Retrospective study of maternal and neonatal outcomes after induction compared to spontaneous start of labour in women with one previous birth in uncomplicated pregnancies ≥ 41+3.

Abstract:
Objectives
To study the association between induction and outcome among two-parous women in uncomplicated pregnancies ≥ 41+3, stratified by first labour delivery mode and conditions present at first delivery.

Methods
The Swedish Medical Birth Register was used to identify 58,964 uncomplicated singleton pregnancies among women with one previous birth between 1998 and 2014. Women with any registered pregnancy complications were excluded to minimise the risk for indication bias. The outcomes considered were emergency caesarean section (CS), and poor neonatal outcome (Apgar score <7 at 5 min, neonatal death, or meconium aspiration).

Results
Women who were induced at their second labour had higher emergency CS rates compared to women in spontaneously started deliveries (adjusted risk ratio, ARR: 2.11; 95% CI: 2.00-2.23). Low Apgar score was more common after induction compared to spontaneously started labours (1.0 vs. 0.7%) (ARR: 1.44; 95% CI: 1.18-1.77). Increased CS rates were also found when comparing induction at 41 + 3 to 41 + 6 weeks to labour at 42 weeks or more, regardless of labour start (ARR 1.39; 95% CI: 1.26-1.52).

Conclusions
We found an increased risk of CS and poor neonatal outcome after second labour induction in prolonged pregnancies. The second labour vaginal success rate after induction was highly dependent, on first labour delivery mode, but also on diagnoses and conditions present at the first delivery.

induction
delivery mode
caesarean section
late term pregnancy
neonatal morbidity
parity
post-term pregnancy


Noninvasive assessments of skin glycated proteins by fluorescence and Raman techniques in diabetics and nondiabetics.

Abstract: Diabetes is a complex metabolic disease and has chronic complications. It has been considered a serious public health problem. The aim of the current study was to evaluate skin glycated proteins through fluorescence and Raman techniques. One hundred subjects were invited to participate in the study. Six volunteers did not attend due to exclusion criteria or a change of mind about participating. Therefore, 94 volunteers were grouped according to age range (20-80 years), health condition (nondiabetic, with insulin resistance [IR] and/or diabetic) and Fitzpatrick skin type (I-VI). The fluorescence spectrometer and the portable Raman spectroscopy system were used to measure glycated proteins from the skin. There was elevated skin autofluorescence in healthy middle-aged and elderly subjects, as well as in patients with IR and/or diabetes. Regarding Raman spectroscopy, changes in the skin hydration state, degradation of type I collagen and greater glycation were related for diabetes and chronological aging. Weak and positive correlation between the skin autofluorescence and the Raman peaks ratio (855/876) related to the glycated proteins was also found. Raman spectroscopy shows several bands for spectral analyses, complementing the fluorescence data. Therefore, this study contributes to understanding of the optical of human skin for noninvasive diabetes screening.

skin
glycation
fluorescence
diabetes
Raman spectroscopy


Economic Burden of Osteoporotic Fracture of the Elderly in South Korea: A National Survey.

Abstract:
BACKGROUND
Osteoporotic fractures (OFs) in the elderly are common worldwide, and the predicted number of the aging population is increasing the burden of OF on health care systems.

OBJECTIVES
To estimate the economic burden of OF in people older than 65 years in South Korea from a societal perspective.

METHODS
National Health Insurance claim databases were used to analyze health care utilization and medical costs of OF in the Korean population (49 million). We identified medical claims records with a diagnosis of OF and estimated the costs from 2007 to 2011.

RESULTS
From 2007 to 2011, there were 244,798 patients with at least one medical insurance claim related to OF. Most patients had a single fracture (80%), whereas 20% of all patients had two or more. For fracture sites, vertebral fracture accounted for 75.6% of all fractures, followed by hip and wrist fractures. The societal cost of OF increased annually, from US $88.8 million in 2007 to US $149.3 million in 2011. Among the entire cost, the direct medical cost was US $134.9 million in 2011, which includes the cost of treatment (US $91.2 million) and long-term care (US $48.1 million). The direct nonmedical cost was US $9.9 million in 2011. Costs associated with morbidity and mortality of OF were excluded.

CONCLUSIONS
The economic burden associated with OF in elderly is expected to rise with the predicted increase in life expectancy and the number of elderly in South Korea. Therefore, effective management of the disease is necessary to reduce the growth in the economic burden of OF.

Kim|Jinhyun|J|
Lee|Eunhee|E|
Kim|Sungjae|S|
Lee|Tae Jin|TJ|

D000368:Aged
D017281:Cost of Illness
D017048:Health Care Costs
D006801:Humans
D058866:Osteoporotic Fractures
D056910:Republic of Korea
D016103:Spinal Fractures
D011795:Surveys and Questionnaires

economic burden
osteoporotic fracture
osteoporosis


Which inorganic structures are the most complex?

Abstract: The discovery of the diffraction of X-rays on crystals opened up a new era in our understanding of nature, leading to a multitude of striking discoveries about the structures and functions of matter on the atomic and molecular scales. Over the last hundred years, about 150,000 of inorganic crystal structures have been elucidated and visualized. The advent of new technologies, such as area detectors and synchrotron radiation, led to the solution of structures of unprecedented complexity. However, the very notion of structural complexity of crystals still lacks an unambiguous quantitative definition. In this Minireview we use information theory to characterize complexity of inorganic structures in terms of their information content.

inorganic structures
structural complexity
information theory
crystallography
structural elucidation


Interactions among variants in P53 apoptotic pathway genes are associated with neurologic deterioration and functional outcome after acute ischemic stroke.

Abstract:
OBJECTIVE
Neurologic deterioration (ND) and functional outcome after ischemic stroke (IS) are not accurately predicted by clinical pictures on admission. The aim of present study was to investigate the association of variants in P53 apoptotic pathway genes with ND and functional outcome after IS.

METHODS
Genotypes of nine variants in apoptosis-relevant genes were measured in patients with acute IS. Gene-gene interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). The primary outcome was ND. ND was diagnosed in patients who worsened ≥2 points (National Institutes of Health Stroke Scale [NIHSS] score) within the first 10 days of stroke onset. The secondary outcome was functional status at 90 days after IS as measured by modified Rankin Scale (mRS) score.

RESULTS
A total of 705 enrolled patients, ND occurred in 174 (24.7%) patients, and 184 (26.1%) patients were poor functional outcome (mRS score > 2). Although the nine variants were not significantly associated with ND and functional outcome by univariate analysis, there was a gene-gene interaction among P53rs1042522, MDM-2rs2279744, and MMP-9 rs3918242 using GMDR analysis. The high-risk interaction among the three variants was independently associated with higher risk of ND (HR, 2.04, 95% CI: 1.22-5.64, p = .018) and poor functional outcome (OR, 2.68, 95% CI: 1.68-7.86, p = .004) after adjusting for the covariates.

CONCLUSION
The interactions among P53 rs1042522, MDM-2 rs2279744, and MMP-9 rs3918242 may increase the risk of ND and poor functional outcome and may be considered as a genetic marker of predicting ND and poor functional outcome after stroke.

Yi|Xingyang|X|0000-0002-1901-5486 Zhou|Qiang|Q| Sui|Guo|G| Ren|Gaoping|G| Tan|Lili|L| Li|Jie|J| Lin|Jing|J| Bao|Shaozhi|S|

D002545:Brain Ischemia
D006801:Humans
D000083242:Ischemic Stroke
D020780:Matrix Metalloproteinase 9
D051736:Proto-Oncogene Proteins c-mdm2
D012307:Risk Factors
D020521:Stroke
D016159:Tumor Suppressor Protein p53


Modified "parachute technique" of partial penectomy: A penile preservation surgery for carcinoma penis.

Abstract: Carcinoma penis is a rare malignancy which mostly occurs after the sixth decade of life. It is managed surgically and partial penectomy is the most common procedure done in carcinoma involving the distal penis. Partial penectomy provides the opportunity of preservation of sexual function and enables the patient to micturate in standing position. The conventional technique of neourethra creation in partial penectomy is slitting the urethra dorsally. We propose an alternative approach to neourethra formation. Technique involves ventral slitting of the urethra followed by suturing which begins at the ventral aspect and continued in a parachute fashion toward the dorsal end. This new technique will help primary physicians and surgeons in providing better surgical results in caring for patients with carcinoma penis.

Ranjan|Satish K|SK|
Ghorai|Rudra P|RP|
Kumar|Sunil|S|
Usha|Preeti|P|
Panwar|Vikas K|VK|
Kundal|Ashikesh|A|

partial penectomy
penile preservation
Carcinoma penis
modified parachute technique


Recent advances in the diagnosis and management of interstitial pneumonia with autoimmune features: the perspective of rheumatologists.

Abstract: Interstitial pneumonia with autoimmune feature (IPAF) is a recently established disease entity that is comprised of interstitial lung diseases with evidence of autoimmune features but that does not fulfill the criteria for definite autoimmune rheumatic diseases. The classification criteria for IPAF were defined by the European Respiratory Society and American Thoracic Society in 2015. However, further studies to establish IPAF subgroups and treatment modalities for each subgroup are still needed. In this review, we discuss recent advances regarding IPAF and raise critical points for the diagnosis and management of patients with IPAF from the perspective of rheumatologists.

Min|Hong Ki|HK|
Kim|Se-Hee|SH|
Lee|Sang-Heon|SH|
Kim|Hae-Rim|HR|

Autoimmune diseases
Lung diseases, interstitial
Prognosis
Rheumatology
Therapy


Arteriosclerosis, Atherosclerosis, and Cardiovascular Health: Joint Relations to the Incidence of Cardiovascular Disease.

Abstract: [Figure: see text].

atherosclerosis
cardiovascular disease
aging
calcium
carotid-femoral pulse wave velocity


Melatonin in Traumatic Brain Injury and Cognition.

Abstract: Traumatic brain injury (TBI) is a leading cause of long-term disability and mortality in young adults. The devastating effects of TBI on emotion regulation, executive functioning, and cognition have been well-established, and recent research links TBI as a risk factor for neurodegenerative diseases such as Alzheimer's disease. Despite an increased focus on the long-term cognitive dysfunction associated with TBI, research into potential treatments has not yet generated consistent successful results in human subjects. Many foundational studies have analyzed the cellular and molecular events involved in the inflammatory and healing processes following TBI, enhancing our understanding of the mechanisms that may contribute to the progression of dementia and cognitive decline in these patients. In this review, we will discuss the emergent research on melatonin within the framework of neuroinflammation and oxidative stress resulting from TBI and possibly preventing further sequelae such as Alzheimer's disease. A literature review was conducted using standard search strategies to query the PubMed database. The following search terms were used with qualifiers of various combinations: TBI, traumatic brain injury, melatonin, treatment, dementia, Alzheimer's, cognition, and neurodegeneration. Selected studies included meta-analyses, literature reviews, and randomized controlled trials (RCT) that evaluated melatonin's role as a potential therapy to prevent post-TBI neurodegeneration, specifically the development of dementia and deficits in memory and cognition. Three independent reviewers assessed all articles for eligibility. After assessment for eligibility, 11 total studies were included. Much of the available data on melatonin in TBI has highlighted its significant neuroprotective and antiinflammatory effects, which can be significant in fighting against the neuroinflammatory processes indicated in neurodegeneration. In animal models, immunohistochemistry and histopathology have allowed researchers to study measures of cell injury such as inflammatory cytokines, edema, and markers of oxidative stress. Though the effects of melatonin in TBI appear to be mediated through mostly indirect mechanisms on inflammatory processes, some research has explored potential mechanisms that could be specific to melatonin. Animal model studies support that melatonin treatment after TBI significantly improves cognition and behavioral outcomes. However, clinical studies with human subjects are scarce. Beyond the apparent general antiinflammatory and antioxidant actions of melatonin, a review of the evidence identified some preliminary research that has suggested the significance of melatonin receptors specifically in TBI. While there is some evidence to suggest that melatonin is able to reduce post-TBI cognitive decline as measured by subject performance on memory tasks, there is a lack of longitudinal data on whether melatonin decreases the risk of developing dementia after TBI. Considering melatonin therapy's promising preclinical data, favorable safety profile, and accessibility, further studies are warranted to assess the effects of melatonin as a post-TBI therapy on human subjects.

Blum|Brian|B|
Kaushal|Shivani|S|
Khan|Sara|S|
Kim|Jae H|JH|
Alvarez Villalba|Clara L|CL|

melatonin
traumatic brain injury
alzheimer's disease
dementia
brain awareness
cl psychiatry
geriatric psychiatry
inflammation
neurology
psychiatry


Epidemiology of Peripheral Artery Disease and Polyvascular Disease.

Abstract: Atherosclerotic lower extremity peripheral artery disease (PAD) is increasingly recognized as an important cause of cardiovascular morbidity and mortality that affects >230 million people worldwide. Traditional cardiovascular risk factors, including advanced age, smoking, and diabetes, are strongly linked to an increase risk of PAD. Although PAD has been historically underappreciated compared with coronary artery disease and stroke, greater attention on PAD in recent years has led to important new epidemiological insights in the areas of thrombosis, inflammation, dyslipidemia, and microvascular disease. In addition, the concept of polyvascular disease, or clinically evident atherosclerosis in multiple arterial beds, is increasingly identified as a particularly malignant cardiovascular disease worthy of special clinical attention and further study. It is noteworthy that PAD may increase the risk of adverse outcomes in similar or even greater magnitude than coronary disease or stroke. In this review, we highlight important new advances in the epidemiology of PAD with a particular focus on polyvascular disease, emerging biomarkers, and differential risk pathways for PAD compared with other atherosclerotic diseases.

epidemiology
peripheral artery disease
risk factors
smoking
vascular diseases


Large for gestational age and macrosomia in pregnancies without gestational diabetes mellitus.

Abstract: Objective: This study aims to estimate the prevalence and risk factors of macrosomia and LGA (large for gestational age) in non-GDM (gestational diabetes mellitus) pregnant women in Fuyang, Anhui Province of China.Methods: A large population-based cohort study was conducted among non-GDM pregnant women aged 18-45 years. Maternal sociodemographic data prior to pregnancy were collected using interviewer-administered standardized questionnaire. Maternal obstetrical delivery records and newborn hospital records were extracted from antenatal care booklets and hospital discharge abstracts. Logistic regression analysis was used to identify the predictors of macrosomia and LGA.Results: The incidence of macrosomia and LGA was 9.2 and 15.9%, respectively. Mothers ≥35 years of age (aOR 2.75, 95% CI 1.98, 3.80), male neonates (aOR 1.68, 95% CI 1.51, 1.89), overweight and obese (aOR 1.61, 95% CI 1.34, 1.92 and aOR 3.05, 95% CI 2.05, 4.56, respectively) were associated with increased risk of macrosomia. Compared with the less educated mothers, the educated mothers were more likely to have increased risk of macrosomia. IFA (iron and folic acid) supplements intake during pregnancy was more likely to deliver macrosomia or LGA (aOR1.32, 95% CI 1.08, 1.49 and aOR1.42, 95% CI 1.24, 1.61, respectively) as compared with no IFA supplements intake. SCr (serum creatinine concentration) >80 µmol/L was related to decreased risk of macrosomia (aOR 0.73, 95% CI 0.61, 0.86) and LGA (aOR 0.67, 95% CI 0.59, 0.77) as compared with normal range (44-80 µmol/L).Conclusions: There was a high prevalence of macrosomia and LGA in non-GDM pregnant women in China. Healthcare educations and reasonable body weight are necessary for pregnant women to prevent macrosomia and LGA. Pregnant women should be checked regularly and have the first prenatal visit as soon as possible.

Hua|Xiao-Guo|XG| Jiang|Wen|W| Hu|Rui|R| Hu|Cheng-Yang|CY| Huang|Kai|K| Li|Feng-Li|FL| Zhang|Xiu-Jun|XJ|

Large for gestational age
macrosomia
prevalence
risk factor
LGA


Detection of pork adulteration by highly-specific PCR assay of mitochondrial D-loop.

Abstract: We describe a highly specific PCR assay for the authentic identification of pork. Accurate detection of tissues derived from pig (Sus scrofa) was accomplished by using newly designed primers targeting porcine mitochondrial displacement (D-loop) region that yielded an unique amplicon of 712 base pairs (bp). Possibility of cross-amplification was precluded by testing as many as 24 animal species (mammals, birds, rodent and fish). Suitability of PCR assay was confirmed in raw (n = 20), cooked (60, 80 and 100 °C), autoclaved (121 °C) and micro-oven processed pork. Sensitivity of detection of pork in other species meat using unique pig-specific PCR was established to be at 0.1%; limit of detection (LOD) of pig DNA was 10 pg (pico grams). The technique can be used for the authentication of raw, processed and adulterated pork and products under the circumstances of food adulteration related disputes or forensic detection of origin of pig species.

Karabasanavar|Nagappa S|NS|
Singh|S P|SP|
Kumar|Deepak|D|
Shebannavar|Sunil N|SN|

D000818:Animals
D017931:DNA Primers
D004272:DNA, Mitochondrial
D005506:Food Contamination
D008460:Meat
D016133:Polymerase Chain Reaction
D034421:Sus scrofa


Abstract: Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnström, Å., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjöberg, J., Xu, D., Westerberg, L. S., Björkholm, M., Claesson, H.-E. Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation.

Han|Hongya|H|
Liang|Xiuming|X|
Ekberg|Monica|M|
Kritikou|Joanna S|JS|
Brunnström|Åsa|Å|
Pelcman|Benjamin|B|
Matl|Maria|M|
Miao|Xinyan|X|
Andersson|Margareta|M|
Yuan|Xiaotian|X|
Schain|Frida|F|
Parvin|Selina|S|
Melin|Eva|E|
Sjöberg|Jan|J|
Xu|Dawei|D|
Westerberg|Lisa S|LS|
Björkholm|Magnus|M|
Claesson|Hans-Erik|HE|

D015971:Gene Expression Regulation, Enzymologic

D000071176:Signaling Lymphocytic Activation Molecule Family

endocytosis
dermatitis
arachidonic acid
cell migration


Room-Temperature Formation of Highly Crystalline Multication Perovskites for Efficient, Low-Cost Solar Cells.

Abstract: A room-temperature perovskite material yielding a power conversion efficiency of 18.1% (stabilized at 17.7%) is demonstrated by judicious selection of cations. Both cesium and methylammonium are necessary for room-temperature formamidinium-based perovskite to obtain the photoactive crystalline perovskite phase and high-quality crystals. This room-temperature-made perovskite material shows great potential for low-cost, large-scale manufacturing such as roll-to-roll processing.

Matsui|Taisuke|T|
Seo|Ji-Youn|JY|
Saliba|Michael|M|
Zakeeruddin|Shaik M|SM|
Grätzel|Michael|M|

perovskite solar cells
room temperature perovskites


Sleep deprivation and false confessions.

Abstract: False confession is a major contributor to the problem of wrongful convictions in the United States. Here, we provide direct evidence linking sleep deprivation and false confessions. In a procedure adapted from Kassin and Kiechel [(1996) Psychol Sci 7(3):125-128], participants completed computer tasks across multiple sessions and repeatedly received warnings that pressing the "Escape" key on their keyboard would cause the loss of study data. In their final session, participants either slept all night in laboratory bedrooms or remained awake all night. In the morning, all participants were asked to sign a statement, which summarized their activities in the laboratory and falsely alleged that they pressed the Escape key during an earlier session. After a single request, the odds of signing were 4.5 times higher for the sleep-deprived participants than for the rested participants. These findings have important implications and highlight the need for further research on factors affecting true and false confessions.

Frenda|Steven J|SJ|
Berkowitz|Shari R|SR|
Loftus|Elizabeth F|EF|
Fenn|Kimberly M|KM|

sleep
sleep deprivation
false confession


A Longitudinal Examination of the Associations Between Shyness, Drinking Motives, Alcohol Use, and Alcohol-Related Problems.

Abstract:
BACKGROUND
The current study evaluated the roles of drinking motives and shyness in predicting problem alcohol use over 2 years.

METHODS
First-year college student drinkers (n = 818) completed assessments of alcohol use and related problems, shyness, and drinking motives every 6 months over a 2-year period.

RESULTS
Generalized linear mixed models indicated that shyness was associated with less drinking, but more alcohol-related problems. Further, shyness was associated with coping, conformity, and enhancement drinking motives, but was not associated with social drinking motives. However, when examining coping motives, moderation analyses revealed that social drinking motives were more strongly associated with coping motives among individuals higher in shyness. In addition, coping, conformity, and enhancement motives, but not social motives, mediated associations between shyness and alcohol-related problems over time. Finally, coping motives mediated the association between the interaction of shyness and social motives and alcohol-related problems.

CONCLUSIONS
Together, the results suggest that shy individuals may drink to reduce negative affect, increase positive affect, and fit in with others in social situations, which may then contribute to greater risk for subsequent alcohol-related problems.

Young|Chelsie M|CM|
DiBello|Angelo M|AM|
Traylor|Zachary K|ZK|
Zvolensky|Michael J|MJ|
Neighbors|Clayton|C|

Coping Motives
Enhancement Motives
Social Motives
Conformity Motives
Social Anxiety


MOF-Beads Containing Inorganic Nanoparticles for the Simultaneous Removal of Multiple Heavy Metals from Water.

Abstract: Pollution of water with heavy metals is a global environmental problem whose impact is especially severe in developing countries. Among water-purification methods, adsorption of heavy metals has proven to be simple, versatile, and cost-effective. However, there is still a need to develop adsorbents with a capacity to remove multiple metal pollutants from the same water sample. Herein, we report the complementary adsorption capacities of metal-organic frameworks (here, UiO-66 and UiO-66-(SH)2) and inorganic nanoparticles (iNPs; here, cerium-oxide NPs) into composite materials. These adsorbents, which are spherical microbeads generated in one step by continuous-flow spray-drying, efficiently and simultaneously remove multiple heavy metals from water, including As(III and V), Cd(II), Cr(III and VI), Cu(II), Pb(II), and Hg(II). We further show that these microbeads can be used as a packing material in a prototype of a continuous-flow water treatment system, in which they retain their metal-removal capacities upon regeneration with a gentle acidic treatment. As proof-of-concept, we evaluated these adsorbents for purification of laboratory water samples prepared to independently recapitulate each of two strongly polluted rivers: the Bone (Indonesia) and Buringanga (Bangladesh) rivers. In both cases, our microbeads reduced the levels of all the metal contaminants to below the corresponding permissible limits established by the World Health Organization (WHO). Moreover, we demonstrated the capacity of these microbeads to lower levels of Cr(VI) in a water sample collected from the Sarno River (Italy). Finally, to create adsorbents that could be magnetically recovered following their use in water purification, we extended our spray-drying technique to simultaneously incorporate two types of iNPs (CeO2 and Fe3O4) into UiO-66-(SH)2, obtaining CeO2/Fe3O4@UiO-66-(SH)2 microbeads that adsorb heavy metals and are magnetically responsive.

inorganic nanoparticles
composite
water treatment
metal removal
metal−organic frameworks


KLF4 suppresses the migration of hepatocellular carcinoma by transcriptionally upregulating monoglyceride lipase.

Abstract: The dysregulation of cellular metabolism, particularly lipid metabolism, is essential for cancer progress. Monoglyceride lipase (MGLL) is an important fatty acid metabolism enzyme, which converts monoacylglycerides to free fatty acids and glycerol. Despite the expression level of MGLL was reported to be downregulated in Hepatocellular carcinoma (HCC), the clinical significances and molecular mechanism of MGLL downregulation remains unknown. In the current study, the clinical significances of MGLL expression were investigated in 95 patients with HCC and the transcription factors of MGLL were identified in HCC cells. We found that MGLL was frequently downregulated in HCC samples, especially in metastatic tumor tissues. Patients with low MGLL expression owned remarkably lower 5 year-overall survival (5-OS). Functionally, we found that MGLL played an important role in HCC cell migration. Overexpression of MGLL suppressed cell migration and depletion of MGLL by shRNA promoted cell migration. Further studies indicated that KLF4 directly bound to the promoter of MGLL and accelerated MGLL expression, which then led to HCC cell migration decrease. Additionally, the expression levels of KLF4 were positive association with MGLL expression in HCC tissues. Collectively, our data suggest that KLF4 is a key regulator of MGLL. The KLF4-MGLL axis plays an essential role in suppressing HCC cell migration.

Yang|Xuejun|X| Zhang|Dongmei|D| Liu|Sha|S| Li|Xiaojie|X| Hu|Wanglai|W| Han|Chuanchun|C|

KLF4
migration
hepatocellular carcinoma
lipid metabolism
MGLL


Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria.

Abstract: Nitric oxide (NO) can be generated endogenously via NO synthases or via the diet following the action of symbiotic nitrate-reducing bacteria in the oral cavity. Given the important role of NO in smooth muscle control there is an intriguing suggestion that cardiovascular homeostasis may be intertwined with the presence of these bacteria. Here, we measured the abundance of nitrate-reducing bacteria in the oral cavity of 25 healthy humans using 16S rRNA sequencing and observed, for 3.5 h, the physiological responses to dietary nitrate ingestion via measurement of blood pressure, and salivary and plasma NO metabolites. We identified 7 species of bacteria previously known to contribute to nitrate-reduction, the most prevalent of which were Prevotella melaninogenica and Veillonella dispar. Following dietary nitrate supplementation, blood pressure was reduced and salivary and plasma nitrate and nitrite increased substantially. We found that the abundance of nitrate-reducing bacteria was associated with the generation of salivary nitrite but not with any other measured variable. To examine the impact of bacterial abundance on pharmacokinetics we also categorised our participants into two groups; those with a higher abundance of nitrate reducing bacteria (> 50%), and those with a lower abundance (< 50%). Salivary nitrite production was lower in participants with lower abundance of bacteria and these individuals also exhibited slower salivary nitrite pharmacokinetics. We therefore show that the rate of nitrate to nitrite reduction in the oral cavity is associated with the abundance of nitrate-reducing bacteria. Nevertheless, higher abundance of these bacteria did not result in an exaggerated plasma nitrite response, the best known marker of NO bioavailability. These data from healthy young adults suggest that the abundance of oral nitrate-reducing bacteria does not influence the generation of NO through the diet, at least when the host has a functional minimum threshold of these microorganisms.

Burleigh|Mia C|MC|
Liddle|Luke|L|
Monaghan|Chris|C|
Muggeridge|David J|DJ|
Sculthorpe|Nicholas|N|
Butcher|John P|JP|
Henriquez|Fiona L|FL|
Allen|Jason D|JD|
Easton|Chris|C|


CSF and clinical data are useful in differentiating CNS inflammatory demyelinating disease from CNS lymphoma.

Abstract:
BACKGROUND
It is often difficult to diagnose central nervous system (CNS) inflammatory demyelinating diseases (IDDs) because they are similar to CNS lymphoma and glioma.

OBJECTIVE
To evaluate whether cerebrospinal fluid (CSF) analysis can differentiate CNS IDDs from CNS lymphoma and glioma.

METHODS
We measured CSF cell counts; concentrations of proteins, glucose, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), and myelin basic protein; and IgG index in patients with multiple sclerosis (MS, n = 64), neuromyelitis optica spectrum disorder (NMOSD, n = 35), tumefactive demyelinating lesion (TDL, n = 17), CNS lymphoma ( n = 12), or glioma ( n = 10). We detected diagnostic markers using logistic regression and receiver operating characteristic (ROC) analyses.

RESULTS
Median CSF IL-10 and sIL-2R levels were higher in CNS lymphoma patients than in MS, NMOSD, or TDL patients. Logistic regression revealed that CSF sIL-2R levels predicted CNS lymphoma. In the ROC analysis of CSF sIL-2R levels, the area under the curve was 0.867, and the sensitivity and specificity were 83.3% and 90.0%, respectively.

CONCLUSION
CSF sIL-2R levels can be used to differentiate CNS lymphoma from CNS IDDs. Further studies may identify other applications of CSF as a diagnostic biomarker.

Ikeguchi|Ryotaro|R| Shimizu|Yuko|Y| Shimizu|Satoru|S| Kitagawa|Kazuo|K|

D016543:Central Nervous System Neoplasms

D020278:Demyelinating Autoimmune Diseases, CNS

cerebrospinal fluid
multiple sclerosis
neuromyelitis optica spectrum disorder
tumefactive demyelinating lesion
Central nervous system lymphoma
interleukin-10
soluble interleukin-2 receptor


Dioxygen and Metabolism; Dangerous Liaisons in Cardiac Function and Disease.

Abstract: The heart must consume a significant amount of energy to sustain its contractile activity. Although the fuel demands are huge, the stock remains very low. Thus, in order to supply its daily needs, the heart must have amazing adaptive abilities, which are dependent on dioxygen availability. However, in myriad cardiovascular diseases, "fuel" depletion and hypoxia are common features, leading cardiomyocytes to favor low-dioxygen-consuming glycolysis rather than oxidation of fatty acids. This metabolic switch makes it challenging to distinguish causes from consequences in cardiac pathologies. Finally, despite the progress achieved in the past few decades, medical treatments have not improved substantially, either. In such a situation, it seems clear that much remains to be learned about cardiac diseases. Therefore, in this review, we will discuss how reconciling dioxygen availability and cardiac metabolic adaptations may contribute to develop full and innovative strategies from bench to bedside.

cardiac function
hypoxia
glycolysis
cardiac metabolism
fatty acids β-oxidation
heart failure
oxidative stress


A Graph-Based Approach for Finding the Dengue Infection Pathways in Humans Using Protein-Protein Interactions.

Abstract: Dengue virus (DENV) is one of the deadly arboviruses, which is primarily transmitted by Aedes aegypti, and causes dengue infection to the humans. According to WHO, every year around 390 million humans are affected by DENV, of which around 50 million deaths are reported. Knowledge of the various diseases caused by the DENV would greatly encourage to understand the infection mechanism and help to design new antiviral drug discovery. We propose a quasi-clique and quasi-biclique algorithm to classify infection gateway proteins of the human body and possible pathways of DENV leading to various diseases. For this, we have examined three networks, dengue-human protein-protein interaction network, human protein interaction network, and human proteins-disease association network. The prediction result states that DENV may lead to various diseases in the human body, including cancer, asthma, ulcerative colitis, multiple sclerosis, premature birth, and so on. Some of the results have recently been validated experimentally. This study may endow with potential targets for more effective anti-dengue remedial contribution.

dengue
pathways
quasi-clique
quasi-biclique
protein–protein interaction


A longitudinal study of the effect of ocular biometrics measures on myopia onset.

Abstract:
PURPOSE
To investigate the relationship between ocular biometrics (OB) and myopia onset.

METHODS
OB data from students in 4 grades (aged from 6 to 14 years) in China were collected in a 1.5-year longitudinal study. Refractive error was assessed with cycloplegic autorefraction.

RESULTS
At baseline, 934 (56.33%) of the subjects (right eye) had myopia. The mean spherical equivalent (SE) and axial length to corneal radius (AL/CR) were - 2.14 ± 1.49 and 3.14 ± 0.11, respectively, in the subjects with myopia and - 0.09 ± 0.21 and 2.98 ± 0.07, respectively, in the subjects without myopia. The correlation between the SE and AL/CR was r = - 0.823 (P < 0.001). The slopes of the SE changing with the AL/CR (and R-squares) were - 0.28 to - 1.80 (0.01-0.14) in the no myopia group, - 3.40 to - 6.20 (0.20-0.48) in the low myopia group, and - 3.37 to - 11.34 (0.16-0.74) in the moderate and high myopia groups. The baseline AL/CR values in grades 1, 3, and 5 were higher in those who developed myopia within 1.5 years. The odds ratio of the AL/CR to myopia onset in 1.5 years was 1.096 (95% confidence interval (CI): 1.060-1.135).

CONCLUSIONS
Of the five indicators, the AL/CR showed the best correlation with the SE. The adjoint and linear relationship between the AL/CR and the SE tended to increase with SE progression. When myopia progressed beyond a certain range, the AL/CR was significantly different in those without initial myopia who developed it within 1.5 years compared with those who did not. After adjusting for age, sex, school, and grade, the interpretation capability of the current AL/CR to myopia onset in 1.5 years was limited.

Longitudinal study
Myopia
AL/CR
Linear
Ocular biometry


A method for evaluating nucleosome stability with a protein-binding fluorescent dye.

Abstract: Nucleosomes are extremely stable histone-DNA complexes that form the building blocks of chromatin, which accommodates genomic DNA within the nucleus. The dynamic properties of chromatin play essential roles in regulating genomic DNA functions, such as DNA replication, recombination, repair, and transcription. Histones are the protein components of nucleosomes, and their diverse modifications and variants increase the versatility of nucleosome structures and their dynamics in chromatin. Therefore, a technique to evaluate the physical properties of nucleosomes would facilitate functional studies of the various nucleosomes. In this report, we describe a convenient assay for evaluating the thermal stability of nucleosomes in vitro.

Taguchi|Hiroyuki|H| Horikoshi|Naoki|N| Arimura|Yasuhiro|Y| Kurumizaka|Hitoshi|H|

Nucleosome
Chromatin
Histone octamer
Histone variant
SYPRO Orange
Tetrasome


A rare presentation of the double inferior vena cava with an anomalous retrocaval right ureter: embryogenesis and clinical implications.

Abstract: On dissection of the abdomen of an adult male cadaver, in addition to the normal inferior vena cava on the right side, an unusual venous channel which connected the left renal vein with the left common iliac vein was found; (probably the left inferior vena cava). The left testicular and the left suprarenal veins were opening into the left renal vein as usual. Other than this, a retrocaval ureter was found on the right side. The works of previous authors have highlighted the incidence of a venacaval duplication and its surgical implications, but here, we are presenting a unique case of a double inferior vena cava with an anomalous retrocaval ureter. A conglomeration of such vascular malformations is of immense surgical importance, and it is indicative of a grossly defective angiogenesis. Keeping in mind the clinical relevance of the variations which were observed, an attempt was made to explain them in the light of the embryogenic development.

Gupta|Pratibha|P| Khullar|Meenakshi|M| Sharma|Ravikant|R| Singh|Richhpal|R|

Retrocaval ureter
Venacaval duplication
Angiogenesis


Reprint of: Uterine plasticity and reproductive fitness.

Abstract: Reproduction in humans is unique in two major aspects. First, the incidence of chromosomally abnormal and developmentally compromised human preimplantation embryos is exceptionally high, and second, the uterus decidualizes spontaneously each cycle, a process also responsible for the menstrual shedding of the endometrium in the absence of pregnancy. Emerging evidence suggests that these distinctive reproductive traits are functionally linked. Thus, the decidual process enables the mother to limit investment in compromised pregnancies, while menstruation imposes a need for constant recruitment of mesenchymal stem cells to regenerate and renew the endometrium each cycle. Endometrial stem cells are immune-privileged compared with other types of adult stem cells, suggesting a role for these cells in accommodating deeply invading semi-allogenic fetal trophoblast. Thus, by coupling reproductive competence to a process of constant tissue renewal, decidualization enables the human uterus to adapt to pregnancy failure and a changing ecology.

Lucas|Emma S|ES|
Salker|Madhuri S|MS|
Brosens|Jan J|JJ|

decidualization
endometrium
stem cell
chromosomal instability
implantation
miscarriage


Using Virtual Reality to Improve Performance and User Experience in Manual Correction of MRI Segmentation Errors by Non-experts.

Abstract: Segmentation of MRI scans is a critical part of the workflow process before we can further analyze neuroimaging data. Although there are several automatic tools for segmentation, no segmentation software is perfectly accurate, and manual correction by visually inspecting the segmentation errors is required. The process of correcting these errors is tedious and time-consuming, so we present a novel method of performing this task in a head-mounted virtual reality interactive system with a new software, Virtual Brain Segmenter (VBS). We provide the results of user testing on 30 volunteers to show the benefits of our tool as a more efficient, intuitive, and engaging alternative compared with the current method of correcting segmentation errors.

Duncan|Dominique|D|0000-0002-6154-9262
Garner|Rachael|R|
Zrantchev|Ivan|I|
Ard|Tyler|T|
Newman|Bradley|B|
Saslow|Adam|A|
Wanserski|Emily|E|
Toga|Arthur W|AW|

Virtual reality
MRI
Segmentation
Imaging
Quality control


Deep learning and manual assessment show that the absolute mitotic count does not contain prognostic information in triple negative breast cancer.

Abstract:
PURPOSE
The prognostic value of mitotic count for invasive breast cancer is firmly established. As yet, however, limited studies have been aimed at assessing mitotic counts as a prognostic factor for triple negative breast cancers (TNBC). Here, we assessed the prognostic value of absolute mitotic counts for TNBC, using both deep learning and manual procedures.

METHODS
A retrospective TNBC cohort (n = 298) was used. The absolute manual mitotic count was assessed by averaging counts from three independent observers. Deep learning was performed using a convolutional neural network on digitized H&E slides. Multivariable Cox regression models for relapse-free survival and overall survival served as baseline models. These were expanded with dichotomized mitotic counts, attempting every possible cut-off value, and evaluated by means of the c-statistic.

RESULTS
We found that per 2 mm2 averaged manual mitotic counts ranged from 1 to 187 (mean 37.6, SD 23.4), whereas automatic counts ranged from 1 to 269 (mean 57.6; SD 42.2). None of the cut-off values improved the models' baseline c-statistic, for both manual and automatic assessments.

CONCLUSIONS
Based on our results we conclude that the level of proliferation, as reflected by mitotic count, does not serve as a prognostic factor for TNBC. Therefore, TNBC patient management based on mitotic count should be discouraged.

D064726:Triple Negative Breast Neoplasms

Mitotic count
Triple negative breast cancer
Artificial intelligence
Prognosis


Clinical Efficacy of Polymyxin B in Patients Infected with Carbapenem-Resistant Organisms.

Abstract:
Purpose
Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the "last resort" choices of CRO infections. We explored the possible factors affecting PMB efficacy.

Patients and Methods
This retrospective study involved CRO-infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had "clinical success" (CS) and "clinical failure" (CF).

Results
A total of 191 patients were enrolled: 110 in the CS group and 81 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700-1443.75) vs 800 (500-1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8-14) vs 8 (6-11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently.

Conclusion
PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose, duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

Lu|Qiong|Q|0000-0002-0126-4978 Li|Guo-Hua|GH| Qu|Qiang|Q| Zhu|Hai-Hong|HH| Luo|Yue|Y| Yan|Han|H| Yuan|Hai-Yan|HY| Qu|Jian|J|

clinical efficacy
polymyxin B
carbapenem-resistant organisms
cumulative dose
adverse effect


Evaluation of the child oral health promotion 'MaliMali' Programme based on schools in the Kingdom of Tonga.

Abstract:
INTRODUCTION
The South Pacific Medical Team (SPMT) has supported oral health care for Tongan juveniles since 1998. This voluntary activity, named the MaliMali ('smile' in Tongan) Programme, is evaluated in detail in this paper.

METHODS
This evaluation was guided by the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. The objectives were to explore: (i) whether the programme was accessible to Tongan schoolchildren (Reach); (ii) the impact of the programme on decayed, missing and filled teeth (DMFT) scores and toothbrushing habits (Effectiveness); (iii) factors that affected the adoption of the programme (Adoption); (iv) whether implementation was consistent with the programme model (Implementation); and (v) the long-term sustainability of the programme (Maintenance).

RESULTS
The MaliMali Programme has grown into an international project, has spread countrywide as a uniform health promotion and is reaching children in need. Following implementation of this programme, the oral health of Tongan juveniles has improved, with a decrease in the mean DMFT index and an increase in toothbrushing. To provide training that will allow Tongans to assume responsibility for the MaliMali Programme in the future, dental health education literature was prepared and workshops on oral hygiene and the MaliMali Programme were held frequently. At present, the programme is predominantly managed by Tongan staff, rather than by Japanese staff.

CONCLUSIONS
This evaluation found the MaliMali Programme to be feasible and acceptable to children and schools in the Kingdom of Tonga. The programme promotes oral health and provides accessible and improved oral health care in the school setting, consistent with the oral health-promoting school framework.

Takeuchi|Reiri|R| Kawamura|Kohji|K| Kawamura|Sayuri|S| Endoh|Mami|M| Uchida|Chizuru|C| Taguchi|Chieko|C| Nomoto|Takato|T| Hiratsuka|Koichi|K| Fifita|Sisilia|S| Fakakovikaetau|Amanaki|A| Kobayashi|Seigo|S|

Kingdom of Tonga
Prevention of dental caries
fluoride
oral health-care system


Per- and polyfluoroalkyl substances (PFASs) in precipitation from mainland China: Contributions of unknown precursors and short-chain (C2C3) perfluoroalkyl carboxylic acids.

Abstract: A nationwide survey was conducted on per- and polyfluoroalkyl substances (PFASs) in precipitation across mainland China. Twenty-two PFASs, including precursors to perfluoroalkyl acids (pre-PFAAs), were investigated in thirty-nine precipitation samples collected from twenty-eight cities. Trifluoroacetate (TFA), perfluorooctanoic acid, and perfluorooctane sulfonic acid (PFOS) were ubiquitous in precipitation. TFA displayed the highest concentrations (8.8-1.8 × 103 ng/L), which were particularly elevated in coastal cities. 6:2 chlorinated polyfluorinated ether sulfonic acid, an alternative to PFOS, was detected for the first time in precipitation at a frequency of 43%. Polyfluoroalkyl phosphoric acid diesters and 6:2 fluorotelomer sulfonic acid were also occasionally detected. PFAS fluxes in the northeastern area (C4C12; 2.0 × 102-3.4 × 103 ng/m2/d) with major PFAS manufacturing facilities were higher than those in the southwestern area (63-1.7 × 103 ng/m2/d). Using total oxidizable precursor (TOP) assay, the occurrence of unknown pre-PFAAs was for the first time uncovered in precipitation with maximum estimated fluxes of C6 and C8 pre-PFAAs at 3.1 × 103 and 4.3 × 103 ng/m2/d, respectively. The relative contribution of ultrashort-chain PFCAs (C2C3) ranged from 22% to 91% of ∑PFASs, while unknown pre-PFAAs accounted for 6%-56% of the total molar concentrations of PFASs. This bears critical concerns on underestimation of PFAS mass load from precipitation to surface environment ascribed to monitoring data solely on known PFASs. Unknown precursors of PFAAs in the atmosphere are yet to be identified for their chemical structures and relevant environmental risks as well.

Chen|Hao|H| Zhang|Lu|L| Li|Mengqi|M| Yao|Yiming|Y| Zhao|Zhen|Z| Munoz|Gabriel|G| Sun|Hongwen|H|

6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 Cl-PFAES)


Mechanical stress.

Abstract: This chapter discusses mechanical stressors that are believed to be associated with work-related musculoskeletal disorders. It starts with an introduction to work-related musculoskeletal disorders (particularly those with high incidences in workplaces, such as disorders of low back, neck/shoulder, hand/wrist, elbow, and knee) in high-risk industries, and those mechanical stressors (such as high forces, awkward postures, high repetitions, excessive contact stress, and harmful human vibrations) in workplaces that are responsible for these disorders. Quantification methods of these mechanical stressors are then discussed. Although various quantification methods such as self-report, observational technique, and direct measurement are discussed, details are focused on many of those well-published observational techniques used by practitioners to assess risk levels of these mechanical stressors in jobs. These methods can quantify job mechanical stressors and provide risk level indications that can be used by practitioners to facilitate their decision making. These methods can also be used to evaluate the improvements of ergonomics interventions by comparing the risk levels quantitatively before and after the interventions.

D001696:Biomechanical Phenomena
D006801:Humans
D009140:Musculoskeletal Diseases
D009784:Occupational Diseases
D012307:Risk Factors
D013314:Stress, Mechanical

work-related musculoskeletal disorders
human vibration
biomechanical risk factors
hand-intensive jobs
job evaluation method
manual material handling
participatory ergonomics
physical exposure quantification
physical workload assessment


Oxidative Direct Arylation Polymerization Using Oxygen as the Sole Oxidant: Facile, Green Access to Bithiazole-Based Polymers.

Abstract: The most appealing oxidant, molecular oxygen, is employed for the first time as the sole oxidant in the transition metal-catalyzed oxidative direct arylation polymerization (C-H/C-H-type DArP), which eliminates by-product formation of stoichiometric metal salts except for water . Compared to conventional approaches, other than the avoidance of an end-capping procedure, the current protocol is remarkably advanced in the aspect of eco-friendliness, step- and cost-economy, and, of special significance, the purity of polymer products. As illustrative examples, six 5,5'-bithiazole-based polymers are synthesized using this new method, demonstrating higher number-average molecular weight (Mn up to 33 700) in better yields (up to 93 %) through only one step. The evolution of C-H/C-H-type DArP from heavy metal salts to O2 alone as the oxidant could solve the problem of metal residues in polymers, which is considered harmful to the performance of devices.


CD20-selective inhibition of CD47-SIRPα "don't eat me" signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab.

Abstract: Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα "don't eat me" signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20pos/CD47pos malignant B-cells, but not of CD20neg/CD47pos cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer antibodies daratumumab (anti-CD38), alemtuzumab (anti-CD52) and obinutuzumab (anti-CD20). In conclusion, RTX-CD47 blocks CD47 "don't eat me" signaling by cancer cells in a CD20-directed manner with essentially no activity towards CD20neg/CD47pos cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies.

van Bommel|Peter E|PE|
He|Yuan|Y|
Schepel|Ilona|I|
Hendriks|Mark A J M|MAJM|
Wiersma|Valerie R|VR|
van Ginkel|Robert J|RJ|
van Meerten|Tom|T|
Ammatuna|Emanuele|E|
Huls|Gerwin|G|
Samplonius|Douwe F|DF|
Helfrich|Wijnand|W|
Bremer|Edwin|E|

rituximab
CD47
SIRPα
bispecific antibody
phagocytosis


Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis.

Abstract:
INTRODUCTION
The aim of this study was to explore the effect of maternal fluorinated steroid therapy on fetuses affected by second-degree immune-mediated congenital atrioventricular block.

MATERIAL AND METHODS
Studies reporting the outcome of fetuses with second-degree immune-mediated congenital atrioventricular block diagnosed on prenatal ultrasound and treated with fluorinated steroids compared with those not treated were included. The primary outcome was the overall progression of congenital atrioventricular block to either continuous or intermittent third-degree congenital atrioventricular block at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used.

RESULTS
Five studies (71 fetuses) were included. The progression rate to congenital atrioventricular block at birth in fetuses treated with steroids was 52% (95% confidence interval 23-79) and in fetuses not receiving steroid therapy 73% (95% confidence interval 39-94). The overall rate of regression to either first-degree, intermittent first-/second-degree or sinus rhythm in fetuses treated with steroids was 25% (95% confidence interval 12-41) compared with 23% (95% confidence interval 8-44) in those not treated. Stable (constant) second-degree congenital atrioventricular block at birth was present in 11% (95% confidence interval 2-27) of cases in the treated group and in none of the newborns in the untreated group, whereas complete regression to sinus rhythm occurred in 21% (95% confidence interval 6-42) of fetuses receiving steroids vs. 9% (95% confidence interval 0-41) of those untreated.

CONCLUSIONS
There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second-degree immune-mediated congenital atrioventricular block.

steroids
Atrioventricular block
ultrasound
autoimmune
fetal echocardiography
fetal heart
heart block


Feedback moderates the effect of prevalence on perceptual decisions.

Abstract: How does the prevalence of a target influence how it is perceived and categorized? A substantial body of work, mostly in visual search, shows that a higher proportion of targets are missed when prevalence is low. This classic low prevalence effect (LPE) involves a shift to a more conservative decision criterion that makes it less likely that observers will call an ambiguous item a target. In contrast, Levari et al. (Science, 360[6396], 1465-1467, 2018) recently reported the opposite effect in a simple categorization task. In their hands, at low prevalence, observers adopted a more liberal criterion, making observers more likely to label ambiguous dots on a blue-purple continuum "blue." They called this "prevalence-induced concept change" (PICC). Here, we report that the presence or absence of feedback is critical. With feedback, observers become more conservative at low prevalence, as in the LPE. Without feedback, they become more liberal, identifying a wider range of stimuli as targets, as in Levari's PICC studies. Stimuli from a shape continuum ranging from rounded ("Bouba") to bumpy ("Kiki") shapes produced similar results. Other variables: response type (2AFC vs. go/no-go), color (blue-purple vs. red-green), and stimuli type (solid color vs. texture) did not influence the criterion shifts. Understanding these effects of prevalence and ways they can be controlled illuminates the context-specific nature of perceptual decisions and may be useful in socially important, low prevalence tasks like cancer screening, airport security, and disease diagnosis in pathology.

Lyu|Wanyi|W|
Levari|David E|DE|
Nartker|Makaela S|MS|
Little|Daniel S|DS|
Wolfe|Jeremy M|JM|

Decision
Prevalence effects
Criterion
Categorical perception


Analysis of Newly Identified and Rare Synonymous Genetic Variants in the RET Gene in Patients with Medullary Thyroid Carcinoma in Polish Population.

Abstract: Gain-of-function germline mutations of the RET proto-oncogene are responsible for initiation of carcinogenesis within the thyroid gland and development of hereditary form of medullary thyroid carcinoma and MEN2 syndrome. Genotype-phenotype correlations are established for most RET mutations, but the importance of the synonymous changes in this gene remains debatable. We aimed to analyze RET gene variants in Polish population. Genetic testing for the RET gene variants was performed with standard methods in 585 people aged 1-85, including 448 patients with medullary thyroid carcinoma and 131 of their first- and second-degree relatives, as well as six patients suspected of MTC/MEN2. Besides the most frequent synonymous changes, p.Leu769Leu, p.Ser836Ser, and p.Ser904Ser, four rare changes-c.1827C>T (p.Cys609Cys), c.2364C>T (p.Ile788Ile), c.2418C>T (p.Tyr806Tyr), and c.2673G>A (p.Ser891Ser)-were found in the RET gene, in the Polish population. Two of the rare changes, p.Cys609Cys and p.Ile788Ile, had not been previously described. The frequency of molecular synonymous variants in the general population was evaluated by testing 400 anonymous blood samples of neonates. Our findings may contribute to a better understanding of the genetic diversity of the RET gene and the involvement of synonymous variants in this diversity.

Sromek|Maria|M| Czetwertyńska|Małgorzata|M| Tarasińska|Magdalena|M| Janiec-Jankowska|Aneta|A| Zub|Renata|R| Ćwikła|Maria|M| Nowakowska|Dorota|D| Chechlińska|Magdalena|M|

D020022:Genetic Predisposition to Disease

D018813:Multiple Endocrine Neoplasia Type 2a

RET gene
Medullary thyroid carcinoma
Thyroid
MEN2
Synonymous mutation


Single Cell Densitometry and Weightlessness Culture of Mesenchymal Stem Cells Using Magnetic Levitation.

Abstract: Magnetic levitation methodology enables density-based separation of microparticles/cells and sustains cell culture in different media. Levitation process can be accomplished via negative magnetophoresis (diamagnetophoresis), where the applied magnetic force compensates gravitational acceleration and the density of the diamagnetic object (e.g., cell) determines its levitation height. Here we describe a portable, sensitive, and cost-effective technology that uses the principles of magnetic levitation to measure single cell density and cell culture under desired conditions.

Anil-Inevi|Muge|M|
Yilmaz|Esra|E|
Sarigil|Oyku|O|
Tekin|H Cumhur|HC|
Ozcivici|Engin|E|

Stem cells
Magnetic levitation
Single cell density
Real-time monitoring
Simulated microgravity


Does SARS-CoV-2 infection cause chronic neurological complications?

Abstract: The current pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has created an unparalleled health crisis. Besides the acute respiratory infection, CoVs are neuroinvasive causing additional inflammation and neurodegeneration. This is likely also true of SARS-CoV-2 given reports of neurological manifestations in coronavirus disease 2019 (COVID-19) positive patients. Older adults > 65 years of age constitute a high-risk group prone to severe infection and death. Despite the higher mortality rate, a majority of cases are expected to recover and survive from this viral outbreak. But, the long-term consequences of SARS-CoV-2 neuroinfection are unknown. We discuss these potential chronic changes to the central nervous system (CNS) in relation to accelerated brain aging and age-related neurodegenerative disorders.

Neurodegeneration
COVID-19
Aging
Alzheimer’s disease
Cellular senescence
Neurotropism


Rotational carotid insufficiency: an unusual cause of bow hunter's syndrome.

Abstract: We report an unusual case in which physiologic neck rotation impeded perfusion through the internal carotid artery. The patient had a history of prior radical neck surgery and radiation for malignancy. He presented withbow hunter's-like symptoms with transient loss of consciousness and right-sided weakness with left lateral neck rotation. A self-expanding peripheral stent was successfully used to treat the patient by preventing rotatory carotid compression. In select patients with prior neck surgery and radiation, carotid injections should be part of a dynamic cerebral angiogram if the vertebral arteries are unremarkable.

neck
artery
stent
blood flow
intervention


Predator confusion is sufficient to evolve swarming behaviour.

Abstract: Swarming behaviours in animals have been extensively studied owing to their implications for the evolution of cooperation, social cognition and predator-prey dynamics. An important goal of these studies is discerning which evolutionary pressures favour the formation of swarms. One hypothesis is that swarms arise because the presence of multiple moving prey in swarms causes confusion for attacking predators, but it remains unclear how important this selective force is. Using an evolutionary model of a predator-prey system, we show that predator confusion provides a sufficient selection pressure to evolve swarming behaviour in prey. Furthermore, we demonstrate that the evolutionary effect of predator confusion on prey could in turn exert pressure on the structure of the predator's visual field, favouring the frontally oriented, high-resolution visual systems commonly observed in predators that feed on swarming animals. Finally, we provide evidence that when prey evolve swarming in response to predator confusion, there is a change in the shape of the functional response curve describing the predator's consumption rate as prey density increases. Thus, we show that a relatively simple perceptual constraint--predator confusion--could have pervasive evolutionary effects on prey behaviour, predator sensory mechanisms and the ecological interactions between predators and prey.

Olson|Randal S|RS|
Hintze|Arend|A|
Dyer|Fred C|FC|
Knoester|David B|DB|
Adami|Christoph|C|

D000818:Animals
D001522:Behavior, Animal
D005075:Biological Evolution
D020387:Food Chain
D008954:Models, Biological
D011235:Predatory Behavior

swarming behaviour
functional response
predator confusion effect
predator visual system
predator–prey coevolution


Sterically Crowded Tris(2-(trimethylsilyl)phenyl)phosphine - Is it Still a Ligand?

Abstract: Tris(2-(trimethylsilyl)phenyl)phosphine, P( o -TMSC 6 H 4 ) 3 , was synthesised and characterised in solution and in the solid state. The large steric bulk prevents most reactions of the phosphorus donor and makes the compound air stable both in the solid state as well as in solution. This shielded phosphine can still undergo three reactions, namely protonation, oxidation to the phosphine oxide under harsh conditions and complexation to Au I , thus forming a complex with linear coordination. Unexpectedly, complexation was unsuccessful with a range of other metal cations. Neither Pd II , Pt II , Zn II nor Hg II reacted and even the remaining coinage metal cations Cu I and Ag I could not be coordinated. Both the parent molecule as well as the reaction products were structurally characterised by single crystal X-ray di raction, and the conformational change of geometry required to accommodate the additional atoms was analysed in detail. Apart from chemical oxidation with H 2 O 2 , P( o -TMSC 6 H 4 ) 3 displays reversible electrochemical oxidation with a potential not unlike the one of sterically unencumbered phosphines for which the oxidation is usually not reversible. P( o -TMSC 6 H 4 ) 3 can thus be considered a model compound for the investigation of the electronic properties of sterically unencumbered phosphines.

phosphine, steric hindrance, structure elucidation, homogeneous catalysis, electrochemistry


Sensitivity of crop cover to climate variability: insights from two Indian agro-ecoregions.

Abstract: Crop productivity in India varies greatly with inter-annual climate variability and is highly dependent on monsoon rainfall and temperature. The sensitivity of yields to future climate variability varies with crop type, access to irrigation and other biophysical and socio-economic factors. To better understand sensitivities to future climate, this study focuses on agro-ecological subregions in Central and Western India that span a range of crops, irrigation, biophysical conditions and socioeconomic characteristics. Climate variability is derived from remotely-sensed data products, Tropical Rainfall Measuring Mission (TRMM - precipitation) and Moderate Resolution Imaging Spectroradiometer (MODIS - temperature). We examined green-leaf phenologies as proxy for crop productivity using the MODIS Enhanced Vegetation Index (EVI) from 2000 to 2012. Using both monsoon and winter growing seasons, we assessed phenological sensitivity to inter-annual variability in precipitation and temperature patterns. Inter-annual EVI phenology anomalies ranged from -25% to 25%, with some highly anomalous values up to 200%. Monsoon crop phenology in the Central India site is highly sensitive to climate, especially the timing of the start and end of the monsoon and intensity of precipitation. In the Western India site, monsoon crop phenology is less sensitive to precipitation variability, yet shows considerable fluctuations in monsoon crop productivity across the years. Temperature is critically important for winter productivity across a range of crop and management types, such that irrigation might not provide a sufficient buffer against projected temperature increases. Better access to weather information and usage of climate-resilient crop types would play pivotal role in maintaining future productivity. Effective strategies to adapt to projected climate changes in the coming decades would also need to be tailored to regional biophysical and socio-economic conditions.

Mondal|Pinki|P|
Jain|Meha|M|
DeFries|Ruth S|RS|
Galford|Gillian L|GL|
Small|Christopher|C|

D003247:Conservation of Natural Resources

Crop productivity
Agriculture
Climate sensitivity
MODIS EVI
Small-holder farmers
South Asia


Painful extraskeletal osteochondroma under the tarsal sesamoid: a case report and review of literature.

Abstract: Extraskeletal osteochondroma is a rare condition. To our knowledge, occurrence in the foot has been very rare. We present here a case wherein the patient developed a painful extraskeletal osteochondroma under the tarsal sesamoid. A fifty-one-year-old man presented at our department with a painful mass on the plantar part of the metatarsal joint of the right big toe. The mass had grown gradually in size for the past 7 months and was associated with pain while walking. Preoperative X-ray and a computed tomography showed that the tumor had no continuity with adjacent bone. Intraoperatively, a bony hard tumor was located in the subcutaneous tissue plantar to the tibial sesamoid. The mass was firmly attached to the sheath of the flexor hallucis brevis tendon. Macroscopically, the tumor was covered with glistering surface. The tumor was carefully dissected from the surrounding soft tissues and was removed. It was diagnosed as extraskeletal osteochondroma histologically. The patient had no recurrence at 1 year after operation.

Okada|Atsushi|A| Hatori|Masahito|M| Hashimoto|Yoshinori|Y| Lee|Emo|E|

Extraskeletal
Osteochondroma
Sesamoid
Foot
Osteochondral lesion


Developing a multidisciplinary approach within the ED towards domestic violence presentations.

Abstract:
AIM
To improve the detection and quality of care of patients who attend the emergency department (ED) with confirmed or suspected domestic abuse (DA).

DESIGN
A quality improvement report on the design, implementation and evaluation of a specialised service and structured training programme to detect and manage DA presentations within an emergency medicine department.

SETTING
The study was set in the ED at the Northern General Hospital, Sheffield, UK.

KEY MEASURES FOR IMPROVEMENT
Key measures for improvement included introducing a service within the ED to help staff manage DA and coordinate responses; improve staff confidence in detecting DA; develop a structured and consistent process by which to manage DA presentations.

STRATEGIES FOR CHANGE
An Independent Domestic Violence Advocate service was introduced into the department in July 2011 through a multiagency agreement. A structured training and education programme was delivered to ED staff. A 'communications form' was developed for DA risk assessment and case management. The process was reviewed quarterly.

RESULTS
One hundred and seventy-two referrals were made to the service (121 distinct clients) over a 12-month period. Staff reported greater confidence in detecting DA, and community partners highlighted the role the service had in improving DA detection and care quality within the city.

CONCLUSIONS
Strong leadership and prioritising the issue within the department has facilitated the development of the process and contributed substantially to its success. Support from community partners has been invaluable in tailoring the service and education programme to the needs of staff and patients within the department.

D000328:Adult
D002983:Clinical Competence
D003299:Cooperative Behavior
D017579:Domestic Violence
D004509:Education, Nursing, Continuing
D016529:Emergency Nursing
D004636:Emergency Service, Hospital
D004739:England
D006801:Humans
D007857:Leadership
D015397:Program Evaluation
D058996:Quality Improvement
D011787:Quality of Health Care
D020377:Self Efficacy


Moving window growth-A method to characterize the dynamic growth of crops in the context of bird abundance dynamics with the example of Skylark (Alauda arvensis).

Abstract: Agricultural field crops differ in their vegetation height, coverage, and temporal development, affecting the abundances of bird species, which are often used as bioindicators. Although this relationship has been observed, no significant methodology exists to describe the dynamics of field crop growth on a landscape scale in connection with the abundance of indicator bird species that allows meaningful interpretation of bird abundance data with respect to crop vegetation parameters during the breeding season. In a field observation program, we monitored 2,900 ha of agricultural landscape to represent both the crop growth processes and the bird abundances. We measured these two parameters in the study area, dominated by winter wheat, winter rapeseed, maize, and fallow fields, and adapted the moving window approach to a new method of "moving window growth" to describe the dynamic development of height and coverage of the crops over time. Simultaneously, Skylarks (Alauda arvensis) territorial behavior was measured concurrently on the same fields and crops. Their dynamic abundance was documented over the breeding season. To test the relationship between crop growth and development and bird abundance, we applied a generalized linear model (GLM) in two ways: (a) without differentiation of crop species and (b) with differentiation of crop species. We found significant relationships between bird abundance and vegetation height and coverage with respect to both individual parameters and their interactions, even without differentiation of the agricultural crops. In general, increasing vegetation height and coverage, especially the interaction, led to decreasing bird abundance values. The model quality increased significantly by including differentiation of specific crops as an explanatory variable indicating a non-homogenous situation between crops. Separate models for individual crop species revealed larger differences in model quality with best and least goodness of fit values for fallow fields and winter rapeseed, respectively. Because of the clear interactions between bird abundance, type of field crop, and vegetation height and coverage, it follows that both habitat suitability assessments of arable fields and the definition of favorable vegetation structures for farmland birds should be crop species-specific.

Hoffmann|Jörg|J| Wittchen|Udo|U| Berger|Gert|G| Stachow|Ulrich|U|0000-0003-0406-0812

crops
Skylark
moving window growth
vegetation structures
dynamic habitat quality
moving window abundance


Geography, Host Genetics, and Cross-Domain Microbial Networks Structure the Skin Microbiota of Fragmented Brazilian Atlantic Forest Frog Populations.

Abstract: The host-associated microbiome plays a significant role in health. However, the roles of factors such as host genetics and microbial interactions in determining microbiome diversity remain unclear. We examined these factors using amplicon-based sequencing of 175 Thoropa taophora frog skin swabs collected from a naturally fragmented landscape in southeastern Brazil. Specifically, we examined (1) the effects of geography and host genetics on microbiome diversity and structure; (2) the structure of microbial eukaryotic and bacterial co-occurrence networks; and (3) co-occurrence between microeukaryotes with bacterial OTUs known to affect growth of the fungal pathogen Batrachochytrium dendrobatidis (Bd). While bacterial alpha diversity varied by both site type and host MHC IIB genotype, microeukaryotic alpha diversity varied only by site type. However, bacteria and microeukaryote composition showed variation according to both site type and host MHC IIB genotype. Our network analysis showed the highest connectivity when both eukaryotes and bacteria were included, implying that ecological interactions may occur among domains. Lastly, anti-Bd bacteria were not broadly negatively co-associated with the fungal microbiome and were positively associated with potential amphibian parasites. Our findings emphasize the importance of considering both domains in microbiome research and suggest that for effective probiotic strategies for amphibian disease management, considering potential interactions among all members of the microbiome is crucial.

microbial networks
amphibian
Brazil's Atlantic Forest
skin microbiome


The Relationship between "Self-Care Ability" and Psychological Changes among Hemodialysis Patients.

Abstract:
Aim
The study investigates and analyzes the relationship among the concepts of demoralization, posttraumatic growth, and self-care ability in patients undergoing hemodialysis.

Methods
The cross-sectional descriptive correlational study was conducted in 2017 on 150 hemodialysis patients selected through census in Buali Hospital, Ardabil, Iran. Demoralization scale, the posttraumatic growth inventory, and self-care questionnaire were used for cross-sectional data collection. Data were analyzed using descriptive statistics, Pearson and Spearman correlation coefficient.

Results
The mean and standard deviation of demoralization, posttraumatic growth, and self-care were 36.25 ± 18.84, 63.17 ± 17.71, and 33.89 ± 6.40, respectively. Self-care ability was positively associated with posttraumatic growth (r = 0.287) and negatively related to demoralization (r = -0.168). Self-care ability was also found to be desirable in 84.7% of the patients.

Conclusions
Hemodialysis patients can experience both positive and negative psychological changes. Self-care ability is associated with reductions in negative psychological problems and increases in positive psychological changes. Health-care providers can, therefore, help hemodialysis patients to improve their psychological conditions by making plans for improving self-care abilities.

Sadeghpour|Fatemeh|F| Heidarzadeh|Mehdi|M| Kohi|Farzad|F| Asadi|Reza|R| Aghamohammadi-Kalkhoran|Masoomeh|M| Abbasi|Faeze|F|

self-care
hemodialysis
Demoralization
posttraumatic growth


Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina.

Abstract: Light profoundly affects our mental and physical health. In particular, light, when not delivered at the appropriate time, may have detrimental effects. In mammals, light is perceived not only by rods and cones but also by a subset of retinal ganglion cells that express the photopigment melanopsin that renders them intrinsically photosensitive (ipRGCs). ipRGCs participate in contrast detection and play critical roles in non-image-forming vision, a set of light responses that include circadian entrainment, pupillary light reflex (PLR), and the modulation of sleep/alertness, and mood. ipRGCs are also found in the human retina, and their response to light has been characterized indirectly through the suppression of nocturnal melatonin and PLR. However, until recently, human ipRGCs had rarely been investigated directly. This gap is progressively being filled as, over the last years, an increasing number of studies provided descriptions of their morphology, responses to light, and gene expression. Here, I review the progress in our knowledge of human ipRGCs, in particular, the different morphological and functional subtypes described so far and how they match the murine subtypes. I also highlight questions that remain to be addressed. Investigating ipRGCs is critical as these few cells play a major role in our well-being. Additionally, as ipRGCs display increased vulnerability or resilience to certain disorders compared to conventional RGCs, a deeper knowledge of their function could help identify therapeutic approaches or develop diagnostic tools. Overall, a better understanding of how light is perceived by the human eye will help deliver precise light usage recommendations and implement light-based therapeutic interventions to improve cognitive performance, mood, and life quality.

intrinsically photosensitive ganglion cell


Cancer patients' experiences with immune checkpoint modulators: A qualitative study.

Abstract:
BACKGROUND
Minimal qualitative data exist on the experiences of cancer patients treated with immune checkpoint inhibitors or costimulatory antibodies. Understanding the day to day experiences of patients being treated with immune checkpoint modulators, and how these relate to their health-related quality of life, can inform future research and lead to better clinical decision-making and care. We report here the first in depth qualitative study to consider patients' diverse and complex experiences with immune checkpoint modulators, with a focus on side effects and how these impact daily life.

METHODS
This single-center qualitative study was based on focus groups and semistructured interviews. Patients who were being treated or who had been treated with immune checkpoint modulators within the last year for a range of cancer diagnoses were recruited. Interpretive description informed our inductive, iterative approach to analysis.

RESULTS
Eight themes were identified, characterizing the complexity of these patients' lived experiences: major categories of side effects experienced and how they impacted patient well-being; the heterogeneous nature of side effects experienced; living with uncertainty; reframing the meaning and severity of SEs; focus on survival, hope, and being positive; acceptance and adaptation; feeling supported; and faith in medical innovation. Throughout their accounts, participants highlighted the profound impact that immune checkpoint modulators had on their daily lives.

CONCLUSION
This is the first in-depth qualitative study into patient accounts of their experiences of treatment with immune checkpoint modulators, related side effects, and how it impacted their daily lives. This research is an integral initial step in developing an instrument that will assess treatment-related side effects in patients treated with this form of therapy.

D064420:Drug-Related Side Effects and Adverse Reactions

D000071066:Patient Reported Outcome Measures

immune checkpoint inhibitors
costimulatory antibodies
Health-related quality of life
immunotherapy
patient experiences


Acute myocardial infarction as presentation of an infiltrative lung neoplasia.

Abstract: We report the case of a 51-year-old woman who presented with acute myocardial infarction as initial symptom of an infiltrative lung neoplasia. The patient was admitted to our center following an out-of-hospital cardiac arrest due to ventricular fibrillation which was cardioverted. On electrocardiography an anterior wall ST-elevation was found and urgent coronary angiography was performed. Left anterior descending coronary artery was occluded and after thrombus aspiration, an image of diffuse loss of lumen diameter and absence of coronary branches was compatible with an extrinsic compression. Such findings along with a lingula consolidation on chest X-ray examination suggested a thoracic neoplasia. Enhanced-chest computed tomography showed a mass located in the lingula with extensive mediastinal infiltration involving pericardium and myocardium. Anatomopathologic examination confirmed the presence of lung adenocarcinoma. <Learning objective: In patients with neoplasms should be suspected cardiac tumor infiltration in those with acute myocardial infarction. Since differential diagnosis between true AMI electrocardiographic (ECG) changes and pseudo-AMI ECG changes in patients with secondary cardiac tumors assumed to be difficult, such TTE or IVUS findings of extra-cardiac tumor could help physicians to make an accurate diagnosis.>.

Uribarri|Aitor|A| Villa|Adolfo|A| Loughlin|Gerard|G| Fernández-Avilés|Francisco|F|

Myocardial infarction
Lung adenocarcinoma
Cardiac metastasis


Chopper-modulated gas chromatography electroantennography enabled using high-temperature MEMS flow control device.

Abstract: We report the design, fabrication and characterization of a microelectromechanical systems (MEMS) flow control device for gas chromatography (GC) with the capability of sustaining high-temperature environments. We further demonstrate the use of this new device in a novel MEMS chopper-modulated gas chromatography-electroantennography (MEMS-GC-EAG) system to identify specific volatile organic compounds (VOCs) at extremely low concentrations. The device integrates four pneumatically actuated microvalves constructed via thermocompression bonding of the polyimide membrane between two glass substrates with microstructures. The overall size of the device is 32 mm×32 mm, and it is packaged in a 50 mm×50 mm aluminum housing that provides access to the fluidic connections and allows thermal control. The characterization reveals that each microvalve in the flow control chip provides an ON to OFF ratio as high as 1000:1. The device can operate reliably for more than 1 million switching cycles at a working temperature of 300 °C. Using the MEMS-GC-EAG system, we demonstrate the successful detection of cis-11-hexadecenal with a concentration as low as 1 pg at a demodulation frequency of 2 Hz by using an antenna harvested from the male Helicoverpa Virescens moth. In addition, 1 μg of a green leafy volatile (GLV) is barely detected using the conventional GC-EAG, while MEMS-GC-EAG can readily detect the same amount of GLV, with an improvement in the signal-to-noise ratio (SNR) of ~22 times. We expect that the flow control device presented in this report will allow researchers to explore new applications and make new discoveries in entomology and other fields that require high-temperature flow control at the microscale.

Zhou|Ming-Da|MD|
Akbar|Muhammad|M|
Myrick|Andrew J|AJ|
Xia|Yiqiu|Y|
Khan|Waleed J|WJ|
Gao|Xiang|X|
Baker|Thomas C|TC|
Zheng|Si-Yang|SY|0000-0002-0616-030X

gas chromatography
electroantennography
MEMS flow control device
microvalve


Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model.

Abstract: The aim of this work was to develop a new in vitro lipolysis-permeation model to predict the in vivo absorption of fenofibrate in self-nanoemulsifying drug delivery systems (SNEDDSs). More specifically, the in vitro intestinal lipolysis model was combined with the mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model. Biosimilar mucus (BM) was added to the surface of the PVPA barriers to closer simulate the intestinal mucosa. SNEDDSs for which pharmacokinetic data after oral dosing to rats was available in the literature were prepared, and the ability of the SNEDDSs to maintain fenofibrate solubilized during in vitro lipolysis was determined, followed by the assessment of drug permeation across the mucus-PVPA barriers. The amount of drug solubilized over time during in vitro lipolysis did not correlate with the AUC (area under the curve) of the plasma drug concentration curve. However, the AUC of the drug permeated after in vitro lipolysis displayed a good correlation with the in vivo AUC (R2 > 0.9). Thus, it was concluded that the in vitro lipolysis-mucus-PVPA permeation model, simulating the physiological digestion and absorption processes, was able to predict in vivo absorption data, exhibiting great potential for further prediction of in vivo performance of SNEDDSs.

Falavigna|Margherita|M|
Klitgaard|Mette|M|
Berthelsen|Ragna|R|
Müllertz|Anette|A|
Flaten|Gøril Eide|GE|

Permeability
Gastrointestinal tract
In vitro model
In vitro/in vivo (IVIVC) correlation
Lipid-based formulation
Oral drug delivery
Poorly water-soluble drug
Precipitation
Self-emulsifying


Dynamic functional connectivity revealed by resting-state functional near-infrared spectroscopy.

Abstract: The brain is a complex network with time-varying functional connectivity (FC) and network organization. However, it remains largely unknown whether resting-state fNIRS measurements can be used to characterize dynamic characteristics of intrinsic brain organization. In this study, for the first time, we used the whole-cortical fNIRS time series and a sliding-window correlation approach to demonstrate that fNIRS measurement can be ultimately used to quantify the dynamic characteristics of resting-state brain connectivity. Our results reveal that the fNIRS-derived FC is time-varying, and the variability strength (Q) is correlated negatively with the time-averaged, static FC. Furthermore, the Q values also show significant differences in connectivity between different spatial locations (e.g., intrahemispheric and homotopic connections). The findings are reproducible across both sliding-window lengths and different brain scanning sessions, suggesting that the dynamic characteristics in fNIRS-derived cerebral functional correlation results from true cerebral fluctuation.

Li|Zhen|Z| Liu|Hanli|H| Liao|Xuhong|X| Xu|Jingping|J| Liu|Wenli|W| Tian|Fenghua|F| He|Yong|Y| Niu|Haijing|H|

(170.2655) Functional monitoring and imaging

(170.3880) Medical and biological imaging


Chronic intermittent ethanol exposure in mice leads to an up-regulation of CRH/CRHR1 signaling.

Abstract:
BACKGROUND
One of the most commonly used approaches to induce ethanol (EtOH) dependence in rodents is EtOH vapor inhalation. This procedure requires the co-administration of pyrazole-an inhibitor of the alcohol dehydrogenase-to obtain stable blood EtOH concentrations (BECs) during the entire induction course. However, pyrazole can produce unwanted side effects. Our goal was to obtain EtOH-dependent mice without pyrazole and to study their behavioral and molecular postdependent phenotype. In particular, we were interested in alterations in the corticotrophin-releasing hormone (CRH) and receptor (CRHR1 and CRHR2) system as a prominent role of CRH in driving the postdependent state via actions in the central extended amygdala (CeA) has been demonstrated in rats but not in postdependent mice.

METHODS
We established an alternative model of chronic intermittent EtOH (CIE) inhalation without the use of pyrazole in C57BL/6N mice. Our CIE exposure protocol involved 8 cycles. One cycle consisted of 8 hours with EtOH inhalation and 8 hours without EtOH. We then examined withdrawal symptoms. After 2 weeks of abstinence, we studied relapse, reinstatement of EtOH-seeking, and stress-induced EtOH self-administration. We also did transcriptional analysis of components of the CRH system during CIE, protracted abstinence, and after stress-induced EtOH self-administration.

RESULTS
CIE exposure without pyrazole resulted in reproducible BECs during the induction procedure. Mice showed strong withdrawal scores during 4 to 12 hours after the last CIE cycle and enhanced stress-induced EtOH self-administration. This postdependent phenotype during abstinence was accompanied by enhanced Crh and Crhr1 transcripts but no change in Crhr2 transcripts in the CeA. Cue-induced EtOH-seeking behavior and relapse (alcohol deprivation effect) were not affected by the inhalation procedure.

CONCLUSIONS
We have established a CIE inhalation protocol without pyrazole in mice and showed excessive EtOH self-administration under mild stress and enhanced CRH/CRHR1 signaling in the CeA.

Eisenhardt|Manuela|M|
Hansson|Anita C|AC|
Spanagel|Rainer|R|
Bilbao|Ainhoa|A|

Ethanol
Inhalation
Pyrazole
Corticotrophin-Releasing Hormone System
Postdependence Model


Talimogene laherparepvec: overview, combination therapy and current practices.

Abstract: Talimogene laherparepvec (T-VEC, Imlygic®, Amgen, CA, USA) is an oncolytic herpes simplex type 1 virus used as intralesional therapy for unresectable metastatic melanoma in a cutaneous, subcutaneous or nodal location. Talimogene laherparepvec selectively replicates within and lyses tumor cells while producing granulocyte macrophage colony-stimulating factor, which may promote an immune mediated antitumor response. The US FDA approved T-VEC in late 2015 following Phase I-III trials that demonstrated safety and efficacy. Future directions for T-VEC include combination therapies with other systemic immunotherapies such as anti-CTLA-4 antibody and anti-PD-1 drugs. Current National Comprehensive Cancer Network (NCCN) practice guidelines have added T-VEC as a primary treatment for stage IIIB/C and stage IVM1a melanoma patients.

O'Donoghue|Cristina|C|
Doepker|Matthew P|MP|
Zager|Jonathan S|JS|

Imlygic
intralesional therapy
metastatic melanoma
GM-CSF
clinical trial
oncolytic therapy
talimogene laherparepvec (T-VEC)


New nitroindazole-porphyrin conjugates: Synthesis, characterization and antibacterial properties.

Abstract: The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.

Eddahmi|Mohammed|M|
Sousa|Vera|V|
Moura|Nuno M M|NMM|
Dias|Cristina J|CJ|
Bouissane|Latifa|L|
Faustino|Maria A F|MAF|
Cavaleiro|José A S|JAS|
Gomes|Ana T P C|ATPC|
Almeida|Adelaide|A|
Neves|Maria G P M S|MGPMS|
Mostapha Rakib|El|E|

Antimicrobial Photodynamic Therapy (aPDT)


Telemedicine for cardiovascular disease continuum: A position paper from the Italian Society of Cardiology Working Group on Telecardiology and Informatics.

Abstract: Telemedicine is the provision of health care services, through the use of information and communication technology, in situations where the health care professional and the patient, or 2 health care professionals, are not in the same location. It involves the secure transmission of medical data and information, through text, sound, images, or other forms needed for the prevention, diagnosis, treatment, and follow-up of a patient. First data on implementation of telemedicine for the diagnosis and treatment of acute myocardial infarction date from more than 10 years ago. Telemedicine has a potential broad application to the cardiovascular disease continuum and in many branches of cardiology, at least including heart failure, ischemic heart disease and arrhythmias. Telemedicine might have an important role as part of a strategy for the delivery of effective health care for patients with cardiovascular disease. In this document the Working Group on Telecardiology and Informatics of the Italian Society of Cardiology intends to remark some key-points regarding potential benefit achievable with the implementation of telemedicine support in the continuum of cardiovascular disease.

Brunetti|Natale Daniele|ND|
Scalvini|Simonetta|S|
Acquistapace|Flavio|F|
Parati|Gianfranco|G|
Volterrani|Maurizio|M|
Fedele|Francesco|F|
Molinari|Giuseppe|G|

Telemedicine
Cardiovascular disease
Position paper
Telecardiology


Minimally Invasive Plating Osteosynthesis in the Treatment of Humeral Shaft Fractures: A Meta-Analysis.

Abstract:
BACKGROUND
Whether minimally invasive plating osteosynthesis (MIPO) or other operative interventions is superior in the treatment of humeral shaft fractures remains controversial. Therefore, we conducted a meta-analysis to quantitatively compare the clinical outcomes of MIPO and other operative interventions in the treatment of humeral shaft fractures.

METHODS
Pubmed, Embase, and Web of Science were systematically searched to identify all available studies comparing clinical outcomes between patients receiving MIPO and other operative interventions. The weight mean difference (WMD) was pooled to compare the operative time, union time, University of California, Los Angeles (UCLA) score, and Mayo elbow performance index (MEPI).The risk ratio (RR) was pooled to compare the union rate, and incidence of complications. Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, according to the heterogeneity among studies.

RESULTS
Nine studies were included in this meta-analysis. Our results suggest that both MIPO and other operative interventions can achieve similar union time, UCLA score, MEPI, and union rate. However, MIPO is associated with better outcomes including shorter operation time, and lower incidence of radial nerve injury.

CONCLUSION
Evidence from this meta-analysis demonstrated that, MIPO is effective but safer than other operative interventions in the treatment of humeral shaft fracture. However, due to the potential limitations in this meta-analysis, randomized controlled trials with larger sample sizes using appropriate blinding methods are needed to confirm these findings.

Zhang|Quan|Q| Sun|Ning|N| Huang|Qiang|Q| Zhu|Shiwen|S| Wu|Xinbao|X|

D019060:Minimally Invasive Surgical Procedures


On the Al-Al11Ce3 Eutectic Transformation in Aluminum-Cerium Binary Alloys.

Abstract: The L ↔ Al + Al11Ce3 technologically important eutectic transformation in Al-Ce binary alloys, containing from 5 to 20 wt.% Ce and ranging from hypo- to hypereutectic compositions, was examined along with the microstructure and properties of its solidified product. A combination of thermal analysis and metallography determined the coordinates of the eutectic point at 644.5 ± 0.6 °C and 10.6 wt.% Ce, clarifying the existing literature ambiguity. Despite the high entropy of melting of the Al11Ce3 phase, in hypoeutectic alloys the eutectic was dominated by the regular morphology of periodically arranged lamellae, typical for non-faceted systems. In the lamellar eutectic, however, the faceting of Al11Ce3 was identified at the atomic scale. In contrast, for hypereutectic compositions, the Al11Ce3 eutectic phase exhibited complex morphology, influenced by the proeutectic Al11Ce3 phase. The Al11Ce3 eutectic phase lost its coherency with Al; it was deduced that a partial coherency was present only at early stages of lamellae growth. The orientation relationships between the Al11Ce3 and Al in the eutectic structure, leading to partial coherency, were determined to be Al ║ Al11Ce3 with Al ║ Al11Ce3 and Al ║ Al11Ce3 with Al ║ Al11Ce3. The Al11Ce3 phase with a hardness of 350 HV and Al matrix having 35 HV in their eutectic arrangement formed in situ composite, with the former playing a role of reinforcement. However, the coarse and mostly incoherent Al11Ce3 eutectic phase provided limited strengthening and the Al-Ce alloy consisting of 100% eutectic reached at room temperature a yield stress of just about 70 MPa.

eutectic
aluminum–cerium alloys
rare earths
solidification