The making of the master clock.

Abstract: A genetic basis for the anatomic master circadian clock in mammals has been found.

D000818:Animals
D057906:Circadian Clocks
D020179:Jet Lag Syndrome
D060850:LIM-Homeodomain Proteins
D008297:Male
D009474:Neurons
D056950:Period Circadian Proteins
D013493:Suprachiasmatic Nucleus
D014157:Transcription Factors

Lhx1
Ror-alpha
VIP
circadian rhythms
suprachiasmatic nucleus


Quantum Language of MicroRNA: Application for New Cancer Therapeutic Targets.

Abstract: MicroRNA (miRNA) is the noncoding gene: therefore, the miRNA gene inheritably controls protein gene expression through transcriptional and post-transcriptional levels. Aberrant expression of miRNA genes causes various human diseases, especially cancers. Although cancer is a complex disease, cancer/miRNA implication has yet been grasped from the perspective of miRNA profile in bed side. Since miRNA is the mobile genetic element, the clinical verification of miRNA in microvesicle of blood is too much straggle to predict potential cancer/miRNA associations without bioinformatical computing. Further, experimental investigation of miRNA/cancer pathways is expensive and time-consuming. While the accumulated data (big data) of miRNA profiles has been on line as the databases in cancers, using the database algorithms for miRNA target prediction have reduced required time for conventional experiments and have cut the cost. Computational prediction of miRNA/target mRNA has shown numerous significant outcomes that are unobtainable only by experimental approaches. However, ID of miRNA in the annotation is an arbitrary number and the ID is not related with miRNA its functions. Therefore, it has not been physicochemically shown why multiple miRNAs in blood or tissues are useful for diagnosis and porgnosis of human diseases or why function of single miRNA in cancer is rendered to oncomir or tumopr suppressor. In addition, it is less cleared why environmental factors, such as temperature, radiation, therapeutic anti-cancer immune or chemical agents can alter the expression of miRNAs in the cell. The ceRNA theory would not be enough for the investigation of such subjects. Given miRNA/target prediction tools, to elucidate such issues with computer simulation we have previously introduced the quantum miRNA/miRNA interaction as a new scoring using big database. The quantum score was implicated in miRNA synergisms in cancer and participated in the miRNA/target interaction on human diseases. On the other hand, ribosomal RNA (rRNA) is the dominant RNA species of the cells. It is well known that ribosomopathies, such as Diamond-Blackfan anemia, dyskeratiosis congenital, Shwachman-Diamond syndrome, 5q-myelodysplastic syndrome, Treacher Collins syndrome, cartilage-hair hypoplasia, North American Indian childhood cirrhosis, isolated congenital asplenia, Bowen-Conradi syndrome and cancer are caused by altered expression of ribosomal proteins or rRNA genes. We have proposed the hypothesis that the interaction among miRNAs from rRNA and/or other cellular miRNAs would be involved into cancer as the ribosomopathy. Subsequently, we found rRNA-derived miRNAs (rmiRNAs) by using the sequence homology search (miPS) with miRNA database (miRBase). Further, the pathway related with cancer between rmiRNA/target protein gene was predicted by miRNA entangling target sorting (METS) algorithm. In this chapter, we describe about the usage of in silico miRNA identification program, miRNA/target prediction search through the database and quantum language of miRNA by the METS, and the ontology analysis. In particular, the METS algorithm according to the quantum value would be useful simulator to discover a new therapeutic target aganist cancer. It may also partly contribute to the elucidation of complex mechanisms and development of agents of anti-cancer.

D000465:Algorithms
D020087:Alu Elements
D019295:Computational Biology
D030561:Databases, Nucleic Acid
D063990:Gene Ontology
D006801:Humans
D035683:MicroRNAs
D009369:Neoplasms
D009690:Nucleic Acid Conformation
D011789:Quantum Theory
D034622:RNA Interference
D058727:RNA, Small Untranslated

Quantum
microRNA
Cancer
Big data
Ribosomal RNA
AluRNA
Biomarker


Detection of Pb(II): Au Nanoparticle Incorporated CuBTC MOFs.

Abstract: In the present investigation, copper benzene tricarboxylate metal organic frameworks (CuBTC MOF) and Au nanoparticle incorporated CuBTC MOF (Au@CuBTC) were synthesized by the conventional solvothermal method in a round bottom flask at 105°C and kept in an oil bath. The synthesized CuBTC MOF and Au@CuBTC MOFs were characterized by structure using X-ray diffraction (XRD) spectroscopic methods including Fourier Transform Infrared spectroscopy, Raman Spectroscopy, X-ray Photoelectron Spectroscopy (XPS), and Energy dispersive spectroscopy (EDS). We also characterized them using morphological techniques such as Field emission scanning electron microscopy (FE-SEM), and electrochemical approaches that included cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). We examined thermal stability by thermogravimetric analysis (TG/DTA) and N2 adsorption-desorption isotherm by Brunauer-Emmett-Teller (BET) surface area method. Both materials were tested for the detection of lead (II) ions in aqueous media. Au nanoparticle incorporated CuBTC MOF showed great affinity and selectivity toward Pb2+ ions and achieved a lower detection limit (LOD) of 1 nM/L by differential pulse voltammetry (DPV) technique, which is far below than MCL for Pb2+ ions (0.03 μM/L) suggested by the United States (U.S.) Environmental Protection Agency (EPA) drinking water regulations.

Bodkhe|Gajanan A|GA|
Hedau|Bhavna S|BS|
Deshmukh|Megha A|MA|
Patil|Harshada K|HK|
Shirsat|Sumedh M|SM|
Phase|Devdatta M|DM|
Pandey|Krishan K|KK|
Shirsat|Mahendra D|MD|

CuBTC MOF
metal organic frameworks
differential pulse voltammetry (DPV)
electrochemical sensor
gold nanoparticles


Integrating transition theory and bioecological theory: a theoretical perspective for nurses supporting the transition to adulthood for young people with medical complexity.

Abstract:
AIMS
To present a discussion of a theoretical perspective developed through integrating Meleis' Transition Theory and Bronfenbrenner's Bioecological Theory of Human Development to inform nursing and advanced nursing practice supporting the transition to adulthood for young people with medical complexity.

BACKGROUND
Theoretical perspectives to inform nursing practice in supporting successful transition are limited, yet nurses frequently encounter young people with medical complexity during the transition to adulthood.

DESIGN
Discussion paper.

DATA
A literature search of CINAHL and Medline was conducted in 2014 and included articles from 2003-2014; informal discussions with families; the author's experiences in a transition program.

IMPLICATIONS FOR NURSING
The integrated theoretical perspective described in this paper can inform nurses and advanced practice nurses on contextual influences, program and intervention development across spheres of influence and outcomes for the transition to adulthood for young people with medical complexity. Young people and their families require effective reciprocal interactions with individuals and services across sectors to successfully transition to adulthood and become situated in the adult world. Intervention must also extend beyond the young person to include providers, services and health and social policy.

CONCLUSION
Nurses can take a leadership role in supporting the transition to adulthood for young people with medical complexity through direct care, case management, education and research. It is integral that nurses holistically consider developmental processes, complexity and contextual conditions that promote positive outcomes during and beyond the transition to adulthood.

Transition Theory
transition to adulthood
advanced nursing practice
Ecological Theory
adolescent
framework
medically fragile
young adult


The role of academic leagues as a strategy for pain education in Brazil.

Abstract:
Purpose
Chronic pain remains undertreated in both developed and developing countries. There are various factors involved in this acknowledged health problem, including lack of pain education. In Brazil, a particular approach was used to mitigate the deficit in pain education. The academic leagues of pain (ALPs) were formed as associations of health undergraduate students with the goal of encouraging students in educational activities, patient care, and pain research. The aim of this study was to evaluate how ALP works and its contribution to pain education and to the inclusion of students in practical and scientific research activities, as well as its legacy in the field of pain.

Patients and methods
An electronic survey was directed to the leagues representatives to collect data referent to how the leagues operate, their individual approach towards pain education, patient care, research activities, and its impact on students after they graduate.

Results
A total of 17 leagues were identified and responded to the survey. Only three of the involved universities offered study of pain as a discipline in their mandatory curriculum. Patient care activities were carried out by 59% of the leagues, 94% provided educational activities. Twelve leagues reported that students were involved in one to four research projects in pain, and 59% of those chose pain as their subject for post-graduation programs. And, 47% of the leagues had students that sought specialization or residency in pain after graduation.

Conclusion
The Brazilian experience with academic leagues of pain has shown that it is possible to address curricular deficiencies in pain education through a strategy not well known in other countries.

Garcia|João Batista Santos|JBS|
Neto|José Osvaldo Barbosa|JOB|
Rodrigues|Thiago Alves|TA|

pain education
chronic pain
medical education
pain management


Transformation from a traditional model to a virtual model of care in orthopaedic surgery: COVID-19 experience and beyond.

Abstract: Virtual encounters have experienced an exponential rise amid the current COVID-19 crisis. This abrupt change, seen in response to unprecedented medical and environmental challenges, has been forced upon the orthopaedic community. However, such changes to adopting virtual care and technology were already in the evolution forecast, albeit in an unpredictable timetable impeded by regulatory and financial barriers. This adoption is not meant to replace, but rather augment established, traditional models of care while ensuring patient/provider safety, especially during the pandemic. While our department, like those of other institutions, has performed virtual care for several years, it represented a small fraction of daily care. The pandemic required an accelerated and comprehensive approach to the new reality. Contemporary literature has already shown equivalent safety and patient satisfaction, as well as superior efficiency and reduced expenses with musculoskeletal virtual care (MSKVC) versus traditional models. Nevertheless, current literature detailing operational models of MSKVC is scarce. The current review describes our pre-pandemic MSKVC model and the shift to a MSKVC pandemic workflow that enumerates the conceptual workflow organization (patient triage, from timely care provision based on symptom acuity/severity to a continuum that includes future follow-up). Furthermore, specific setup requirements (both resource/personnel requirements such as hardware, software, and network connectivity requirements, and patient/provider characteristics respectively), and professional expectations are outlined. MSKVC has already become a pivotal element of musculoskeletal care, due to COVID-19, and these changes are confidently here to stay. Readiness to adapt and evolve will be required of individual musculoskeletal clinical teams as well as organizations, as established paradigms evolve. Cite this article: Bone Joint Open 2020;1-6:272-280.

King|Dominic|D|
Emara|Ahmed K|AK|
Ng|Mitchell K|MK|0000-0002-5831-055X
Evans|Peter J|PJ|
Estes|Kelly|K|
Spindler|Kurt P|KP|
Mroz|Thomas|T|
Patterson|Brendan M|BM|
Krebs|Viktor E|VE|
Pinney|Stephen|S|
Piuzzi|Nicolas S|NS|0000-0003-3007-7538
Schaffer|Jonathan L|JL|

COVID-19
Musculoskeletal Virtual Care
Triage
Beyond COVID-19
Telehealth
Telemedicine
Virtual visits


A retrospective observational study of leucoreductive strategies to manage patients with acute myeloid leukaemia presenting with hyperleucocytosis.

Abstract: Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre-induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 10(9) /l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre-induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998-2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 10(9) /l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 10(9) /l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre-induction leucoreduction.

Kuo|Kevin H M|KH|
Callum|Jeannie L|JL|
Panzarella|Tony|T|
Jacks|Lindsay M|LM|
Brandwein|Joseph|J|
Crump|Michael|M|
Curtis|John E|JE|
Gupta|Vikas|V|
Lipton|Jeffrey H|JH|
Minden|Mark D|MD|
Sher|Graham D|GD|
Schimmer|Aaron D|AD|
Schuh|Andre C|AC|
Yee|Karen W L|KW|
Keating|Armand|A|
Messner|Hans A|HA|

acute myeloid leukaemia
hyperleucocytosis
leukapheresis
hydroxycarbamide
leucostasis


Comparison of Cricothyroid Membrane Puncture Anesthesia and Topical Anesthesia for Awake Fiberoptic Intubation: A Double-Blinded Randomized Controlled Trial.

Abstract: Background: Awake fiberoptic intubation (AFOI) is commonly used for patients with a difficult airway. The purpose of this study was to evaluate the efficacy of cricothyroid membrane puncture anesthesia and topical anesthesia during AFOI. Methods: A total of 70 patients (the American Society of Anesthesiologists score I-III) with anticipated difficult airways scheduled for nonemergency surgery with AFOI were randomly slated to receive cricothyroid membrane puncture anesthesia (n = 35) or topical anesthesia (n = 35). Each group received dexmedetomidine at a dose of 1.0 μg/kg and sufentanil at a dose of 0.2 μg/kg over 10 min for conscious sedation before intubation. The endoscopy intubation, post-intubation condition, and endoscopy tolerance as scored by the anesthetists were observed. The satisfaction of the operator regarding the procedure and the satisfaction of the patient 24 h after the surgery were also recorded. We recorded the success rate of the first intubation, intubation time, and hemodynamic changes during the procedure and also the adverse events. Results: Better intubation scores, operator satisfaction, and satisfaction of the patient were observed in the cricothyroid membrane puncture anesthesia group than in the topical anesthesia group (p < 0.05). The intubation time in the cricothyroid membrane puncture anesthesia group was less than that in the topical anesthesia group (p < 0.05). There were no significant differences in the patient tolerance scores, the success rate of the first intubation, hemodynamic changes, and adverse events between both the groups. Conclusion: Compared with topical anesthesia, cricothyroid membrane puncture anesthesia provided better intubation conditions and less intubation time with greater satisfaction of the patient and operator during endoscopic intubation. Clinical Trial Registration: URL: http://www.chictr.org.cn/showproj.aspx?proj=42636, Identifier: ChiCTR 1900025820.

Wang|Shaocheng|S| Hu|Chaoli|C| Zhang|Tingting|T| Zhao|Xuan|X| Li|Cheng|C|


Reducing Physical Aggression in High School Students in KwaZulu-Natal: A Cluster Randomized Trial.

Abstract: Youth violence is of public health and social concern. A South African cluster randomized trial (434 grade 10 students, 16 schools), used the Integrated Model for Behavior Change conceptual framework to implement a 20 module classroom-based intervention program. The study contributes to the literature and used a strong analytical technique since mixed effects linear regression assessed the impact of the intervention on physical violence endpoints and other socioeconomic confounders/factors. The intervention reduced students' experiencing physical violence compared to controls and social pressure for this, yet no differences were found for hitting others. Our results support findings that school programs against violence can reduce students' experience of physical violence, but translation of these findings to reduce the actual hitting of others may need further approaches and/or more time.

Taylor|Myra|M|
Sartorius|Benn|B|
Naidoo|Saloshni|S|
Vries|Hein de|H|

youth violence
physical abuse
school-based intervention


Carbazate modified dextrans as scavengers for carbonylated proteins.

Abstract: A series of biocompatible and non- toxic polysaccharide molecules have been successfully fabricated and explored their potential application for scavenging the carbonyl species in vitro. These macromolecules were dextrans with different hydrazide substitution ratios determined by TNBS assay, NMR and FTIR characterization. The colorimetric assay had demonstrated that these macromolecules could effectively scavenge acrolein, oxidized bovine serum albumin (BSA) in buffer solutions as well as carbonyl proteins from serum. The scavengers could achieve twice more scavenging effects for modified dextrans with high molecular weight (Mw = 100,000) than those of low ones (Mw = 40,000) with the same substitution ratio. Protein gel electrophoresis confirmed that the formation of the complex between carbonyls and modified dextrans resulted in appearance of slower bands. It also revealed that such macromolecules could protect cultured cells against the toxicity of acrolein or its derivatives. The proposed macromolecules indicated a very promising capability as scavengers for oxidative stress plus its derivatives without side effects.

Zhou|Bo|B|
Gao|Ming|M|
Feng|Xianjing|X|
Huang|Lanli|L|
Huang|Quanxin|Q|
Kootala|Sujit|S|
Larsson|Tobias E|TE|
Zheng|Li|L|
Bowden|Tim|T|

Protein gel electrophoresis
Oxidative stress
Carbonyl scavengers
Human blood serum
Hydrazide-carbonyl click chemistry
Protein carbonyl groups


Impact of antibiotic administration on blood culture positivity at the beginning of sepsis: a prospective clinical cohort study.

Abstract:
OBJECTIVES
Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy.

METHODS
Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity.

RESULTS
In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3-0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy.

CONCLUSIONS
Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.

Scheer|C S|CS|
Fuchs|C|C|
Gründling|M|M|
Vollmer|M|M|
Bast|J|J|
Bohnert|J A|JA|
Zimmermann|K|K|
Hahnenkamp|K|K|
Rehberg|S|S|
Kuhn|S-O|SO|

Blood culture
Positivity
Sepsis
Antibiotic therapy
Pathogen


Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the Synapsin Promoter and AAV-PHP.B.

Abstract: Widespread genetic modification of cells in the central nervous system (CNS) with a viral vector has become possible and increasingly more efficient. We previously applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid promoter and achieved wide-scale CNS transduction in neonatal and adult rats. However, this method transduces a variety of tissues in addition to the CNS. Thus we studied intravenous AAV9 gene transfer with a synapsin promoter to better target the neurons. We noted in systematic comparisons that the synapsin promoter drives lower level expression than does the CBA promoter. The engineered adeno-associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did enhance the efficiency of expression. Combining the synapsin promoter with AAV-PHP.B could therefore be advantageous in terms of combining two refinements of targeting and efficiency. Wide-scale expression was used to model a disease with widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)-related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43 expression. Intracerebroventricular injections were also explored to limit TDP-43 expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced gene transfer and ALS disease modeling in adult rats.

Jackson|Kasey L|KL|
Dayton|Robert D|RD|
Deverman|Benjamin E|BE|
Klein|Ronald L|RL|

targeting
synapsin promoter
promoter
gene transfer
adeno-associated virus
amyotrophic lateral sclerosis
TDP-43
gene therapy


Polyporus Umbellatus Protects Against Renal Fibrosis by Regulating Intrarenal Fatty Acyl Metabolites.

Abstract: Background: Chronic renal failure (CRF) results in significant dyslipidemia and profound changes in lipid metabolism. Polyporus umbellatus (PPU) has been shown to prevent kidney injury and subsequent kidney fibrosis. Methods: Lipidomic analysis was performed to explore the intrarenal profile of lipid metabolites and further investigate the effect of PPU and its main bioactive component, ergone, on disorders of lipid metabolism in rats induced by adenine. Univariate and multivariate statistical analyses were performed for choosing intrarenal differential lipid species in CRF rats and the intervening effect of n-hexane extract of PPU and ergone on CRF rats. Results: Compared with control group, decreased creatinine clearance rate indicated declining kidney function in CRF group. Based on the lipidomics, we identified 65 lipid species that showed significant differences between CRF and control groups. The levels of 12 lipid species, especially fatty acyl lipids including docosahexaenoic acid, docosapentaenoic acid (22n-3), 10,11-Dihydro-12R-hydroxy-leukotriene C4, 3-hydroxydodecanoyl carnitine, eicosapentaenoic acid, hypogeic acid and 3-hydroxypentadecanoic acid had a strong linear correlation with creatinine clearance rate, which indicated these lipid species were associated with impaired renal function. In addition, receiver operating characteristics analysis showed that 12 lipid species had high area under the curve values with high sensitivity and specificity for differentiating CRF group from control group. These changes are related to the perturbation of fatty acyl metabolism. Treatment with PPU and ergone improved the impaired kidney function and mitigated renal fibrosis. Both chemometrics and cluster analyses showed that rats treated by PPU and ergone could be separated from CRF rats by using 12 lipid species. Intriguingly, PPU treatment could restore the levels of 12 lipid species, while treatment with ergone could only reverse the changes of six fatty acids in CRF rats. Conclusion: Altered intrarenal fatty acyl metabolites were implicated in pathogenesis of renal fibrosis. PPU and ergone administration alleviated renal fibrosis and partially improved fatty acyl metabolism. These findings suggest that PPU exerted its renoprotective effect by regulating fatty acyl metabolism as a potential biochemical mechanism. Therefore, these findings indicated that fatty acyl metabolism played an important role in renal fibrosis and could be considered as an effective therapeutic avenue against renal fibrosis.

Wang|Yan-Ni|YN|
Wu|Xia-Qing|XQ|
Zhang|Dan-Dan|DD|
Hu|He-He|HH|
Liu|Jian-Ling|JL|
Vaziri|Nosratola D|ND|
Guo|Yan|Y|
Zhao|Ying-Yong|YY|
Miao|Hua|H|

Polyporus umbellatus
chronic renal failure
lipidomics
ergone
fatty acid metabolism
mass spectrometry
ultra-performance liquid chromatography


The accuracy of the auto-stop function of different endodontic devices in detecting the apical constriction.

Abstract:
BACKGROUND
Electronic apex locators (EALs) are modern devices used to determine the working length during root canal preparation. The newest endodontic motors provide an integrated EAL with auto-stop function to prevent instrumentation beyond the predefined working length during rotary root canal preparation. The aim of this study was to compare the accuracy of the auto-stop function of the VDW.Gold RECIPROC motor (VDW, Munich, Germany), the EndoPilot motor (Schlumbohm, Brokstedt, Germany) and the manual measurement with Raypex 6 (VDW, Munich, Germany) to detect the apical constriction (AC).

METHODS
Ninety human teeth were chosen and randomly assigned to three experimental groups (30 teeth each): VDW.Gold RECIPROC motor continuous measuring (RCM), EndoPilot continuous measuring (ECM) and Raypex 6 manual measuring (RMM). When the measurement file reached the AC, the file was fixed in the tooth. The tooth was embedded in acrylic resin and the root tip was exposed, so that the histologic structure of the root canal and the file tip was visible for microscopic analysis. Afterwards, the distance of the file tip to the AC (DAC) was automatically computed with a specially developed software tool.

RESULTS
The mean DAC were -13.18 μm (SD 88.46 μm) for RMM, -22.70 μm (SD 91.57 μm) for RCM and 18.74 μm (SD 88.11 μm) for ECM. The differences were not statistically significant (P = 0.181). The rates for instrumentation beyond the AC were not statistically different (Chi2 = 4.753, p = 0.096).

CONCLUSIONS
All measurement methods showed a high accuracy in detecting the AC. The auto-stop function of these endodontic motors is a reliable addition to the endodontic armamentarium.

D003762:Dental Instruments
D004867:Equipment Design
D006801:Humans
D066298:In Vitro Techniques
D011897:Random Allocation
D018915:Root Canal Preparation
D019227:Tooth Apex

Apical constriction
Apex locator
Reciproc
EndoPilot
Raypex 6


The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5xFAD APP/PS1 Mouse Model.

Abstract: Alzheimer's disease (AD) is the most common cause of dementia in the aging population. Evidence implicates elevated soluble oligomeric Aβ as one of the primary triggers during the prodromic phase leading to AD, effected largely via hyperphosphorylation of the microtubule-associated protein tau. At low, physiological levels (pM-nM), however, oligomeric Aβ has been found to regulate synaptic plasticity as a neuromodulator. Through mutational analysis, we found a core hexapeptide sequence within the N-terminal domain of Aβ (N-Aβcore) accounting for its physiological activity, and subsequently found that the N-Aβcore peptide is neuroprotective. Here, we characterized the neuroprotective potential of the N-Aβcore against dysfunction of synaptic plasticity assessed in ex vivo hippocampal slices from 5xFAD APP/PS1 mice, specifically hippocampal long-term potentiation (LTP) and long-term depression (LTD). The N-Aβcore was shown to reverse impairment in synaptic plasticity in hippocampal slices from 5xFAD APP/PS1 model mice, both for LTP and LTD. The reversal by the N-Aβcore correlated with alleviation of downregulation of hippocampal AMPA-type glutamate receptors in preparations from 5xFAD mice. The action of the N-Aβcore depended upon a critical di-histidine sequence and involved the phosphoinositide-3 (PI3) kinase pathway via mTOR (mammalian target of rapamycin). Together, the present findings indicate that the non-toxic N-Aβcore hexapeptide is not only neuroprotective at the cellular level but is able to reverse synaptic dysfunction in AD-like models, specifically alterations in synaptic plasticity.

Forest|Kelly H|KH|
Taketa|Ruth|R|
Arora|Komal|K|
Todorovic|Cedomir|C|
Nichols|Robert A|RA|

neuroprotection
hippocampal slice
long-term potentiation
long-term depression
Alzheimer’s disease
beta amyloid (Aβ)


Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

Abstract: The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

Llorens|Franc|F|
Kruse|Niels|N|
Karch|André|A|
Schmitz|Matthias|M|
Zafar|Saima|S|
Gotzmann|Nadine|N|
Sun|Ting|T|
Köchy|Silja|S|
Knipper|Tobias|T|
Cramm|Maria|M|
Golanska|Ewa|E|
Sikorska|Beata|B|
Liberski|Pawel P|PP|
Sánchez-Valle|Raquel|R|
Fischer|Andre|A|
Mollenhauer|Brit|B|
Zerr|Inga|I|

α-Synuclein
Biomarkers
Sporadic Creutzfeldt-Jakob
Cerebrospinal fluid
Electrochemiluminescence
ELISA


Acute effect of fine particulate matter on blood pressure, heart rate and related inflammation biomarkers: A panel study in healthy adults.

Abstract: Epidemiological evidence of short-term fine particulate matter (PM2.5) exposure on blood pressure (BP), heart rate (HR) and related inflammation biomarkers has been inconsistent. We aimed to explore the acute effect of PM2.5 on BP, HR and the mediation effect of related inflammation biomarkers. A total of 32 healthy college students were recruited to perform 4 h of exposure at two sites with different PM2.5 concentrations in Wuhan between May 2019 and June 2019. The individual levels of PM2.5 concentration, BP and HR were measured hourly for each participant. Blood was drawn from each participant after each visit and we measured the levels of inflammation markers, including serum high-sensitivity C-reactive protein and plasma fibrinogen. Linear mixed-effect models were to explore the acute effect of PM2.5 exposure on BP, HR, and related inflammation biomarkers. In addition, we evaluated related inflammation biomarkers as the mediator in the association of PM2.5 and cardiovascular health indicators. The results showed that a 10 μg/m3 increment in PM2.5 concentration was associated with an increase of 0.84 (95% CI: 0.54, 1.15) beats/min (bpm) in HR and a 3.52% (95% CI: 1.60%, 5.48%) increase in fibrinogen. The lag effect model showed that the strongest effect on HR was observed at lag 3 h of PM2.5 exposure [1.96 bpm (95% CI: 1.19, 2.75)], but for fibrinogen, delayed exposure attenuated the association. Increased fibrinogen levels may account for 39.07% (P = 0.44) of the elevated HR by PM2.5. Null association was observed when it comes to short-term PM2.5 exposure and BP. Short-term exposure to PM2.5 was associated with elevated HR and increased fibrinogen levels. But our finding was not enough to suggest that exposure to PM2.5 might induce adverse cardiovascular effects by the pathway of inflammation.

Li|Zhaoyuan|Z| Liu|Yisi|Y| Lu|Tianjun|T| Peng|Shouxin|S| Liu|Feifei|F| Sun|Jinhui|J| Xiang|Hao|H|

Acute effect
Heart rate
Mediation effect
Fibrinogen
Individual PM(2.5) exposure


Age-related macular degeneration and cognitive impairment show similarities in changes of neutral lipids in peripheral blood mononuclear cells.

Abstract: Starting from previous studies showing that patients with cognitive deficit present neutral lipids (NLs) accumulation in cytoplasm of their peripheral blood mononuclear cells (PBMCs) and considering that there is epidemiological evidence linking age-related macular degeneration (AMD) to cognitive deficit, the first purpose of this study was to test whether neutral lipids also accumulated in PBMCs from AMD subjects. Moreover, the impact of statin use on AMD was explored and whether such use in AMD subjects was associated with NLs accumulation in PBMCs. The study was conducted on 222 subjects: 136 AMD (36 of which - 26.5% - using statins], 48 cognitive deficit (20 of which - 41.7% - using statins) and 38 healthy controls (4 of which -10.1% - using statins), AMD lesions were assessed from color fundus photographs. Mini-mental state examination (MMSE), demographics, lifestyle factors and medical history were collected at interview. MMSE score was categorized as normal (24-30), and impaired (<24), NLs content was evaluated by oil red 0 (ORO) staining method. ORO determination showed that neutral lipids were generally absent or very low (score between 0 and 1) in healthy controls while most of PBMCs from cognitive deficit and AMD had ORO staining levels scoring 2-4. Post hoc analysis (Bonferroni) in a one-way ANOVA revealed that ORO score was significantly higher in cognitive deficit and AMD subjects compared to healthy controls and in cognitive deficit compared to AMD. Bonferroni-test also showed that AMD subjects had significantly lower total cholesterol (TC) levels compared to healthy controls while high density lipoprotein-cholesterol (HDL-C) did not reach statistical significance. The results also revealed a significant higher number of statin-users in AMD compared to healthy controls. Likewise when cognitive deficit vs healthy controls was analyzed, the number of statin users were found to be significant higher in cognitive deficit than in healthy controls. There were no significant differences in statin use between AMD and cognitive deficit. Compared to healthy controls, statin use in cognitive deficit and AMD groups was significantly associated with ORO scores of 2-4. This data supports the hypothesis that AMD and cognitive deficit share similar complex pathophysiology and risk factors including NLs accumulation in their PBMCs, although this does not necessarily imply that one disease causes the other. In addition, they provide further evidence that statin use may increase the risk of AMD.

Peiretti|Enrico|E| Mandas|Antonella|A| Abete|Claudia|C| Vinci|Michela|M| Piludu|Stefania|S| Casu|Maura|M| Caminiti|Giulia|G| Dessì|Sandra|S| Fossarello|Maurizio|M|

age-related macular degeneration
cognitive impairment
cholesterol-ester


Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models.

Abstract: Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models. Vascular remodeling associated with improved perfusion was shown by Hoechst 33342 staining and by increased microvessel density together with decreased mean vascular areas and fewer branched vessels in tumor tissues, as determined by immunohistochemical staining for endothelial marker CD31. Quantitative RT-PCR analysis of normal host cells in the stroma of xenograft tumors showed that eribulin altered the expression of mouse (host) genes in angiogenesis signaling pathways controlling endothelial cell-pericyte interactions, and in the epithelial-mesenchymal transition pathway in the context of the tumor microenvironment. Eribulin also decreased hypoxia-associated protein expression of mouse (host) vascular endothelial growth factor by ELISA and human CA9 by immunohistochemical analysis. Prior treatment with eribulin enhanced the anti-tumor activity of capecitabine in the MDA-MB-231 xenograft model. These findings suggest that eribulin-induced remodeling of abnormal tumor vasculature leads to a more functional microenvironment that may reduce the aggressiveness of tumors due to elimination of inner tumor hypoxia. Because abnormal tumor microenvironments enhance both drug resistance and metastasis, the apparent ability of eribulin to reverse these aggressive characteristics may contribute to its clinical benefits.

Funahashi|Yasuhiro|Y|
Okamoto|Kiyoshi|K|
Adachi|Yusuke|Y|
Semba|Taro|T|
Uesugi|Mai|M|
Ozawa|Yoichi|Y|
Tohyama|Osamu|O|
Uehara|Taisuke|T|
Kimura|Takayuki|T|
Watanabe|Hideki|H|
Asano|Makoto|M|
Kawano|Satoshi|S|
Tizon|Xavier|X|
McCracken|Paul J|PJ|
Matsui|Junji|J|
Aoshima|Ken|K|
Nomoto|Kenichi|K|
Oda|Yoshiya|Y|

D023041:Xenograft Model Antitumor Assays

eribulin mesylate
tumor microenvironment
vascular remodeling
Breast cancer
tumor vasculature


Selecting for changes in average "parity curve" pattern of litter size in Large White pigs.

Abstract: This study aimed to analyse genetic background of variation in reproductive performance between parities of a sow and to investigate selection strategies to change the "parity curve". Total number born (TNB) recorded in Large White sows was provided by Topigs Norsvin. Analysis with basic (BM) and random regression (RRM) models was done in ASReml 4.1. The BM included only a fixed "parity curve", while RRM included 3rd order polynomials for additive genetic and permanent sow effects. Parameters from RRM were used in simulations in SelAction 2.1. Based on Akaike information criterion, RRM was a better model for TNB data. Genetic variance and heritability estimates of TNB from BM and RRM were increasing with parity from parity 2. Genetically, parity 1 is the most different from parities 7 to 10, whereas most similar to parities 2 and 3. This indicates presence of genetic variation to change the "parity curve". Based on simulations, the selection to increase litter size in parity 1 only increases TNB in all parities, but does not change the observed shape of "parity curve", whereas selection for increased TNB in parity 1 and reduced TNB in parity 5 decreases differences between parities, but also reduces overall TNB in all parities. Changing the "parity curve" will be difficult as the genetic and phenotypic relationships between the parities are hard to overcome even when selecting for one parity.

sows
total number born
random regression
reproduction traits
within-sow variation


Evaluation of an automated ultraviolet-C light disinfection device and patient hand hygiene for reduction of pathogen transfer from interactive touchscreen computer kiosks.

Abstract: Touchscreens are a potential source of pathogen transmission. In our facility, patients and visitors rarely perform hand hygiene after using interactive touchscreen computer kiosks. An automated ultraviolet-C touchscreen disinfection device was effective in reducing bacteriophage MS2, bacteriophage ϕX174, methicillin-resistant Staphylococcus aureus, and Clostridium difficile spores inoculated onto a touchscreen. In simulations, an automated ultraviolet-C touchscreen disinfection device alone or in combination with hand hygiene reduced transfer of the viruses from contaminated touchscreens to fingertips.

Alhmidi|Heba|H|
Cadnum|Jennifer L|JL|
Piedrahita|Christina T|CT|
John|Amrita R|AR|
Donskey|Curtis J|CJ|

Bacteriophage MS-2
Bacteriophage ΦX174
Hand sanitizer


Practical Approaches for High-Risk Surgical Patients with Acute Cholecystitis: The Percutaneous Approach versus Endoscopic Alternatives.

Abstract: In high-risk surgical patients with acute cholecystitis who are not candidates for early laparoscopic cholecystectomy, gallbladder (GB) drainage is an alternative treatment option. Percutaneous transhepatic gallbladder drainage (PTGBD) is a recommended first line intervention because of its high efficacy and feasibility in most centers. However, with the advent of endoscopic accessories and technology, endoscopic GB drainage has been chosen as a more favorable choice by endoscopists. Endoscopic transpapillary gallbladder drainage (ETGBD) can be performed under either fluoroscopic or peroral cholangioscopic guidance via endoscopic retrograde cholangiopancreatography by the transpapillary placement of a long double-pigtail stent. In a patient with common bile duct stones, this procedure is accompanied with stone removal. ETGBD is especially useful for acute cholecystitis patients who are contraindicated for PTGBD or those with severe coagulopathy, thrombocytopenia, and abnormal anatomy. Moreover, the advantage of ETGBD is its preservation of the external GB structure. Thereby it would not disturb the future cholecystectomy. Recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using plastic, fully covered metallic, or lumen-apposing metal stents transmurally has emerged as a modality for GB drainage with higher technical and clinical success rates. EUS-GBD can provide a more permanent GB drainage than PTGBD and ETGBD.


IRX3 is a genetic modifier for birth weight, adolescent obesity and transaminase metabolism.

Abstract:
OBJECTIVE
IRX3 expression has been functionally associated in obesity-associated long-distance susceptibility loci, but the effect of the IRX3 genetic variants on human obesity and obesity-related metabolism remains uncertain.

METHODS
To determine the genetic role of IRX3, we conducted a molecular epidemiological analysis using three haplotype tagging single nucleotide polymorphisms (SNPs; rs8053360, rs3751723 and rs12445085) and one nonsynonymous SNP (rs1126960) at the IRX3 locus in 333 junior and senior high school students from a northeast Chinese population.

RESULTS
We identified significant associations between IRX3 SNPs and birth weight, body mass index (BMI), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio. The rs8053360 CC and rs1126960 GG genotypes were associated with increased birth weight and BMI, especially in females. Individuals with the rs12445085 TT genotype had significantly higher levels of AST and ALT, whereas individuals with the rs1126960 GG genotype had a significantly lower AST/ALT ratio than did individuals with other genotypes. However, no significant relationships were found between any of the IRX3 SNPs and metabolic syndrome or diabetes.

CONCLUSIONS
IRX3 genetic variants associate with birth weight, BMI and AST/ALT-related transaminase metabolism, supporting the role of IRX3 as an obesity-associated susceptibility gene.

Liu|C|C| Chu|C|C| Zhang|J|J| Wu|D|D| Xu|D|D| Li|P|P| Chen|Y|Y| Liu|B|B| Pei|L|L| Zhang|L|L| Liu|S|S| Qi|T|T| Lou|X-Y|XY| Li|L|L|

D020022:Genetic Predisposition to Disease

IRX3
Birth weight
obesity
transaminase metabolism
polymorphism


Erosion of trust in humanitarian agencies: what strategies might help?

Abstract: Aid agencies (AAs) provide a range of humanitarian and health related assistance globally. However, the trust placed on them is eroding. Evidence for this includes accusations of a decline in their humanitarianism, and the increasing number of conflicts with host states. An analysis of the concerns expressed yields two possible reasons: a relative lack of transparency of their work and weak accountability mechanisms. This is further supported by the existing milieu: an absence of internationally accepted instrument or mechanism to check the credentials of INGOs and an opaque system of close links between some of the INGOs and their donors. The article suggests two global strategies to tackle these issues: (a) Increase transparency by establishing a global register of aid agencies. This should have basic information: their main goals and activities, countries they are active in, number of employees, annual turnover of funds (updated regularly), principal financing sources and nature of links with donors. This could also be available as printed manual that should be freely available to client countries. (b) Ensure accountability by developing templates of fair legal instruments (to facilitate and regulate work), and a set of generic rules and procedures of engagement for the interactions between agencies and client states. These should be institutionalized within the regulatory frameworks of countries and included in the Codes of Conduct of NGOs.

trust aid transparency accountability philanthropy


Management of mediastinal syndromes in pediatrics: a new challenge of ultrasound guidance to avoid high-risk general anesthesia.

Abstract: Adverse events associated with anesthetic management of anterior mediastinal masses in pediatrics are common. To avoid an extremely hazardous general anesthesia, the use of real-time ultrasonography offers an effective alternative in high-risk cases. We report the anesthetic management including a light sedation and ultrasound guidance for regional anesthesia, surgical node biopsy, and placement of a central venous line in two children with an anterior symptomatic mediastinal mass. For pediatric patients with clinical and/or radiologic signs of airway compression, ultrasound guidance provides safety technical assistance to avoid general anesthesia and should be performed for the initial diagnostic and therapeutic procedures.

Sola|Chrystelle|C| Choquet|Olivier|O| Prodhomme|Olivier|O| Capdevila|Xavier|X| Dadure|Christophe|C|

mediastinal syndromes
ultrasound guidance
regional anesthesia
pediatrics anesthesia


A Semi-Infinite Programming based algorithm for determining T-optimum designs for model discrimination.

Abstract: T-optimum designs for model discrimination are notoriously difficult to find because of the computational difficulty involved in solving an optimization problem that involves two layers of optimization. Only a handful of analytical T-optimal designs are available for the simplest problems; the rest in the literature are found using specialized numerical procedures for a specific problem. We propose a potentially more systematic and general way for finding T-optimal designs using a Semi-Infinite Programming (SIP) approach. The strategy requires that we first reformulate the original minimax or maximin optimization problem into an equivalent semi-infinite program and solve it using an exchange-based method where lower and upper bounds produced by solving the outer and the inner programs, are iterated to convergence. A global Nonlinear Programming (NLP) solver is used to handle the subproblems, thus finding the optimal design and the least favorable parametric configuration that minimizes the residual sum of squares from the alternative or test models. We also use a nonlinear program to check the global optimality of the SIP-generated design and automate the construction of globally optimal designs. The algorithm is successfully used to produce results that coincide with several T-optimal designs reported in the literature for various types of model discrimination problems with normally distributed errors. However, our method is more general, merely requiring that the parameters of the model be estimated by a numerical optimization.

Duarte|Belmiro P M|BP|
Wong|Weng Kee|WK|
Atkinson|Anthony C|AC|

Semi-Infinite Programming
Global optimization
Continuous design
Equivalence theorem
Maximum likelihood design
Minimax program


Autologous fat grafting for the treatment of velopharyngeal insufficiency: state of the art.

Abstract:
BACKGROUND
Autologous fat grafting to the velopharynx has been described for treatment of velopharyngeal insufficiency for over a decade. The aim of this review was to evaluate outcomes of autologous fat grafting for velopharyngeal insufficiency.

METHODS
A computerized search was performed across multiple databases. Studies involving patients undergoing autologous fat grafting for velopharyngeal insufficiency treatment that reported at least one pre- and post-intervention outcome measure were included.

RESULTS
A systematic search revealed eleven studies that satisfied inclusion criteria. All were case series or noncomparative observational studies. Three reported on isolated posterior pharyngeal wall augmentation, while eight involved augmentation of the pharyngeal arches, velum and/or posterior pharyngeal wall. In general, selected patients had plateaued with regards to speech therapy and had small-to-moderate velopharyngeal closure defects. Although most patients had a cleft palate diagnosis, the proportion that had previous velopharyngoplasty, or other related diagnoses was highly variable. In all but one report outcome measures included perceptual speech assessment. Objective measures such as nasalance and fat graft take were inconsistently reported. Overall, results of fat grafting for velopharyngeal insufficiency were variable and depended on assessment modality. One case of obstructive sleep apnea was reported.

CONCLUSIONS
Despite potential benefits of autologous fat grafting for velopharyngeal insufficiency, questions remain as to patient selection, safety, and optimal graft volume and injection sites. This review underscores the need for standardized assessment methods and prospective comparative studies or randomized controlled trials to compare fat grafting with established velopharyngoplasty techniques to better define indications for its use.

D000273:Adipose Tissue
D002972:Cleft Palate
D006801:Humans
D013064:Speech Disorders
D016896:Treatment Outcome
D014681:Velopharyngeal Insufficiency

Autologous fat grafting
Velopharyngeal insufficiency
Outcomes
Speech
Cleft palate


Clinical evaluation of porous hydroxyapatite bone graft (Periobone G) with and without collagen membrane (Periocol) in the treatment of bilateral grade II furcation defects in mandibular first permanent molars.

Abstract:
BACKGROUND
Furcation invasions represent one of the most demanding therapeutic challenges in periodontics. This investigation assessed and compared the clinical efficacy of hydroxyapatite bone graft material when used alone and with collagen membrane in the treatment of grade II furcation defects.

MATERIALS AND METHODS
Ten patients with comparable bilateral furcation defects in relation to mandibular first molars were selected and treated in a split-mouth design. After the hygiene phase of therapy was completed, the groups were selected randomly either for treatment with hydroxyapatite bone graft (Periobone G) alone or with a combination of bone graft and guided tissue regeneration (GTR) membrane (Periocol). Clinical parameters like plaque index, gingival index, vertical probing depth, horizontal probing depth, clinical attachment level, position of marginal gingiva, and the amount of bone fill were used at baseline and at 3 and 6 months postoperatively.

RESULTS
At 6 months, both surgical procedures resulted in statistically significant reduction in vertical and horizontal probing depths and gain in the clinical attachment level.

CONCLUSION
The use of combination technique yielded superior results compared to sites treated with bone graft alone. However, the difference was not statistically significant.

Prathap|Sruthy|S|
Hegde|Shashikanth|S|
Kashyap|Rajesh|R|
Prathap|M S|MS|
Arunkumar|M S|MS|

hydroxyapatite
Collagen
furcation defects
guided tissue regeneration
surgical flaps


Understanding Objections to One Anastomosis (Mini) Gastric Bypass: A Survey of 417 Surgeons Not Performing this Procedure.

Abstract:
BACKGROUND
Despite published experience with thousands of patients, the uptake of One Anastomosis/Mini Gastric Bypass (OAGB/MGB) has been less than enthusiastic and many surgeons still harbour objections to this procedure. The purpose of this study was to understand these objections scientifically.

METHODS
Bariatric surgeons from around the world were invited to participate in a questionnaire-based survey on SurveyMonkey®. Surgeons already performing this procedure were excluded.

RESULTS
Four hundred seventeen bariatric surgeons (from 42 countries) not currently performing OAGB/MGB took the survey. There were 211/414 (50.97%) and 188/414 (45.41%) respondents who expressed concerns that it will lead to an increased risk of gastric and oesophageal cancers respectively. A total of 62/416 (14.9%) and 201/413 (n = 48.6%) surgeons respectively felt that OAGB/MGB was associated with a higher early (30-day) and late complication rate compared to the RYGB. Moreover, 7.8% (n = 32/411) and 16.26% (n = 67/412) of the respondents were concerned that OAGB/MGB carried a higher early (30-day) and late mortality, respectively, in comparison with the RYGB. There were 79/410 (19.27%) and 88/413 (21.3%) respondents who were concerned that OAGB/MGB was not an effective procedure for weight loss and co-morbidity resolution, respectively. A total of 258/411 (62.77%) respondents reported that OAGB/MGB was not approved by their national society as a mainstream bariatric procedure; 51.0% of these surgeons would start performing this procedure if it was.

CONCLUSIONS
Surgeons not performing OAGB/MGB cite a number of concerns for not performing this operation. This survey is the first scientific attempt to understand these objections scientifically.

Mahawar|Kamal K|KK|
Borg|Cynthia-Michelle|CM|
Kular|Kuldeepak Singh|KS|
Courtney|Michael J|MJ|
Sillah|Karim|K|
Carr|William R J|WRJ|
Jennings|Neil|N|
Madhok|Brijesh|B|
Singhal|Rishi|R|
Small|Peter K|PK|

Objections
Mini gastric bypass
Oesophageal cancer
Bile reflux
Gastric cancer
Malnutrition
Omega loop gastric bypass
One anastomosis gastric bypass
Single anastomosis gastric bypass


MicroRNA-30c-2-3p regulates ER stress and induces apoptosis in ovarian cancer cells underlying ER stress.

Abstract: Ovarian cancer is a common gynecologic cancer with a high rate of recurrence, drug resistance, and mortality, thereby necessitating novel molecular target therapies. Ovarian cancer as a solid tumor has constantly been challenged by endoplasmic reticulum stress (ERS). Currently, XBP1 as a therapeutic target in solid tumors plays a key role in adaptation to ERS. Single-stranded RNAs usually modulate posttranscriptional of the gene activity. miR-30c-2-3p has been demonstrated to inhibit the expression of XBP1. Here, we evaluated the effect of miR-30c-2-3p on controlling XBP1-CHOP-BIM and its apoptotic effects on ovarian cancer cell lines during ERS. The ER stress was assessed using Thioflavin T staining in OVCAR3 and SKOV3 cells. The expression of ER stress genes was measured by QRT-PCR. The protein levels of XBP1(s), BIP/GRP78, CHOP, and BIM were evaluated using Western blotting. Cell viability and apoptosis in STF-083010 and Tunicamycin (Tm) co-treated cells were evaluated using BrdU, MTT, Annexin V-FITC/PI staining, and caspase-12 and -3 activities assays. We found that miR-30c-2-3p significantly decreased the folding capacity of ER, leading to ERS intensification (P<0.05). Additionally, the Western blot analysis showed the modest up-regulation of CHOP and BIM with pro-apoptotic activity and down-regulation of the BIP protein. Furthermore, mimic miR-30c-2-3p transfection not only decreased cell proliferation but also induced cell death in ovarian cancer cells in response to the Tm-treatment. Our results indicated that the apoptotic pathway was induced possibly through activation of caspases -12 and -3 and elevation of the Bax/Bcl-2 ratio. Overall, the present paper adds new evidence to the possible treatment of miR-30c-2-3p via impeding the XBP1 transcription in ovarian cancer cells provoking apoptotic pathways by XBP1/CHOP/BIM mediators.


Urokinase Receptor Regulates Adhesion of Progenitor Cardiac Cells to Vitronectin.

Abstract: Vitronectin, extracellular matrix protein, plays an important role in embryonic development and in organ and tissue reparation. A unique characteristic of vitronectin is specific binding of various biological molecules, including urokinase receptor (uPAR), extracellular matrix components, adhesion receptors, growth factors, thus supporting the modulation of cell behavior. Vitronectin is in fact not found in intact myocardium, while after infarction its level increases significantly, which correlates with accumulation of uPAR+ progenitor cardiac cells in the focus. The cells isolated from the heart of wild type mice are characterized by higher adhesion to vitronectin than progenitor cardiac cells from the myocardium of uPAR knockout mice. In addition, inhibition of urokinase receptor with specific antibodies on the surface of the progenitor cardiac cells of wild type mice leads to attenuation of their adhesive activity and flattening on vitronectin matrix, which can be important for their distribution in the postinfarction myocardium and realization of the reparative functions.

Dergilev|K V|KV|
Tsokolaeva|Z I|ZI|
Beloglazova|I B|IB|
Zubkova|E S|ES|
Ratner|E I|EI|
Molokotina|Yu D|YD|
Parfenova|E V|EV|

D055293:Receptors, Urokinase Plasminogen Activator

urokinase receptor
adhesion
vitronectin
progenitor cells of the heart


Prevalence and associated factors of fear of childbirth in six European countries.

Abstract:
OBJECTIVES
This study set out to compare the prevalence, content and associated factors of fear of childbirth in six European countries.

METHOD
A cross-sectional study of 6870 pregnant women attending routine antenatal care in Belgium, Iceland, Denmark, Estonia, Norway and Sweden (Bidens).

MAIN OUTCOME MEASURE
Severe fear of childbirth, defined as a Wijma Delivery Expectancy Questionnaire score of ≥85.

RESULTS
Eleven percent of all women reported severe fear of childbirth, 11.4% among primiparous and 11.0% among multiparous women. There were significant differences between the countries for prevalence of severe fear of childbirth, varying from 4.5% in Belgium to 15.6% in Estonia for primiparous women and from 7.6% in Iceland to 15.2% in Sweden for multiparous women. After adjusting for age, education and gestational age, only primiparous women from Belgium had significantly less fear of childbirth, AOR 0.35 (0.19-0.52) compared to Norway (largest participating group). Exploratory factor analyses revealed significant differences between the countries for the six factors extracted.

CONCLUSION
FOC appears to be an international phenomenon, existing with similar proportions in the participating European countries, except for primiparous women in Belgium who in our study reported significantly less severe fear of childbirth. Our study suggests that the content of fear of childbirth may differ between countries.

Lukasse|Mirjam|M|
Schei|Berit|B|
Ryding|Elsa Lena|EL|
|||


Toxicity of serum albumin on microglia upon seeding effect of amyloid peptide.

Abstract: We demonstrate in vitro cross-seeding of bovine serum albumin (BSA) in the presence of Aβ25-35 and their cytotoxic effects on microglial cells. To investigate the cross-seeding of BSA in the presence of Aβ25-35 fibrils, we examined how Aβ25-35 fibrils can function as seeds to trigger and accelerate BSA fibrillogenesis using ThT, intrinsic fluorescence, ANS fluorescence and transmission electron microscopy (TEM). Moreover, the effects of these fibrils on microglial viability were measured using MTT and Annexin V/propidium iodide (PI) staining. Although Aβ25-35 is toxic against microglia, it acted as seed and affected the aggregation pathway and accelerated the fibrillogenesis of BSA in vitro, resulted in an enhanced cytotoxic effect in comparison with Aβ25-35 or BSA alone. These observations thought to be helpful to understand the molecular mechanism of enhanced toxicity due to the coexistence of the aggregation prone proteins/peptides,. then cross-seeding effect on microglial cells that may involve in neurodegenerative diseases such as Alzheimer's disease (AD).

Ferdousi|Maryam|M|
Habibi-Rezaei|Mehran|M|
Balalaie|Saeed|S|
Ramezanpour|Sorour|S|
Sabouni|Farzaneh|F|
Poursasan|Najmeh|N|
Sabokdast|Manijheh|M|
Moosavi-Movahedi|Ali A|AA|

serum albumin
microglia
cross-seeding
Aβ25-35
Alzheimer’s disease


Microvascular reconstruction of segmental mandibular defects without tracheostomy.

Abstract:
OBJECTIVE
To report our experience with mandibular resection and reconstruction using vascularized bone-containing free flaps without an elective tracheostomy.

STUDY DESIGN
Case series with chart review.

SETTING
Tertiary referral hospital center.

SUBJECTS AND METHODS
Sixty-six patients undergoing mandibular reconstruction with vascularized bone-containing free flaps without an elective tracheostomy were identified between 1995 and 2013. We describe patient, tumor, and surgical factors and report perioperative outcomes in this population.

RESULTS
Most patients underwent fibula free flap reconstruction (n = 61, 92.44%). The 4 most frequent indications for resection were osteoradionecrosis, parotid carcinoma, oral squamous cell carcinoma, and osteomyelitis. Bone defects ranging from 4.0 to 13.0 cm were reconstructed, and associated soft-tissue defects were reconstructed with skin paddle sizes ranging from 24.0 to 450.0 cm(2). There was only 1 patient with a bilateral central mandibular defect, and there were no tongue/pharyngeal soft-tissue defects or bilateral neck dissections. One case required emergent tracheostomy on postoperative day 1, and 2 more patients developed respiratory complications. There were no cases of perioperative death or flap failure.

CONCLUSION
Mandibular free flap reconstruction is feasible without an elective tracheostomy in a subset of carefully selected patients without bilateral central mandibular defects, tongue/pharynx defects, or bilateral neck dissection.

Moubayed|Sami P|SP|
Barker|Daniel A|DA|
Razfar|Ali|A|
Nabili|Vishad|V|
Blackwell|Keith E|KE|

tracheostomy
free flap
mandibular reconstruction
complications


DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 Mpro inhibitors.

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition constant [K i] = 20 nM). CDD-1713, a smaller two-building-block analog (MW = 353.3 g/mol) of CDD-1714, is a reversible covalent inhibitor of Mpro (K i = 45 nM) that binds in the protease pocket, has specificity over human proteases, and shows in vitro efficacy in a SARS-CoV-2 infectivity model. Subsequently, key regions of CDD-1713 that were necessary for inhibitory activity were identified and a potent (K i = 37 nM), smaller (MW = 323.4 g/mol), and metabolically more stable analog (CDD-1976) was generated. Thus, screening of DNA-encoded chemical libraries can accelerate the discovery of efficacious drug-like inhibitors of emerging viral disease targets.

Chamakuri|Srinivas|S|
Lu|Shuo|S|
Ucisik|Melek Nihan|MN|
Bohren|Kurt M|KM|0000-0002-3183-4118
Chen|Ying-Chu|YC|
Du|Huang-Chi|HC|
Faver|John C|JC|0000-0002-0181-9283
Jimmidi|Ravikumar|R|
Li|Feng|F|0000-0002-9680-4614
Li|Jian-Yuan|JY|
Nyshadham|Pranavanand|P|
Palmer|Stephen S|SS|
Pollet|Jeroen|J|0000-0003-1420-4015
Qin|Xuan|X|
Ronca|Shannon E|SE|
Sankaran|Banumathi|B|
Sharma|Kiran L|KL|0000-0002-1988-389X
Tan|Zhi|Z|
Versteeg|Leroy|L|
Yu|Zhifeng|Z|0000-0001-7278-8253
Matzuk|Martin M|MM|0000-0002-1445-8632
Palzkill|Timothy|T|
Young|Damian W|DW|

covalent inhibitors
antiviral
drug discovery


Gastrointestinal Histoplasmosis Mimicking Crohn's Disease.

Abstract: Disseminated histoplasmosis is a life-threatening disease usually seen in immunocompromised patients living in endemic areas. We present an apparently immunocompetent patient with gastrointestinal histoplasmosis who was initially diagnosed with biopsy-proven Crohn's disease. Following discontinuation of anti-inflammatory drugs and institution of antifungal therapy, his gastrointestinal illness completely improved. Specific fungal staining should be routinely included in histopathologic assessment of tissue specimens diagnosed as Crohn's disease.

gastrointestinal histoplasmosis
alcoholism
inflammatory bowel disease


Therapeutic Targeting of CDK7 Suppresses Tumor Progression in Intrahepatic Cholangiocarcinoma.

Abstract: Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy with high mortality and lack of effective therapeutic targets. Here, we found that expression of cyclin-dependent kinase 7 (CDK7) was significantly associated with higher tumor grade and worse prognosis in 96 ICC specimens. Depletion of CDK7 significantly inhibited cell growth, induced a G2/M cell cycle arrest, and reduced the migratory and invasive potential in ICC cells. Subsequent experiments demonstrated that ICC cells were highly sensitive to the CDK7 inhibitor THZ1. A low concentration of THZ1 markedly inhibited cell growth, cell cycle, migration, and invasion in ICC cell lines. RNA-sequencing (RNA-seq) analysis revealed that THZ1 treatment decreased the levels of massive oncogene transcripts, particularly those associated with cell cycle and cell migration. Quantitative reverse transcriptase PCR (qRT-PCR) analysis confirmed that transcription of oncogenes involved in cell cycle regulation (AURKA, AURKB, CDC25B, CDK1, CCNA2, and MKI67) and the c-Met pathway (c-Met, AKT1, PTK2, CRK, PDPK1, and ARF6) was selectively repressed by THZ1. In addition, THZ1 exhibited significant anti-tumor activity in a patient-derived xenograft (PDX) model of ICC, without causing detectable side effects.

Chen|Hua-Dong|HD| Huang|Chen-Song|CS| Xu|Qiong-Cong|QC| Li|Fuxi|F| Huang|Xi-Tai|XT| Wang|Jie-Qin|JQ| Li|Shi-Jin|SJ| Zhao|Wei|W| Yin|Xiao-Yu|XY|

D060888:Real-Time Polymerase Chain Reaction

Intrahepatic cholangiocarcinoma
Cyclin-dependent Kinase 7
Cell cycle
THZ1
c-Met


Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

Abstract: Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses.

Garnacho|Carmen|C|
Dhami|Rajwinder|R|
Solomon|Melani|M|
Schuchman|Edward H|EH|
Muro|Silvia|S|

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

type B Niemann-Pick disease
acid sphingomyelinase deficiency
ICAM-1 targeting
enzyme replacement therapy
polymer nanocarriers
pulmonary effects


Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism.

Abstract: The current study was performed to investigate mitochondrial protection and anti-aging activity of Astragalus polysaccharides (APS) and the potential underlying mechanism. Lipid peroxidation of liver and brain mitochondria was induced by Fe(2+)-Vit C in vitro. Thiobarbituric acid (TBA) colorimetry was used to measure the content of thiobarbituric acid reactive substances (TBARS). Mouse liver mitochondrial permeability transition (PT) was induced by calcium overload in vitro and spectrophotometry was used to measure it. The scavenging activities of APS on superoxide anion (O(2) (•-)) and hydroxyl radical (•OH), which were produced by reduced nicotinamide adenine dinucleotide (NADH)-N-Methylphenazonium methyl sulfate (PMS) and hydrogen peroxide (H(2)O(2))-Fe(2+) system respectively, were measured by 4-nitrobluetetrazolium chloride (NBT) reduction and Fenton reaction colorimetry respectively. The Na(2)S(2)O(3) titration method was used to measure the scavenging activities of APS on H(2)O(2). APS could inhibit TBARS production, protect mitochondria from PT, and scavenge O(2) (•-), •OH and H(2)O(2) significantly in a concentration-dependent manner respectively. The back of the neck of mice was injected subcutaneously with D-galactose to induce aging at a dose of 100 mg/kg/d for seven weeks. Moreover, the activities of catalase (CAT), surperoxide dismutase (SOD) and glutathione peroxidase (GPx) and anti-hydroxyl radical which were assayed by using commercial monitoring kits were increased significantly in vivo by APS. According to this research, APS protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting mitochondrial PT and increasing the activities of antioxidases. Therefore, APS has the effect of promoting health.

Li|Xing-Tai|XT| Zhang|Ya-Kui|YK| Kuang|Hai-Xue|HX| Jin|Feng-Xin|FX| Liu|De-Wen|DW| Gao|Ming-Bo|MB| Liu|Ze|Z| Xin|Xiao-Juan|XJ|

D017392:Thiobarbituric Acid Reactive Substances

anti-aging
Astragalus polysaccharides
mitochondria
mitochondrial permeability transition
reactive oxygen species
antioxidant


Prevalence of daytime urinary incontinence and related risk factors in primary school children in Turkey.

Abstract:
PURPOSE
Urinary incontinence is one of the major urinary symptoms in children and adolescents and can lead to major distress for the affected children and their parents. In accordance with the definitions of the Standardization Committee of the International Children's Continence Society, daytime urinary incontinence (DUI) is uncontrollable leakage of urine during the day. The aim of this cross-sectional study was to investigate the prevalence and associated risk factors of DUI in Turkish primary school children.

MATERIALS AND METHODS
The questionnaire, which covered sociodemographic variables and the voiding habits of the children, was completed by the parents of 2,353 children who were attending primary school in Denizli, a developing city of Turkey. The children's voiding habits were evaluated by use of the Dysfunctional Voiding and Incontinence Symptoms Score, which is a validated questionnaire. Children with a history of neurological or urological diseases were excluded.

RESULTS
The participation rate was 91.9% (2,164 people). The overall prevalence of DUI was 8.0%. The incidence of DUI tended to decrease with increasing age and was not significantly different between genders (boys, 8.8%; girls, 7.3%; p=0.062). Age, maternal education level, family history of daytime wetting, settlement (urban/rural), history of constipation, urinary tract infection, and urgency were independent risk factors of DUI.

CONCLUSIONS
Our findings showed that DUI is a common health problem in primary school children. In an effort to increase awareness of children's voiding problems and the risk factors for urinary dysfunction in the population, educational programs and larger school-based screening should be carried out, especially in regions with low socioeconomic status.

Bolat|Deniz|D|
Acar|Ismail Cenk|IC|
Zumrutbas|Ali Ersin|AE|
Eskicorapci|Saadettin|S|
Sancak|Eyup Burak|EB|
Zencir|Mehmet|M|
Turan|Tahir|T|
Sinik|Zafer|Z|

Prevalence
Risk factors
Child
Diurnal enuresis
Urination disorders


The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

Abstract: Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

Maniam|Jayanthi|J|
Antoniadis|Christopher P|CP|
Morris|Margaret J|MJ|

D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1

D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

early-life stress
limited nesting
sucrose
hepatic triglyceride
11-Beta hydroxysteroid dehydrogenase 1
glucose/insulin tolerance


The Potential Impact of Preventive HIV Vaccines in China: Results and Benefits of a Multi-Province Modeling Collaboration.

Abstract: China's commitment to implementing established and emerging HIV/AIDS prevention and control strategies has led to substantial gains in terms of access to antiretroviral treatment and prevention services, but the evolving and multifaceted HIV/AIDS epidemic in China highlights the challenges of maintaining that response. This study presents modeling results exploring the potential impact of HIV vaccines in the Chinese context at varying efficacy and coverage rates, while further exploring the potential implications of vaccination programs aimed at reaching populations at highest risk of HIV infection. A preventive HIV vaccine would add a powerful tool to China's response, even if not 100% efficacious or available to the full population.

Harmon|Thomas|T| Guo|Wei|W| Stover|John|J| Wu|Zunyou|Z| Kaufman|Joan|J| Schneider|Kammerle|K| Liu|Li|L| Feng|Liao|L| Schwartländer|Bernard|B|

prevention vaccines China modeling HIV/AIDS Sichuan research


Hepatocyte growth factor: A regulator of inflammation and autoimmunity.

Abstract: Hepatocyte growth factor (HGF) is a pleiotropic cytokine that has been extensively studied over several decades, but was only recently recognized as a key player in mediating protection of many types of inflammatory and autoimmune diseases. HGF was reported to prevent and attenuate disease progression by influencing multiple pathophysiological processes involved in inflammatory and immune response, including cell migration, maturation, cytokine production, antigen presentation, and T cell effector function. In this review, we discuss the actions and mechanisms of HGF in inflammation and immunity and the therapeutic potential of this factor for the treatment of inflammatory and autoimmune diseases.

Molnarfi|Nicolas|N|
Benkhoucha|Mahdia|M|
Funakoshi|Hiroshi|H|
Nakamura|Toshikazu|T|
Lalive|Patrice H|PH|

Inflammation
Autoimmunity
HGF
Autoimmune regulator
Therapy
c-Met


Plasminogen kringle 5 induces endothelial cell apoptosis by triggering a voltage-dependent anion channel 1 (VDAC1) positive feedback loop.

Abstract: Human plasminogen kringle 5 (K5) is known to display its potent anti-angiogenesis effect through inducing endothelial cell (EC) apoptosis, and the voltage-dependent anion channel 1 (VDAC1) has been identified as a receptor of K5. However, the exact role and underlying mechanisms of VDAC1 in K5-induced EC apoptosis remain elusive. In the current study, we showed that K5 increased the protein level of VDAC1, which initiated the mitochondrial apoptosis pathway of ECs. Our findings also showed that K5 inhibited the ubiquitin-dependent degradation of VDAC1 by promoting the phosphorylation of VDAC1, possibly at Ser-12 and Thr-107. The phosphorylated VDAC1 was attenuated by the AKT agonist, glycogen synthase kinase (GSK) 3β inhibitor, and siRNA, suggesting that K5 increased VDAC1 phosphorylation via the AKT-GSK3β pathway. Furthermore, K5 promoted cell surface translocation of VDAC1, and binding between K5 and VDAC1 was observed on the plasma membrane. HKI protein blocked the impact of K5 on the AKT-GSK3β pathway by competitively inhibiting the interaction of K5 and cell surface VDAC1. Moreover, K5-induced EC apoptosis was suppressed by VDAC1 antibody. These data show for the first time that K5-induced EC apoptosis is mediated by the positive feedback loop of "VDAC1-AKT-GSK3β-VDAC1," which may provide new perspectives on the mechanisms of K5-induced apoptosis.

Li|Lei|L| Yao|Ya-Chao|YC| Gu|Xiao-Qiong|XQ| Che|Di|D| Ma|Cai-Qi|CQ| Dai|Zhi-Yu|ZY| Li|Cen|C| Zhou|Ti|T| Cai|Wei-Bin|WB| Yang|Zhong-Han|ZH| Yang|Xia|X| Gao|Guo-Quan|GQ|

D000071679:Glycogen Synthase Kinase 3 beta

D061307:Human Umbilical Vein Endothelial Cells

D050995:Voltage-Dependent Anion Channel 1

Apoptosis
Phosphorylation
Bax
Cell Biology
Cell Signaling
Cell Surface Receptor
Cellular Regulation
Glycogen Synthase Kinase 3 (GSK-3)
Molecular Cell Biology
PI 3-Kinase (PI3K)


Prevalence of neuropathic pain in knee or hip osteoarthritis: A systematic review and meta-analysis.

Abstract:
OBJECTIVE
Discordance between radiographic and pain severity in osteoarthritis (OA) has led researchers to investigate other pain mechanisms, including neuropathic pain. Accurate identification of any neuropathic pain in hip or knee OA is important for appropriate management, but neuropathic pain prevalence is unknown. We aimed to obtain an overall prevalence estimate by systematically reviewing and meta-analysing the prevalence of neuropathic pain in people with hip or knee OA.

METHOD
Observational studies which measured neuropathic pain in people aged 18 years and older with hip or knee OA were considered for inclusion. Electronic databases were searched up to February 2016. Two reviewers independently identified eligible studies and assessed methodological quality. Prevalence estimates and 95% confidence intervals were calculated using random effects meta-analytic techniques.

RESULTS
Nine studies met the inclusion criteria. Study samples were from general population, hospital and community settings and all used self-report questionnaires to determine neuropathic pain. The overall prevalence estimate was 23% (95% CI: 10-39%), with considerable heterogeneity (I2 = 97.9%, p < 0.001). This estimate was largely unchanged with subgroup analyses based on index joint, questionnaire type, setting and consideration of other potential causes of neuropathic pain. However, the estimate for two studies that excluded other potential causes of neuropathic pain was substantially higher (32%, 95% CI: 29-35%).

CONCLUSIONS
Neuropathic pain prevalence in people with knee or hip OA is considerable at 23%, and may be higher after other potential causes of neuropathic pain are excluded. Concerns regarding the validity of neuropathic pain questionnaires, selection bias, methodological quality and study heterogeneity suggest caution with interpretation of these findings. Prevalence studies using standardised criteria for neuropathic pain are required.

French|Helen P|HP|
Smart|Keith M|KM|
Doyle|Frank|F|

Pain Knee Hip Osteoarthritis Epidemiology


Comparison of Nutritional Compositions and Essential Oil Profiles of Different Parts of a Dill and Two Fennel Cultivars.

Abstract: Fennel and dill are widely used as food additives owing to their various biological activities, such as antioxidants, antimicrobials, food-preservatives, and seasoning capacities. Herein, the nutritional composition and essential oil (EO) chemical profiles of fruits, umbels, stalks, and roots from one dill and two fennel cultivars were evaluated. The fruits had the highest content of crude protein (≥15%), crude fat (≥8%), and phosphorus (≥0.5%), and exhibited the highest total energy (≥20 MJ/kg) and EO yield (≥2%). Moreover, estragole (86.56% in Fdf), anethole (71.17% in Fhf), fenchone (16.74% in Fhf), limonene (50.19% in Agf), and carvone (42.41% in Agf) were the main components of the EOs generated from the fruits. The chemical profiles of EOs in the roots were significantly different from those of the aerial parts of the fennel and dill; thus, the roots and aerial parts could be distinguished based on myristicin (Variable Importance in Projection (VIP) = 1.90399) and apiol (VIP = 1.85922). The EO components of the aerial parts varied remarkably, and the chemical markers for differentiating these three cultivars were anethole (VIP = 1.36571), estragole (VIP = 1.30292), and carvone (VIP = 1.11947). Overall, our results provide a noteworthy chemical basis for further development of fennel and dill, especially as food additives.

Hao|Yuanpeng|Y|0000-0001-8302-4363 Kang|Jiamu|J| Guo|Xiaoqi|X| Yang|Rui|R| Chen|Yuliang|Y| Li|Jingyi|J| Shi|Lei|L|

food additives
Apiaceae plants
efficient utilization
multivariate analysis
plant parts


Exploring How Postmillennial Pharmacy Students Balance Life Priorities and Avoid Situations Known to Deplete Resilience.

Abstract: Objective. Students are facing increasing academic pressures that can contribute to poor wellbeing. Evidence to inform the development of better student support services is weak. This study aimed to explore Bachelor of Pharmacy students' self-reported life priorities and ways they strategize to avoid resilience-depleting events on a day-to-day basis.Methods. Postmillennial (those born after 1996) pharmacy students enrolled in their final year of pharmacy school were introduced to the coaching concepts of the Wheel of Life and anti-goals. Students' top eight life priorities were collected and categorized. Students were asked to submit one anti-goal targeting a strategy used to avoid resilience depletion. Anti-goals were coded according to student priority areas and overarching themes were interpreted.Results. The top priorities of 110 final-year pharmacy students were: family, finance, health, friends/relationships, study, career prospects, fitness, personal growth, travel, and mental health/wellbeing. Priorities were both similar and dissimilar to traditional coaching priorities. Sixty-eight anti-goals were coded. The themes "being prepared" and "being present" were used to summarize strategies that students employed to avoid resilience depletion.Conclusion. The life priorities of newer student generations may be changing to be more individualistic and include a greater focus on self-help, while maintaining the core priorities of family, health, and finance. These findings uphold the notion that student support mechanisms must be modernized to accommodate students' needs.

Dresser|Jacob D|JD|
Whitfield|Karen M|KM|
Kremer|Lisa J|LJ|
Wilby|Kyle J|KJ|

D004512:Education, Pharmacy
D006801:Humans
D008603:Mental Health
D000071252:Mentoring
D012580:Schools, Pharmacy
D013339:Students, Pharmacy


Prospective Cohort Analysis of DRG Stimulation for Failed Back Surgery Syndrome Pain Following Lumbar Discectomy.

Abstract:
INTRODUCTION
Surgical lumbar discectomy is a commonly performed routine spinal procedure that is usually undertaken to alleviate lumbar radicular symptoms caused by a herniated intervertebral disc. Surgical lumbar discectomy can also lead to chronic postsurgical leg and/or back pain (failed back surgery syndrome [FBSS]), a condition that can be refractory to conventional medical management. Early clinical results on the use of dorsal root ganglion (DRG) stimulation for FBSS have supported the use of this treatment alternative.

METHODS
A multicenter, single-arm, observational cohort study enrolled patients who had chronic pain following surgical lumbar discectomy, had failed conservative treatments, and reported pain intensity of at least 6 out of 10 in the primary region of pain. Data were collected on pain, quality of life, disability, and mood at baseline and through 12 months.

RESULTS
Thirteen patients underwent a trial of DRG stimulation; 11 (84.6%; 95% confidence interval = 57.8% to 95.7%) had good outcomes and underwent permanent device placement. Pain was reduced from a score of 8.64 (±0.92) at baseline to 2.40 (±2.38; n = 9) after 12 months of treatment, a 72.05% average reduction (P < 0.001). Similar improvements were observed across the secondary clinical measures, and safety data were in line with published rates.

DISCUSSION
These results suggest that DRG stimulation induces pain relief in subjects diagnosed with FBSS. These reductions in pain were also associated with improvements in quality of life and disability. Additional prospective studies are warranted to further investigate this potential application of DRG stimulation, as well as to optimize patient selection, lead placement, and programming strategies.

Kallewaard|Jan Willem|JW|
Nijhuis|Harold|H|
Huygen|Frank|F|
Wille|Frank|F|
Zuidema|Xander|X|
van de Minkelis|Johan|J|
Raza|Adil|A|

stimulation
failed back surgery syndrome
back
pain
dorsal root ganglia
neuromodulation
neuropathic
spinal cord stimulation


Attitudes of people working in mental health non-governmental organisations in Australia: A comparison with other mental health professionals.

Abstract: Research suggests that stigma impacts help-seeking behaviour and health outcomes for people affected by mental illness. This study compared the attitudes of Australian non-governmental organisation support workers towards people with mental illness with those of other health professionals. Three hundred and seventy four support workers were randomly allocated to answer questions about one of the six vignettes. Results indicated that non-governmental organisation support workers held more positive attitudes towards people with mental illness than those of general practitioners, psychiatrists and psychologists measured in prior research. These results suggest that non-governmental organisations may be a more positive and comfortable entry and referral point for mental health clients.

Rose|Grenville|G|
von Hippel|Courtney|C|
Brener|Loren|L|
von Hippel|Bill|B|

mental health
non-governmental organisations
health professionals
help-seeking behaviour
allied health professional
inclusion
social stigma


The two facets of species sensitivity: Stress and disturbance on coralligenous assemblages in space and time.

Abstract: Marine coastal ecosystems are affected by a vast array of human-induced disturbances and stresses, which are often capable of overwhelming the effects of natural changes. Despite the conceptual and practical difficulty in differentiating between disturbance and stress, which are often used interchangeably, the two terms bear different ecological meanings. Both are external agents, but the former causes mortality or physical damage (subtraction of biomass), whereas the latter causes physiological alteration (reduction in productivity). Sensitivity of marine organisms may thus have a dual connotation, being influenced in different ways by disturbance and by stress following major environmental change. Coralligenous assemblages, which shape unique biogenic formations in the Mediterranean Sea, are considered highly sensitive to change. In this paper, we propose a method to differentiate between disturbance and stress to assess the ecological status of the coralligenous assemblages. Disturbance sensitivity level (DSL) and stress sensitivity level (SSL) of the sessile organisms thriving in the coralligenous assemblages were combined into the integrated sensitivity level of coralligenous assemblages (ISLA) index. Changes in the coralligenous status were assessed in space, along a gradient of stress (human-induced pressures) at several sites of the western Mediterranean, and in time, from a long-term series (1961-2008) at Mesco Reef (Ligurian Sea) that encompasses a mass mortality event in the 1990s. The quality of the coralligenous assemblages was lower in highly urbanised sites than that in sites in both marine protected areas and areas with low levels of urbanisation; moreover, the quality of the assemblages at Mesco Reef decreased during the last 50years. Reduction in quality was mainly due to the increase in stress-tolerant and/or opportunist species (e.g. algal turfs, hydroids and encrusting sponges), the disappearance of the most sensitive macroalgae (e.g. Udoteaceae and erect Rhodophyta) and macro-invertebrates (e.g. Savalia savaglia, Alcyonium coralloides and Smittina cervicornis), and the appearance of invasive alien algal species. Although the specific indices of SSL or DSL well illustrated the changes in the spatial or temporal datasets, respectively, their integration in the ISLA index was more effective in measuring the change experienced by the coralligenous assemblages in both space and time.

Montefalcone|Monica|M|
Morri|Carla|C|
Bianchi|Carlo Nike|CN|
Bavestrello|Giorgio|G|
Piazzi|Luigi|L|

Sensitivity
Stress
Disturbance
Coralligenous assemblages
Mediterranean Sea
ISLA index
Ecological quality


In silico docking studies of Lupeol with MAPK pathway proteins- Raf-1, MEK & ERK.

Abstract: Lupeol, A triterpenoid found in variety of plants is reported to have beneficial medicinal effects on several ailments. Lupeol is also found to show inhibitory effect on proliferation of breast cancer cells. Metastasis is considered to be a major cause for worldwide deaths related to cancer. Ras related MAPK Signaling Pathway is one of the crucial pathways leading to metastasis. Lupeols binding possibility with Ras is already reported. In present study, Interaction between with downstream proteins of Ras- MAPK pathway, Raf ,MEK ,ERK1/2 and their corresponding domains are studied using STRING Database and their structures are retrieved in PDB Format. Lupeols binding affinity with downstream proteins of these signaling proteins at their interacting domains are analyzed. Here in silico docking approach to identify binding sites of each of these proteins with Lupeol is used. FDA approved standard drug molecule CH5126766 was used as reference ligand. Lupeol shows potent binding at significant sites with extremely high affinity. Since it binds with all the proteins involved in the pathway with high efficiency it is an important compound which can be developed as a therapeutic molecule.

Bhatt|Mital H|MH|
Prajapati|Chirag K|CK|
Reddy|M N|MN|

D048049:Extracellular Signal-Regulated MAP Kinases

D020929:Mitogen-Activated Protein Kinase Kinases

Docking
Lupeol
MAPK
Raf-1
MEK
ERK Metastasis


Volunteer transitions and physical and psychological health among older adults in Taiwan.

Abstract:
OBJECTIVES
This study examines the relationship between transitions in volunteering activity and physical and psychological health outcomes among older adults in Taiwan.

METHOD
We used 3 waves of a longitudinal survey from Taiwan (1999, 2003, and 2007) including 1,847 older adults aged 58-74. We categorized volunteer activity over time into 5 categories and used generalized estimating equations to examine the relationship between volunteer transition group membership and health outcomes.

RESULTS
Approximately, 3% of older volunteers kept volunteering and 7% stopped or started their volunteering over time. Engaging in any volunteering, including continuous volunteering, discrete volunteering, active-to-inactive volunteering, and inactive-to-active volunteering, was significantly associated with better self-rated health and higher life satisfaction when compared with the nonvolunteering group. Only those in the continuous volunteer group and those who shifted from inactive-to-active volunteering showed a positive association with better physical function and less depression, compared with the nonvolunteering group.

DISCUSSION
The results suggest that the positive relationship between volunteering and health may decline when older adults discontinue or withdraw from volunteering. More research is needed to explore the mechanism behind older people's desistance from, persistence in, and resumption of volunteer engagement.


Religious coping methods predict depression and quality of life among end-stage renal disease patients undergoing hemodialysis: a cross-sectional study.

Abstract:
BACKGROUND
Poor quality of life (QOL) and a high prevalence of depression have been identified among end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). We aimed to evaluate the associations between religious/spiritual (R/S) coping methods and both QOL and depression among ESRD patients undergoing hemodialysis (HD).

METHODS
The sample included 161 ESRD patients over 18 years of age who had been undergoing HD for more than 3 months. R/S coping methods were assessed using the Religious Coping Questionnaire (RCOPE). The RCOPE generates scores (from 1 to 5) for positive and negative R/S coping methods. The higher the score, the more frequent the use of that coping method. Depression was evaluated using the 20-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). Scores on the CES-D range from 0 to 60. A cutoff of 18 was used to define depression. QOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36); this survey was used to generate scores for the eight dimensions of QOL, which can vary from 0 (worst) to 100 (best).

RESULTS
We identified a depression prevalence of 27.3%. Positive R/S coping scores were higher among non-depressed than depressed patients (2.98 vs. 2.77; p = 0.037). Positive R/S coping scores were negatively correlated with depression scores (r = -0.200; p = 0.012) and were an independent protective factor for depression (OR = 0.13; CI 95% = 0.02-0.91; p = 0.039). Regarding QOL, a positive correlation was identified between positive R/S coping scores and scores related to general health (r = 0.171; p = 0.030) and vitality (r = 0.183; p = 0.019), and an inverse correlation was identified between negative R/S coping scores and scores in the social functioning (r = -0.191; p = 0.015) and mental health (r = -0.214; p = 0.006) dimensions. In addition, positive R/S coping scores were an independent predictor of higher scores in the bodily pain (β = 14.401; p = 0.048) and vitality (β = 12.580; p = 0.022) dimensions. In contrast, negative R/S coping scores independently predicted lower social functioning scores (β = -21.158; p = 0.017).

CONCLUSIONS
Our results provide further evidence suggesting that R/S coping methods may be associated with QOL and depression among HD patients. In our opinion, the use of religious resources should be encouraged among HD patients, and psycho-spiritual interventions should be attempted to target religious struggles (negative R/S coping) in patients undergoing HD.

Capote Júnior|José Roberto Frota Gomes|JRFG|

Cavalcante Filho|José Renan Miranda|JRM|

Dos Santos Filho|José Nilson Gadelha|JNG|

Depression
Quality of life
Spirituality
Religion and medicine
Renal dialysis