Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine.

Abstract: To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-β+/Δβ-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity.

Zika virus vaccine
self-replicating mRNA
IFNAR1 knockout mice
type I interferon response


A Low-Cost Neutral Zinc-Iron Flow Battery with High Energy Density for Stationary Energy Storage.

Abstract: Flow batteries (FBs) are one of the most promising stationary energy-storage devices for storing renewable energy. However, commercial progress of FBs is limited by their high cost and low energy density. A neutral zinc-iron FB with very low cost and high energy density is presented. By using highly soluble FeCl2 /ZnBr2 species, a charge energy density of 56.30 Wh L-1 can be achieved. DFT calculations demonstrated that glycine can combine with iron to suppress hydrolysis and crossover of Fe3+ /Fe2+ . The results indicated that an energy efficiency of 86.66 % can be obtained at 40 mA cm-2 and the battery can run stably for more than 100 cycles. Furthermore, a low-cost porous membrane was employed to lower the capital cost to less than $ 50 per kWh, which was the lowest value that has ever been reported. Combining the features of low cost, high energy density and high energy efficiency, the neutral zinc-iron FB is a promising candidate for stationary energy-storage applications.

Xie|Congxin|C| Duan|Yinqi|Y| Xu|Wenbin|W| Zhang|Huamin|H| Li|Xianfeng|X|0000-0002-8541-5779

flow batteries
energy storage
glycine
porous membranes
zinc-iron batteries


Trigeminal sensory nerve patterns in dentine and their responses to attrition in rat molars.

Abstract:
OBJECTIVE
Our goal was to define trigeminal nerve ending quantities and patterns in rat molar dentine, their responses to attrition (tooth wear), and their associated odontoblasts and connections with pulpal plexuses.

DESIGN
Trigeminal ganglia were labeled for axonal transport of 3H-proteins to dentinal nerve endings in male rats (3-13 months old). Autoradiography detected radio-labeled dentinal tubules as indicators of nerve ending locations. Quantitative morphometry was done (ANOVA, t-tests), and littermates were compared for attrition and innervation.

RESULTS
There were six dentinal patterns, only two of which had an associated neural plexus of Raschkow and cell-free zone (Den-1, Den-2). Other nerves entered dentin from bush-like endings near elongated odontoblasts (Den-B), as single fibers (Den-X), as networks in predentine (PdN), or as single fibers in tertiary dentine at cusp tips (Den-S). There were at least 186,600 innervated dentinal tubules within the set of three right maxillary molars of the best-labeled rat, and similar densities were found in other rats. Attrition levels differed among cusps and in littermates (t-test p < 0.02-0.0001), but the matched right/left cusps per rat were similar. Innervations of tertiary and enamel-free dentine (Den-S, Den-X) were preserved in all rats. Den-B and Den-2 coronal patterns were unchanged unless displaced by dentinogenesis. Den-1 losses occurred in older cusps, while Den-2 patterns increased near cervical and intercuspal odontoblasts.

CONCLUSIONS
The extensive molar dentinal innervation had unique distributions per rat per cusp that depended on region (buccal, middle, palatal) and attrition, but only two of six patterns connected to a plexus of Raschkow.

Byers|Margaret R|MR|
Calkins|Dianne F|DF|

Odontoblasts
Axonal transport
Plexus of Raschkow
Dental innervation
Pulp-dentine complex


How the World's Children Hear: A Narrative Review of School Hearing Screening Programs Globally.

Abstract:
Objective
School hearing screening may mitigate the effects of childhood hearing loss through early identification and intervention. This study provides an overview of existing school hearing screening programs around the world, identifies gaps in the literature, and develops priorities for future research.

Data Sources
A structured search of the PubMed, Embase, and Cochrane Library databases.

Review Methods
A total of 65 articles were included according to predefined inclusion criteria. Parameters of interest included age groups screened, audiometric protocols, referral criteria, use of adjunct screening tests, rescreening procedures, hearing loss prevalence, screening test sensitivity and specificity, and loss to follow-up.

Conclusions
School hearing screening is mandated in few regions worldwide, and there is little accountability regarding whether testing is performed. Screening protocols differ in terms of screening tests included and thresholds used. The most common protocols included a mix of pure tone screening (0.5, 1, 2, and 4 kHz), otoscopy, and tympanometry. Estimates of region-specific disease prevalence were methodologically inaccurate, and rescreening was poorly addressed. Loss to follow-up was also a ubiquitous concern.

Implications for Practice
There is an urgent need for standardized school hearing screening protocol guidelines globally, which will facilitate more accurate studies of hearing loss prevalence and determination of screening test sensitivity and specificity. In turn, these steps will increase the robustness with which we can study the effects of screening and treatment interventions, and they will support the development of guidelines on the screening, diagnostic, and rehabilitation services needed to reduce the impact of childhood hearing loss.

Yong|Michael|M|
Panth|Neelima|N|
McMahon|Catherine M|CM|
Thorne|Peter R|PR|
Emmett|Susan D|SD|

children
school
school hearing screening
hearing loss
tympanometry
audiometry
otoacoustic emissions


Evidence for the involvement of a GABAergic mechanism in the effectiveness of natural and synthetically modified incensole derivatives in neuropharmacological disorders: A computational and pharmacological approach.

Abstract: In the course of our continuing exploration for novel bioactive lead compounds (s) from the species Boswellia, we have recently reported incensole derivatives isolated from Boswellia papyrifera Hochst. Given the known antidepressant-like effects of incensole and incensole acetate, we herein present that the low dose intraperitoneal administration of incensole derivatives, namely, incensfuran and incensone, showed significant antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). Furthermore, these compounds were evaluated for their anxiolytic potential in the elevated plus maze (EPM) and light dark box (LDB) tests and anticonvulsant effects in pentylenetetrazole (PTZ)-induced seizure tests. In the EPM test, administration of these compounds led to dose-dependent increases in open arm entries and in the time spent in EPM open arms. Similar results were obtained in the LDB test, wherein compounds these caused significant increases in the number of transitions between lit and dark compartments and the time spent in the lit compartment. The anxiolytic-like effects in the EPM were not reversed by pretreatment with flumazenil, whereas PTZ and bicuculline (BIC) completely abolished the anxiolytic effects, showing the involvement of the non-benzodiazepine binding sites of GABAA receptors. All four compounds induced significantly elevated brain GABA levels, indicating the involvement of a GABAergic mechanism. Additionally, molecular docking was conducted to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. Moreover, these compounds also possess drug-like properties and excellent ADMET profiles.

Al-Harrasi|Ahmed|A|
Khan|Ajmal|A|
Rehman|Najeeb Ur|NU|
Al-Shidhani|Sulaiman|S|
Karim|Nasiara|N|
Khan|Imran|I|
Halim|Sobia Ahsan|SA|
Al-Rawahi|Ahmed|A|
Hussain|Javid|J|
Csuk|Rene|R|

Incensole
Incensfuran
Incensone
Anxiolytic
Anticonvulsant
Molecular docking
ADMET prediction
Antidepressant
Homology modelling


"It's like a mirror image of my illness": Exploring Patient Perceptions About Illness Using Health Mind Mapping-a Qualitative Study.

Abstract:
BACKGROUND
A patient's self-management of chronic disease is influenced in part by their explanatory model of illness (EMI) and daily lived experiences (DLE). Unfortunately, assessing patient's EMI and using this information to engage patients in chronic illness self-management continues to be a challenge.

OBJECTIVE
"Health mind mapping" (HMM) is a novel process that captures a patient's EMI and DLE through the use of a graphic representation of ideas. We aimed to explore patient's experiences using HMM.

DESIGN
Qualitative study utilizing semi-structured interviews.

PARTICIPANTS
Adult patients with uncontrolled type 2 diabetes from a primary care clinic.

APPROACH
A facilitator guided 20 participants through the process of developing a health mind map. Subsequently, each participant completed a semi-structured interview about their experience with the process and perceptions about how their maps could be used. The process and interviews were video and audio recorded. We conducted a content analysis of the maps and a thematic analysis, using an inductive approach, of the interview data.

RESULTS
Participants explored a wide range of EMs and DLEs in their HMM process. Participants reported that the HMM process (1) helped to develop insight about self and illness; (2) was a catalyst for wanting to take actions to improve illness; and (3) represented an opportunity to actively share illness experiences. They reported potential uses of the map: (1) to communicate about their illness to others in their social network; (2) to communicate about their illness to providers; (3) to help others with diabetes manage their illness; and (4) to encourage ongoing engagement in diabetes self-care.

CONCLUSIONS
Participants reported that HMM helped them develop new insight about their illness and was a catalyst for encouraging them to take control of their illness. HMM has the potential to facilitate communication with providers and engage patients in collaborative goal setting to improve self-care in chronic illness.

Buitron de la Vega|Pablo|P|
Coe|Christopher|C|
Paasche-Orlow|Michael K|MK|
Clark|Jack A|JA|
Waite|Katherine|K|
Sanchez|Maria Jose|MJ|
Armstrong|Emily|E|
Bokhour|Barbara G|BG|

D007722:Health Knowledge, Attitudes, Practice

explanatory models of illness
daily lived experiences
health mind mapping
diabetes


Soybean SAT1 (Symbiotic Ammonium Transporter 1) encodes a bHLH transcription factor involved in nodule growth and NH4+ transport.

Abstract: Glycine max symbiotic ammonium transporter 1 was first documented as a putative ammonium (NH4(+)) channel localized to the symbiosome membrane of soybean root nodules. We show that Glycine max symbiotic ammonium transporter 1 is actually a membrane-localized basic helix-loop-helix (bHLH) DNA-binding transcription factor now renamed Glycine max bHLH membrane 1 (GmbHLHm1). In yeast, GmbHLHm1 enters the nucleus and transcriptionally activates a unique plasma membrane NH4(+) channel Saccharomyces cerevisiae ammonium facilitator 1. Ammonium facilitator 1 homologs are present in soybean and other plant species, where they often share chromosomal microsynteny with bHLHm1 loci. GmbHLHm1 is important to the soybean rhizobium symbiosis because loss of activity results in a reduction of nodule fitness and growth. Transcriptional changes in nodules highlight downstream signaling pathways involving circadian clock regulation, nutrient transport, hormone signaling, and cell wall modification. Collectively, these results show that GmbHLHm1 influences nodule development and activity and is linked to a novel mechanism for NH4(+) transport common to both yeast and plants.

Chiasson|David M|DM|
Loughlin|Patrick C|PC|
Mazurkiewicz|Danielle|D|
Mohammadidehcheshmeh|Manijeh|M|
Fedorova|Elena E|EE|
Okamoto|Mamoru|M|
McLean|Elizabeth|E|
Glass|Anthony D M|AD|
Smith|Sally E|SE|
Bisseling|Ton|T|
Tyerman|Stephen D|SD|
Day|David A|DA|
Kaiser|Brent N|BN|

D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

D018506:Gene Expression Regulation, Plant

legume
nitrogen fixation
nitrogen transport


Non-Enzymatic Glucose Detection Based on NiS Nanoclusters@NiS Nanosphere in Human Serum and Urine.

Abstract: Herein, we report a non-enzymatic electrochemical glucose sensing platform based on NiS nanoclusters dispersed on NiS nanosphere (NC-NiS@NS-NiS) in human serum and urine samples. The NC-NiS@NS-NiS are directly grown on nickel foam (NF) (NC-NiS@NS-NiS|NF) substrate by a facile, and one-step electrodeposition strategy under acidic solution. The as-developed nanostructured NC-NiS@NS-NiS|NF electrode materials successfully employ as the enzyme-mimic electrocatalysts toward the improved electrocatalytic glucose oxidation and sensitive glucose sensing. The NC-NiS@NS-NiS|NF electrode presents an outstanding electrocatalytic activity and sensing capability towards the glucose owing to the attribution of great double layer capacitance, excessive electrochemical active surface area (ECASA), and high electrochemical active sites. The present sensor delivers a limit of detection (LOD) of ~0.0083 µM with a high sensitivity of 54.6 µA mM-1 cm-2 and a wide linear concentration range (20.0 µM-5.0 mM). The NC-NiS@NS-NiS|NF-based sensor demonstrates the good selectivity against the potential interferences and shows high practicability by glucose sensing in human urine and serum samples.

Arivazhagan|Mani|M|
Manova Santhosh|Yesupatham|Y|
Maduraiveeran|Govindhan|G|

NiS nanomaterials
biomedical applications
chemically modified electrode
electrocatalytic oxidation
electrochemical deposition
glucose sensor


Influence of serum lipids on the incidence and progression of diabetic retinopathy and macular oedema: Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular genetics Study-II.

Abstract:
IMPORTANCE
The importance of lipids on incidence and progression of diabetic retinopathy has not been studied in the Indian population.

BACKGROUND
To elucidate the influence of serum lipid control on the incidence and progression of diabetic retinopathy and diabetic macular oedema in subjects with type 2 diabetes.

DESIGN
Population-based longitudinal observational study in a hospital setting.

PARTICIPANTS
Eight hundred ninety subjects were examined at baseline and follow-up.

METHODS
Diabetic retinopathy was graded per Modified Early Treatment Diabetic Retinopathy Study scales; 45°, 4-field dilated stereoscopic digital photography was performed with an additional 30°, 7-field for those who had retinopathy. Macular oedema was evaluated per Proposed International Clinical Diabetic Retinopathy and Diabetic Macular Oedema Disease Severity Scales.

MAIN OUTCOME MEASURES
Association of serum lipids and incidence and progression of diabetic retinopathy.

RESULTS
Poor control of total cholesterol was associated with the incidence of sight-threatening retinopathy (odds ratio = 7.2 [95% confidence interval: 1.5-34.3], P = 0.012) and macular oedema (odds ratio = 5.5 [95% confidence interval: 1.4-27.4], P = 0.037) after adjusting for potential confounders. Poor control of triglycerides was associated with progression to proliferative diabetic retinopathy (odds ratio = 3.2 [95% confidence interval: 1.1-10.5], P = 0.048). Risk for incident macular oedema (P = 0.041) and progression to proliferative diabetic retinopathy (P = 0.028) was greater when all lipid types were abnormal.

CONCLUSIONS AND RELEVANCE
Poor control of lipids is a risk factor for incidence of and progression to late stages of retinopathy. Abnormal levels of all lipid types are associated with risk of incident macular oedema and progression to proliferative diabetic retinopathy.

Srinivasan|Sangeetha|S| Raman|Rajiv|R|0000-0001-5842-0233 Kulothungan|Vaitheeswaran|V| Swaminathan|Gayathri|G| Sharma|Tarun|T|

diabetic retinopathy
diabetic macular oedema
cholesterol
triglyceride
risk factor


An overarching approach for acute care delivery: extension of the acute care model to the entire inpatient admission.

Abstract: The acute care model has been proposed as a framework for quality improvement in emergency care to improve care delivery and patient flow. There is currently an absence of an overarching model inclusive of other relevant care settings, such as the inpatient ward or the intensive care unit (ICU), involved in the care of an acute illness episode. This gap limits our ability to optimize patient outcomes, improve flow, and reduce waste through all stages of acute illness. We propose that a unified approach to improve quality of care for acute illness may be achieved by extending the acute care model to the inpatient care setting.

Zackoff|Matthew W|MW|
Iyer|Srikant|S|
Dewan|Maya|M|

Acute care model
quality
standardization


Prophylactic Treatment of Migraine.

Abstract: Migraine is a common chronic neurological disease characterized by episodic attacks of headache and associated symptoms. The pharmacological treatment of migraine may be acute or prophylactic, and patients with frequent, severe headaches often require both approaches. Prophylactic treatment is used to reduce the frequency, duration, or severity of attacks, to enhance the benefits of acute treatments, and to improve patient's ability to function normally. Prophylactic treatment may also prevent progression from episodic migraine to chronic migraine and may result in reductions in health-care cost. The currently available pharmacological options for migraine prophylaxis include a wide array of medications. The major medication groups for prophylactic treatment include β-blockers, anticonvulsant, drugs such as topiramate and valproate, antidepressant drugs, such as amitriptyline and selective serotonin and selective serotonin-norepinephrine reuptake inhibitors (SNRIs), calcium channel antagonists and neurotoxins. The agent for prophylactic treatment should be chosen based on the efficacy and side-effect profile of the drug, and the patient's coexistent and comorbid conditions.


BRCA1 mutation spectrum, functions, and therapeutic strategies: The story so far.

Abstract: BRCA1 gene mutations account for about 25-28% of hereditary Breast Cancer as BRCA1 is included in the category of high penetrance genes. Except for few commonmutations, there is a heterogenous spectrum of BRCA1 mutations in various ethnic groups. 185AGdel and 5382ins Care the most common BRCA1 alterations (founder mutations) which have been identified in most of the population. This review has been compiled with an aim to consolidate the information on genetic variants reported in BRCA1 found in various ethnic groups, their functional implications if known; involvement of BRCA1 in various cellular pathways/processes and potential BRCA1 targeted therapies. The pathological variations of BRCA1 vary among different ethical groups. A systematic search in PubMed and Google scholar for the literature on BRCA1 gene was carried out to figure out structure and function of BRCA1 gene. BRCA1 is a large protein having 1863 amino acids with multiple functional domains and interacts with multiple proteins to carry out various crucial cellular processes. BRCA1 plays a major role in maintaining genome integrity, transcription regulation, chromatin remodeling, cell cycle checkpoint control, DNA damage repair, chromosomal segregation, and apoptosis. Studies investigating the phenotypic response of mutant BRCA1 protein and comparing it to wildtype BRCA1 protein are clinically important as they are involved in homologous recombination and other repair mechanisms. These studies may help in developing more targetted therapies, detecting novel interacting partners, identification of new signaling pathways that BRCA1 is a part of or downstream target genes that BRCA1 affects.

Sharma|Babita|B|
Preet Kaur|Raman|R|
Raut|Sonali|S|
Munshi|Anjana|A|

BRCA1
Mutations
DNA damage repair
Breastcancer


High prevalence of HIV among men who have sex with men in Zhejiang, China: a respondent-driven sampling survey.

Abstract:
OBJECTIVES
To examine the prevalence of HIV and risk behaviours among men who have sex with men (MSM) and to explore the feasibility of using respondent-driven sampling in this population in order to conduct customised interventions among MSM in the future.

DESIGN
Cross-sectional study.

SETTING
Zhejiang, China.

PARTICIPANTS
1316 MSM.

PRIMARY AND SECONDARY OUTCOME MEASURES
HIV prevalence rates and factors associated with HIV infection; sociodemographic and behavioural information of participants, syphilis prevalence rates.

RESULTS
The adjusted prevalence of HIV and syphilis were 13.8% and 11.4%, respectively. Multivariate analysis showed that higher educational level, support treatment of HIV, negative syphilis are protective factors of HIV infection. MSM who had heterosexual behaviour before and whose primary sexual partner was HIV-positive were less likely to be infected with HIV compared with their counterparts, while frequency of sexual behaviour with primary sexual partner was positively associated with HIV infection.

CONCLUSIONS
This survey confirmed a high HIV prevalence among MSM in Zhejiang province. MSM are extremely vulnerable to HIV infection and comprehensive interventions are urgently needed to slow the spread of HIV among MSM.

Pan|Xiaohong|X| Wu|Minni|M| Ma|Qiaoqin|Q| Wang|Hui|H| Ma|Wenzhe|W| Zeng|Shidian|S| Chen|Junfang|J| Zhang|Yan|Y| Miao|Dandan|D| Zhou|Xin|X| Jiang|Tingting|T| He|Lin|L| Xia|Yan|Y| Peng|Zhihang|Z| Xia|Shichang|S|


Frightened of the pulp? A qualitative analysis of undergraduate student confidence and stress during the management of deep caries and the exposed pulp.

Abstract:
AIM
To evaluate sources of student confidence and stress during the management of deep carious lesions and the exposed pulp during undergraduate clinics. Further aims were to identify barriers and facilitators, which could result in educational or practical improvements in the delivery of teaching and provision of treatment in this area.

METHODOLOGY
A exploratory qualitative study design was used, based on recorded focus group interviews, guided by 12 predetermined questions. The discussions were transcribed verbatim and analysed by inductive qualitative content analysis. Common categories were identified to aid understanding. Forty undergraduate dental students from 4th and 5th years in Dublin Dental University Hospital participated in the study.

RESULTS
Student stress and confidence were multifactorial and broadly linked to specific domains: clinical procedure, academic education, clinical training, evaluation/grading, organization and equipment, vital pulp biomaterial and the patient. Most students expressed a preference for one-stage selective carious removal to soft dentine rather than potential pulp exposure in deep carious lesions, noting that although it helped to decrease their immediate stress, it also caused longer-term concern by leaving caries close to the pulp. Nevertheless, their confidence was affected by limited clinical experience of carrying out selective removal procedures in deep caries. A recurrent finding was students citing high levels of stress after pulp exposure. Feelings including anger, fear, embarrassment and denial were associated with pulp exposure during deep caries management. Generally, the students felt able to manage pulp capping procedures, but were less certain about partial pulpotomy, suggesting that although they are aware of its advantages, they were unsure about the appropriate volume of pulp tissue to remove. To reduce stress, students suggested that laboratory teaching should employ new 3-D printed solutions and clinics should establish clear consensus amongst supervising teachers about the best way to manage the exposed pulp.

CONCLUSIONS
Students lacked confidence as they neared the pulp and prefer selective caries removal techniques, which reduce the likelihood of pulp exposure. Students identified stressors and suggested improvements in several domains that would improve confidence. These ameliorations could lead to enhancements in student ability to perform these conservative techniques, and improve the provision of treatment in this area.

confidence
stress
deep caries
exposed pulp
focus groups
dental students
vital pulp treatment


Aβ monomer induces phosphorylation of Tau at Ser-214 through β2AR-PKA-JNK signaling pathway.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with synaptic dysfunction, pathological accumulation of β-amyloid peptide 1-42 (Aβ1-42 ), and neuronal loss. The self-association of Aβ1-42 monomers (Aβ-M) into soluble oligomers seems to be crucial for the development of neurotoxicity. Previous publications have shown that Aβ oligomers and dimers might play key roles in inducing AD. The role of Aβ-M was rarely investigated and still unclear in AD. To understand the effects of Aβ-M on neurons and other cell types in the brain could be the key to understand its function. In our study, we found that Aβ-M expression slowly induced cell apoptosis within 48 hours after transfection, β2 adrenergic receptor (β2AR) interacted with Aβ-M in the pull-down and the yeast two-hybrid assays, and Aβ-M played a major role in inducing phosphorylation of Tau at Ser-214, c-Jun N-terminal kinase (JNK) at Thr-183/Tyr-185, p70 ribosomal protein S6 kinase (p70S6K) at Thr-389. We also discovered that β2AR, G protein-coupled receptor kinase 2 (GRK2), and protein kinase A (PKA) mediated the phosphorylation of Tau and JNK. Aβ-M induced phosphorylation of Tau at Ser-214 through both β2AR-cAMP/PKA-JNK and β2AR-GRK signaling pathways. Mitogen-activated protein kinase kinase (MEK) mediated the phosphorylation of p70S6K induced by Aβ-M.

Wu|Hao|H| Wei|Shuangshuang|S| Huang|Yonglin|Y| Chen|Lintao|L| Wang|Yuerong|Y| Wu|Xinli|X| Zhang|Zhuandan|Z| Pei|Yechun|Y| Wang|Dayong|D|

D055372:AMP-Activated Protein Kinases
D000544:Alzheimer Disease
D016229:Amyloid beta-Peptides
D000818:Animals
D017209:Apoptosis
D045744:Cell Line, Tumor
D002478:Cells, Cultured
D006801:Humans
D048670:MAP Kinase Kinase 4
D051379:Mice
D010446:Peptide Fragments
D010766:Phosphorylation
D018343:Receptors, Adrenergic, beta-2
D015398:Signal Transduction
D016875:tau Proteins

monomer
Tau
JNK
Alzheimer’s disease
amyloid β peptide


Serine is required for the maintenance of redox balance and proliferation in the intestine under oxidative stress.

Abstract: Serine has critical roles in maintaining cell growth and redox balance in cancer cells. However, the role of exogenous serine played in oxidative response and proliferation in normal mammalian intestine need to be further elucidated. We used a mouse model and intestinal porcine epithelial cells (IPEC-J2) to reveal that exogenous serine deficiency did not lead to redox imbalance and inhibition of proliferation in the intestine. However, serine deficiency exacerbated oxidative stress, mitochondrial dysfunction, apoptosis, and inhibition of proliferation in IPEC-J2 cells challenged by hydrogen peroxide, while serine supplementation rescued redox imbalance and those proliferation defects. Importantly, serine supplementation restored the glutathione content and decreased the accumulation of reactive oxygen species, while no such effects were observed when glutathione synthesis was inhibited. Additionally, serine supplementation increased nuclear nrf2 expression in IPEC-J2 cells. These results suggested that serine alleviates oxidative stress through supporting glutathione synthesis and activating nrf2 signaling. We further found that serine supplementation activated the mTOR pathway, while inhibition of mTOR diminished the effects of serine on promoting proliferation, suggesting critical roles of the mTOR pathway in this context. Taken together, our study underlines the importance of serine in the maintenance of redox status and proliferation in the intestine and reveals a novel potential mechanism that mediates these effects.

He|Liuqin|L| Long|Jing|J| Zhou|Xihong|X| Liu|Yonghui|Y| Li|Tiejun|T| Wu|Xin|X|

cell growth
apoptosis
glutathione
reactive oxygen species


Prevalence of suicide ideation, planning and attempts among Supplemental Nutrition Assistance Program participants in the United States.

Abstract:
BACKGROUND
Suicide represents a substantial public health problem in the U.S. Programs like the Supplemental Nutrition Assistance Program (SNAP)-which provides services for U.S. adults who are food insecure-could be an appropriate venue for suicide prevention strategies targeting high-risk individuals.

METHODS
This cross-sectional study used multiple logistic regression to determine odds ratios (ORs) and 95% confidence intervals (CIs) for suicide ideation, planning and attempt among those who participated in SNAP vs. nonparticipants. The National Survey of Drug Use and Health provided a representative sample of U.S. adults for 2012-2018 (n = 288,730).

RESULTS
SNAP participants were more likely than nonparticipants to have serious suicidal thoughts (crude OR=1.89; 95% CI=1.79-1.99), to have a plan for suicide (crude OR=2.35; 95% CI=2.16-2.56) or to attempt suicide (crude OR=2.89; 95% CI=2.54-3.29). Associations remained for those aged <50 in age-stratified analyses that accounted for survey year, demographics, socioeconomic status, self-rated health and mental health service use.

LIMITATIONS
SNAP was assessed at the household level; thus, those who reported suicidal thoughts and/or behaviors may not personally interact with SNAP.

CONCLUSION
Using a large, nationally-representative sample of U.S. adults, this study documented greater prevalence of suicide-related outcomes among those who participate in SNAP. Suicide prevention among SNAP participants may provide a unique means to reach individuals who are often hard to engage in other health services.

Bergmans|Rachel S|RS|
Jannausch|Mary|M|
Ilgen|Mark A|MA|

Suicide
Community psychiatry
Epidemiology
Food assistance
Food insecurity


Protein Expression Correlates Linearly with mRNA Dose over Up to Five Orders of Magnitude In Vitro and In Vivo.

Abstract: Messenger RNA is rapidly gaining significance as a therapeutic modality. Here, we address the dependence of dose-response functions on the type of delivery vehicle, cell line, and incubation time. Knowledge of these characteristics is crucial for the application of mRNA. As delivery vehicles, a lipid-based formulation and the cell-penetrating peptide Pepfect14 (PF14) were employed. As cell lines, we included a glomerular endothelial cell line (mGEnC) as a model for differentiated cells, HeLa cells, and SKOV-3 ovarian carcinoma cells. Uptake and expression were detected by flow cytometry, using a Cy5-labelled mRNA coding for enhanced green fluorescent protein (EGFP). There was a linear correlation of dose, uptake, and expression, and this correlation was maintained for over up to 72 h. Through application of a multistep kinetic model, we show that differences in expression levels can already be explained by the number of mRNAs packaged per delivery vehicle. Using luciferase as a reporter protein, linearity of expression was observed over 5 orders of magnitude in vitro and 3 orders of magnitude in vivo. Overall, the results demonstrate that mRNA provides excellent quantitative control over protein expression, also over extended periods of time.

van Asbeck|Alexander H|AH|
Dieker|Jürgen|J|
Oude Egberink|Rik|R|0000-0001-9950-9517
van den Berg|Lennard|L|
van der Vlag|Johan|J|
Brock|Roland|R|

messenger RNA
dose response function
drug delivery
nanomedicine


Experience of living with knee osteoarthritis: a systematic review of qualitative studies.

Abstract:
OBJECTIVES
Systematically review the qualitative literature on living with knee osteoarthritis from patient and carer perspectives.

DESIGN
Systematic review of qualitative studies. Five electronic databases (CINAHL, Embase, MEDLINE, PsycINFO, SPORTDiscus) were searched from inception until October 2018. Data were synthesised using thematic and content analysis.

PARTICIPANTS
Studies exploring the experiences of people living with knee osteoarthritis, and their carers were included. Studies exploring experiences of patients having participated in specific interventions, including surgery, or their attitudes about the decision to proceed to knee replacement were excluded.

RESULTS
Twenty-six articles reporting data from 21 studies about the patient (n=665) and carer (n=28) experience of living with knee osteoarthritis were included. Seven themes emerged: (i) Perceived causes of knee osteoarthritis are multifactorial and lead to structural damage to the knee and deterioration over time (n=13 studies), (ii) Pain and how to manage it predominates the lived experience (n=19 studies), (iii) Knee osteoarthritis impacts activity and participation (n=16 studies), (iv) Knee osteoarthritis has a social impact (n=10 studies), (v) Knee osteoarthritis has an emotional impact (n=13 studies), (vi) Interactions with health professionals can be positive or negative (n=11 studies), (vii) Knee osteoarthritis leads to life adjustments (n=14 studies). A single study reporting the perspectives of carers reported similar themes. Psychosocial impact of knee osteoarthritis emerged as a key factor in the lived experience of people with knee osteoarthritis.

CONCLUSIONS
This review highlights the value of considering patient attitudes and experiences including psychosocial factors when planning and implementing management options for people with knee osteoarthritis. Trial registration number CRD42018108962.

Wallis|Jason A|JA|
Taylor|Nicholas F|NF|
Bunzli|Samantha|S|0000-0002-5747-9361
Shields|Nora|N|

knee
osteoarthritis
systematic review
qualitative
lived experience


Abstract:
Aim
To create awareness of Kawasaki disease in the dental community as it is a rare disease and some cases might go unnoticed due to lack of knowledge of the treating dentist. Thus proper knowledge helps in the timely diagnosis of the disease and decrease the mortality rate in these patients. Children who show the oral features of this disease should be treated seriously by the dentist.

Background
Kawasaki disease is a rare acute systemic vasculitis disorder reported in the dental literature. Clinical features include high fever, redness of palms and soles of the feet, conjunctivitis, oropharyngeal mucositis and lymphadenopathy. The cardiac involvement in the form of myocarditis, aneurysms, pericarditis is also seen and is caused by inflammation of vessels of the heart.

Case description
Here we present a rare case of an 8-year-old girl who presented to the department of Pediatric Dentistry with the chief complaint of recurrent painless swelling of the lower lip. This rare presentation of lower lip swelling has not been cited in the oral manifestation of Kawasaki disease before.

Clinical significance
The disease has high mortality and morbidity rate if not treated early, and hence an early diagnosis and treatment are important in managing this condition. The oral findings are a characteristic feature of this serious disease, hence, many cases might first report to the dental clinician only. Dentists should always remain alert in handling patients having a history of Kawasaki disease because of the possibility of recurrence of the disease. As these patients have valvular heart defects, they might require prophylactic antibiotic treatment before the needed dental procedure.

Conclusion
Despite this, there seems to be less aware of this disease among the dentist, hence this condition goes unnoticed leading to few citations of this disease in the dental literature.

How to cite this article
Verma L, Passi S, Kaur G, Gupta J, Joshi M. Recurrent Kawasaki Disease Presenting to Dentists: "Think Beyond Dentition". Int J Clin Pediatr Dent, 2018;11(6):532-535.

Verma|Leena|L| Passi|Sidhi|S| Kaur|Gagandeep|G| Gupta|Jyoti|J| Joshi|Mitul|M|

Recurrent
Kawasaki disease
Orofacial features


Stimulation by abscisic acid of the activity of phosphoenolpyruvate carboxylase in leaf disks of Amaranthus hypochondriacus L., C4 plant: role of pH and protein levels.

Abstract: C4 plants can more efficiently fix carbon in drought, high temperatures, and limitations of nitrogen or CO2. Primary carboxylation is mediated by phosphoenolpyruvate carboxylase (PEPC, 4.1.1.31) in mesophyll cytosol of C4 plants. Studies on hormonal regulation of C4 PEPC have been quite limited. We have examined the activity/regulation of PEPC by abscisic acid (ABA), a plant hormone, in the leaves of Amaranthus hypochondriacus. PEPC activity was enhanced upon 1-h incubation with 20 μM ABA by about 30% in dark and more than 2-fold in light. Glucose-6-phosphate activation of PEPC was enhanced, and sensitivity to L-malate was decreased after ABA treatment. Butyric acid (a weak acid) decreased PEPC activity and restricted the stimulation by ABA. In contrast, methylamine (an alkalinizing agent) increased the PEPC activity and enhanced the effect of ABA. ABA increased the levels of PEPC protein as well as its mRNA. Butyric acid/methylamine modulated the changes induced by ABA of PEPC protein and mRNA levels, indicating that acidification/alkalinization of leaf disks was very important. Our results emphasize the marked modulation of PEPC in C4 plants, by ABA. Such modulation by ABA could be significant when C4 plants are under water stress, when ABA is known to accumulate. When present, cycloheximide decreased the PEPC protein levels and restricted the extent of activation by ABA. We conclude that the enhancement by ABA of PEPC activity depends on cellular alkalinization as well as elevated PEPC protein levels.

Aloor|Bindu Prasuna|BP|
Avasthi|Uday Kiran|UK|
Raghavendra|Agepati S|AS|

D000040:Abscisic Acid
D027721:Amaranthus
D020148:Butyric Acid
D003513:Cycloheximide
D006863:Hydrogen-Ion Concentration
D008744:Methylamines
D010730:Phosphoenolpyruvate Carboxylase
D018515:Plant Leaves
D010940:Plant Proteins

PEPC
Butyric acid
Methylamine
Acidification
Cycloheximide
Alkalization


Clinical relevance of cholesterol homeostasis genes in colorectal cancer.

Abstract: Accumulation of cholesterol is a well-known feature in cancer. Preclinical studies suggest the contribution of various cholesterol regulators in CRC. However, their clinical relevance remains poorly understood. The aim of the present study is to evaluate the expression of these modulators in CRC and elucidate their diagnostic and prognostic value. mRNA levels of HMGCR, SREBF2, NR1H3 and NR1H2 were downregulated in tumors in local and TCGA cohort. The expression of LDLR, ABCA1 and SCARB1 was not consistent in the two cohorts. Western Blot analysis showed the increased levels of LDLR and reduced levels of LXR in early stage patients. Tumoral SREBP2 levels were enhanced in early stage whereas decreased in late stage. The individual expression of HMGCR, SREBF2, NR1H3 and NR1H2 did not have the potential to be used as independent prognostic marker, however, the combined expression of these genes associated with poor clinical outcome independent of lymph node metastasis, distant metastasis and advanced stage. This work sheds light on deregulation of cholesterol uptake and efflux pathways and provides novel leads in the development of biomarkers and therapeutic regimens that can detect and target CRC at initial stages.

Sharma|Bhoomika|B| Gupta|Vikas|V| Dahiya|Divya|D| Kumar|Hemanth|H| Vaiphei|Kim|K| Agnihotri|Navneet|N|

D015972:Gene Expression Regulation, Neoplastic

D051782:Sterol Regulatory Element Binding Protein 2

HMGCR
SREBF2
LDLR
Cholesterol efflux
Liver X receptors


Comparison of operational characteristics for binary tests with clustered data.

Abstract: Although statistical methodology is well-developed for comparing diagnostic tests in terms of their sensitivity and specificity, comparative inference about predictive values is not. In this paper, we consider the analysis of studies comparing operating characteristics of two diagnostic tests that are measured on all subjects and have test outcomes from multiple sites with varying number of sites among subjects. We have developed a new approach for comparing sensitivity, specificity, positive predictive value, and negative predictive value with simple variance calculation and, in particular, focus on comparing tests using difference of positive and negative predictive values. Simulation studies are conducted to show the performance of our approach. We analyze real data on patients with lung cancer, based on their diagnostic tests, to illustrate the methodology.

D001699:Biometry
D003198:Computer Simulation
D003955:Diagnostic Tests, Routine
D006801:Humans
D015233:Models, Statistical
D011237:Predictive Value of Tests
D012680:Sensitivity and Specificity

sensitivity
specificity
positive predictive value
negative predictive value
clustered binary outcome


Non-Invasive Ultrasonic Description of Tumor Evolution.

Abstract:
PURPOSE
There is a clinical need to better non-invasively characterize the tumor microenvironment in order to reveal evidence of early tumor response to therapy and to better understand therapeutic response. The goals of this work are first to compare the sensitivity to modifications occurring during tumor growth for measurements of tumor volume, immunohistochemistry parameters, and emerging ultrasound parameters (Shear Wave Elastography (SWE) and dynamic Contrast-Enhanced Ultrasound (CEUS)), and secondly, to study the link between the different parameters.

METHODS
Five different groups of 9 to 10 BALB/c female mice with subcutaneous CT26 tumors were imaged using B-mode morphological imaging, SWE, and CEUS at different dates. Whole-slice immunohistological data stained for the nuclei, T lymphocytes, apoptosis, and vascular endothelium from these tumors were analyzed.

RESULTS
Tumor volume and three CEUS parameters (Time to Peak, Wash-In Rate, and Wash-Out Rate) significantly changed over time. The immunohistological parameters, CEUS parameters, and SWE parameters showed intracorrelation. Four immunohistological parameters (the number of T lymphocytes per mm2 and its standard deviation, the percentage area of apoptosis, and the colocalization of apoptosis and vascular endothelium) were correlated with the CEUS parameters (Time to Peak, Wash-In Rate, Wash-Out Rate, and Mean Transit Time). The SWE parameters were not correlated with the CEUS parameters nor with the immunohistological parameters.

CONCLUSIONS
US imaging can provide additional information on tumoral changes. This could help to better explore the effect of therapies on tumor evolution, by studying the evolution of the parameters over time and by studying their correlations.

Griffon|Jerome|J|
Buffello|Delphine|D|
Giron|Alain|A|0000-0003-0888-6312
Bridal|S Lori|SL|
Lamuraglia|Michele|M|

tumor microenvironment
tumor growth
SWE
CEUS
histological biomarkers
tumor neo angiogenesis


Why Do I Have to Drive Now? Post Hoc Explanations of Takeover Requests.

Abstract:
OBJECTIVE
It was investigated whether providing an explanation for a takeover request in automated driving influences trust in automation and acceptance.

BACKGROUND
Takeover requests will be recurring events in conditionally automated driving that could undermine trust as well as acceptance and, therefore, the successful introduction of automated vehicles.

METHOD
Forty participants were equally assigned to either an experimental group provided with an explanation of the reason for a takeover request or a control group without explanations. In a simulator drive, both groups experienced three takeover scenarios that varied in the obviousness of their causation. Participants rated their acceptance before and after the drive and rated their trust before and after each takeover situation.

RESULTS
All participants rated acceptance on the same high level before and after the drive, independent of the condition. The control group's trust ratings remained unchanged by takeover requests in all situations, but the experimental group showed decreased trust after experiencing a takeover caused by roadwork. Participants provided with explanation felt more strongly that they had understood the system and the reasons for the takeovers.

CONCLUSION
A takeover request did not lower trust or acceptance. Providing an explanation for a takeover request had no impact on trust or acceptance but increased the perceived understanding of the system.

APPLICATION
The results provide insights into users' perception of automated vehicles, takeover situations, and a fundament for future interface design for automated vehicles.

takeover request
automated driving
trust in automation
human–automation interaction
technology acceptance


Voltage-gated calcium channels contribute to spontaneous glutamate release directly via nanodomain coupling or indirectly via calmodulin.

Abstract: Neurotransmitter release occurs either synchronously with action potentials (evoked release) or spontaneously (spontaneous release). Whether the molecular mechanisms underlying evoked and spontaneous release are identical, especially whether voltage-gated calcium channels (VGCCs) can trigger spontaneous events, is still a matter of debate in glutamatergic synapses. To elucidate this issue, we characterized the VGCC dependence of miniature excitatory postsynaptic currents (mEPSCs) in various synapses with different coupling distances between VGCCs and synaptic vesicles, known as a critical factor in evoked release. We found that most of the extracellular calcium-dependent mEPSCs were attributable to VGCCs in cultured autaptic hippocampal neurons and the mature calyx of Held where VGCCs and vesicles were tightly coupled. Among loosely coupled synapses, mEPSCs were not VGCC-dependent at immature calyx of Held and CA1 pyramidal neuron synapses, whereas VGCCs contribution was significant at CA3 pyramidal neuron synapses. Interestingly, the contribution of VGCCs to spontaneous glutamate release in CA3 pyramidal neurons was abolished by a calmodulin antagonist, calmidazolium. These data suggest that coupling distance between VGCCs and vesicles determines VGCC dependence of spontaneous release at tightly coupled synapses, yet VGCC contribution can be achieved indirectly at loosely coupled synapses.

Lee|Byoung Ju|BJ|
Yang|Che Ho|CH|
Lee|Seung Yeon|SY|
Lee|Suk-Ho|SH|
Kim|Yujin|Y|
Ho|Won-Kyung|WK|

Voltage-gated calcium channels
Spontaneous glutamate release
Coupling distance


Effect of surfactant concentration and solidification temperature on the characteristics and stability of nanostructured lipid carrier (NLC) prepared from rambutan (Nephelium lappaceum L.) kernel fat.

Abstract: Nanostructured lipid carrier (NLC) was fabricated from rambutan (Nephelium lappaceum L.) kernel fat stabilized with Tween 80 in this present work. The influence of the Tween 80 concentration (0.025, 0.05, 0.1, 0.2, 0.5 and 1.0wt%) and solidification temperature (5 and 25°C) on the characteristics and stability of the NLC were investigated. The results showed that an increase in the Tween 80 concentration caused decreased zeta-potential (ζ-potential) and particle size (Z-average) with no significant effect on the polydispersity index (PDI). Lipid particles in the NLC at all Tween 80 concentrations had a tendency to grow and the PDI tended to increase due to Ostwald ripening upon storage over 28days. At least 0.2wt% Tween 80 concentrations could be used to stabilize 1wt% rambutan NLC. The solidification temperature affected the microstructure, melting behavior and stability of rambutan NLC. Pre-solidification at 5°C could create stable NLC with monodispersed-spherical lipid particles. Consequently, these stable NLC particles produced from rambutan kernel fat may serve as useful carriers for the delivery of bioactive lipophilic nutraceuticals.

Surfactant concentration
Solidification temperature
Nanostructure lipid carrier
Rambutan kernel fat
Particle characteristics
Physical stability


The applicability of community of inquiry framework to online nursing education: A cross-sectional study.

Abstract: The Community of Inquiry (CoI) framework has the potential to contribute to online education by addressing the nexus of pedagogy, technology, and learners' needs. However, there has been limited investigation of the application of CoI to Australian online tertiary education, with the awareness of CoI amongst Australian nurse educators being unknown. This paper reports on a project which used an online survey to investigate the level of awareness of the CoI framework and its applicability to the design of online and blended courses in Australian higher education nursing schools. Most respondents ranked the core concepts of the CoI framework as applicable for nursing education, but only 20% of the participants were familiar with the CoI framework before they participated in the survey. While nearly 90% of the participants viewed instructional design and a theoretical framework as essential for building an online course, 70% of respondents indicated that they did not use an explicit theoretical framework to guide the design or the evaluation of their nursing teaching and learning. These results provide the impetus for further investigation of factors influencing the development of online nurse education including the specific consideration of CoI frameworks.

Smadi|Omar|O| Parker|Steve|S| Gillham|David|D| Müller|Amanda|A|

Online nursing education
Theoretical framework
Community of inquiry applicability
Community of inquiry awareness


Aflatoxins ingestion and canine mammary tumors: There is an association?

Abstract: The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60).

Frehse|M S|MS|
Martins|M I M|MI|
Ono|E Y S|EY|
Bracarense|A P F R L|AP|
Bissoqui|L Y|LY|
Teixeira|E M K|EM|
Santos|N J R|NJ|
Freire|R L|RL|

Aflatoxin
Dogs
Fumonisin
Zearalenone
Mammary cancer
Risk factors


Multimorbidity and the risk of major adverse kidney events: findings from the UK Biobank cohort.

Abstract:
Background
Multimorbidity [the presence of two or more long-term conditions (LTCs)] is associated with a heightened risk of mortality, but little is known about its relationship with the risk of kidney events.

Methods
Associations between multimorbidity and major adverse kidney events [MAKE: the need for long-term kidney replacement therapy, doubling of serum creatinine, fall of estimated glomerular filtration rate (eGFR) to <15 mL/min/1.73 m2 or 30% decline in eGFR] were studied in 68 505 participants from the UK Biobank cohort. Participants were enrolled in the study between 2006 and 2010. Associations between LTC counts and MAKE were tested using survival analyses accounting for the competing risk of death.

Results
Over a median follow-up period of 12.0 years, 2963 participants had MAKE. There were associations between LTC count categories and the risk of MAKE [one LTC adjusted subhazard ratio (sHR) = 1.29, 95% confidence interval (CI) 1.15-1.45; two LTCs sHR = 1.74 (95% CI 1.55-1.96); and three or more LTCs sHR = 2.41 (95% CI 2.14-2.71)]. This finding was more pronounced when only cardiometabolic LTCs were considered [one LTC sHR = 1.58 (95% CI 1.45-1.73); two LTCs sHR = 3.17 (95% CI 2.80-3.59); and three or more LTCs sHR = 5.24 (95% CI 4.34-6.33)]. Combinations of LTCs associated with MAKE were identified. Diabetes, hypertension and coronary heart disease featured most commonly in high-risk combinations.

Conclusions
Multimorbidity, and in particular cardiometabolic multimorbidity, is a risk factor for MAKE. Future research should study groups of patients who are at high risk of progressive kidney disease based on the number and type of LTCs.

multimorbidity
mortality
cardiometabolic
comorbidity
condition clusters
kidney outcomes


Progress with peptide scanning to study structure-activity relationships: the implications for drug discovery.

Abstract:
INTRODUCTION
Peptides have gained renewed interest as candidate therapeutics. However, to bring them to a broader clinical use, challenges such as the rational optimization of their pharmacological properties remain. Peptide scanning techniques offer a systematic framework to gain information on the functional role of individual amino acids of a peptide. Due to progress in mastering new chemical synthesis routes targeting amino acid backbone, they are currently diversified. Structure-activity relationship (SAR) analyses such as alanine- or enantioneric- scanning can now be supplemented by N-substitution, lactam cyclisation- or aza-amino scanning procedures addressing not only SAR considerations but also the peptide pharmacological properties.

AREAS COVERED
This review highlights the different scanning techniques currently available and illustrates how they can impact drug discovery.

EXPERT OPINION
Progress in peptide scanning techniques opens new perspectives for peptide drug development. It comes with the promise of a paradigm change in peptide drug design in which peptide drugs will be closer to the parent peptides. However, scanning still remains assimilable to a trial and error strategy that could benefit from being combined with specific in silico approaches that start reaching maturity.

D000596:Amino Acids
D015195:Drug Design
D055808:Drug Discovery
D006801:Humans
D010455:Peptides
D013329:Structure-Activity Relationship

Peptide scanning
Aza-amino
Peptide drug development
Ala-
D-
N-alkyl scanning
Positional-
Pro-
gamma-lactam


Race and contrast-induced nephropathy in patients undergoing coronary angiography and cardiac catheterization.

Abstract: Contrast-induced nephropathy (CIN) is an acute worsening of renal function after receiving intravascular contrast during a procedure. Some of the predisposing factors include underlying diabetes, chronic kidney disease, congestive heart failure, periprocedural hypotension, anemia, contrast volume, and osmolality of contrast; however, it remains unclear if risk varies for CIN with race and ethnicity. There is evidence in the literature showing the link between race/ethnicity and the discrepancies in the utilization of preventive care services and the resources related to cardiovascular and renal health. While these disparities continue to exist and affect some of the predictors of CIN, this review will explore the extent to which race and ethnicity directly affect CIN.

Chawla|Raveen|R|
Turlington|Jeremy|J|
Arora|Pradeep|P|
Jovin|Ion S|IS|

D058186:Acute Kidney Injury
D000818:Animals
D006328:Cardiac Catheterization
D003287:Contrast Media
D017023:Coronary Angiography
D003324:Coronary Artery Disease
D014943:Global Health
D006801:Humans
D015994:Incidence
D044469:Racial Groups
D012307:Risk Factors

Race
Contrast-induced nephropathy
Cardiac catheterization
Disparity
Outcome research


Analysis of surfaces for characterization of fungal burden - Does it matter?

Abstract:
OBJECTIVES
Mycological contamination of occupational environments can be a result of fungal spores' dispersion in the air and on surfaces. Therefore, it is very important to assess it in both types of the samples. In the present study we assessed fungal contamination in the air and in the surface samples to show relevance of surfaces sampling in complementing the results obtained in the air samples.

MATERIAL AND METHODS
In total, 42 settings were assessed by the analysis of air and surfaces samples. The settings were divided into settings with a high fungal load (7 poultry farms and 7 pig farms, 3 cork industries, 3 waste management plants, 2 wastewater treatment plants and 1 horse stable) and a low fungal load (10 hospital canteens, 8 college canteens and 1 maternity hospital). In addition to culture-based methods, molecular tools were also applied to detect fungal burden in the settings with a higher fungal load.

RESULTS
From the 218 sampling sites, 140 (64.2%) presented different species in the examined surfaces when compared with the species identified in the air. A positive association in the high fungal load settings was found between the presence of different species in the air and surfaces. Wastewater treatment plants constituted the setting with the highest number of different species between the air and surface.

CONCLUSIONS
We observed that surfaces sampling and application of molecular tools showed the same efficacy of species detection in high fungal load settings, corroborating the fact that surface sampling is crucial for a correct and complete analysis of occupational scenarios.

Viegas|Carla|C|
Faria|Tiago|T|
Meneses|Márcia|M|
Carolino|Elisabete|E|
Viegas|Susana|S|
Gomes|Anita Quintal|AQ|
Sabino|Raquel|R|

D060888:Real-Time Polymerase Chain Reaction

occupational environments
surface samples
air samples
high fungal load settings
fungal burden assessment
low fungal load settings


Salvianolate lyophilized injection (SLI) strengthens blood-brain barrier function related to ERK1/2 and Akt signaling pathways.

Abstract: The salvianolate lyophilized injection (SLI) has been widely used for the treatment of acute cerebral infarction; however, the molecular mechanism of how it strengthens blood brain barrier (BBB) function is not well understood. Here, we investigated the effects of SLI on BBB function in bEnd.3 cells as well as in rats. In oxygen glucose deprivation/reoxygenation (OGD/R)-damaged bEnd.3 cells, SLI increased transepithelial electrical resistance and decreased sodium fluorescein flux. SLI-treated cells showed increased expression of tight junction proteins, including Zonula occludens-1 (ZO-1), Claudin-5 and Occludin. Furthermore, SLI led to the decrease of phosphorylation of ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of SLI on barrier function were abolished in cells in which ERK1/2 and Ak signaling were inhibited. Moreover, in MCAO model rats, SLI effectively alleviated brain leakage of Evans blue, increased brain tissue ZO-1 expression and inhibited phosphorylation of ERK1/2 and Akt. Overall, these data suggest that SLI strengthens BBB function was interrelated ERK1/2 and Akt signaling pathways in cerebral vascular diseases.

Zhao|Chun|C| Li|Xueli|X| Li|Xiaojin|X| Xu|Yangyang|Y| Ma|Mengmeng|M| Wang|Shaoxia|S| Chai|Lijuan|L| Guo|Hong|H| Hu|Limin|L|

Salvianolate lyophilized injection
ERK1/2
Akt
Blood brain barrier
Tight junction


Is There Evidence of Cost Benefits of Electronic Medical Records, Standards, or Interoperability in Hospital Information Systems? Overview of Systematic Reviews.

Abstract:
BACKGROUND
Electronic health (eHealth) interventions may improve the quality of care by providing timely, accessible information about one patient or an entire population. Electronic patient care information forms the nucleus of computerized health information systems. However, interoperability among systems depends on the adoption of information standards. Additionally, investing in technology systems requires cost-effectiveness studies to ensure the sustainability of processes for stakeholders.

OBJECTIVE
The objective of this study was to assess cost-effectiveness of the use of electronically available inpatient data systems, health information exchange, or standards to support interoperability among systems.

METHODS
An overview of systematic reviews was conducted, assessing the MEDLINE, Cochrane Library, LILACS, and IEEE Library databases to identify relevant studies published through February 2016. The search was supplemented by citations from the selected papers. The primary outcome sought the cost-effectiveness, and the secondary outcome was the impact on quality of care. Independent reviewers selected studies, and disagreement was resolved by consensus. The quality of the included studies was evaluated using a measurement tool to assess systematic reviews (AMSTAR).

RESULTS
The primary search identified 286 papers, and two papers were manually included. A total of 211 were systematic reviews. From the 20 studies that were selected after screening the title and abstract, 14 were deemed ineligible, and six met the inclusion criteria. The interventions did not show a measurable effect on cost-effectiveness. Despite the limited number of studies, the heterogeneity of electronic systems reported, and the types of intervention in hospital routines, it was possible to identify some preliminary benefits in quality of care. Hospital information systems, along with information sharing, had the potential to improve clinical practice by reducing staff errors or incidents, improving automated harm detection, monitoring infections more effectively, and enhancing the continuity of care during physician handoffs.

CONCLUSIONS
This review identified some benefits in the quality of care but did not provide evidence that the implementation of eHealth interventions had a measurable impact on cost-effectiveness in hospital settings. However, further evidence is needed to infer the impact of standards adoption or interoperability in cost benefits of health care; this in turn requires further research.

cost
electronic medical records
standards
health information exchange
benefits and costs
medical information exchange


Design, development, and evaluation of a local sensor-based gait phase recognition system using a logistic model decision tree for orthosis-control.

Abstract:
BACKGROUND
Functionality and versatility of microprocessor-controlled stance-control knee-ankle-foot orthoses (M-SCKAFO) are dictated by their embedded control systems. Proper gait phase recognition (GPR) is required to enable these devices to provide sufficient knee-control at the appropriate time, thereby reducing the incidence of knee-collapse and fall events. Ideally, the M-SCKAFO sensor system would be local to the thigh and knee, to facilitate innovative orthosis designs that allow more flexibility for ankle joint selection and other orthosis components. We hypothesized that machine learning with local sensor signals from the thigh and knee could effectively distinguish gait phases across different walking conditions (i.e., surface levels, walking speeds) and that performance would improve with gait phase transition criteria (i.e., current states depend on previous states).

METHODS
A logistic model decision tree (LMT) classifier was trained and tested (five-fold cross-validation) on gait data that included knee flexion angle, thigh-segment angular velocity, and thigh-segment acceleration. Twenty features were extracted from 0.1 s sliding windows for 30 able-bodied participants that walked on different surfaces (level, down-slope, up-slope, right cross-slope, left cross-slope) at a various walking speeds (self-paced (1.33 m/s, SD = 0.04 m/s), 0.8, 0.6, 0.4 m/s). The LMT-based GPR model was also tested with another validation set containing similar features and surfaces from 12 able-bodied volunteers at self-paced walking speeds (1.41 m/s, SD = 0.34 m/s). A "Transition Sequence Verification and Correction" (TSVC) algorithm was applied to correct for continuous class prediction and to improve GPR performance.

RESULTS
The LMT had a tree size of 1643 with 822 leaf nodes, with a logistic regression model at each leaf node. The local sensor LMT-based GPR model identified loading response, push-off, swing, and terminal swing phases with overall classification accuracy of 98.38 for the initial training set (five-fold cross-validation) and 90.60% for the validation set. Applying TSVC increased classification accuracy to 98.72% for the initial training set and 98.61% for the validation set. Sensitivity, specificity, precision, F-score, and Matthew's correlation coefficient results suggest strong evidence for the feasibility of an LMT-based GPR system for real-time orthosis control.

CONCLUSIONS
The novel machine learning GPR model that used sensor features local to the thigh and knee was viable for dynamic knee-ankle-foot orthosis-control. This highly accurate GPR model was generalizable when combined with TSVC. Our approach could reduce sensor system complexity as compared with other M-SCKAFO approaches, thereby enabling customizable advantages for end-users through modular unit orthosis designs.

Farah|Johnny D|JD|0000-0001-9060-4761
Baddour|Natalie|N|
Lemaire|Edward D|ED|

Gait phase recognition
Decision tree
Sensors
Machine learning
Knee ankle foot orthosis
Microprocessor
Stance control


Green synthesis of lignin nano- and micro-particles: Physicochemical characterization, bioactive properties and cytotoxicity assessment.

Abstract: Lignin particles (LPs) have gained prominence due to their biodegradability and bioactive properties. LP production at nano and micro scale produced from organosolv lignin and the understanding of size's effect on their properties is unexplored. This work aimed to produce and characterize lignin nanoparticles and microparticles using a green synthesis process, based on ethanol-solubilized lignin and water. Spherical shape LPs, with a mean size of 75 nm and 215 nm and with a low polydispersity were produced, as confirmed by transmission electron microscopy and dynamic light scattering. LPs thermal stability improved over raw lignin, and the chemical structure of lignin was not affected by the production method. The antimicrobial tests proved that LPs presented a bacteriostatic effect on Escherichiacoli and Salmonella enterica. Regarding the antioxidant potential, LPs had a good antioxidant activity that increased with the reaction time and LPs concentration. LPs also presented an antioxidant effect against intracellular ROS, reducing the intracellular ROS levels significantly. Furthermore, the LPs showed a low cytotoxic effect in Caco-2 cell line. These results showed that LPs at different scales (nano and micro) present biological properties and are safe to be used in different high value industrial sectors, such as biomedical, pharmaceutical and food.

Freitas|Filipa M C|FMC|
Cerqueira|Miguel A|MA|
Gonçalves|Catarina|C|
Azinheiro|Sarah|S|
Garrido-Maestu|Alejandro|A|
Vicente|António A|AA|
Pastrana|Lorenzo M|LM|
Teixeira|José A|JA|
Michelin|Michele|M|

Cytotoxicity Antioxidant Biocompatibility Lignocellulose Nanotechnology


Genome-wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population.

Abstract:
BACKGROUND
Fasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin.

RESULTS
We conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10-4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort.

CONCLUSIONS
Previous studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

Chung|Ren-Hua|RH|
Chiu|Yen-Feng|YF|
Hung|Yi-Jen|YJ|
Lee|Wen-Jane|WJ|
Wu|Kwan-Dun|KD|
Chen|Hui-Ling|HL|
Lin|Ming-Wei|MW|
Chen|Yii-Der I|YI|
Quertermous|Thomas|T|
Hsiung|Chao A|CA|

Copy number variations
Fasting glucose
Fasting insulin
Family-based association analysis


Perioperative management of adult patients with a history of stroke or transient ischaemic attack undergoing elective non-cardiac surgery.

Abstract: It is increasingly common for physicians and anaesthetists to be asked for advice in the medical management of surgical patients who have an incidental history of stroke or transient ischaemic attack (TIA). Advising clinicians requires an understanding of the common predictors, outcomes and management of perioperative stroke. The most important predictor of perioperative stroke is a previous history of stroke, and outcomes associated with such an event are extremely poor. The perioperative management of this patient group needs careful consideration to minimise the thrombotic risk and a comprehensive, individualised approach is crucial. Although there is literature supporting the management of such patients undergoing cardiac surgery, evidence is lacking in the setting of non-cardiac surgical intervention. This article reviews the current evidence and provides a pragmatic interpretation to inform the perioperative management of patients with a history of stroke and/or TIA presenting for elective non-cardiac surgery.

Mehdi|Zehra|Z| Birns|Jonathan|J| Partridge|Judith|J| Bhalla|Ajay|A| Dhesi|Jugdeep|J|

perioperative
stroke
non-cardiac surgery
Anticoagulation
Antiplatelet


Spectroscopic studies on the antioxidant activity of ellagic acid.

Abstract: Ellagic acid (EA, C14H6O8) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anticarcinogenesis and anti-oxidation properties. In vitro radical scavenging and antioxidant capacity of EA were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. EA inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), α-tocopherol and ascorbic acid displayed 69.8%, 66.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, EA had an effective DPPH• scavenging, ABTS+ scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that EA can be used in the pharmacological, food industry and medicine because of these properties.

Antioxidant activity
Ellagic acid
Free radicals
Reducing power
Metal chelating


Nutritional properties and consumer evaluation of donkey bresaola and salami: comparison with conventional products.

Abstract: Nutritional properties and consumer evaluation were performed in bresaola and salami from donkey meat compared with respective conventional products. Donkey bresaola and salami showed higher content of protein and lower content of fat than beef bresaola and pork salami. Significant differences in the unsaturation level of fatty acids were found. Particularly, donkey meat products showed lower saturated fatty acids, higher polyunsatured fatty acid content and better nutritional indices than conventional beef bresaola and pork salami. Furthermore, donkey meat products, especially bresaola, showed the highest content of essential amino acids. Both donkey meat products resulted to be more tender than conventional products, in addition donkey bresaola showed also higher consumer acceptability. Our investigation demonstrates the possibility of processing donkey meat into products comparable to traditional ones with a high nutritional value.

Marino|R|R|
Albenzio|M|M|
Della Malva|A|A|
Muscio|A|A|
Sevi|A|A|

Bresaola
Salami
Donkey meat
Nutraceutical properties


Mild Hyperhomocysteinemia Causes Anxiety-like Behavior and Brain Hyperactivity in Rodents: Are ATPase and Excitotoxicity by NMDA Receptor Overstimulation Involved in this Effect?

Abstract: Mild hyperhomocysteinemia is a risk factor for psychiatric and neurodegenerative diseases, whose mechanisms between them are not well-known. In the present study, we evaluated the emotional behavior and neurochemical pathways (ATPases, glutamate homeostasis, and cell viability) in amygdala and prefrontal cortex rats subjected to mild hyperhomocysteinemia (in vivo studies). The ex vivo effect of homocysteine on ATPases and redox status, as well as on NMDAR antagonism by MK-801 in same structures slices were also performed. Wistar male rats received a subcutaneous injection of 0.03 µmol Homocysteine/g of body weight or saline, twice a day from 30 to 60th-67th days of life. Hyperhomocysteinemia increased anxiety-like behavior and tended to alter locomotion/exploration of rats, whereas sucrose preference and forced swimming tests were not altered. Glutamate uptake was not changed, but the activities of glutamine synthetase and ATPases were increased. Cell viability was not altered. Ex vivo studies (slices) showed that homocysteine altered ATPases and redox status and that MK801, an NMDAR antagonist, protected amygdala (partially) and prefrontal cortex (totally) effects. Taken together, data showed that mild hyperhomocysteinemia impairs the emotional behavior, which may be associated with changes in ATPase and glutamate homeostasis, including glutamine synthetase and NMDAR overstimulation that could lead to excitotoxicity. These findings may be associated with the homocysteine risk factor on psychiatric disorders development and neurodegeneration.

Mild hyperhomocysteinemia
Receptors
Glutamate homeostasis
Anxiety disorders
Cell survival
N-Methyl-D-Aspartate
Sodium–Potassium-exchanging ATPase


Utility decrements associated with side effects in schizophrenia.

Abstract:
OBJECTIVE
Most of the existing studies investigating the impact of schizophrenia on utility have focused on the different stages of the disease. The objective of this study was to describe and quantify the impact of treatment-related side-effects on utility in patients with schizophrenia, using data from an observational study.

METHODS
This study used data from the European Schizophrenia Cohort (EuroSC), a multi-center 2-year cohort study conducted in France, England, and Germany. The EQ-5D questionnaire was completed every 6 months, as well as the Subjective Side Effect Rating Scale, assessing patient distress over extrapyramidal symptoms (EPS), weight gain, sedation, and sexual dysfunction, used to assess whether or not the patient experienced the side-effect. At first a bivariate analysis was conducted to describe utility values with and without side-effects. Then, a random effects regression analysis was performed on utility, where random effects were controlled for repeated measures on the same subjects, with potential confounding factors. Finally, findings were compared with those of previous publications.

RESULTS
This sample consisted of 1208 patients with schizophrenia. At the baseline visit, the most reported side-effect was EPS (almost 60% of patients), followed by sedation and weight gain (∼50% of patients for each), and sexual dysfunction (almost 30% of patients). Significant association with severity of symptoms, functioning abilities, and utility were found. Patients reporting none of the studied side-effects had an average EQ-5D index score of 0.81, found to be higher than scores of patients reporting EPS (0.70), sexual dysfunction (0.67), sedation (0.70), or weight gain (0.72). The random effects model reported a utility decrement of 0.042 for EPS, 0.022 for weight gain, 0.022 for sexual dysfunction, and 0.019 for sedation. Although the external validation was difficult due to the different methods or definitions of the side-effects, as well as the paucity of data for weight gain, sedation and sexual dysfunction, the results were generally consistent with previous studies.

CONCLUSION
This study aimed at quantifying the direct impact of main side-effects associated with antipsychotics on patients' utility. RESULTS suggested a significant direct impact of side-effects, with EPS being the most impactful.

Millier|A|A| Amri|I|I| Boyer|L|L| Auquier|P|P| Toumi|M|M|

D064420:Drug-Related Side Effects and Adverse Reactions

Utility Schizophrenia Side-effects Antipsychotics Quality-of-life


Inter-individual differences in trait anxiety shape the functional connectivity between the bed nucleus of the stria terminalis and the amygdala during brief threat processing.

Abstract: An influential framework suggests that the central nucleus of the amygdala (CeA) is involved in phasic responses to threat, while the bed nucleus of the stria terminalis (BNST) mediates sustained anxiety. However, this model has been questioned, proposing that the role of the BNST is not limited to sustained threat contexts. Rather, amygdala and BNST also seem to work in concert in the processing of discrete and briefly presented threat-related stimuli, likely dependent on inter-individual differences in anxiety. A direct test of this assumption with sufficient experimental power is missing in human research and the degree to which individual differences in trait anxiety moderate phasic responses and functional connectivity of amygdala and BNST during threat processing remains unclear. The current event-related functional magnetic resonance imaging (fMRI) study investigated activation and connectivity of amygdala and BNST, as well as modulating effects of trait anxiety, during processing of briefly presented threat-related relative to neutral standardized pictures in 93 psychiatrically healthy individuals. Both amygdala and BNST activation was increased during presentation of threat-related relative to neutral pictures. Furthermore, functional connectivity between BNST and amygdala in response to threat was positively associated with trait anxiety. These findings suggest that amygdala and BNST form a functional unit during phasic threat processing whereby their connectivity is shaped by inter-individual differences in trait anxiety.

Brinkmann|Leonie|L|
Buff|Christine|C|
Feldker|Katharina|K|
Neumeister|Paula|P|
Heitmann|Carina Y|CY|
Hofmann|David|D|
Bruchmann|Maximilian|M|
Herrmann|Martin J|MJ|
Straube|Thomas|T|

Bed nucleus of the stria terminalis (BNST)


Adjuvant radiation versus observation with salvage radiation after gross-total resection of WHO grade II meningiomas: a propensity score-adjusted analysis.

Abstract:
OBJECTIVE
After gross-total resection (GTR) of a newly diagnosed WHO grade II meningioma, the decision to treat with radiation upfront or at initial recurrence remains controversial. A comparison of progression-free survival (PFS) between observation and adjuvant radiation fails to account for the potential success of salvage radiation, and a direct comparison of PFS between adjuvant and salvage radiation is hampered by strong selection bias against salvage radiation cohorts in which only more aggressive, recurrent tumors are included. To account for the limitations of traditional PFS measures, the authors evaluated radiation failure-free survival (RFFS) between two treatment strategies after GTR: adjuvant radiation versus observation with salvage radiation, if necessary.

METHODS
The authors performed a retrospective review of patients who underwent GTR of newly diagnosed WHO grade II meningiomas at their institution between 1996 and 2019. They assessed traditional PFS in patients who underwent adjuvant radiation, postoperative observation, and salvage radiation. For RFFS, treatment failure was defined as time from initial surgery to failure of first radiation. To assess the association between treatment strategy and RFFS while accounting for potential confounders, a multivariable Cox regression analysis adjusted for the propensity score (PS) and inverse probability of treatment weighted (IPTW) Cox regression analysis were performed.

RESULTS
A total of 160 patients underwent GTR and were included in this study. Of the 121 patients who underwent observation, 32 (26.4%) developed recurrence and required salvage radiation. PFS at 3, 5, and 10 years after observation was 75.1%, 65.6%, and 45.5%, respectively. PFS at 3 and 5 years after salvage radiation was 81.7% and 61.3%, respectively. Of 160 patients, 39 received adjuvant radiation, and 3- and 5-year PFS/RFFS rates were 86.1% and 59.2%, respectively. In patients who underwent observation with salvage radiation, if necessary, the 3-, 5-, and 10-year RFFS rates were 97.7%, 90.3%, and 87.9%, respectively. Both PS and IPTW Cox regression models demonstrated that patients who underwent observation with salvage radiation treatment, if necessary, had significantly longer RFFS (PS model: hazard ratio [HR] 0.21, p < 0.01; IPTW model: HR 0.21, p < 0.01).

CONCLUSIONS
In this retrospective, nonrandomized study, adjuvant radiation after GTR of a WHO II meningioma did not add significant benefit over a strategy of observation and salvage radiation at initial recurrence, if necessary, but results must be considered in the context of the limitations of the study design.

Momin|Arbaz A|AA|
Soni|Pranay|P|
Shao|Jianning|J|
Nowacki|Amy S|AS|
Suh|John H|JH|
Murphy|Erin S|ES|
Chao|Samuel T|ST|
Angelov|Lilyana|L|
Mohammadi|Alireza M|AM|
Barnett|Gene H|GH|
Recinos|Pablo F|PF|
Kshettry|Varun R|VR|

adjuvant radiation
salvage radiation
gross-total resection
recurrence
atypical meningiomas
oncology


Bird Diversity and Structure in Different Land-use Types in Lowland South-Central Mindanao, Philippines.

Abstract: Birds are crucial to maintaining the balance of many ecosystems by providing various ecological services. The diversity of birds and their feeding guilds in different land-use types were investigated in south-central Mindanao to elucidate the effect of disturbance and habitat modification on bird communities. Point count method was employed to identify birds in three habitat types: i) agroforests; ii) ricefields; iii) roads and heavily disturbed areas. A total of 1114 bird sightings were recorded that included 33 species of 24 families; of these, 3 were Philippine endemics, and 5 were migrant species. Among all of the habitat types, the highest species diversity was found in agroforests (1/D = 16.148), and the lowest was recorded from roads and heavily disturbed habitats. The species composition of agroforests was more similar to ricefields than to areas with high levels of disturbance, such as roads. The characteristic of the vegetation and the availability of food resources may be vital to the diversity of birds in every habitat as evidenced by the high species richness of frugivores and insectivores in agroforests and ricefields, respectively, where food source is largely available. The observation of Streptopelia tranquebarica was a new record for Mindanao, and it was particularly sighted in ricefields. Therefore, this study indicates that land-use change and modification may alter bird diversity structure, and the maintenance of the vegetation in land-use types as food and resource, and as habitat is essential to the conservation of the native and ecologically-important bird species in south-central Mindanao.

Tanalgo|Krizler Cejuela|KC|
Pineda|John Arislyn Fuentes|JA|
Agravante|Maricel Estolloso|ME|
Amerol|Zabide Mamalo|ZM|

Feeding Guild
Agroforest
Frugivores
Conservation
Avifauna


The complete chloroplast genome sequence of coastal psammophyte, Ixeris repens (Asteraceae, subtribe Crepidinae), in Korea.

Abstract: We report the first complete chloroplast genome sequence of psammophyte, Ixeris repens, on the coastal dunes in Korea. The complete plastid genome is 153,017 bp in total length, with one large single copy (LSC; 84,242 bp), one small single copy (SSC; 18,495 bp), and two inverted repeat (IR) regions (IRa and IRb, each with 25,140 bp). The overall GC content is 37.6% and the genome contains 130 genes, including 85 protein-coding, 37 transfer RNA and 8 ribosomal RNA genes. Phylogenetic analysis based on 17 representative plastomes of the family Asteraceae suggests that Ixeris repens is sister to congeneric species I. polycephala with strong bootstrap support (100%) and also that monophyletic Ixeris is sister to the clade containing Taraxacum, Youngia, Lapsanastrum, and Crepidiastrum.

Lee|Woong|W| Yang|JiYoung|J| Kim|Seung-Chul|SC| Pak|Jae-Hong|JH|

psammophyte
Ixeris repens
Subtribe Crepidinae
plastid genome


Using genetically modified tomato crop plants with purple leaves for absolute weed/crop classification.

Abstract:
BACKGROUND
Weed/crop classification is considered the main problem in developing precise weed-management methodologies, because both crops and weeds share similar hues. Great effort has been invested in the development of classification models, most based on expensive sensors and complicated algorithms. However, satisfactory results are not consistently obtained due to imaging conditions in the field.

RESULTS
We report on an innovative approach that combines advances in genetic engineering and robust image-processing methods to detect weeds and distinguish them from crop plants by manipulating the crop's leaf color. We demonstrate this on genetically modified tomato (germplasm AN-113) which expresses a purple leaf color. An autonomous weed/crop classification is performed using an invariant-hue transformation that is applied to images acquired by a standard consumer camera (visible wavelength) and handles variations in illumination intensities.

CONCLUSION
The integration of these methodologies is simple and effective, and classification results were accurate and stable under a wide range of imaging conditions. Using this approach, we simplify the most complicated stage in image-based weed/crop classification models.

Lati|Ran N|RN|
Filin|Sagi|S|
Aly|Radi|R|
Lande|Tal|T|
Levin|Ilan|I|
Eizenberg|Hanan|H|

D007089:Image Enhancement
D018551:Lycopersicon esculentum
D010858:Pigmentation
D018515:Plant Leaves
D030821:Plants, Genetically Modified
D058728:Weed Control

image-processing
anthocyanin
hue-invariant transformation
site-specific weed management


Folliculitis decalvans-like pustular plaques on the limbs sparing the scalp.

Abstract: Folliculitis decalvans is a neutrophilic cicatricial alopecia characterised by progressive pustular folliculitis. Folliculitis decalvans is seen as a condition usually limited exclusively to the scalp and rarely affects the limbs. We present a case of a 63-year-old man with a 3-year history of progressive pustular folliculitis with inflammatory patches and central scarring alopecia on both forearms and a circumscribed patch on his right lower leg. His presentation, clinical course and isolation of Staphylococcus aureus together with the histopathological findings all supported a folliculitis decalvans-like pustular folliculitis limited to the limbs. Biopsies revealed follicular pustules, gross interfollicular fibrosis with plasma cells and concentric perifollicular fibrosis with lymphocytes, all features seen with folliculitis decalvans. The positive response to antibiotics combined with topical corticosteroids mirrored the response seen with scalp folliculitis decalvans. In contrast to the previously reported cases, the patient had no evidence of folliculitis decalvans on the scalp.

limbs
folliculitis decalvans
neutrophilic cicatricial alopecia
pustular folliculitis


Cancer incidence in urban, rural, and densely populated districts close to core cities in Bavaria, Germany.

Abstract:
OBJECTIVE
An ecologic study on the level of districts was performed to evaluate the possible association between district type and risk of cancer in Bavaria, Southern Germany.

METHODS
Cancer incidence data for the years 2003-2012 were obtained from the population-based cancer registry Bavaria according to sex and cancer site. Data on district type, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption were obtained from publicly available sources. The possible association between district type and cancer risk adjusted for age, socio-economic area deprivation, particulate matter exposure, tobacco consumption, and alcohol consumption was evaluated using multivariable multi-level negative binomial regression.

RESULTS
We found a significantly reduced cancer risk in densely populated districts close to core cities and/or rural districts compared to core cities with respect to the cancer sites mouth and pharynx (women only), liver (both sexes), larynx (both sexes), lung (both sexes), melanoma of the skin (both sexes), mesothelioma (men only), connective and soft tissue (both sexes), corpus uteri, other urinary tract (men only), urinary bladder (both sexes), and non-Hodgkin lymphoma (both sexes).

CONCLUSION
Our findings require further monitoring. Since the apparently increased cancer risk in core cities may be related to lifestyle factors, preventive measures against lifestyle-related cancer could be specifically targeted at populations in deprived core cities.

Cancer incidence
Urban
Rural
Ecologic studies
Cancer registries
Socio-economic area deprivation
Lifestyle
Prevention
Environment


Primary orbital melanoma: A report of a case and comprehensive review of the literature.

Abstract: Purpose: To review the clinical features and treatment-associated outcomes of primary orbital melanoma among cases reported in the literature and to present a case treated with orbital exenteration and post-operative radiotherapy.Methods: Case reports and case series on primary orbital melanoma published in the literature between 1980 and 2020 were reviewed. Data collected included patient demographics, presenting ocular symptoms, diagnostic imaging, histology, management, and outcomes.Results: Eighty-eight cases of primary orbital melanoma were reviewed. The average age at presentation was 45 years and 58% of patients were male. The most common presenting symptoms and signs were proptosis (73%), decreased visual acuity (32%), pain (14%), diplopia (15%), and palpable mass (9%). Imaging frequently showed a well-circumscribed enhancing lesion. Diagnosis was made by histology in all cases, and orbital blue nevus was identified in 42%. In the majority of cases, treatment consisted of orbital exenteration (54%) or excision (38%). Adjuvant radiotherapy was given in 47% of cases. For the 72 patients with reported outcomes, 36% had metastases, 15% had local recurrence, and 32% died of metastatic disease. Patients who received surgery and radiotherapy had improved survival compared to those who received surgery alone (p = .01). There was no difference in survival between those who underwent orbital exenteration or excision (p = .16).Conclusions: Primary orbital melanoma is a rare malignancy and should be considered in patients with a history of unilateral proptosis and a well-defined orbital mass on imaging. Surgery remains the mainstay of treatment. Adjuvant radiotherapy may improve patient survival.

Adetunji|Modupe O|MO|
McGeehan|Brendan|B|
Lee|Vivian|V|
Maguire|Maureen G|MG|
Briceño|César A|CA|

primary orbital melanoma
orbit
exenteration
radiotherapy
Cancer


Role of Cbp, p300 and Akt in valproic acid induced neural tube defects in CD-1 mouse embryos.

Abstract: Valproic acid (VPA), an antiepileptic and mood-stabilizing drug, is prescribed to women of reproductive age. VPA is associated with a 1-2% increase in neural tube defects in offspring following gestational exposure and results in epigenetic modifications induced by perturbations in transcription cofactors. Cbp and p300, two transcription cofactors, play key roles in embryonic neural development. p300 is a downstream target of Akt, a protein kinase B associated with cell survival and anti-apoptotic mechanisms, as part of the Akt-p300 axis. We examined the effects of in utero VPA exposure on Cbp, p300, and Akt in gestational day (GD)9, GD10 and GD13 CD-1 mouse embryos following a teratogenic maternal dose of 400 mg/kg. Embryos were collected at 0, 1, 3 and 6 h post-dosing on GD9, 24 h post-dosing on GD10 and on GD13. GD10 embryos were grouped according to the status of neural tube closure in control, closed and open groups. GD13 heads were grouped as control, exposed but non-exencephalic and exencephalic. Our data indicate that Cbp, p300 and Akt mRNA levels were downregulated at 1 and 3 h post-exposure in GD9 embryos while Cbp and p300 protein levels remained stable. Akt protein levels were significantly increased 1 h post-exposure. No significant changes were observed in either mRNA or protein expression in embryos with closed or open neural tubes compared to the control group at GD10. Downregulated expression of Cbp, p300, and Akt may play a key role in VPA-induced neural tube defects considering their vitally important role in embryonic development.

D000014:Abnormalities, Drug-Induced
D000818:Animals
D050882:CREB-Binding Protein
D015536:Down-Regulation
D050881:E1A-Associated p300 Protein
D004622:Embryo, Mammalian
D051379:Mice
D009436:Neural Tube Defects
D051057:Proto-Oncogene Proteins c-akt
D014635:Valproic Acid

Akt
Valproic acid
Neural tube defects
Mouse embryo
Teratogen
Cbp/p300


A survey of health awareness and physical activity among Japanese undergraduate rehabilitation students.

Abstract: [Purpose] We aimed to investigate students' awareness of their general physical activity and current physical activity habits. [Participants and Methods] One hundred and eighteen undergraduate students in rehabilitation courses volunteered to participate in this survey. The participants were required to answer a questionnaire related to their health awareness and physical activity habits. A χ2 test was used to demonstrate the relationships between each category of the selected items. [Results] Undergraduate rehabilitation students felt very or moderately healthy when asked to subjectively describe the current condition of their health. Most of them liked and had more interest in exercise or sports activities. However, more than 60% of them felt that their participation in physical activities had decreased since they entered college. [Conclusion] Undergraduate students in rehabilitation courses lacked motivation to exercise and participate in physical activities in college. Students who did not have a habit of exercising or participating in sports activities may have lacked motivation because they were busy with school; however, they had a high level of positivity towards exercise or sports activities. Therefore, it is important for them to actively participate in exercise and/or physical activity with a specific purpose in mind.

Health education
Health promotion
Life activity


Crystal structure of 7-iodo-4-oxo-4H-chromene-3-carbaldehyde.

Abstract: In the title compound, C10H5IO3, an iodinated 3-formyl-chromone derivative, the non-H atoms are essentially coplanar (r.m.s. deviation = 0.0344 Å), with the largest deviation from the least-squares plane [0.101 (3) Å] being found for the formyl O atom. In the crystal, mol-ecules are linked through stacking inter-actions [centroid-centroid distance between the benzene rings = 3.700 (3) Å] and C-H⋯O hydrogen bonds. Halogen bonds between the I atoms at 7-position and the formyl O atoms [I1⋯O3 = 3.056 (2) Å, C6-I1⋯O3 = 173.18 (8)° and I1⋯O3-C10 = 111.12 (18)°] are also formed along [110], resulting in sheets perpendicular to the c axis, constructed by C-H⋯O hydrogen bonds and I⋯O halogen bonds.

crystal structure
hydrogen bond
halogen bond
π–π stacking