyclic-AMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 were measured using immunohistochemistry or immunoblotting. Depression-like behaviors in OVX + Stress-exposed mice improved after chronic treatment with BE360. BE360 treatment in OVX + Stress-exposed mice increased p-CREB, BDNF, and Bcl-2 expressions in the hippocampus. Immunohistochemistry showed that the number of BrdU/DCX double-positive cells in the DG of the hippocampus, which decreased significantly in OVX + Stress-exposed mice, increased after subchronic treatment with BE360. The present study demonstrates that BE360 exerts antidepressant effects via hippocampal neurogenesis, potentially activated through CREB/BDNF, Bcl-2 signaling pathways. These results indicate that BE360 may have therapeutic potential against postmenopausal depression.

Sakuma|Wakana|W| Nakagawasai|Osamu|O| Nemoto|Wataru|W| Odaira|Takayo|T| Ogawa|Takumi|T| Ohta|Kiminori|K| Endo|Yasuyuki|Y| Tan-No|Koichi|K|

D017362:Cyclic AMP Response Element-Binding Protein

D020845:Selective Estrogen Receptor Modulators

Selective estrogen receptor modulator
Carborane compound
Depression
Neurogenesis
Menopause
Ovariectomy


Interplay between the Mediterranean diet and C-reactive protein genetic polymorphisms towards inflammation in adolescents.

Abstract:
AIM
From a nutrigenetics perspective, we aim to investigate the moderating role of the Mediterranean diet and each of its subgroups in the association between C-reactive protein (CRP) gene polymorphisms and CRP blood concentration in adolescents.

METHODS
In 562 adolescents (13-17 y) of the European HELENA study, data was available on circulating CRP levels as inflammatory biomarker, three CRP gene SNPs (rs3093068, rs1204, rs1130864), food intake determined by a self-administered computerized 24 h-dietary recall for 2 days, and body composition. A 9-point Mediterranean diet score and each food subgroup were tested as moderator via SNP*diet interaction. Analyzes were adjusted for age, sex, puberty, adiposity and socioeconomic status.

RESULTS
The minor allele frequencies of rs3093068 and rs1130864 SNPs (GG and TT, respectively) were associated with higher CRP concentrations, while rs1205 (CT/TT) was associated with lower CRP concentrations. There were significant interactions between rs3093068 and Mediterranean diet (B = -0.1139, p = 0.011), or the fish food subgroup (B = -0.0090, p = 0.022), so that those with the highest genetic CRP risk underwent the highest CRP attenuation by a healthier diet. Although the effect of diet and SNP was substantial, the explained variance by interaction was only 1%.

CONCLUSION
Greater adherence to the Mediterranean diet and particularly its fish component was associated with a lower CRP blood concentrations especially in those at highest genetic risk due to the rs3093068 SNP.

Arouca|Aline B|AB|
Meirhaeghe|Aline|A|
Dallongeville|Jean|J|
Moreno|Luis A|LA|
Lourenço|Gustavo Jacob|GJ|
Marcos|Ascensión|A|
Huybrechts|Inge|I|
Manios|Yannis|Y|
Lambrinou|Christina-Paulina|CP|
Gottrand|Frederic|F|
Kafatos|Anthony|A|
Kersting|Mathilde|M|
Sjöström|Michael|M|
Widhalm|Kurt|K|
Ferrari|Marika|M|
Molnár|Denes|D|
González-Gross|Marcela|M|
Forsner|Maria|M|
De Henauw|Stefaan|S|
Michels|Nathalie|N|
|||

D020022:Genetic Predisposition to Disease

Mediterranean diet
C-reactive protein
Inflammation
Interaction
Nutrigenomics
Single nucleotide polymorphism


Dilute acid hydrolysis of spoiled wheat grains: Analysis of chemical, rheological and spectral characteristics.

Abstract: In this work, hydrolysis of spoiled wheat grains using dilute acid (5, 10%; 1 N HCl) was investigated and the effect of hydrolysis conditions on reducing sugars, soluble proteins, rheology and infrared spectra of the hydrolysates was determined. Hydrolysis with 10% acid concentration released more quantities of reducing sugar (16.47 mg/mL) at shorter hydrolysis times whereas 5% acid concentration produced higher protein content (28.74 mg/mL) for similar durations. Flow characteristics demonstrated an increased apparent viscosity of the hydrolysates retrieved after 4.5 h of hydrolysis possibly due to breakdown of hemicelluloses and lignin into sugars. Infrared spectroscopy showed release of carbonates after 1.5 h and 5.5 h of hydrolysis perhaps due to oxidation of lignin or a reaction between acid and sugars. The study highlights that acid hydrolysis would be a rapid and cost effective approach to produce fermentable hydrolysates for bio-processing industry applications while generating an avenue for waste grain utilization.

Acid hydrolysis
Rheology
Reducing sugars
Infrared spectroscopy
Spoiled grains


Assessing Allied Health-Care Professional Time in Pediatric Type 1 Diabetes: Associations With Clinical Factors, Technology and Social Determinants.

Abstract:
OBJECTIVES
The factors associated with allied health-care professional (HCP) time spent face-to-face with patients in clinic have not been well described in type 1 diabetes (T1D) given the introduction of resource-intensive technologies and gaps in socioeconomic circumstances. The objective of this study was to evaluate clinical and social factors associated with nonphysician HCP time in a pediatric T1D practice.

METHODS
Nonphysician HCP workload data, including time spent in direct clinical care over a 1-year period and nonclinic contacts, were linked to data from 723 pediatric subjects with T1D and evaluated in relation to key demographic, social and diabetes treatment factors.

RESULTS
HCPs spent 145.7 min per patient on a median of 3 clinic visits, with certified diabetes educators (CDEs) being responsible for most clinic interactions compared with psychosocial staff. CDE time varied considerably according to T1D duration, with new-onset patients (≤1 year) taking a median of 392.0 min compared with 114.5 min for their established counterparts (p<0.0001). Among the established group (n=629), CDE time was strongly associated with continuous subcutaneous insulin infusion therapy initiation, psychosocial service use, glycated hemoglobin (A1C) and degree of marginalization (p<0.0001). Overall, CDE time increased by 8.6 min for each 1.0% increase in A1C (p=0.022) and by 16.3 min for each 1-U increase in marginalization (p=0.01).

CONCLUSIONS
We observed HCP time was associated with multiple clinical factors in addition to overall marginalization. Although initial investments in education and continuous subcutaneous insulin infusion training were considerable, our results suggest that these lead to a decrease in time spent in clinic over time, and is largely driven by lower A1C.

Clarke|Antoine B M|ABM|
Ahsan|Hanaa|H|
Harrington|Jennifer|J|
Mahmud|Farid H|FH|

pediatric
delivery of health care
diabète sucré de type 1
déterminants sociaux de la santé
facteurs temps
prestation de soins de santé
pédiatrique
social determinants of health
time factors
type 1 diabetes mellitus


Long-term outcomes of end-stage kidney disease for patients with IgA nephropathy: A multi-centre registry study.

Abstract:
BACKGROUND
Clinical outcomes of patients with end-stage kidney disease (ESKD) receiving renal replacement therapy (RRT) secondary to IgA nephropathy (IgAN) have not been well described.

AIM
To investigate the characteristics, treatments and outcomes of ESKD because of kidney-limited IgAN and Henoch-Schönlein purpura nephritis (HSPN) in the Australian and New Zealand RRT populations.

METHODS
All ESKD patients who commenced RRT in Australia and New Zealand between 1971 and 2012 were included. Dialysis and transplant outcomes were evaluated in both a contemporary cohort (1998-2012) and the entire cohort (1971-2012).

RESULTS
Of 63 297 ESKD patients, 3721 had kidney-limited IgAN, and 131 had HSPN. For the contemporary cohort of IgAN patients on dialysis (n = 2194), 10-year patient survival was 65%. Of 1368 contemporary IgAN patients who received their first renal allograft, 10-year patient, overall renal allograft and death-censored renal allograft survival were 93%, 82% and 88%, respectively. Using multivariable Cox regression analysis, patients with IgAN had favourable dialysis patient survival (adjusted hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.57-0.69), overall renal allograft survival (HR 0.67, 95% CI 0.57-0.79) and renal transplant patient survival (HR 0.58, 95% CI 0.45-0.74) compared with ESKD controls. Similar results were found in the entire cohort and when using competing-risks models. Compared with kidney-limited IgAN patients, those with HSPN had worse dialysis patient survival (HR 1.94, 95% CI 1.02-3.69), overall renal allograft survival (HR 3.40, 95% CI 1.00-11.55) and renal transplant patient survival (HR 3.50, 95% CI 1.03-11.92).

CONCLUSION
IgAN ESKD was associated with better dialysis and renal transplant outcomes compared with other forms of ESKD. The survival outcomes of ESKD patients with HSPN were worse than kidney-limited IgAN.

Zhang|Lei|L|
Liu|Xusheng|X|
Pascoe|Elaine M|EM|
Badve|Sunil V|SV|
Boudville|Neil C|NC|
Clayton|Philip A|PA|
De Zoysa|Janak|J|
Hawley|Carmel M|CM|
Kanellis|John|J|
McDonald|Stephen P|SP|
Peh|Chen Au|CA|
Polkinghorne|Kevan R|KR|
Johnson|David W|DW|

D001315:Australia
D016009:Chi-Square Distribution
D018450:Disease Progression
D005922:Glomerulonephritis, IGA
D006085:Graft Survival
D006801:Humans
D011695:IgA Vasculitis
D015994:Incidence
D053208:Kaplan-Meier Estimate
D007676:Kidney Failure, Chronic
D016030:Kidney Transplantation
D015999:Multivariate Analysis
D009520:New Zealand
D016016:Proportional Hazards Models
D012042:Registries
D006435:Renal Dialysis
D018570:Risk Assessment
D012307:Risk Factors
D013997:Time Factors
D016896:Treatment Outcome

outcomes
end-stage kidney disease
IgA nephropathy
Henoch-Schönlein purpura
dialysis
renal transplantation


Factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization: A retrospective cohort study.

Abstract:
AIM
This study aimed to investigate the factors predicting overall response and overall survival in hepatocellular carcinoma patients undergoing balloon-occluded transcatheter arterial chemoembolization (B-TACE).

METHODS
Sixty-six patients treated with B-TACE at a Japanese tertiary referral hospital between January 2011 and August 2015 were included in this retrospective cohort study.

RESULTS
The overall response was classified as complete response, partial response, stable disease, and progressive disease in 35 (53.0%), 7 (10.6%), 13 (19.7%), and 11 (16.7%) patients, respectively. The response rate was 63.6%, and the disease control rate was 83.3%. The number of tumors (hazard ratio [HR], 4.44; 95% confidence interval [CI], 1.26-15.7; P = 0.021) and α-fetoprotein level (HR, 11.40; 95% CI, 2.75-46.9; P < 0.001) were significantly associated with the tumor response in a multivariate analysis. The 1-, 2-, and 3-year survival rates were 76.8% (95% CI, 64.5-85.3%), 57.3% (95% CI, 42.3-69.7%), and 46.7% (95% CI, 30.7-61.2%), respectively. The median survival time was 902 days. Albumin (≥3.4 g/dL) (HR, 0.28; 95% CI, 0.12-0.63; P = 0.002) and overall response (complete response and partial response) (HR, 0.33; 95% CI, 0.16-0.71; P = 0.004) were factors significantly associated with overall survival in a multivariate analysis. No mortalities were observed, but biloma requiring percutaneous transhepatic biliary drainage occurred in one patient (1.5%).

CONCLUSION
Balloon-occluded transcatheter arterial chemoembolization may exert a good antitumor effect and result in good overall survival in select hepatocellular carcinoma patients.

Hatanaka|Takeshi|T| Arai|Hirotaka|H| Shibasaki|Mitsuhiko|M| Tojima|Hiroki|H| Takizawa|Daichi|D| Toyoda|Mitsuo|M| Takayama|Hisashi|H| Abe|Takehiko|T| Sato|Ken|K| Kakizaki|Satoru|S| Yamada|Masanobu|M|


Thyroid calcifications: a pictorial essay.

Abstract: Incidental diagnosis of thyroid nodules is very common on adult neck ultrasonography examination. Thyroid calcifications are encountered in benign thyroid nodules and goiters as well as in thyroid malignancy. Depiction and characterization of such calcifications within a thyroid nodule may be a key element in the thyroid nodule diagnosis algorithm. The goal of this paper is to display typical radio-pathological correlations of various thyroid pathologies of benign and malignant conditions in which the calcification type diagnosis can play a key role in the final diagnosis of the thyroid nodule.

Lacout|Alexis|A|
Chevenet|Carole|C|
Thariat|Juliette|J|
Marcy|Pierre Yves|PY|

calcifications
ultrasonography
Thyroid cancer
macrocalcifications
microcalcifications


Biota from the coastal wetlands of Praia da Vitória (Terceira, Azores, Portugal): Part 3 - Birds.

Abstract:
Background
The data presented here come from field observations of Aves between August 2013 and October 2018 as part of a LIFE research project aiming to preserve and restore three coastal wetlands from Praia da Vitória (Terceira Island, Azores, Portugal). Systematic monthly observations were carried out for five years in order to provide a checklist and monitoring of bird species and subspecies observed in three sites: Paul da Praia da Vitória (PPV), Paul do Belo Jardim (PBJ) and Paul da Pedreira do Cabo da Praia (PPCP). Main objectives were to determine their ornithological richness while also adding data to the overall knowledge of Azorean Avifauna and to monitor seasonal and between-year variation on species abundance.

New information
During a five-year observation period (2013-2018), a total of 82,985 birds belonging to 108 species/subspecies were observed. From this, 16,663 were in PPV, 11,793 from PBJ and 54,529 from PPCP. The total richness was 55, 40 and 85, respectively. Three species are first records for the Azores: Aythya americana (Eyton, 1838); Chlidonias leucopterus (Temminck, 1815) and Tringa brevipes (Vieillot, 1816). One species is a new record for Terceira Island: Lophodytes cucullatus (Linnaeus, 1758).

Wetlands Terceira Azores Aves Ornitofauna.


Biomimetic Total Synthesis of (±)-Homodimericin A.

Abstract: A biomimetic total synthesis of racemic homodimericin A was achieved in seven steps, including two cascade reactions. Aqueous buffer solutions are found to help both the oxidative dimerization cascade and the intramolecular Diels-Alder cascade. This synthetic sequence validates key steps in the biogenetic proposal of homodimericin A.

total synthesis
homodimericin
cascade reactions
Negishi coupling
biomimetic synthesis


A Paradigm Shift: Rehabilitation Robotics, Cognitive Skills Training, and Function After Stroke.

Abstract: Introduction: Robot-assisted therapy for upper extremity (UE) impairments post-stroke has yielded modest gains in motor capacity and little evidence of improved UE performance during activities of daily living. A paradigm shift that embodies principles of motor learning and exercise dependent neuroplasticity may improve robot therapy outcomes by incorporating active problem solving, salience of trained tasks, and strategies to facilitate the transfer of acquired motor skills to use of the paretic arm and hand during everyday activities. Objective: To pilot and test the feasibility of a novel therapy protocol, the Active Learning Program for Stroke (ALPS), designed to complement repetitive, robot-assisted therapy for the paretic UE. Key ALPS ingredients included training in the use of cognitive strategies (e.g., STOP, THINK, DO, CHECK) and a goal-directed home action plan (HAP) to facilitate UE self-management and skill transfer. Methods: Ten participants with moderate impairments in UE function >6 months after stroke received eighteen 1-h treatment sessions 2-3/x week over 6-8 weeks. In addition to ALPS training, individuals were randomly assigned to either robot-assisted therapy (RT) or robot therapy and task-oriented training (RT-TOT) to trial whether the inclusion of TOT reinforced participants' understanding and implementation of ALPS strategies. Results: Statistically significant group differences were found for the upper limb subtest of the Fugl-Meyer Assessment (FMA-UE) at discharge and one-month follow-up favoring the RT group. Analyses to examine overall effects of the ALPS protocol in addition to RT and RT-TOT showed significant and moderate to large effects on the FMA-UE, Motor Activity Log, Wolf Motor Function Test, and hand portion of the Stroke Impact Scale. Conclusion: The ALPS protocol was the first to extend cognitive strategy training to robot-assisted therapy. The intervention in this development of concept pilot trial was feasible and well-tolerated, with good potential to optimize paretic UE performance following robot-assisted therapy.

Fasoli|Susan E|SE|
Adans-Dester|Catherine P|CP|

stroke
upper extremity (UE)
motor learning
cognitive strategy training
activity performance
robot-assisted therapy (RAT)
transfer of training strategies


Injury severity analysis of pedestrian and bicyclist trespassing crashes at non-crossings: A hybrid predictive text analytics and heterogeneity-based statistical modeling approach.

Abstract: Non-motorists involved in rail-trespassing crashes are usually more vulnerable to receiving major or fatal injuries. Previous research has used traditional quantitative crash data for understanding factors contributing to injury outcomes of non-motorists in train involved collisions. However, usually overlooked crash narratives can provide useful and unique contextual crash-specific information regarding factors associated with injury outcomes. The main objective of this study is to harness the rapid advancements in more sophisticated qualitative analysis procedures for identifying thematic concepts in unstructured crash narrative data. A two-staged hybrid approach is proposed where text mining is applied first to extract valuable information from crash narratives followed by inclusion of the new variables derived from text mining in formulation of advanced statistical models for injury outcomes. By using ten-year (2006-2015) non-motorist non-crossing trespassing injury data obtained from the Federal Railroad Administration, statistical procedures and advanced machine learning text analytics are applied to extract unique information on contributory factors of trespassers' injury outcomes. The key concepts are systematically categorized into trespasser, injury, train, medical, and location related factors. A total of 13 unique variables are extracted from the thematic concepts that are not present in traditional tabular crash data. The analysis reveals a positive statistically significant association between presence of crash narrative and trespasser's injury outcome (coded as minor, major, and fatal injury). Compared to crashes with minor injuries, crashes involving major and fatal injuries are more likely to be reported with crash narratives. A crosstabulation of new variables derived from text mining with injury outcomes revealed that trespassers with confirmed suicide attempts, trespassers wearing headphones, or talking on cell phones are more likely to receive fatal injuries. Among other factors identified, trespassers under alcohol influence, trespasser hit by commuter train, and advance warnings by engineer are associated with more severe (major and fatal) trespasser injury outcomes. Accounting for unobserved heterogeneity and controlling for other factors, fixed and random parameter discrete outcome models are developed to understand the heterogeneous correlations between trespasser injury outcomes and the new crash specific explanatory variables derived from text mining - providing deeper insights. Practical implications and future research directions are discussed.

Wali|Behram|B|
Khattak|Asad J|AJ|
Ahmad|Numan|N|

Heterogeneity-based discrete outcome modeling


Alignment independent 3D-QSAR, quantum calculations and molecular docking of Mer specific tyrosine kinase inhibitors as anticancer drugs.

Abstract: Mer receptor tyrosine kinase is a promising novel cancer therapeutic target in many human cancers, because abnormal activation of Mer has been implicated in survival signaling and chemoresistance. 3D-QSAR analyses based on alignment independent descriptors were performed on a series of 81 Mer specific tyrosine kinase inhibitors. The fractional factorial design (FFD) and the enhanced replacement method (ERM) were applied and tested as variable selection algorithms for the selection of optimal subsets of molecular descriptors from a much greater pool of such regression variables. The data set was split into 65 molecules as the training set and 16 compounds as the test set. All descriptors were generated by using the GRid INdependent descriptors (GRIND) approach. After variable selection, GRIND were correlated with activity values (pIC50) by PLS regression. Of the two applied variable selection methods, ERM had a noticeable improvement on the statistical parameters of PLS model, and yielded a q (2) value of 0.77, an [Formula: see text] of 0.94, and a low RMSEP value of 0.25. The GRIND information contents influencing the affinity on Mer specific tyrosine kinase were also confirmed by docking studies. In a quantum calculation study, the energy difference between HOMO and LUMO (gap) implied the high interaction of the most active molecule in the active site of the protein. In addition, the molecular electrostatic potential energy at DFT level confirmed results obtained from the molecular docking. The identified key features obtained from the molecular modeling, enabled us to design novel kinase inhibitors.

Shiri|Fereshteh|F|
Pirhadi|Somayeh|S|
Ghasemi|Jahan B|JB|

Molecular docking
Mer receptor tyrosine kinase
Fractional factorial design
Enhanced replacement method
GRIND


CO2 enrichment modulates ammonium nutrition in tomato adjusting carbon and nitrogen metabolism to stomatal conductance.

Abstract: Ammonium (NH4(+)) toxicity typically occurs in plants exposed to high environmental NH4(+) concentration. NH4(+) assimilating capacity may act as a biochemical mechanism avoiding its toxic accumulation but requires a fine tuning between nitrogen assimilating enzymes and carbon anaplerotic routes. In this work, we hypothesized that extra C supply, exposing tomato plants cv. Agora Hybrid F1 to elevated atmospheric CO2, could improve photosynthetic process and thus ameliorate NH4(+) assimilation and tolerance. Plants were grown under nitrate (NO3(-)) or NH4(+) as N source (5-15mM), under two atmospheric CO2 levels, 400 and 800ppm. Growth and gas exchange parameters, (15)N isotopic signature, C and N metabolites and enzymatic activities were determined. Plants under 7.5mM N equally grew independently of the N source, while higher ammonium supply resulted toxic for growth. However, specific stomatal closure occurred in 7.5mM NH4(+)-fed plants under elevated CO2 improving water use efficiency (WUE) but compromising plant N status. Elevated CO2 annulled the induction of TCA anaplerotic enzymes observed at non-toxic NH4(+) nutrition under ambient CO2. Finally, CO2 enrichment benefited tomato growth under both nutritions, and although it did not alleviate tomato NH4(+) tolerance it did differentially regulate plant metabolism in N-source and -dose dependent manner.

Vega-Mas|Izargi|I|
Marino|Daniel|D|
Sánchez-Zabala|Joseba|J|
González-Murua|Carmen|C|
Estavillo|Jose María|JM|
González-Moro|María Begoña|MB|

Nitrogen assimilation
Ammonium tolerance
Elevated CO(2)
Nitrate nutrition
Solanum lycopersicum L.
TCA cycle


Bioorthogonal hydroxyethyl cellulose-based scaffold crosslinked via click chemistry for cartilage tissue engineering applications.

Abstract: In this study, azide and alkyne moieties were introduced to the structure of citric acid-modified hydroxyethyl cellulose (HEC) and then through a bioorthogonal click chemistry method: Strain-promoted azide-alkyne cycloaddition, a novel crosslinked HEC scaffold (click sample) was obtained. Chemical modifications and successful crosslinking of the samples were assessed with FTIR and 1H NMR spectroscopy. Lyophilized samples exhibited a porous interconnected microarchitecture with desirable features for commensurate cartilage tissue engineering applications. As the stability of scaffolds improved upon crosslinking, considerable water uptake and swelling degree of ~650% could still be measured for the click sample. Offering Young's modulus of ~10 MPa and tensile strength of ~0.43 MPa, the mechanical characteristics of click sample were comparable with those of normal cartilage tissue. Various in vitro biological assays, including MTT analysis, cellular attachment, histological staining with safranin O, and real-time PCR decisively approved significant biocompatibility, chondrogenic ability, and bioorthogonal features of click sample.

Nouri-Felekori|Mohammad|M| Nezafati|Nader|N| Moraveji|Marzie|M| Hesaraki|Saeed|S| Ramezani|Tayebe|T|

Scaffold
Crosslink
Click chemistry
Cartilage tissue engineering
Hydroxyethyl cellulose


Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

Abstract:
OBJECTIVES
We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis.

BACKGROUND
TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies.

METHODS
Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon.

RESULTS
A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days.

CONCLUSIONS
Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Zhao|Zhen-Gang|ZG|
Feng|Yuan|Y|
Liao|Yan-Biao|YB|
Li|Yi-Jian|YJ|
Xiong|Tian-Yuan|TY|
Ou|Yuan-Weixiang|YW|
Wang|Zi-Jie|ZJ|
Wei|Jia-Fu|JF|
Peng|Yong|Y|
Wei|Xin|X|
Xu|Yuan-Ning|YN|
Pedersen|Wesley R|WR|
Chen|Mao|M|
Leon|Martin B|MB|

D000082882:Bicuspid Aortic Valve Disease

D065467:Transcatheter Aortic Valve Replacement

dilatation
balloon valvuloplasty
aortic valve insufficiency


BIN1 Induces the Formation of T-Tubules and Adult-Like Ca2+ Release Units in Developing Cardiomyocytes.

Abstract: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are at the center of new cell-based therapies for cardiac disease, but may also serve as a useful in vitro model for cardiac cell development. An intriguing feature of hESC-CMs is that although they express contractile proteins and have sarcomeres, they do not develop transverse-tubules (T-tubules) with adult-like Ca2+ release units (CRUs). We tested the hypothesis that expression of the protein BIN1 in hESC-CMs promotes T-tubules formation, facilitates CaV 1.2 channel clustering along the tubules, and results in the development of stable CRUs. Using electrophysiology, [Ca2+ ]i imaging, and super resolution microscopy, we found that BIN1 expression induced T-tubule development in hESC-CMs, while increasing differentiation toward a more ventricular-like phenotype. Voltage-gated CaV 1.2 channels clustered along the surface sarcolemma and T-tubules of hESC-CM. The length and width of the T-tubules as well as the expression and size of CaV 1.2 clusters grew, as BIN1 expression increased and cells matured. BIN1 expression increased CaV 1.2 channel activity and the probability of coupled gating within channel clusters. Interestingly, BIN1 clusters also served as sites for sarcoplasmic reticulum (SR) anchoring and stabilization. Accordingly, BIN1-expressing cells had more CaV 1.2-ryanodine receptor junctions than control cells. This was associated with larger [Ca2+ ]i transients during excitation-contraction coupling. Our data support the view that BIN1 is a key regulator of T-tubule formation and CaV 1.2 channel delivery. By studying the role of BIN1 during the differentiation of hESC-CMs, we show that BIN1 is also important for CaV 1.2 channel clustering, junctional SR organization, and the establishment of excitation-contraction coupling. Stem Cells 2019;37:54-64.

D048868:Adaptor Proteins, Signal Transducing

BIN1
T-tubules
CaV1.2
Calcium release units
Cardiac myocytes
hESC


Bovine arch anatomy influences recoarctation rates in the era of the extended end-to-end anastomosis.

Abstract:
OBJECTIVES
Arch branching has never been shown to influence recoarctation after extended end-to-end anastomosis via thoracotomy, yet in each study bovine arch identification is grossly underreported. This study aims to (1) assess chart review reliability in bovine arch identification; (2) determine recoarctation risk with a bovine arch; and (3) explore an anatomic explanation for recurrent arch obstruction based on arch anatomy.

PATIENTS
A total of 49 consecutive patients underwent thoracotomy with extended end-to-end aortic coarctation repair at a single institution (2007-2012).

METHODS
Echocardiograms from these patients were reviewed for arch anatomy and compared with the echocardiographic reports. Recurrent arch obstruction was defined as an echocardiographic gradient across the repair of 20 mm Hg or greater. For cases with angiographic images (n = 17), a scaled clamping distance between the left subclavian artery and the maximal proximal clamp location on orthogonal projections was then calculated across arch anatomies.

RESULTS
Chart review identified 6.1% (3/49) of patients with a bovine arch compared with 28.6% (14/49) on targeted image review. A total of 28.6% (4/14) of patients with a bovine arch had a follow-up gradient of 20 mm Hg or greater. Only 5.7% (2/35) of patients with normal arch branching had a follow-up gradient of 20 mm Hg or greater. The mean clamping index was significantly diminished in patients with bovine arch anatomy.

CONCLUSIONS
Arch anatomy often goes undocumented on preoperative imaging, yet children undergoing extended end-to-end repair with bovine arch anatomy are at a significantly increased risk of recoarctation. This may be due to a reduced clampable distance to facilitate repair. These results should be considered in the preoperative assessment, parental counseling, and surgical approach for children with discrete aortic coarctation.

Turek|Joseph W|JW|
Conway|Brian D|BD|
Cavanaugh|Nicholas B|NB|
Meyer|Alex M|AM|
Aldoss|Osamah|O|
Reinking|Benjamin E|BE|
El-Hattab|Ahmed|A|
Rossi|Nicholas P|NP|

bovine arch
coarctation of the aorta
congenital heart disease
outcomes
pediatric


One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review.

Abstract:
BACKGROUND
Hepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.

METHODS
We conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.

RESULTS
Of 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3-5 years for two-dose programs. Vaccine efficacy was >98% over 0.1-7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.

CONCLUSION
Experience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.

Andani|Anar|A|
van Damme|Pierre|P|
Bunge|Eveline M|EM|
Salgado|Fernanda|F|
van Hoorn|Rosa C|RC|
Hoet|Bernard|B|

Systematic review
Incidence
Antibody persistence
Non-live hepatitis A vaccine
Pediatric immunization schedule


Comparison of lipids, fatty acids and volatile compounds of various kumquat species using HS/GC/MS/FID techniques.

Abstract:
BACKGROUND
Kumquat (Fortunella spp.) is one of the important fruit species that has been introduced into Turkey recently. It is well adapted to the Mediterranean region in Turkey. Early research of kumquat was started on adaptation and pomological traits, and only a few studies have been concerned with chemical content. After understanding the health benefits of kumquat fruits farmers started their plantations in Turkey. Thus in this study the fruits of five kumquat species - Fortunella margarita (Lour.) Swingle, F. crassifolia Swingle, F. obovata Hort. ex Tanaka, F. hindsii (Champ. ex Benth.) Swingle, and limequat [Citrus aurantifolia × F. japonica (Thumb.)] - were compared based on their lipids, fatty acids and volatile profiles. The lipids, fatty acids and volatile profiles were determined by using gas chromatography with flame ionisation detection (GC/FID) and headspace gas chromatography mass spectrometry (HS-GC/MS) techniques. Volatile constituents of kumquat fruits were isolated by a headspace method.

RESULTS
The total lipid content (%) of kumquat species ranged from 0.26% to 0.37%. The polyunsaturated fatty acids were detected in a higher amount compared to the monounsaturated fatty acids and saturated fatty acids, respectively. The headspace technique led to the identification of 39 compounds and among a total of 39 constituents identified, d-limonene was the most abundant compound, comprising 67.78-88.72%. The results indicated that kumquats are rich in dietary and health benefits.

CONCLUSION
Thirty-nine compounds were identified and terpenes were the major chemical group in all kumquat genotypes. Esters, alcohols, aldehydes and ketones were also detected. The present study revealed that the kumquat fruits have a valuable levels of health beneficial chemo-preventive effects and genotypes varied based on their lipid, fatty acids and volatile constituents.

Güney|Murat|M|
Oz|Ayse Tulin|AT|
Kafkas|Ebru|E|

fatty acids
volatiles
kumquat
GC/MS
headspace


Exercise Pills for Drug Addiction: Forced Moderate Endurance Exercise Inhibits Methamphetamine-Induced Hyperactivity through the Striatal Glutamatergic Signaling Pathway in Male Sprague Dawley Rats.

Abstract: Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3β expression. However, the phosphorylation levels of Ser9-GSK-3β were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3β activation by the regulation of the striatal glutamate signaling pathway.

D000071679:Glycogen Synthase Kinase 3 beta

hyperactivity
glutamatergic signaling pathway
methamphetamine
GSK-3β
drug abuse
forced endurance exercise


A near atomic structure of the active human apoptosome.

Abstract: In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.

D053477:Apoptotic Protease-Activating Factor 1

human
apoptosome
procaspase-9
programmed cell death
biophysics
cell biology
structural biology


Predictors of Failure in Fast-Track Cardiac Surgery.

Abstract:
OBJECTIVES
Fast-track (FT) management of cardiac surgery patients is associated with early extubation and reduced length of intensive care unit (ICU) stay, with potential benefit of reduced hospital costs. The authors examined perioperative factors and their influence on failure of FT and what implications this failure had.

DESIGN
Prospective data collection from all adult cardiac surgeries between 2011 and 2013.

SETTING
Single-institution study.

PARTICIPANTS
The study included 2,770 consecutive adult cardiac surgery patients.

INTERVENTIONS
All participants underwent adult cardiac surgeries. Of those, 451 (16.3%) patients were selected to undergo FT management.

MEASUREMENTS AND MAIN RESULTS
Failure of FT was defined as early (admission to ICU on day of surgery) or late (patients later admitted to the ICU from the ward). Univariate and multivariate regression analyses were used to identify which variables predicted FT failure. Of the 451 patients included in this study, 138 (30.6%) failed the FT, with 115 (83.3%) early failures and 23 (16.7%) late failures. Predictors of failure were reduced renal function, hypertension, age, EuroSCORE, cardiopulmonary bypass time, first lactate or base deficit after surgery (all p<0.01), and cross-clamp time (p<0.05). Multivariate analysis showed that the strongest predictor of failure was glomerular filtration rate (GFR)<65 mL/min/BSA (sensitivity, 54%; specificity, 61%; likelihood ratio, 1.39; area under receiver operating characteristics curve, 0.59; 95% confidence interval, 0.53-0.64). Median length of hospital stay was longer for the failed group (5 v 7 days, p<0.001). There were no mortalities in any of the patients selected for FT.

CONCLUSIONS
A number of perioperative factors are associated with failure to FT, the strongest predictor being GFR. Failure to FT can lead to significantly longer hospital stay.

Youssefi|Pouya|P| Timbrell|David|D| Valencia|Oswaldo|O| Gregory|Peter|P| Vlachou|Caterina|C| Jahangiri|Marjan|M| Edsell|Mark|M|

D000293:Adolescent
D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D006348:Cardiac Surgical Procedures
D005260:Female
D005919:Glomerular Filtration Rate
D006801:Humans
D007902:Length of Stay
D008297:Male
D008875:Middle Aged
D011182:Postoperative Care
D011183:Postoperative Complications
D011237:Predictive Value of Tests
D011300:Preoperative Care
D011446:Prospective Studies
D013997:Time Factors
D017211:Treatment Failure
D055815:Young Adult

fast-track
cardiac surgery
glomerular filtration rate
postoperative care


The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection.

Abstract: Leishmaniasis is a devastating disease that disfigures or kills nearly two million people each year. Establishment and persistence of infection by the obligate intracellular parasite Leishmania requires repeated uptake by macrophages and other phagocytes. Therefore, preventing uptake could be a novel therapeutic strategy for leishmaniasis. Amastigotes, the life cycle stage found in the human host, bind Fc receptors and enter macrophages primarily through immunoglobulin-mediated phagocytosis. However, the host machinery that mediates amastigote uptake is poorly understood. We have previously shown that the Arg (also known as Abl2) non-receptor tyrosine kinase facilitates L. amazonensis amastigote uptake by macrophages. Using small-molecule inhibitors and primary macrophages lacking specific Src family kinases, we now demonstrate that the Hck, Fgr and Lyn kinases are also necessary for amastigote uptake by macrophages. Src-mediated Arg activation is required for efficient uptake. Interestingly, the dual Arg and Src kinase inhibitor bosutinib, which is approved to treat cancer, not only decreases amastigote uptake, but also significantly reduces disease severity and parasite burden in Leishmania-infected mice. Our results suggest that leishmaniasis could potentially be treated with host-cell-active agents such as kinase inhibitors.

Wetzel|Dawn M|DM|0000-0002-3990-7043
Rhodes|Emma L|EL|
Li|Shaoguang|S|
McMahon-Pratt|Diane|D|
Koleske|Anthony J|AJ|

Src Kinase Phagocytosis Leishmania Macrophage Abl


Antibiotic use during repair of obstetrical anal sphincter injury: a quality improvement initiative.

Abstract:
OBJECTIVE
To evaluate the effects of a quality improvement initiative regarding the administration of antibiotics at the time of obstetric anal sphincter injury (OASIS) repair.

METHODS
At University of Michigan-a tertiary care center in Ann Arbor, MI, USA, we implemented a quality improvement intervention aimed at administering a single dose of broad-spectrum antibiotics at the time of OASIS repair. Best practice recommendations and reminders were presented to the department. Cefazolin plus metronidazole or clindamycin plus gentamycin were the recommended antibiotics. The effects of this intervention were assessed based on a chart review of deliveries between January 4, 2014 and February 13, 2019, which included patient data both pre-initiative and post-initiative to compare the prevalence of antibiotic use at the time of OASIS repair.

RESULTS
Recommended antibiotic use increased from 0.3% (1/372) pre-initiative to 75.7% (106/140) post-initiative (P < 0.001), and any antibiotic use increased from 6.5% (24/372) to 82.9% (116/140, P < 0.001). The proportion of cases complicated by wound infection/breakdown decreased by 55% after the quality improvement intervention (3.2% pre-intervention vs 1.4% post-intervention, P = 0.22).

CONCLUSION
Following a departmental quality improvement intervention aimed at increasing antibiotic administration at the time of OASIS repair, antibiotic use increased 13-fold. Although underpowered to detect a significant difference in wound complications, our study showed a clinically meaningful decrease in wound infection/breakdown with antibiotic administration.

Cox|Caroline K|CK|
Bugosh|Meghan D|MD|
Fenner|Dee E|DE|
Smith|Roger|R|
Swenson|Carolyn W|CW|

obstetric anal sphincter injury
quality improvement
OASIS
antibiotic prophylaxis
postpartum infection
sphincter repair


Recent advances in preventing stroke recurrence.

Abstract: Recent advances in secondary stroke prevention include new evidence in hypertension, nutrition, anticoagulation, antiplatelet therapy, intracranial stenosis, percutaneous closure of patent foramen ovale, and lipid-lowering therapy. Individualized therapy for hypertension based on phenotyping with plasma renin and aldosterone markedly improves blood pressure control in patients with resistant hypertension. A Mediterranean diet can reduce the risk of stroke by nearly half. The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%. There are problems with clopidogrel that can be overcome by using ticagrelor, and new anticoagulant drugs markedly improve anticoagulation for stroke prevention, particularly in atrial fibrillation. There are pharmacokinetic problems with dabigatran that deserve attention. Intensive medical therapy is better than stenting for intracranial stenosis, and new therapies directed at proprotein convertase subtilisin-kexin type 9 (PCSK9) will revolutionize lipid-lowering therapy. In the past, it was estimated that rational therapy could reduce recurrent stroke by about 80%. With recent advances, we should be able to do even better.

stroke recurrence
hypertension
anticoagulation
antiplatelet
intracranial stenosis
diet
B12 deficiency
LDL cholesterol


Input and output organization of the mesodiencephalic junction for cerebro-cerebellar communication.

Abstract: Most studies investigating the impact of the cerebral cortex (CC) onto the cerebellum highlight the role of the pons, which provides the mossy fibers to the cerebellum. However, cerebro-cerebellar communication may also be mediated by the nuclei of the mesodiencephalic junction (MDJ) that project to the inferior olive (IO), which in turn provides the climbing fibers to the molecular layer. Here, we uncover the precise topographic relations of the inputs and outputs of the MDJ using multiple, classical, and transneuronal tracing methods as well as analyses of mesoscale cortical injections from Allen Mouse Brain. We show that the caudal parts of the CC predominantly project to the principal olive via the rostral MDJ and that the rostral parts of the CC predominantly project to the rostral medial accessory olive via the caudal MDJ. Moreover, using triple viral tracing technology, we show that the cerebellar nuclei directly innervate the neurons in the MDJ that receive input from CC and project to the IO. By unraveling these topographic and prominent, mono- and disynaptic projections through the MDJ, this work establishes that cerebro-cerebellar communication is not only mediated by the pontine mossy fiber system, but also by the climbing fiber system.

Wang|Xiaolu|X|
Novello|Manuele|M|
Gao|Zhenyu|Z|
Ruigrok|Tom J H|TJH|
De Zeeuw|Chris I|CI|

cerebral cortex
mesodiencephalic junction (MDJ)
inferior olive
climbing fiber
cerebellar nuclei
RRID:SCR_001622
RRID:SCR_002798


Effects of berberine and cinnamic acid on palmitic acid-induced intracellular triglyceride accumulation in NIT-1 pancreatic β cells.

Abstract:
OBJECTIVE
To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells.

METHODS
Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction.

RESULTS
PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study.

CONCLUSION
It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.

Zhao|Li|L| Jiang|Shu-Jun|SJ| Lu|Fu-Er|FE| Xu|Li-Jun|LJ| Zou|Xin|X| Wang|Kai-Fu|KF| Dong|Hui|H|

berberine
cinnamic acid
Jiaotai Pill
palmitic acid
lipid
NIT-1 cells
Chinese medicine


Adjusting for unmeasured confounding using validation data: Simplified two-stage calibration for survival and dichotomous outcomes.

Abstract: In epidemiology, one typically wants to estimate the risk of an outcome associated with an exposure after adjusting for confounders. Sometimes, outcome and exposure and maybe some confounders are available in a large data set, whereas some important confounders are only available in a validation data set that is typically a subset of the main data set. A generally applicable method in this situation is the two-stage calibration (TSC) method. We present a simplified easy-to-implement version of the TSC for the case where the validation data are a subset of the main data. We compared the simplified version to the standard TSC version for incidence rate ratios, odds ratios, relative risks, and hazard ratios using simulated data, and the simplified version performed better than our implementation of the standard version. The simplified version was also tested on real data and performed well.

Hjellvik|Vidar|V|0000-0002-2379-9906
De Bruin|Marie L|ML|
Samuelsen|Sven O|SO|
Karlstad|Øystein|Ø|
Andersen|Morten|M|
Haukka|Jari|J|0000-0003-1450-6208
Vestergaard|Peter|P|
de Vries|Frank|F|
Furu|Kari|K|

unmeasured confounding
validation data
two-stage calibration
epidemiology
bias correction


Propagation of Gaussian and Laguerre-Gaussian vortex beams through mouse brain tissue.

Abstract: Light transmission of Gaussian (G) and Laguerre-Gaussian (LG) vortex beams in mouse brain tissue is investigated. Transmittance is measured with different orbital angular momentums (OAM) at various tissue thicknesses. In both ballistic and diffusive regions, transmittances of G and LG beams show no significant difference. The transition point from ballistic to diffusive region for the mouse brain tissue is determined at about 480 μm. The observed transmittances of the G and LG beams show independence on OAM modes, which may be attributed to poorly understood interference effects from brain tissue.

Shi|Lingyan|L| Lindwasser|Lukas|L| Wang|Wubao|W| Alfano|Robert|R| Rodríguez-Contreras|Adrián|A|

propagation
vortex
brain
Laguerre Gaussian beam
ballistic light


The Microbiota of the Extremely Preterm Infant.

Abstract: Colonization of the extremely preterm infant's gastrointestinal tract and skin begins in utero and is influenced by a variety of factors, the most important including gestational age and environmental exposures. The composition of the intestinal and skin microbiota influences the developing innate and adaptive immune responses with short-term and long-term consequences including altered risks for developing necrotizing enterocolitis, sepsis, and a wide variety of microbe-related diseases of children and adults. Alteration of the composition of the microbiota to decrease disease risk is particularly appealing for this ultra-high-risk cohort that is brand new from an evolutionary standpoint.

Microbiota
Skin
Necrotizing enterocolitis
Dysbiosis
Intestinal tract
Late-onset sepsis
Oral cavity


Diosgenin attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.

Abstract: Activation of hepatic stellate cells (HSC) plays a pivotal role in the development of hepatic fibrosis. Transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor responsible for the activation of HSC. Diosgenin is a steroidal saponin found in several plants including Solanum and Dioscorea species, and it inhibited high glucose-induced renal tubular fibrosis. However, the effects of diosgenin against hepatic fibrosis remain elusive. Therefore, in this study, we investigated the effects of diosgenin on TGF-β1-induced HSCs and elucidate the possible mechanism of its anti-fibrotic effect. Our results demonstrated that diosgenin inhibited TGF-β1-induced HSC proliferation, reduced the expression of collagen I and α-smooth muscle actin (α-SMA), as well as the expression of TGF-β receptor I (TGF-β RI) and II. Moreover, diosgenin suppressed TGF-β1-induced phosphorylation of Smad3 in HSCs. In conclusion, our data demonstrate that diosgenin inhibited HSC-T6 cell proliferation and activation, at least in part, via the TGF-β1/Smad signaling pathway. These results provide that diosgenin may have potential to treat liver fibrosis.

Xie|Wei-Lin|WL| Jiang|Rong|R| Shen|Xiao-Lu|XL| Chen|Zhi-Yu|ZY| Deng|Xiao-Ming|XM|

Diosgenin
hepatic stellate cells (HSC)
transforming growth factor-β1 (TGF-β1)


Assessment spermatogenic cell apoptosis and the transcript levels of metallothionein and p53 in Meretrix meretrix induced by cadmium.

Abstract: Cadmium (Cd) has been widely used in industry and can accumulate in the water, soil, and food. Meretrix meretrix is one of the marine shellfishes cultivated for economic purpose in China. The increasing Cd levels in coastal marine water could adversely affect the economic benefits of shellfish cultivation. In the present study, M. meretrix were exposed to different Cd2+ concentrations (0, 1.5, 3, 6, and 12 mg L-1) for 5 d to evaluate the effects of Cd on spermatogenic cell. The Cd accumulation, survival rate and the indices of oxidative stress and apoptosis were determined in the spermatogenic cells of M. meretrix. The expression levels of p53 and metallothionein (MT) mRNA were also measured in the spermatogenic cells. Cd accumulation and the mortality rate of spermatogenic cells were found to increase in a dose-response manner with Cd2+ concentrations. Histopathology changes, especially the damage of membranous structure, were more severe as the Cd2+ levels in the testis became higher. The indexes of oxidative stress, including reactive oxygen species, malondialdehyde, protein carbonyl derivates and DNA-protein crosslinks all increased after exposure to Cd2+. However, the total antioxidant capacity gradually decreased with the increasing Cd2+ concentration. In addition, exposure to Cd2+ increased the apoptotic rate and caspase-3 and 9 activities but decreased the level of mitochondrial membrane potential and cytochrome C oxidase in the spermatogenic cells. MT mRNA expression increased in lower Cd2+ concentration treated groups whereas decreased in higher groups, while the p53 mRNA expression increased in a dose-response manner with Cd2+ and was positively correlated with the oxidative damage indices. These results indicated that Cd2+ caused oxidative stress and p53 induced apoptosis in the spermatogenic cells, and thus decreased the survival rate of sperm cells. This finding highlights that Cd can reduce the reproductive capacity of M. meretrix, thus threatening to wild shellfish populations and reducing the efficiency of shellfish farming.

Gao|Yilu|Y|
Hong|Jiameng|J|
Guo|Yuke|Y|
Chen|Mengxu|M|
Chang|Alan K|AK|
Xie|Lei|L|
Ying|Xueping|X|

Spermatogenic cell
Apoptosis
Meretrix meretrix
Cd
Gene expression


Differentially Methylated Region-Representational Difference Analysis (DMR-RDA): A Powerful Method to Identify DMRs in Uncharacterized Genomes.

Abstract: Over the last years, it has become increasingly clear that environmental influences can affect the epigenomic landscape and that some epigenetic variants can have heritable, phenotypic effects. While there are a variety of methods to perform genome-wide analyses of DNA methylation in model organisms, this is still a challenging task for non-model organisms without a reference genome. Differentially methylated region-representational difference analysis (DMR-RDA) is a sensitive and powerful PCR-based technique that isolates DNA fragments that are differentially methylated between two otherwise identical genomes. The technique does not require special equipment and is independent of prior knowledge about the genome. It is even applicable to genomes that have high complexity and a large size, being the method of choice for the analysis of plant non-model systems.

Epigenetics
DNA methylation
Complex genomes
Genome comparison
Genome representation
Non-model plants
Polymerase chain reaction
Subtractive hybridization


Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

Abstract:
BACKGROUND
The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMS patients in relation to cognition.

METHODS
In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMS patients (11 males, mean age 51.2 ± 11.9 years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8 years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient.

RESULTS
When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMS patients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMS patients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = - 0.393; p = 0.03).

CONCLUSION
PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.

Cocozza|Sirio|S|
Pontillo|Giuseppe|G|
Russo|Camilla|C|
Russo|Cinzia Valeria|CV|
Costabile|Teresa|T|
Pepe|Alessio|A|
Tedeschi|Enrico|E|
Lanzillo|Roberta|R|
Brescia Morra|Vincenzo|V|
Brunetti|Arturo|A|
Inglese|Matilde|M|
Petracca|Maria|M|

D020528:Multiple Sclerosis, Chronic Progressive

Cerebellum
Progressive multiple sclerosis
Functional connectivity
Resting state fMRI


Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders.

Abstract: Opioid peptides released during digestion of dietary proteins such as casein, were suggested to contribute to autism development, leading to the announcement of opioid excess hypothesis of autism. This paper examines role of enzyme proline dipeptidyl peptidase-4 (DPPIV; EC 3.4.14.5) and it is exogenous substrate, β-casomorphin-7 (BCM7) in autism etiology. Our study included measurements of DPPIV and BCM7 concentrations in serum and urine, which were analyzed with ELISA assays and activity of DPPIV was measured by colorimetric test. The effect of opioid peptides from hydrolysed bovine milk on DPPIV gene expression in peripheral blood mononuclear cells (PBMC) in autistic and healthy children was determined using the Real-Time PCR (Polymerase Chain Reaction) method. Our research included 51 healthy children and 86 children diagnosed with autism spectrum disorder (ASD, ICDF84). We determined that the concentration of BCM7 in serum was significantly, 1.6-fold, higher in the ASD group than in controls (p < 0.0001). Concentration of DPPIV was found to also be significantly higher in serum from ASD children compared to the control group (p < 0.01), while we did not notice significant difference in enzymatic activity of serum DPPIV between the two study groups. We confirmed correlation according to the gender between analyzed parameters. The inspiration for this study emanated from clinical experience of the daily diet role in relieving the symptoms of autism. Despite this, we have concluded that milk-derived opioid peptides and DPPIV are potentially factors in determining the pathogenesis of autism; conducted studies are still limited and require further research.

proline dipeptidyl peptidase-4
autism spectrum disorder
β-casomorphin-7
bovine milk
food allergy


Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

Abstract: Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

Laura|Bongiovanni|B|
Nicola|Di Girolamo|DG|
Alessandro|Montani|M|
Leonardo|Della Salda|DS|
Paolo|Selleri|S|

Civet
Viverridae
Diet
Necrotizing pancreatitis


Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

Abstract: Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits.

D065908:Transcranial Direct Current Stimulation

Transcranial direct current stimulation
Dorsolateral prefrontal cortex
Self-regulation
Affective picture appraisal
Cigarette craving
Cognitive control


Antagonistic Effect of Short Neuropeptide F on Allatotropin-Inhibited Feeding Motivation of the Silkworm Larva, Bombyx mori.

Abstract: Here, we demonstrated an antagonistic effect of short neuropeptide F (sNPF) in modulating feeding motivation in the silkworm Bombyx mori; sNPF reduced the feeding-delaying effects caused by administration of an inhibitory peptide, allatotropin (AT). In situ hybridization and MALDI-TOF MS analysis revealed the presence of three subtypes of sNPFs (sNPF-1, -2, and -3) in the midgut enteroendocrine cells. Ca2+-imaging analyses revealed that three subtypes of sNPF receptors (sNPFRs) (BNGR-A7, -A10, and -A11) showed different affinities with the three subtypes of sNPFs. In addition, sNPF activated its signaling via ERK phosphorylation in the midgut, while mixture of sNPF and AT reduced the phosphorylation level, agreeing with the results of behavioral assay. Together, our current findings suggest that intestinal sNPF positively modulates the feeding motivation by reducing the inhibitory effects by AT within the midgut.

Matsumoto|Sumihiro|S| Ohara|Ayako|A| Nagai-Okatani|Chiaki|C| Zhou|Yi-Jun|YJ| Fujinaga|Daiki|D| Seike|Hitomi|H| Nagata|Shinji|S|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

antagonistic effect
short neuropeptide F
feeding motivation
Bombyx mori
allatotropin
BNGRs


Intratumoral lactate metabolism in Barrett's esophagus and adenocarcinoma.

Abstract:
BACKGROUND
Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions.

RESULTS
Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0-3.1). MTCO1 expression was not correlated to clinicopathological variables or survival.

MATERIALS AND METHODS
MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated.

CONCLUSIONS
Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.

Huhta|Heikki|H|
Helminen|Olli|O|
Palomäki|Sami|S|
Kauppila|Joonas H|JH|
Saarnio|Juha|J|
Lehenkari|Petri P|PP|
Karttunen|Tuomo J|TJ|


Current perspective on eicosanoids in asthma and allergic diseases: EAACI Task Force consensus report, part I.

Abstract: Eicosanoids are biologically active lipid mediators, comprising prostaglandins, leukotrienes, thromboxanes, and lipoxins, involved in several pathophysiological processes relevant to asthma, allergies, and allied diseases. Prostaglandins and leukotrienes are the most studied eicosanoids and established inducers of airway pathophysiology including bronchoconstriction and airway inflammation. Drugs inhibiting the synthesis of lipid mediators or their effects, such as leukotriene synthesis inhibitors, leukotriene receptors antagonists, and more recently prostaglandin D2 receptor antagonists, have been shown to modulate features of asthma and allergic diseases. This review, produced by an European Academy of Allergy and Clinical Immunology (EAACI) task force, highlights our current understanding of eicosanoid biology and its role in mediating human pathology, with a focus on new findings relevant for clinical practice, development of novel therapeutics, and future research opportunities.

asthma
lipid mediators
prostaglandins
leukotrienes
inflammation
food allergy
rhinitis


Comparison in Quantities from Including Angles Comprising Lines of Hypha Themselves in Histological Images between Mucorales and Aspergillus.

Abstract:
BACKGROUND
The rate of aspergillosis has decreased due to improvements in therapy. The rate of mucormycosis, however, has gradually increased in recent years. Both aspergillosis and mucormycosis produce histologically similar hyphae, pointing to the need for an objective tool to distinguish between them.

METHODS
Three aspergillosis cases and three mucormycosis cases were selected from autopsy cases in our hospital. Representative histological images were captured and hyphal angles in extravascular and intravascular lesions were calculated.

RESULTS
For both extravascular and intravascular lesions, the average hyphal angle of aspergillosis was acute, and the standard deviation was less than that of mucormycosis. In aspergillosis, the average hyphal angle for extravascular lesions was acute, and the standard deviation was less than that for intravascular lesions. However, for mucormycosis, there was no significant difference in both the average and standard deviation of the hyphal angles.

CONCLUSION
Surgical pathologists should carefully examine the histological characteristics of the fungus to correctly identify specimens and be able to administer proper therapies.

Tochigi|Naobumi|N| Sadamoto|Sota|S| Shinozaki|Minoru|M| Wakayama|Megumi|M| Shibuya|Kazutoshi|K|


Clinical study of apatinib combined with EGFR-TKI in the treatment of chronic progression after EGFR-TKI treatment in non-small cell lung cancer (ChiCTR1800019185).

Abstract: This clinical trial (ChiCTR1800019185) is designed to be an open-label, prospective, single-center, single arm exploratory research study. The study will recruit non-small cell lung cancer patients (NSCLC) with slow progression after first-line treatment with EGFR-TKI drugs. Slow progression will be confirmed by the presence of serum carcinoembryonic antigen or imaging evaluation. The primary aim is to assess progression-free survival after EGFR-TKIs treatment combined with apatinib 250 mg once daily. The secondary objectives are to evaluate objective efficacy, disease control rates, quality of life, overall survival, and safety. From September 2018 to September 2020, under specific entry and discharge standards, we plan to enroll 38 eligible patients until the end of the study. We hope that our study will help to explore a new way of combining the small molecular inhibitors of antiangiogenesis with EGFR-TKIs to overcome acquired drug resistance.

Li|Xin|X| Liu|Minghui|M| Zhang|Hongbing|H| Liu|Hongyu|H| Chen|Jun|J|0000-0002-2362-5359

D000971:Antineoplastic Combined Chemotherapy Protocols

Apatinib
EGFR-TKIs
non-small cell lung cancer
slow progression


Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases.

Abstract: Alpha-lipoic acid is a naturally occurring substance, essential for the function of different enzymes that take part in mitochondria's oxidative metabolism. It is believed that alpha-lipoic acid or its reduced form, dihydrolipoic acid have many biochemical functions acting as biological antioxidants, as metal chelators, reducers of the oxidized forms of other antioxidant agents such as vitamin C and E, and modulator of the signaling transduction of several pathways. These above-mentioned actions have been shown in experimental studies emphasizing the use of alpha-lipoic acid as a potential therapeutic agent for many chronic diseases with great epidemiological as well economic and social impact such as brain diseases and cognitive dysfunctions like Alzheimer disease, obesity, nonalcoholic fatty liver disease, burning mouth syndrome, cardiovascular disease, hypertension, some types of cancer, glaucoma and osteoporosis. Many conflicting data have been found concerning the clinical use of alpha-lipoic acid in the treatment of diabetes and of diabetes-related chronic complications such as retinopathy, nephropathy, neuropathy, wound healing and diabetic cardiovascular autonomic neuropathy. The most frequent clinical condition in which alpha-lipoic acid has been studied was in the management of diabetic peripheral neuropathy in patients with type 1 as well type 2 diabetes. Considering that oxidative stress, a imbalance between pro and antioxidants with excessive production of reactive oxygen species, is a factor in the development of many diseases and that alpha-lipoic acid, a natural thiol antioxidant, has been shown to have beneficial effects on oxidative stress parameters in various tissues we wrote this article in order to make an up-to-date review of current thinking regarding alpha-lipoic acid and its use as an antioxidant drug therapy for a myriad of diseases that could have potential benefits from its use.

Gomes|Marilia Brito|MB|
Negrato|Carlos Antonio|CA|

Alpha-lipoic acid
Chronic diseases
Biochemical action
Diabetes mellitus


Finally making sense of the double-slit experiment.

Abstract: Feynman stated that the double-slit experiment "…has in it the heart of quantum mechanics. In reality, it contains the only mystery" and that "nobody can give you a deeper explanation of this phenomenon than I have given; that is, a description of it" [Feynman R, Leighton R, Sands M (1965) The Feynman Lectures on Physics]. We rise to the challenge with an alternative to the wave function-centered interpretations: instead of a quantum wave passing through both slits, we have a localized particle with nonlocal interactions with the other slit. Key to this explanation is dynamical nonlocality, which naturally appears in the Heisenberg picture as nonlocal equations of motion. This insight led us to develop an approach to quantum mechanics which relies on pre- and postselection, weak measurements, deterministic, and modular variables. We consider those properties of a single particle that are deterministic to be primal. The Heisenberg picture allows us to specify the most complete enumeration of such deterministic properties in contrast to the Schrödinger wave function, which remains an ensemble property. We exercise this approach by analyzing a version of the double-slit experiment augmented with postselection, showing that only it and not the wave function approach can be accommodated within a time-symmetric interpretation, where interference appears even when the particle is localized. Although the Heisenberg and Schrödinger pictures are equivalent formulations, nevertheless, the framework presented here has led to insights, intuitions, and experiments that were missed from the old perspective.

Aharonov|Yakir|Y|
Cohen|Eliahu|E|
Colombo|Fabrizio|F|
Landsberger|Tomer|T|
Sabadini|Irene|I|
Struppa|Daniele C|DC|
Tollaksen|Jeff|J|

Heisenberg picture
double slit experiment
modular momentum
two-state vector formalism


Adopting an external focus of attention alters intracortical inhibition within the primary motor cortex.

Abstract:
AIM
Although it is well established that an external (EF) compared to an internal (IF) or neutral focus of attention enhances motor performance, little is known about the underlying neural mechanisms. This study aimed to clarify whether the focus of attention influences not only motor performance but also activity of the primary motor cortex (M1) when executing identical fatiguing tasks of the right index finger (first dorsal interosseous). Transcranial magnetic stimulation (TMS) at intensities below motor threshold was applied over M1 to assess and compare the excitability of intracortical inhibitory circuits.

METHODS
In session 1, 14 subjects performed an isometric finger abduction at 30% of their maximal force to measure the time to task failure (TTF) with either an IF or EF. In session 2, the same task was performed with the other focus. In sessions 3 and 4, subthreshold TMS (subTMS) and paired-pulse TMS were applied to the contralateral M1 to compare the activity of cortical inhibitory circuits within M1 during EF and IF.

RESULTS
With an EF, TTF was significantly prolonged (P = 0.01), subTMS-induced electromyographical suppression enhanced (P = 0.001) and short-interval intracortical inhibition (SICI) increased (P = 0.004).

CONCLUSION
The level of intracortical inhibition was previously shown to influence motor performance. Our data shed new light on the ability to instantly modulate the activity of inhibitory circuits within M1 by changing the type of attentional focus. The increased inhibition with EF might contribute to the better movement efficiency, which is generally associated with focusing externally.

Kuhn|Y-A|YA| Keller|M|M| Ruffieux|J|J| Taube|W|W|

motor cortex
transcranial magnetic stimulation
time to task failure
short-interval intracortical inhibition
cognitive manipulation
movement control


A role for activated Cdc42 in glioblastoma multiforme invasion.

Abstract: Cdc42 is a Rho-GTPase which plays a major role in regulating cell polarity and migration by specifying the localization of filopodia. However, the role of Cdc42 in GBM invasion has not been thoroughly investigated. We generated stable doxycycline-inducible clones expressing wild type (WT)-, constitutively active (CA)-, and dominant negative (DN)-Cdc42 in three different human glioma cell lines. Expression of CA-Cdc42 significantly increased the migration and invasive properties of malignant glioma cells compared to WT and DN-Cdc42 cell clones, and this was accompanied by a greater number of filopodia and focal adhesion structures which co-localize with phosphorylated focal adhesion kinase (FAK). By mass spectrometry and immunoprecipitation studies, we demonstrated that activated Cdc42 binds to IQGAP1. When implanted orthotopically in mice, the CA-Cdc42 expressing glioma cells exhibited enhanced local migration and invasion, and led to larger tumors, which significantly reduced survival. Using the Cancer Genome Atlas dataset, we determined that high Cdc42 expression is associated with poorer progression free survival, and that Cdc42 expression is highest in the proneural and neural subgroups of GBM. In summary, our studies demonstrate that activated Cdc42 is a critical determinant of the migratory and invasive phenotype of malignant gliomas, and that its effect may be mediated, at least in part, through its interaction with IQGAP1 and phosphorylated FAK.

Okura|Hidehiro|H|
Golbourn|Brian J|BJ|
Shahzad|Uswa|U|
Agnihotri|Sameer|S|
Sabha|Nesrin|N|
Krieger|Jonathan R|JR|
Figueiredo|Carlyn A|CA|
Chalil|Alan|A|
Landon-Brace|Natalie|N|
Riemenschneider|Alexandra|A|
Arai|Hajime|H|
Smith|Christian A|CA|
Xu|Songli|S|
Kaluz|Stefan|S|
Marcus|Adam I|AI|
Van Meir|Erwin G|EG|
Rutka|James T|JT|

D015972:Gene Expression Regulation, Neoplastic

cdc42
glioblastoma
invasion
migration
IQGAP1 and pFAK


Mixed chimerism and graft loss in pediatric recipients of an alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease.

Abstract:
BACKGROUND
Reduced-intensity conditioning (RIC) regimens can mitigate the toxicity of hematopoietic cell transplantation (HCT) in children with non-malignant diseases, but are associated with increased risk for post-transplant mixed donor/recipient chimerism (MC) and/or graft loss (GL). Intervention with donor lymphocytes or stem cell boosts (DLI/boost) may be necessary, but there is limited information about timing and results of intervention.

PROCEDURE
We retrospectively evaluated 31 consecutive pediatric recipients of an alemtuzumab-based RIC HCT at the Children's Hospital of Philadelphia from May 2007 to December 2012 to determine the incidence of MC, GL, and use of DLI/boost. All patients received alemtuzumab with either fludarabine (150 mg/m(2) )/melphalan (140 mg/m(2) ) (n = 30) or fludarabine/busulfan (n = 1), and unmanipulated marrow grafts from related (48%) or matched unrelated (52%) donors.

RESULTS
Of surviving patients, 67% and 44% displayed MC and MC with ≤80% donor contribution (MC ≤ 80%), respectively. Rates of MC, MC ≤ 80%, DLI/boost, and GL were significantly higher in recipients of proximal/intermediate (100%, 73%, 46%, and 46%, respectively) compared to distal alemtuzumab (44%, 25%, 6%, and 6%, respectively). Event-free and overall survival was significantly lower in HLH compared with non-HLH patients. Twenty percent of patients required DLI/boost, and DLI/boost did not affect the incidence of GL.

CONCLUSIONS
RIC with proximal/intermediate alemtuzumab is associated with high rates of MC, need for DLI/boost, and GL.

Oshrine|Benjamin R|BR|
Olson|Timothy S|TS|
Bunin|Nancy|N|

D018380:Hematopoietic Stem Cell Transplantation

reduced-intensity conditioning
non-malignant disease
alemtuzumab
CAMPATH
bone marrow transplant