Physicochemical and Rheological Properties of a Transparent Asphalt Binder Modified with Nano-TiO2.

Abstract: Transparent binder is used to substitute conventional black asphalt binder and to provide light-colored pavements, whereas nano-TiO2 has the potential to promote photocatalytic and self-cleaning properties. Together, these materials provide multifunction effects and benefits when the pavement is submitted to high solar irradiation. This paper analyzes the physicochemical and rheological properties of a transparent binder modified with 0.5%, 3.0%, 6.0%, and 10.0% nano-TiO2 and compares it to the transparent base binder and conventional and polymer modified binders (PMB) without nano-TiO2. Their penetration, softening point, dynamic viscosity, master curve, black diagram, Linear Amplitude Sweep (LAS), Multiple Stress Creep Recovery (MSCR), and Fourier Transform Infrared Spectroscopy (FTIR) were obtained. The transparent binders (base and modified) seem to be workable considering their viscosity, and exhibited values between the conventional binder and PMB with respect to rutting resistance, penetration, and softening point. They showed similar behavior to the PMB, demonstrating signs of polymer modification. The addition of TiO2 seemed to reduce fatigue life, except for the 0.5% content. Nevertheless, its addition in high contents increased the rutting resistance. The TiO2 modification seems to have little effect on the chemical functional indices. The best percentage of TiO2 was 0.5%, with respect to fatigue, and 10.0% with respect to permanent deformation.

asphalt binder
transparent binder
self-cleaning
FTIR
TiO2
light-colored asphalt
nanomaterials
photocatalytic asphalt
viscoelastic properties


Identification of Nanocellulose Retention Characteristics in Porous Media.

Abstract: The application of nanotechnology to the petroleum industry has sparked recent interest in increasing oil recovery, while reducing environmental impact. Nanocellulose is an emerging nanoparticle that is derived from trees or waste stream from wood and fiber industries. Thus, it is taken from a renewable and sustainable source, and could therefore serve as a good alternative to current Enhanced Oil Recovery (EOR) technologies. However, before nanocellulose can be applied as an EOR technique, further understanding of its transport behavior and retention in porous media is required. The research documented in this paper examines retention mechanisms that occur during nanocellulose transport. In a series of experiments, nanocellulose particles dispersed in brine were injected into sandpacks and Berea sandstone cores. The resulting retention and permeability reduction were measured. The experimental parameters that were varied include sand grain size, nanocellulose type, salinity, and flow rate. Under low salinity conditions, the dominant retention mechanism was adsorption and when salinity was increased, the dominant retention mechanism shifted towards log-jamming. Retention and permeability reduction increased as grain size decreased, which results from increased straining of nanocellulose aggregates. In addition, each type of nanocellulose was found to have significantly different transport properties. Experiments with Berea sandstone cores indicate that some pore volume was inaccessible to the nanocellulose. As a general trend, the larger the size of aggregates in bulk solution, the greater the observed retention and permeability reduction. Salinity was found to be the most important parameter affecting transport. Increased salinity caused additional aggregation, which led to increased straining and filter cake formation. Higher flow rates were found to reduce retention and permeability reduction. Increased velocity was accompanied by an increase in shear, which is believed to promote breakdown of nanocellulose aggregates.

nanocellulose
retention
petroleum
oil
nanoparticle
cellulose nanocrystals
energy
petrochemical


Biphasic calcium phosphates (BCP) of hydroxyapatite (HA) and tricalcium phosphate (TCP) as bone substitutes: Importance of physicochemical characterizations in biomaterials studies.

Abstract: The data presented in this article are related to the research article entitled "Biphasic calcium phosphates bioceramics (HA/TCP): Concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research" [1]. This article provides in depth study of BCP bone substitutes as valuable option in the field of tissue engineering. However, there are discrepancies in the literature regarding the ideal physicochemical properties of BCP and the ideal balance between different phase compositions for enhanced bone tissue engineering (M. Ebrahimi, M.G. Botelho, S.V. Dorozhkin, 2016; M. Ebrahimi, P. Pripatnanont, S. Suttapreyasri, N. Monmaturapoj, 2014) [1,2]. This is found to be mainly because of improper characterization of BCP bioceramics in basic studies and lack of standard study protocols in in vitro and in vivo research. This data article along with original article provide the basic data required for ideal characterization of BCP and other bioceramics in an attempt to provide basic standardized protocols for future studies.

Biphasic calcium phosphate
Characterization
Study protocol
Bone tissue engineering


Amino Groups of Chitosan Are Crucial for Binding to a Family 32 Carbohydrate Binding Module of a Chitosanase from Paenibacillus elgii.

Abstract: We report here the role and mechanism of specificity of a family 32 carbohydrate binding module (CBM32) of a glycoside hydrolase family 8 chitosanase from Paenibacillus elgii (PeCsn). Both the activity and mode of action of PeCsn toward soluble chitosan polymers were not different with/without the CBM32 domain of P. elgii (PeCBM32). The decreased activity of PeCsn without PeCBM32 on chitosan powder suggested that PeCBM32 increases the relative concentration of enzyme on the substrate and thereby enhanced enzymatic activity. PeCBM32 specifically bound to polymeric and oligomeric chitosan and showed very weak binding to chitin and cellulose. In isothermal titration calorimetry, the binding stoichiometry of 2 and 1 for glucosamine monosaccharide (GlcN) and disaccharide (GlcN)2, respectively, was indicative of two binding sites in PeCBM32. A three-dimensional model-guided site-directed mutagenesis and the use of defined disaccharides varying in the pattern of acetylation suggested that the amino groups of chitosan and the polar residues Glu-16 and Glu-38 of PeCBM32 play a crucial role for the observed binding. The specificity of CBM32 has been further elucidated by a generated fusion protein PeCBM32-eGFP that binds to the chitosan exposing endophytic infection structures of Puccinia graminis f. sp. tritici Phylogenetic analysis showed that CBM32s appended to chitosanases are highly conserved across different chitosanase families suggesting their role in chitosan recognition and degradation. We have identified and characterized a chitosan-specific CBM32 useful for in situ staining of chitosans in the fungal cell wall during plant-fungus interaction.

Das|Subha Narayan|SN|
Wagenknecht|Martin|M|
Nareddy|Pavan Kumar|PK|
Bhuvanachandra|Bhoopal|B|
Niddana|Ramana|R|
Balamurugan|Rengarajan|R|
Swamy|Musti J|MJ|
Moerschbacher|Bruno M|BM|
Podile|Appa Rao|AR|

chitosan
chitosanase
Paenibacillus elgii
glycoside hydrolase
chitin
site-directed mutagenesis
in situ staining
carbohydrate-binding protein
isothermal titration calorimetry (ITC)


Link of Patient Care Outcome to Occupational Differences in Response to Human Resource Management: A Cross-Sectional Comparative Study on Hospital Doctors and Nurses in China.

Abstract: This study assessed the link of patient care outcome to occupational differences in response to human resource management. A cross-sectional survey was conducted in three large regional hospitals in China. A total of 700 questionnaires were distributed to doctors, nurses, allied health workers, and managers and 499 (71%) were completed. Data were analyzed using a final sample of 193 doctors and 180 nurses. Quality of patient care was rated by the participants using a modified version of the Victorian Patient Satisfaction Questionnaire. Human resource management was measured on seven aspects: job security, recruitment, training, transformational leadership, information sharing, job quality, and teams. The differences between doctors and nurses in response to the human resource management practices and their associations with quality of care were compared through independent samples t-tests, correlational analyses, and moderator regressions. Doctors gave a higher rating on quality of patient care than their nurse counterparts. 'Training', 'transformational leadership', and 'information sharing' were more likely to be associated with higher ratings on quality of patient care in nurses. By contrast, a greater association between 'teams' and quality of patient care was found in doctors. Although doctors and nurses in China are exposed to the same hospital management environment, professional differences may have led them to respond to management practices in different ways.

China
quality of care
health professionals
health services management
high performance work systems


Evaluating the measures taken to contain a Candida auris outbreak in a tertiary care hospital in South India: an outbreak investigational study.

Abstract:
BACKGROUND
Candida auris infections are an emerging global threat with poor clinical outcome, high mortality rate, high transmission rate and outbreak potential. The objective of this work is to describe a multidisciplinary approach towards the investigation and containment of a Candida auris outbreak and the preventive measures adopted in a resource limited setting.

METHODS
This outbreak investigational study was conducted at a 1300-bedded tertiary care academic hospital in South India. The study included 15 adult inpatients with laboratory confirmed Candida auris isolates. The outbreak cluster was identified in adult patients admitted from September 2017 to 2019. The system response consisted of a critical alert system for laboratory confirmed Candida auris infection and multidisciplinary 'Candida auris care team' for patient management. The team implemented stringent Infection Prevention and Control (IPC) measures including patient cohorting, standardized therapy and decolonization, staff training, prospective surveillance and introduction of Candida auris specific care bundle.

RESULTS
Two outbreak clusters were identified; first cluster occurring between October and November 2017 and the second cluster in May 2018. The cohorts consisted of 7 and 8 Candida auris positive patients in the first and second waves of the outbreak respectively with a total survival rate of 93% (14/15). Deployment of containment measures led to gradual decline in the incidence of adult Candida auris positive cases and prevented further cluster formation.

CONCLUSIONS
The sustained implementation of guideline and evidence-based IPC measures and training of healthcare workers for improving awareness on systematically following standardized protocols of Candida auris related IPC practices successfully contained Candida auris outbreaks at our hospital. This demonstrates the feasibility of establishing a multidisciplinary model and bundling of practices for preventing Candida auris outbreaks in a Low- and Middle-income country.

Sathyapalan|Dipu Thareparambil|DT|
Antony|Remya|R|
Nampoothiri|Vrinda|V|
Kumar|Anil|A|
Shashindran|Nandita|N|
James|Jini|J|
Thomas|Jisha|J|
Prasanna|Preetha|P|
Sudhir|Akkulath Sangita|AS|
Philip|Jeslyn Mary|JM|
Edathadathil|Fabia|F|
Prabhu|Binny|B|
Singh|Sanjeev|S|
Moni|Merlin|M|

Containment
Candida auris
Outbreak
Multidisciplinary
Implementation
Infection prevention and control
Bundle
Hand hygiene
Index case
Low-and middle- income country


Dual graft living donor liver transplantation - a case report.

Abstract:
BACKGROUND
Living donor liver transplantation (LDLT) has emerged as an equally viable option to deceased donor liver transplant for treating end stage liver disease patients. Optimising the recipient outcome without compromising donor safety is the primary goal of LDLT. Achieving the adequate graft to recipient weight ratio (GRWR) is important to prevent small for size syndrome which is an uncommon but potentially lethal complication of LDLT.

CASE PRESENTATION
Here we describe a case of successful dual lobe liver transplant for a 32 years old patient with ethanol related end stage liver disease. A right lobe graft without middle hepatic vein and another left lateral sector graft were transplanted successfully. Recipient and both donors recovered uneventfully.

CONCLUSION
Dual lobe liver transplant is a feasible strategy to achieve adequate GRWR without compromising donor safety.

Living donor liver transplantation
Deceased donor liver transplantation
End stage liver disease
Graft to recipient weight
Future liver remnant
Small-for-size syndrome


Effective Delivery of Arsenic Trioxide to HPV-Positive Cervical Cancer Cells Using Optimised Liposomes: A Size and Charge Study.

Abstract: Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines-human keratinocytes (HK) and human colon cells (CRL-1790)-were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers.

Akhtar|Anam|A|
Wang|Scarlet Xiaoyan|SX|
Ghali|Lucy|L|
Bell|Celia|C|
Wen|Xuesong|X|

D000970:Antineoplastic Agents
D000077237:Arsenic Trioxide
D001152:Arsenicals
D045744:Cell Line, Tumor
D002470:Cell Survival
D004339:Drug Compounding
D016503:Drug Delivery Systems
D005260:Female
D006801:Humans
D008081:Liposomes
D010087:Oxides
D030361:Papillomavirus Infections
D010316:Particle Size
D055672:Static Electricity
D002583:Uterine Cervical Neoplasms

cervical cancer
liposome
arsenic trioxide (ATO)
drug delivery
human papilloma virus (HPV)


Abnormal cortical sensorimotor activity during "Target" sound detection in subjects with acute acoustic trauma sequelae: an fMRI study.

Abstract: The most common consequences of acute acoustic trauma (AAT) are hearing loss at frequencies above 3 kHz and tinnitus. In this study, we have used functional Magnetic Resonance Imaging (fMRI) to visualize neuronal activation patterns in military adults with AAT and various tinnitus sequelae during an auditory "oddball" attention task. AAT subjects displayed overactivities principally during reflex of target sound detection, in sensorimotor areas and in emotion-related areas such as the insula, anterior cingulate and prefrontal cortex, in premotor area, in cross-modal sensory associative areas, and, interestingly, in a region of the Rolandic operculum that has recently been shown to be involved in tympanic movements due to air pressure. We propose further investigations of this brain area and fine middle ear investigations, because our results might suggest a model in which AAT tinnitus may arise as a proprioceptive illusion caused by abnormal excitability of middle-ear muscle spindles possibly link with the acoustic reflex and associated with emotional and sensorimotor disturbances.

Job|Agnès|A| Pons|Yoann|Y| Lamalle|Laurent|L| Jaillard|Assia|A| Buck|Karl|K| Segebarth|Christoph|C| Delon-Martin|Chantal|C|

Acoustic trauma
fMRI
Tinnitus
Middle ear
Proprioception


Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6-month longitudinal investigation.

Abstract: The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal-reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post-anterior cruciate ligament reconstruction (ACLr). This longitudinal, case-control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor-evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal-reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post-surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post-surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post-surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal-reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal-reflexive excitability may help improve postoperative outcomes, while later-stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.

Lepley|A S|AS|
Gribble|P A|PA|
Thomas|A C|AC|
Tevald|M A|MA|
Sohn|D H|DH|
Pietrosimone|B G|BG|

D059549:Anterior Cruciate Ligament Reconstruction

Knee injury
muscle inhibition
neuromuscular function
transcranial magnetic stimulation


Hillsborough part 2: advance decisions and futile treatment.

Abstract: In the second article on the impact of the Hillsborough football stadium disaster on healthcare law, Richard Griffith discusses the case of Tony Bland, who suffered prolonged hypoxia due to the crushing crowd surge, leaving him in a persistent vegetative state. Some 3 years after the incident, the judicial committee of the House of Lords was asked to rule on whether it would be lawful to withdraw his artificial nutrition and hydration, resulting in death. The opinions of the law lords in Airedale NHS Trust v Bland [1993] continue to inform health law 25 years after the disaster, shaping and developing the use of advance decisions to refuse treatment and setting out when it would be lawful to withdraw futile life-sustaining treatment.

Futile treatment
Advance decisions to refuse treatment
Best interests
Self-determination


The Role of Domain-General Cognitive Abilities and Decimal Labels in At-Risk Fourth-Grade Students' Decimal Magnitude Understanding.

Abstract: The purpose of the study was to determine whether individual differences in at-risk 4th graders' language comprehension, nonverbal reasoning, concept formation, working memory, and use of decimal labels (i.e., place value, point, incorrect place value, incorrect fraction, or whole number) are related to their decimal magnitude understanding. Students (n = 127) completed 6 cognitive assessments, a decimal labeling assessment, and 3 measures of decimal magnitude understanding (i.e., comparing decimals to the fraction [Formula: see text] benchmark task, estimating where decimals belong on a 0-1 number line, and identifying fraction and decimal equivalencies). Each of the domain-general cognitive abilities predicted students' decimal magnitude understanding. Using place value labels was positively correlated with students' decimal magnitude understanding, whereas using whole-number labels was negatively correlated with students' decimal magnitude understanding. Language comprehension, nonverbal reasoning, and concept formation were positively correlated with students' use of place value labels. By contrast, language comprehension and nonverbal reasoning were negatively correlated with students' use of whole number labels. Implications for the development of decimal magnitude understanding and design of effective instruction for at-risk students are discussed.

Malone|Amelia S|AS|
Loehr|Abbey M|AM|
Fuchs|Lynn S|LS|

individual differences
mathematics
rational numbers


Benefits and challenges of molecular diagnostics for childhood tuberculosis.

Abstract: Expanding tuberculosis (TB)-diagnostic services, including access to rapid tests, is a World Health Organization (WHO) strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB)-complex nucleic acids can be used directly on specimens from patients suspected of having TB. Recently, several commercial molecular tests were developed to detect MTB and determine the drug resistance (DR) based on detection of specific genetic mutations conferring resistance. The first to be endorsed by the WHO was molecular line-probe assay technology. This test uses polymerase chain reaction (PCR) and reverse-hybridization methods to rapidly identify MTB and DR-related mutations simultaneously. More recently, the WHO endorsed Xpert MTB/RIF, Cepheid Inc, CA, USA, a fully automated assay used for TB diagnosis that relies upon PCR techniques for detection of TB and rifampicin resistance-related mutations. Other promising molecular TB assays for simplifying PCR-based testing protocols and increasing their accuracy are under development and evaluation. Although we lack a practical gold standard for the diagnosis of childhood TB, its bacteriological confirmation is always recommended to be sought whenever possible prior to a diagnostic decision being made. Conventional diagnostic laboratory TB tests are less efficient for children as compared with adults, because sufficient sputum samples are more difficult to collect from infants and young children, and their disease is often paucibacillary, resulting in smear-negative disease. These inherent challenges associated with childhood TB are due to immunological- and pathophysiological-response differences relative to those observed in adults. Several recent meta-analyses showed low sensitivity estimates of PCR-based TB assays for paucibacillary forms of TB (extrapulmonary TB and smear-negative pulmonary disease), which represent the vast majority of childhood TB cases. Despite the lack of evidence regarding use of the rapid molecular assays to identify TB and detect DR in children, and due to the clinical nature of childhood TB, TB-expert groups recommend including rapid methods for TB identification and DR detection in diagnostic algorithms for children suspected of both smear-positive and -negative pulmonary or extrapulmonary TB, both with or without human immunodeficiency virus (HIV)-coinfection, when combined with standard methods (including clinical, microbiological, and radiological assessment) for diagnosing active TB and conventional DR. Since 2011, the WHO has specifically recommended use of the Xpert MTB/RIF test as an initial diagnostic tool for children with suspected HIV-associated TB or multidrug-resistant TB based on successful treatment data related to adults. Implementation of the rapid molecular assays for rapid detection of TB and DR should occur in laboratories with proven capability to run molecular tests and where quality control systems are implemented. Molecular approaches should be more largely tested in children, given their status as the group in whom the diagnostic dilemma is most pronounced. These tests should also be included in specific childhood TB diagnostic algorithms adapted to the local/national context in combination with other strategies for improving diagnostics, including more effective specimen collection.


Skeletal muscle CaV1.1 channelopathies.

Abstract: CaV1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known CaV1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of CaV1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo- and normokalemic periodic paralysis, malignant hyperthermia susceptibility, CaV1.1-related myopathies, and myotonic dystrophy type 1. In addition, the CaV1.1 function in EC coupling is perturbed in Native American myopathy, arising from mutations in the CaV1.1-associated protein STAC3. Here, we first address general considerations concerning the possible roles of CaV1.1 in disease and then discuss the state of the art regarding the pathophysiology of the CaV1.1-related skeletal muscle diseases with an emphasis on molecular disease mechanisms.

D048868:Adaptor Proteins, Signal Transducing

Skeletal muscle
Malignant hyperthermia susceptibility
Myotonic dystrophy
Native American myopathy
CaV1.1-myopathy
Hypokalemic periodic paralysis
Voltage-gated calcium channel


Outcomes Following Operative Treatment of Adolescent Mallet Fractures.

Abstract:
Background
Many surgeons advocate for surgical intervention of adult mallet fractures that involve either subluxation of the distal interphalangeal (DIP) joint or those that involve more than one-third of the articular surface. However, the efficacy of operative treatment and complication rates are unclear regarding the adolescent population.

Questions/Purposes
The goal of this study is to evaluate the clinical outcomes following operative fixation of bony mallet fractures in the adolescent population.

Methods
Seventeen patients with bony mallet fractures treated surgically were retrospectively reviewed. Twelve patients were treated by closed reduction with extension block pinning. The other patients underwent an open reduction and pin fixation. The average age was 15.2 years (13-18). Most injuries were sport related. The average time from injury to presentation was 17 days and from injury to surgery was 24.5 days. Nine patients had subluxation at the DIP joint and all involved at least one-third of the articular surface.

Results
The average time from surgery to pin removal was 28 days (19-46). All distal phalanx physis were closed or nearly closed. One patient reported pain at the final follow-up. Two patients (11.8%) had major complications. One had an extension contracture postoperatively, did not attend therapy, and re-fractured 5 months later requiring reoperation. The second was treated delayed (32 days) and lost fixation, requiring revision surgery and antibiotics for a superficial infection. Two patients with delayed treatment (32 and 44 days) had an extensor lag (11.8%).

Conclusions
Operative treatment of mallet fractures with subluxation or involving more than one-third of the articular surface appears effective. Pin removal 4 weeks postoperatively appears adequate. Complications occurred with delayed presentation and non-compliance.

Chen|Andrew T|AT|0000-0001-8662-5295
Conry|Keegan T|KT|
Gilmore|Allison|A|
Son-Hing|Jochen P|JP|
Liu|Raymond W|RW|

mallet fracture
extension block pinning
adolescent fractures


The Third Stage of Labour in the Extremely Obese Parturient.

Abstract:
BACKGROUND
Maternal obesity has been associated with an increased risk for an abnormal progression of labour; however, less is known about the length of the third stage of labour and its relation to maternal obesity.

OBJECTIVE
To determine if the length of the third stage of labour is increased in extremely obese women and its possible correlation with an increased risk for postpartum hemorrhage.

STUDY DESIGN
This was a retrospective cohort study of deliveries from January 2008 to December 2015 at our university hospital. Women with a BMI ≥40 and a vaginal delivery were compared with the next vaginal delivery of a woman with a BMI <30. There were 147 women with a BMI ≥40 compared with 157 with a BMI <30. Outcomes evaluated the length of the third stage of labour and the risk for postpartum hemorrhage and included antepartum, intrapartum, and perinatal complications.

RESULTS
Subjects in the extreme obese group were more likely to be African American, older, diabetic (pregestational and gestational), hypertensive, pre-eclamptic, had a preterm delivery, and underwent an induction of labour. The overall length of the third stage of labour was significantly longer in the extreme obese group, 5 minutes (3, 8 [25th and 75th percentiles]) compared with 4 minutes (3,7) (P = 0.0374) in the non-obese group. Postpartum hemorrhage occurred more often in the extreme obese group (N = 16/147; 11%) compared with the non-obese group (N = 5/157; 3%) (P = 0.01). There were no differences between groups in respect to the following: gravidity, parity, length of the second stage of labour, birth weight, GA at delivery, Apgar score, cord blood gases, hematocrit change, need for postpartum transfusion, operative delivery, and development of chorioamnionitis. After an adjustment for ethnicity, maternal age, diabetes, preeclampsia, preterm labour, hypertension, and induction/augmentation, the analysis failed to show a significant difference in estimated blood loss and postpartum hemorrhage between the groups.

CONCLUSIONS
The length of the third stage of labour is longer in the extreme obese parturient. Postpartum hemorrhage also occurs more often, but after adjustments for confounding variables, it is no longer significant.

Cummings|Kelly F|KF|
Helmich|Melissa S|MS|
Ounpraseuth|Songthip T|ST|
Dajani|Nafisa K|NK|
Magann|Everett F|EF|

third stage of labour
obesity
hemorrhage
Pregnancy


Optimization of Efficient Neuron Models With Realistic Firing Dynamics. The Case of the Cerebellar Granule Cell.

Abstract: Biologically relevant large-scale computational models currently represent one of the main methods in neuroscience for studying information processing primitives of brain areas. However, biologically realistic neuron models tend to be computationally heavy and thus prevent these models from being part of brain-area models including thousands or even millions of neurons. The cerebellar input layer represents a canonical example of large scale networks. In particular, the cerebellar granule cells, the most numerous cells in the whole mammalian brain, have been proposed as playing a pivotal role in the creation of somato-sensorial information representations. Enhanced burst frequency (spiking resonance) in the granule cells has been proposed as facilitating the input signal transmission at the theta-frequency band (4-12 Hz), but the functional role of this cell feature in the operation of the granular layer remains largely unclear. This study aims to develop a methodological pipeline for creating neuron models that maintain biological realism and computational efficiency whilst capturing essential aspects of single-neuron processing. Therefore, we selected a light computational neuron model template (the adaptive-exponential integrate-and-fire model), whose parameters were progressively refined using an automatic parameter tuning with evolutionary algorithms (EAs). The resulting point-neuron models are suitable for reproducing the main firing properties of a realistic granule cell from electrophysiological measurements, including the spiking resonance at the theta-frequency band, repetitive firing according to a specified intensity-frequency (I-F) curve and delayed firing under current-pulse stimulation. Interestingly, the proposed model also reproduced some other emergent properties (namely, silent at rest, rheobase and negligible adaptation under depolarizing currents) even though these properties were not set in the EA as a target in the fitness function (FF), proving that these features are compatible even in computationally simple models. The proposed methodology represents a valuable tool for adjusting AdEx models according to a FF defined in the spiking regime and based on biological data. These models are appropriate for future research of the functional implication of bursting resonance at the theta band in large-scale granular layer network models.

Marín|Milagros|M|
Sáez-Lara|María José|MJ|
Ros|Eduardo|E|
Garrido|Jesús A|JA|

neuron model
granule cell
spiking resonance
adaptive exponential integrate-and-fire
cerebellum
model simplification
point neuron


Efficacy and safety of intralesional steroid injection in the treatment of melasma.

Abstract:
BACKGROUND
The etiopathogenesis of melasma is not yet completely elucidated; however, certain inflammatory cytokines are involved in its pathogenesis as interleukin (IL) 1a, IL 1b, IL6, prostaglandin (PG) D2and PGE2. Corticosteroid suppressive effect on these cytokines may explain its therapeutic effect in the treatment of melasma.

AIMS
To assess the efficacy and safety of intralesional triamcinolone versus Kligman's formula in treatment of melasma.

METHODS
This study included 2 groups of female patients with melasma; group1 (treatment group) included 22 patients who were treated by intralesional injection of triamcinolone acetonide at a concentration of 4 mg/mL once monthly for four sessions as a maximum and group 2 (control group), included 22 patients who were treated by Kligman's formula once daily for 3 months. All patients were evaluated by dermoscope before treatment and at each follow-up visit to record any adverse effects of treatment.

RESULTS
The severity of melasma, assessed by MASI score, significantly decreased in both groups at the end of third month. There was no statistically significant difference in the therapeutic response between both groups. No side effects were reported with triamcinolone injection except for mild pain during injection, while Kligman's formula was associated with dermatitis, irritation, and burning sensation.

CONCLUSIONS
Triamcinolone injection at low concentration could be an effective treatment modality of melasma.


The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue.

Abstract:
PURPOSE
The purpose of this study was to determine whether exercise or/and cold exposure regulate mitochondria biogenesis-related gene expression in soleus and inguinal adipose tissue of mice.

METHODS
Forty ICR 5-week old male mice were divided into four groups: thermoneutrality-untrained (23 ± 1 °C in room temperature, n=10), cold-water immersion (24 ± 1 °C, n=10), exercise in neutral temperature (34 ± 1 °C, n=10), and exercise in cold temperature (24 ± 1 °C, n=10). The mice performed swimming exercise (30 min to 60 min, 5 times) for 8 weeks. After 8 weeks, we confirmed mitochondrial biogenesis-related gene expression changes for peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factors 1 (NRF1), and mitochondrial transcription factor A (Tfam) in soleus muscle and inguinal adipose tissue, and the related protein expression in soleus muscle.

RESULTS
In soleus muscle, PGC-1α expression significantly increased in response to cold exposure (p = 0.006) and exercise (p = 0.05). There was also significant interaction between exercise and cold exposure (p = 0.005). Only exercise had a significant effect on NRF1 relative expression (p=0.001). Neither cold exposure nor the interaction showed significant effects (p = 0.1222 and p = 0.875, respectively). Relative Tfam expression did not show any significant effect from exercise. In inguinal adipose tissue, relative PGC-1α expression did not significantly change in any group. NRF1 expression showed a significant change from exercise (p = 0.01) and cold exposure (p = 0.011). There was also a significant interaction between exercise and cold exposure (p = 0.000). Tfam mRNA expression showed a significant effect from exercise (p=0.000) and an interaction between exercise and cold exposure (p=0.001). Only temperature significantly affected PGC-1α protein levels (p=0.045). Neither exercise nor the interaction were significant (p = 0.397 and p = 0.292, respectively). NRF1 protein levels did not show a significant effect in any experimental treatments. Tfam protein levels showed a significant effect in the exercise group (p=0.012), but effects of neither cold exposure nor the interaction were significant (p = 0.085 and p=0.374, respectively).

CONCLUSION
Exercise and cold exposure promoted increased expression of mitochondrial biogenesis- related genes in soleus muscle. Only cold exposure had a significant effect on PGC-1α protein expression and only exercise had a significant effect on Tfam protein expression. In inguinal adipose tissue, there was interaction between exercise and cold exposure in expression of mitochondrial biogenesis-related genes.

Exercise
Cold exposure
Mitochondrial biogenesis
PGC-1α
Tfam
NRF-1


Osteoarthritis alters the patellar bones subchondral trabecular architecture.

Abstract: Following the principles of "morphology reveals biomechanics," the cartilage-osseous interface and the trabecular network show defined adaptation in response to physiological loading. In the case of a compromised relationship, the ability to support the load diminishes and the onset of osteoarthritis (OA) may arise. To describe and quantify the changes within the subchondral bone plate (SBP) and trabecular architecture, 10 human OA patellae were investigated by CT and micro-CT. The results are presented in comparison to a previously published dataset of 10 non-OA patellae which were evaluated in the same manner. The analyzed OA samples showed no distinctive mineralization pattern in regards to the physiological biomechanics, but a highly irregular disseminated distribution. In addition, no regularity in bone distribution and architecture across the trabecular network was found. We observed a decrease of material as the bone volume and trabecular thickness/number were significantly reduced. In comparison to non-OA samples, greatest differences for all parameters were found within the first mm of trabecular bone. The differences decreased toward the fifth mm in a logarithmic manner. The interpretation of the logarithmic relation leads to the conclusion that the main impact of OA on bony structures is located beneath the SBP and lessens with depth. In addition to the clear difference in material with approximately 12% less bone volume in the first mm in OA patellae, the architectural arrangement is more rod-like and isotropic, accounting for an architectural decrease in stability and support. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1982-1989, 2017.

Hoechel|Sebastian|S| Deyhle|Hans|H| Toranelli|Mireille|M| Müller-Gerbl|Magdalena|M|

3D micro-CT
human patella
osteoarthritic trabecular changes
subchondral bone plate mineralization


Evaluation of the Relationship between Serum Lipid Profile andOral Lichen Planus.

Abstract: Background and aims. Oral lichen planus (OLP) is an immunologic disorder. A large number of studies have reported that lipid rafts have a key role in receptor signaling of lymphocytes. Here, we explore the potential of lipid rafts as targets for the development of a new class of agents to down-modulate immune responses and treat autoimmune diseases. Materials and methods. The present cross-sectional study evaluated 88 patients referring to the Department of Oral Medicine in 3 groups (Group 1: erosive OLP; Group 2: non-erosive OLP; Group 3: healthy). A total of 3 mL of blood sample was taken from each subject and the serum levels of cholesterol, triglycerides, HDL and LDL were determined. The mean outcomes of each group were compared with each other and analyzed two by two. Results. The results of statistical analyses showed no significant differences in mean HDL and LDL serum levels between the three groups. The results of post hoc LSD test showed that mean serum levels of subjects with erosive and non-erosive lichen planus were higher than those in healthy subjects. In relation to triglyceride serum levels, the mean serum levels of triglycerides were higher in erosive and non-erosive OLP patients compared to healthy subjects. Conclusion. Triglyceride and cholesterol can be considered to have a critical role in the incidence of lichen planus and in its manifestations as predisposing factors.

Mehdipour|Masoumeh|M|
Taghavi Zenouz|Ali|A|
Davoodi|Farnaz|F|
Gholizadeh|Narges|N|
Damghani|Hossein|H|
Helli|Sanaz|S|
Safarnavadeh|Maryam|M|


Peripheral dentinogenic ghost cell tumor-report of two cases and review of the literature.

Abstract: Peripheral dentinogenic ghost cell tumor (DGCT) is a rare and non-aggressive benign odontogenic tumor. They usually affect the elderly and are predominantly located in the anterior region of the jaws. Their differential diagnosis includes reactive/inflammatory gingival lesions. We report here two cases of peripheral DGCT in a 73-year-old female and a 48-year-old male patient and review the cases published in the literature. Both lesions presented as a nodular lesion in the mandible, and panoramic radiography showed no abnormalities. Microscopically, it was observed to be an ameloblastomatous epithelial proliferation associated with clusters of ghost cells and dysplastic dentin. Immunohistochemistry revealed positivity for cytokeratin 19 and a low Ki-67 proliferative index. Based on histopathological features and the absence of radiographic findings, a diagnosis of peripheral DGCT was rendered. The low number of cases published of peripheral DGCT makes case reports important in providing information that helps in their diagnoses and management.

da Silva Barros|Caio César|CC|https://orcid.org/0000-0003-3103-3588

de Souto Medeiros|Maurília Raquel|MR|https://orcid.org/0000-0001-6715-3114

da Costa Miguel|Márcia Cristina|MC|https://orcid.org/0000-0002-6661-2566

da Silveira|Éricka Janine Dantas|ÉJD|https://orcid.org/0000-0003-2128-0147

Peripheral
Ghost Cells
Dentinogenic ghost cell tumor
Odontogenic tumors


Chemical-shift-resolved ¹⁹F NMR spectroscopy between 13.5 and 135 MHz: Overhauser-DNP-enhanced diagonal suppressed correlation spectroscopy.

Abstract: Overhauser-DNP-enhanced homonuclear 2D (19)F correlation spectroscopy with diagonal suppression is presented for small molecules in the solution state at moderate fields. Multi-frequency, multi-radical studies demonstrate that these relatively low-field experiments may be operated with sensitivity rivalling that of standard 200-1000 MHz NMR spectroscopy. Structural information is accessible without a sensitivity penalty, and diagonal suppressed 2D NMR correlations emerge despite the general lack of multiplet resolution in the 1D ODNP spectra. This powerful general approach avoids the rather stiff excitation, detection, and other special requirements of high-field (19)F NMR spectroscopy.

19F NMR spectroscopy
ODNP-enhanced correlation spectroscopy
Overhauser DNP
differential enhancement
dynamic nuclear polarization


Population age structure and the cost of municipal waste collection. A case study from the Czech Republic.

Abstract: Waste management is a common public service whose provision is the responsibility of local governments. As is usual with public services, the question of its efficiency naturally arises. The majority of studies focus on such efficiency from the perspective of the provider. This is based on the assumption that waste collection expenditure is a function of available equipment and municipal characteristics. In our opinion this approach has its limitations, and therefore we have used a novel approach based on the demand from municipal citizens for waste collection services. We build on previous results obtained from data concerning social and demographic characteristics, and focus on the relationship between age and expenditure on municipal solid waste, concentrating specifically on the ageing of the population. The ageing of societies in general is a very topical issue, but there is rather little focus in research on the effects of ageing on the demand for various public services. The research that does exist in the area of waste management that takes the age factor into account typically only makes a very rough division of the population into age categories such as children, people of working age and elderly people. Such wide groups naturally contain people with a large variety of needs, and therefore often lead to ambiguous results. The goal of our paper is to examine this topic in more detail, and to estimate the effects of various age categories of municipal citizens on municipal waste expenditure. We use models with age categories differentiated by decades, an approach which provides significantly more detailed information than the age variables used in other studies in this area. We use population age and waste management expenditure data collected from more than 6100 municipalities in the Czech Republic in 2011 and 2014. The results of our investigation have shown that senior citizens of a certain age (approximately at the onset of retirement) have a surprisingly strong influence on waste management expenditure.

D002947:Cities
D003365:Costs and Cost Analysis
D018153:Czech Republic
D006801:Humans
D012037:Refuse Disposal
D062611:Solid Waste
D018505:Waste Management

Municipal solid waste management expenditure


The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study.

Abstract:
OBJECTIVE
To evaluate the efficacy and safety of soybean-derived phosphatidylserine (SB-PS) (300 mg/day) in improving cognitive performance in elderly with memory complaints, following a short duration of 12 weeks' SB-PS administration.

METHODS
SB-PS was administered daily for 12 weeks to 30 elderly volunteers with memory complaints (age range 50-90 years). Cognitive performance was determined by a computerized test battery and by the Rey Auditory Verbal Learning Test (Rey-AVLT). Physical examination and blood safety parameters were part of the extensive safety analysis of PS that was performed.

RESULTS
The computerized test results showed that SB-PS supplementation significantly increased the following cognitive parameters: memory recognition (P = 0.004), memory recall (P = 0.006), executive functions (P = 0.004), and mental flexibility (P = 0.01). The Rey-AVLT indicated that, following SB-PS administration, total learning and immediate recall improved significantly (P = 0.013 and P = 0.007, respectively). Unexpected results from the safety tests suggested that SB-PS significantly reduces both systolic (P = 0.043) and diastolic (P = 0.003) blood pressure. SB-PS consumption was well tolerated and no serious adverse events were reported during the study.

CONCLUSION
This exploratory study demonstrates that SB-PS may have favorable effects on cognitive function in elderly with memory complaints. In addition, the study suggests that SB-PS is safe for human consumption and may serve as a safe alternative to phosphatidylserine extracted from bovine cortex. These results encourage further extended studies in order to establish the safety and efficacy of SB-PS treatment.

Richter|Yael|Y| Herzog|Yael|Y| Lifshitz|Yael|Y| Hayun|Rami|R| Zchut|Sigalit|S|

phosphatidylserine cognitive memory learning AAMI


Serious illness conversations in pulmonary hypertension.

Abstract: Pulmonary arterial hypertension has evolved from a fatal disease with few treatment options to a chronic condition with improved survival. This improvement is possible through development of effective therapies as well as the expansion of risk stratification scores to assist clinical decision making. Despite improved disease control, quality of life, and overall prognosis, many challenges remain. The treatment itself is burdensome, with significant impact on quality of life. Many patients with pulmonary arterial hypertension still present with advanced, often end-stage disease. Increased use of mechanical circulatory support and catheter-based interventions have expanded use of extracorporeal life support and right ventricle assist devices. For these reasons as well as the long-term relationships pulmonary hypertension physicians have with patients and their families, navigating the course of the illness in a considered, proactive way is essential. Understanding individual goals and revisiting them as they change over time requires comfort with the conversation itself. There are many barriers and challenges to having effective, compassionate conversations in the clinical setting with time constraints being the most often cited. Compressed visits are necessarily focused on the clinical aspects, therapy and medication adherence and tolerance. Clinicians are sometimes wary of diminishing hope in the face of ongoing treatment. Having sufficient experience and comfort with these discussions can be empowering. In this paper, we discuss the challenges involved and propose a framework to assist in incorporating these discussions into clinical care.

quality of life
communication
goals of care
serious news
values-concordant care


Antiviral effect of fufang yinhua jiedu (FFYH) granules against influenza A virus through regulating the inflammatory responses by TLR7/MyD88 signaling pathway.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Fufang-Yinhua-Jiedu Granules (FFYH) optimized from a Yin-Qiao-San, as traditional Chinese medicine (TCM), was used to treat influenza and upper respiratory tract infection and was recommended for the prevention and treatment of SARS in 2003 and current COVID-19 in Anhui Province in 2020.

AIM OF STUDY
In the clinical studies, FFYH was very effective for the treatment of influenza, but the mechanism of action against influenza A virus remains unclear. In the present study, we investigated the antiviral effect of FFYH against influenza A virus in vitro and vivo. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was investigated for the first time.

MATERIALS AND METHODS
CPE inhibition assay and HA assay were used to evaluate the in vitro antiviral effects of FFYH against influenza A virus H1N1, H3N2, H5N1, H7N9 and H9N2. Mice were used to evaluate the antiviral effect of FFYH in vivo with ribavirin and lianhuaqingwen as positive controls. RT-PCR was used to quantify the mRNA transcription of TNF-α, IL-6, IFN-γ, IP10, and IL-1β mRNA. ELISA was used to examine the expression of inflammatory factors such as TNF-α, IL-6, IFN-γ, IP10, and IL-1β in sera. The blood parameters were analyzed with auto hematology analyzer. Moreover, the potential mechanism of FFYH against influenza A virus in vivo was also investigated.

RESULTS
FFYH showed a broad-spectrum of antiviral activity against H1N1, H3N2, H5N1, H7N9, and H9N2 influenza A viruses. Furthermore, FFYH dose-dependently increased the survival rate, significantly prolonged the median survival time of mice, and markedly reduced lung injury caused by influenza A virus. Also, FFYH significantly improve the sick signs, food taken, weight loss, blood parameters, lung index, and lung pathological changes. Moreover, FFYH could markedly inhibit the inflammatory cytokine expression of TNF-α, IL-6, IFN-γ, IP10, IL-10, and IL-1β mRNA or protein via inhibition of the TLR7/MyD88/NF-κB signaling pathway in vivo.

CONCLUSION
FFYH not only showed a broad-spectrum of anti-influenza virus activity in vitro, but also exhibited a significant protective effect against lethal influenza virus infection in vivo. Furthermore, our results indicated that the in vivo antiviral effect of FFYH against influenza virus may be attributed to suppressing the expression of inflammatory cytokines via regulating the TLR7/MyD88/NF-κB signaling pathway. These findings provide evidence for the clinical treatment of influenza A virus infection with FFYH.

Zhang|Yuqian|Y| Wang|Ronghua|R| Shi|Weiqing|W| Zheng|Zhihui|Z| Wang|Xiaoquan|X| Li|Cheng|C| Zhang|Shuofeng|S| Zhang|Pinghu|P|

D053594:Myeloid Differentiation Factor 88

Antivirals
Influenza A virus
TLR7/MyD88
Fufang-yinhua-jiedu granules
Acute lung injury


A Comparative Analysis of Speed Profile Models for Ankle Pointing Movements: Evidence that Lower and Upper Extremity Discrete Movements are Controlled by a Single Invariant Strategy.

Abstract: Little is known about whether our knowledge of how the central nervous system controls the upper extremities (UE), can generalize, and to what extent to the lower limbs. Our continuous efforts to design the ideal adaptive robotic therapy for the lower limbs of stroke patients and children with cerebral palsy highlighted the importance of analyzing and modeling the kinematics of the lower limbs, in general, and those of the ankle joints, in particular. We recruited 15 young healthy adults that performed in total 1,386 visually evoked, visually guided, and target-directed discrete pointing movements with their ankle in dorsal-plantar and inversion-eversion directions. Using a non-linear, least-squares error-minimization procedure, we estimated the parameters for 19 models, which were initially designed to capture the dynamics of upper limb movements of various complexity. We validated our models based on their ability to reconstruct the experimental data. Our results suggest a remarkable similarity between the top-performing models that described the speed profiles of ankle pointing movements and the ones previously found for the UE both during arm reaching and wrist pointing movements. Among the top performers were the support-bounded lognormal and the beta models that have a neurophysiological basis and have been successfully used in upper extremity studies with normal subjects and patients. Our findings suggest that the same model can be applied to different "human" hardware, perhaps revealing a key invariant in human motor control. These findings have a great potential to enhance our rehabilitation efforts in any population with lower extremity deficits by, for example, assessing the level of motor impairment and improvement as well as informing the design of control algorithms for therapeutic ankle robots.

Michmizos|Konstantinos P|KP|
Vaisman|Lev|L|
Krebs|Hermano Igo|HI|

stroke
cerebral palsy
ankle movements
neurorehabilitation of motor function
rehabilitation robotics
sensorimotor control


Transitory FGF treatment results in the long-lasting suppression of the proliferative response to repeated FGF stimulation.

Abstract: FGF applied as a single growth factor to quiescent mouse fibroblasts induces a round of DNA replication, however continuous stimulation results in arrest in the G1 phase of the next cell cycle. We hypothesized that FGF stimulation induces the establishment of cell memory, which prevents the proliferative response to repeated or continuous FGF application. When a 2-5 days quiescence period was introduced between primary and repeated FGF treatments, fibroblasts failed to efficiently replicate in response to secondary FGF application. The establishment of "FGF memory" during the first FGF stimulation did not require DNA synthesis, but was dependent on the activity of FGF receptors, MEK, p38 MAPK and NFκB signaling, and protein synthesis. While secondary stimulation resulted in strongly decreased replication rate, we did not observe any attenuation of morphological changes, Erk1/2 phosphorylation and cyclin D1 induction. However, secondary FGF stimulation failed to induce the expression of cyclin A, which is critical for the progression from G1 to S phase. Treatment of cells with a broad range histone deacetylase inhibitor during the primary FGF stimulation rescued the proliferative response to the secondary FGF treatment suggesting that the establishment of "FGF memory" may be based on epigenetic changes. We suggest that "FGF memory" can prevent the hyperplastic response to cell damage and inflammation, which are associated with an enhanced FGF production and secretion. "FGF memory" may present a natural obstacle to the efficient application of recombinant FGFs for the treatment of ulcers, ischemias, and wounds.

Poole|Ashleigh|A| Knowland|Nicholas|N| Cooper|Emily|E| Cole|Rebecca|R| Wang|Hongchuan|H| Booth|Lucas|L| Kacer|Doreen|D| Tarantini|Francesca|F| Friesel|Robert|R| Prudovsky|Igor|I|

D000818:Animals
D002453:Cell Cycle
D002465:Cell Movement
D049109:Cell Proliferation
D019938:Cyclin D1
D004261:DNA Replication
D005346:Fibroblast Growth Factors
D016193:G1 Phase
D006655:Histone Deacetylases
D020935:MAP Kinase Signaling System
D051379:Mice
D016328:NF-kappa B
D015398:Signal Transduction

FGF
DNA SYNTHESIS
NFκB
CELL MIGRATION
CELL “MEMORY”
HDAC


Analysis and modeling of enhanced green fluorescent protein diffusivity in whey protein gels.

Abstract: During gastric digestion, hydrolysis of proteins by pepsin contributes largely to the breakdown of protein-rich food. We hypothesized that the effect of pepsin is limited by its diffusivity, which is co-determined by the food structure and the local pH in the food during digestion. To investigate the principle mechanism of enzyme diffusion in food matrices, we used enhanced green fluorescent protein (EGFP) as probe to study the diffusivity of proteins in whey protein isolate gels, using fluorescence correlation spectroscopy (FCS). Gels made with different ionic strength showed distinctive elastic moduli but did not show differences in diffusivity of EGFP. Some models for diffusion in hydrogels yield good description of the obtained data, and can approximate the enzyme diffusion in diverse food matrices. However, the enzyme pepsin is more complicated than the probe EGFP, to yield more accurate predictions, electrostatic and enzyme-substrate interaction also need to be considered.

Luo|Qi|Q|
Sewalt|Erik|E|
Borst|Jan Willem|JW|
Westphal|Adrie H|AH|
Boom|Remko M|RM|
Janssen|Anja E M|AEM|

Modeling
Diffusion
Whey protein gel
Gastric digestion
Pepsin
FCS
GFP


Determinants of parasitoid communities of willow-galling sawflies: habitat overrides physiology, host plant and space.

Abstract: Studies on the determinants of plant-herbivore and herbivore-parasitoid associations provide important insights into the origin and maintenance of global and local species richness. If parasitoids are specialists on herbivore niches rather than on herbivore taxa, then alternating escape of herbivores into novel niches and delayed resource tracking by parasitoids could fuel diversification at both trophic levels. We used DNA barcoding to identify parasitoids that attack larvae of seven Pontania sawfly species that induce leaf galls on eight willow species growing in subarctic and arctic-alpine habitats in three geographic locations in northern Fennoscandia, and then applied distance- and model-based multivariate analyses and phylogenetic regression methods to evaluate the hierarchical importance of location, phylogeny and different galler niche dimensions on parasitoid host use. We found statistically significant variation in parasitoid communities across geographic locations and willow host species, but the differences were mainly quantitative due to extensive sharing of enemies among gallers within habitat types. By contrast, the divide between habitats defined two qualitatively different network compartments, because many common parasitoids exhibited strong habitat preference. Galler and parasitoid phylogenies did not explain associations, because distantly related arctic-alpine gallers were attacked by a species-poor enemy community dominated by two parasitoid species that most likely have independently tracked the gallers' evolutionary shifts into the novel habitat. Our results indicate that barcode- and phylogeny-based analyses of food webs that span forested vs. tundra or grassland environments could improve our understanding of vertical diversification effects in complex plant-herbivore-parasitoid networks.

Nyman|Tommi|T|
Leppänen|Sanna A|SA|
Várkonyi|Gergely|G|
Shaw|Mark R|MR|
Koivisto|Reijo|R|
Barstad|Trond Elling|TE|
Vikberg|Veli|V|
Roininen|Heikki|H|

vertical diversification effects
community barcoding
enemy-free space
speciation
tritrophic food webs


Study on antidepressant mechanism of Radix Bupleuri-Radix Paeoniae Alba herb pair by metabonomics combined with 1H nuclear magnetic resonance and ultra-high-performance liquid chromatography-tandem mass spectrometry detection technology.

Abstract:
OBJECTIVES
Radix Bupleuri-Radix Paeoniae Alba (BP), a traditional Chinese medicine herb pair, has treated depression by coordinating the liver in Chinese classical medicine books and modern research. This study aims to verify the antidepressant effect of BP by behavioural examination, and reveal the underlying antidepressant mechanisms of BP.

METHODS
The antidepressant effects in chronic unpredictable mild stress (CUMS) of BP were observed by behavioural indicators and 1H nuclear magnetic resonance (1H-NMR) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabonomics techniques combined with the related analysis platforms.

KEY FINDINGS
BP could significantly improve the depressive behaviour of CUMS rats. Compared with the model group, body weight (P < 0.05), the number of crossing (P < 0.001) and rearing (P < 0.01) and sucrose preference rate (P < 0.01) were significantly enhanced, and the immobility time was shortened in the forced swimming test (P < 0.001) of the BP group. In metabonomics study, 35 depression-related metabolites were identified by 1H NMR and UHPLC-MS/MS metabonomics by comparing model and control groups. BP could significantly retrieve 17 depression-related metabolites. Thirteen depression-related metabolic pathways were found through Met-PA and BP could regulate seven metabolic pathways.

CONCLUSIONS
BP herb pair had significantly antidepressant effect, which provides a basis for further finding drug targets.

Zhou|Yuzhi|Y|0000-0002-2034-5626 Li|Tian|T| Zhu|Shiwei|S| Gong|Wenxia|W| Qin|Xuemei|X| Du|Guanhua|G|

herb pair
metabonomics
CUMS
Radix Bupleuri
Radix Paeoniae Alba


Carbapenemase-Producing Enterobacteriaceae and Nonfermentative Bacteria, the Philippines, 2013-2016.

Abstract: During 2013-2016, we isolated blaNDM- and blaVIM-harboring Enterobacteriaceae and nonfermentative bacteria from patients in the Philippines. Of 130 carbapenem-resistant isolates tested, 45 were Carba NP-positive; 43 harbored blaNDM, and 2 harbored blaVIM. Multidrug-resistant microbial pathogen surveillance and antimicrobial drug stewardship are needed to prevent further spread of New Delhi metallo-β-lactamase variants.

Velasco|John Mark|JM|
Valderama|Maria Theresa|MT|
Peacock|Trent|T|
Warawadee|Nirdnoy|N|
Nogrado|Kathyleen|K|
Navarro|Fatima Claire|FC|
Chua|Domingo|D|
Apichai|Srijan|S|
Sirigade|Ruekit|R|
Macareo|Louis R|LR|
Swierczewski|Brett|B|

carbapenemase-producing
Enterobacteriaceae
nonfermentative bacteria
bacteria
the Philippines
carbapenem-resistant
New Delhi metallo-β-lactamase–producing
antimicrobial resistance
enteric infections
military treatment facility
multidrug resistance


Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

Abstract:
BACKGROUND
The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses.

METHODS
A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response.

RESULTS
Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD.

CONCLUSION
HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016.

Shafirstein|Gal|G|
Rigual|Nestor R|NR|
Arshad|Hassan|H|
Cooper|Michele T|MT|
Bellnier|David A|DA|
Wilding|Gregory|G|
Tan|Wei|W|
Merzianu|Mihai|M|
Henderson|Barbara W|BW|

photodynamic therapy
larynx
dysplasia
carcinoma in situ
squamous cell carcinoma


Amelogenesis imperfecta: Four case reports.

Abstract: Amelogenesis Imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner. AI is a serious problem that reduces oral health-related quality of life and causes some physiological problems. We presented here four case reports of AI (Hypoplastic and Hypomaturation) which we diagnosed on the basis of classical clinical and radiographic features.

Mehta|Dhaval N|DN|
Shah|Jigna|J|
Thakkar|Bhavik|B|

Amelogenesis imperfecta
enamel hypoplasia
hypoplastic teeth


An uncertainty estimate of the prevalence of stunting in national surveys: the need for better precision.

Abstract:
BACKGROUND
Stunting is determined by using the World Health Organization (WHO) child growth standard which was developed using precise measurements. However, it is unlikely that large scale surveys maintain the same level of rigour and precision when measuring the height of children. The population measure of stunting in children is sensitive to over-dispersion, and the high prevalence of stunting observed in surveys in low and middle-income countries (LMIC) could partly be due to lower measurement precison.

OBJECTIVES
To quantify the incongruence in the dispersion of height-for-age in national surveys of < 5 y children, in relation to the standard WHO Multicenter Growth Reference Study (MGRS), and propose a measure of uncertainty in population measures of stunting.

METHODS
An uncertainty factor was proposed and measured from the observed incongruence in dispersion of the height-for-age of < 5 y children in the MGRS against carefully matched populations from the Demographic Health Survey of 17 countries ('test datasets', based on the availability of data). This also allowed for the determination of uncertainty-corrected prevalence of stunting (height-for-age Z score < - 2) in < 5 y children.

RESULTS
The uncertainty factor was estimated for 17 LMICs. This ranged from 0.9 to 2.1 for Peru and Egypt respectively (reference value 1). As an explicit country example, the dispersion of height-for-age in the Indian National Family Health Survey-4 test dataset was 39% higher than the MGRS study, with an uncertainty factor of 1.39. From this, the uncertainty-adjusted Indian national stunting prevalence estimate reduced to 18.7% from the unadjusted estimate of 36.2%.

CONCLUSIONS
This study proposes a robust statistical method to estimate uncertainty in stunting prevalence estimates due to incongruent dispersions of height measured in national surveys for children < 5 years in relation to the WHO height-for-age standard. The uncertainty is partly due to population heterogeneity, but also due to measurement precision, and calls for better quality in these measurements.

National Family Health Survey-4 (NFHS-4)

WHO multicentre growth reference study (MGRS)


Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.

Abstract: Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. One hundred forty-four individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0 ± 9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤3 (p <0.0001), earlier disease onset (p <0.0001), and lack of blepharoptosis surgery (p = 0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted.

Youssof|Sarah|S| Schrader|Ronald|R| Bear|David|D| Morrison|Leslie|L|

Oculopharyngeal muscular dystrophy
Outcome measures
Time-to-event analysis
Mobility impairment
Natural history


Synthesis and pharmacological evaluation of novel bisindolylalkanes analogues.

Abstract: In an effort to develop potent anti-cancer chemopreventive agents that act on topoisomerase II, a novel series of bisindolylalkanes analogues such as 3,3'-(thiochroman-4,4-diyl)bis(1H-indole) are synthesized. Structures of all compounds are elucidated by (1)H NMR, (13)C NMR and HRMS. Anti-proliferative activities for all of these compounds are investigated by the method of MTT assay on 7 human cancer lines. Most of them showed antitumor activities in vitro, the half maximal inhibitory concentration (IC50) value is 7.798 μg/mL of 3a against MCF7. Compound 3a showed comparable topoisomerase II inhibitory activity to etoposide (VP-16) at 100 μM concentration. The rest of the compounds also showed varying degree topoisomerase II inhibitory activity.

Song|Ya-Li|YL| Dong|Yun-Fang|YF| Yang|Tao|T| Zhang|Chao-Chao|CC| Su|Li-Min|LM| Huang|Xin|X| Zhang|Dong-Nuan|DN| Yang|Geng-Liang|GL| Liu|Yu-Xin|YX|

D004354:Drug Screening Assays, Antitumor

Bisindolylalkane
Topoisomerase II
Anticancer
Indole
Thiochroman-4-one


Medical System Choice: Information That Affects the Selection of Healthcare Provider in Australia?

Abstract: Many complementary and alternative medical practices (CAM) are readily assessable in Australia alongside Allopathic practitioners. Although CAM practices are prevalent, little is known about how patients seek and use information when deciding which system to consult. We report some preliminary findings of a longitudinal study, designed to solicit factors that influence the Australian public when selecting from diverse medical systems. Fifty-four general public participants, willing to provide their confidential and anonymous opinion were included. The magnitudes of importance, critical in influencing factors, were screened. Results indicated a medical system was selected for its effectiveness, safety, credentials and care (p<0.001). Consultation time, convenience, cost, empowerment and rapport were less important factors (p<0.001) influencing selection of a medical system. The level of choices by participants [χ2 (1, N=54) = 53.445, p<0.001] follow similar trends found for those in conventional medical systems. This contrasts with findings in other locations, where cost and time were major contributing factors when selecting medical systems.

Sahama|Tony|T| Stranieri|Andrew|A| Butler-Henderson|Kerryn|K| Golden|Isaac|I|

D001315:Australia
D002755:Choice Behavior
D000529:Complementary Therapies
D006282:Health Personnel
D006801:Humans
D008137:Longitudinal Studies

Medical System
Longitudinal Study
Diverse Medical Systems
Influencing Factors
Empowerment


The Dynamics of Lamin a During the Cell Cycle.

Abstract: Lamin proteins play an essential role in maintaining the nuclear organization and integrity; and lamin A, in particular, plays a major role in the whole volume of the nuclear interior. Although the nucleus is highly organized, it is rather dynamic, it affects crucial nuclear processes and its organization must change as cells progress through the cell cycle. Although many aspects of these changes are already known, the role of lamin A during nuclear assembly and disassembly as well as its underlying mechanisms remains controversial. Here we used live cells imaging and Continuous Photobleaching (CP) method to shed light on the dynamics and mechanisms of lamin A during the cell cycle, combined with imaging flow cytometry measurements, which provides the high-throughput capabilities of flow cytometry with single-cell imaging. As a major analysis tool, we used spatial correlation algorithm for allocating the distribution of lamin A, chromatin and tubulin, as well as their mutual colocalization. Furthermore, we analyzed the distribution of lamin A along the nuclear lamina and in the nucleus interior during the cell cycle. Our results indicate that at the beginning of the cell division that include prophase, metaphase and anaphase, lamin A is distributed throughout the cytoplasm and its concentration in the chromosomal regions is reduced, whereas the spatial correlation between lamin A and tubulin is increased. It implies that lamin A also disassembled in the whole cellular volume. At the telophase and early G1, lamin A is concentrated in the whole volume of the newly formed nuclei of the daughter cells and it assembles to the lamina. We also explored the functional aspects of lamin A during the cell cycle and its binding to the chromatin versus the freely diffusion form. We found that the fraction of the bound proteins of lamin A in the S phase increased, relative to the G1 phase, which means that during replication, the concentration of lamin A on the chromatin increases. All these results shed light on the function of lamin A throughout the cell cycle.

lamin a
cell cycle
continuous photobleaching
chromatin
imagestream
live-cells imaging
nucleus organization


A new method for hydroxyl radical detection by chemiluminescence of flue-cured tobacco extracts.

Abstract: Chemiluminescence (CL) reactions usually take place in a severely restricted pH regime, thereby confining their application in media at different pH. In this paper, the CL behavior of tobacco-methanol extract (TME) was explored. Surprisingly, TME exhibited CL behavior upon mixing with Fe2+/H2O2, HRP/H2O2 and gold nanoparticles/H2O2 oxidation systems, i.e., in acidic, neutral and alkaline solution respectively. Addition of different reactive oxygen species scavengers verified that the hydroxyl radical (OH) triggers TME CL reactions. Then, the CL behavior of TME was applied to determine OH in tetrachloro-1,4-benzoquinone (TCBQ)/H2O2 system in acidic, neutral and alkaline solutions. CL intensity correlated most strongly (R2 = 0.99) with TCBQ concentration, which was used as a means to indirectly denote OH concentration. This implies that OH could be determined by a TME CL method in a semi-quantitative way regardless of pH value. Therefore, the TME CL method may be a promising method for OH determination in various OH-generating systems.

Wang|Dabin|D| Yu|Weisong|W| Pang|Xueli|X| Cao|Jianmin|J| Qiu|Jun|J| Kong|Fanyu|F|

Hydroxyl radical detection
Chemiluminescence
pH
Tobacco-methanol extract


Dihydroartemisinin enhances VEGFR1 expression through up-regulation of ETS-1 transcription factor.

Abstract: Angiogenesis is required for tumor growth. Dihydroartemisinin (DHA), a the effective anti-malarial derivative of artemisinin, demonstrated potent anti-angiogenic activities that closely related to the regulation of vascular endothelial growth factor (VEGF) signaling cascade. VEGF receptor 1 (VEGFR1), a receptor in endothelial cells (ECs), coordinately regulate angiogenic activity triggered by ligand-receptor binding. Here we aimed to explore the effects of DHA on VEGFR1 expression in ECs. We found that DHA significantly increases VEGFR1 expression in human umbilical vein endothelial cells (HUVECs). In addition, DHA significantly upregulates the level of V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1 (ETS-1), a transcriptional factor which binds to the human VEGFR1 promoter. ChIP assay showed that DHA increases ETS-1 binding to the -52 ETS motif on the VEGFR1 promoter. Knockdown of ETS-1 by RNA interference abolished DHA-induced increase of VEGFR1 expression. Taken together, we demonstrated that DHA elevates VEGFR1 expression via up-regulation of ETS-1 transcription in HUVECs.

Niu|Na|N| Yu|Changmei|C| Li|Liqun|L| Liu|Qiang|Q| Zhang|Wenqian|W| Liang|Kaili|K| Zhu|Youming|Y| Li|Jing|J| Zhou|Xia|X| Tang|Jinbao|J| Liu|Ju|J|


Distal humerus shear-fractures: "Built-on" surgical technique.

Abstract: When treating a distal humeral shear fracture, comminution of the lateral column may preclude the reconstruction of the lateral articular fragments. In this article a new strategy for the management lateral column comminuted shear-fractures (LCCSF) is presented, called the "built-on" surgical technique. Three goals are obtained by this technique: (1) Restoration of the lateral column bone stock; (2) Provision of a solid scaffold for the repair of the lateral ulnar collateral ligament (LUCL); and (3) Provision of a sable platform for the reconstruction and fixation of the articular fragments. We will obtain these goals through the following surgical steps: 1/ Reconstruction of the lateral trochlea. 2/ Reconstruction of the lateral column 3/ Fixation of the Capitellum 4/ Reconstruction of the LUCL.

Rapariz|Jose M|JM|
Martin|Silvia|S|
Far-Riera|Aina|A|
Lirola-Palmero|Serafin|S|

distal humerus
shear fractures
fractures
lateral column
Capitellar and trochlear fractures


Aptamer and bifunctional enzyme co-functionalized MOF-derived porous carbon for low-background electrochemical aptasensing.

Abstract: To improve the efficiency of aptasensors, a signal amplification strategy by coupling tyrosinase (Tyr)-triggered redox cycling with nanoscale porous carbon (NCZIF) has been proposed. The NCZIF was obtained by calcining ZIF-8 crystals in an inert atmosphere. It had high surface areas, great biocompatibility, and ease of functionalization, which was beneficial for immobilizing sufficient Tyr and aptamer covalently. When the target prostate-specific antigen (PSA) was present, the NCZIF functionalized with Tyr and an aptamer bound to the aptamer-modified Au electrode specifically through the sandwich structure. Then, Tyr acted to oxidize the electroinactive phenol, which led to low-background signal, in the substrate to electroactive catechol, and triggered the redox cycling under the action of NADH. The low detection limit of the proposed electrochemical aptasensor for PSA was 0.01 ng mL-1, and the wide detection range was from 0.01 to 50 ng mL-1. The use of ZIF-8 derived porous carbon and Tyr-triggered redox cycling system provided a promising solution for the development of simple, rapid, reliable, and low-background aptasensing methods, which had great potential in the field of disease diagnosis and biomedicine.

Wan|Hui|H| Cao|Xiyue|X| Liu|Min|M| Zhang|Feifei|F| Sun|Chao|C| Xia|Jianfei|J| Wang|Zonghua|Z|

Bifunctional enzyme
Signal amplification
Nanoscale porous carbon
Prostate-specific antigen
Electrochemical aptasensor


Stepped-Wedge Cluster Randomised Trial of Social Prescribing of Forest Therapy for Quality of Life and Biopsychosocial Wellbeing in Community-Living Australian Adults with Mental Illness: Protocol.

Abstract: Social Prescribing (SP) involves linking individuals with mental illness to local health and welfare services to improve quality of life (QoL) and biopsychosocial wellbeing. SP programs address psychosocial wellbeing by linking individuals to group activities. Forest Therapy (FT) is a group nature walk with prescribed activities that promote mindfulness, relaxation, and shared experience. Improvements in psychological and physical wellbeing have been demonstrated in FT, but psychosocial impacts have not been widely investigated. This study will implement an SP FT intervention and assess the impacts on QoL and biopsychosocial wellbeing. Participants will include 140 community-living adults with mental illness at Sydney/Gold Coast, Australia. A stepped-wedge cluster randomised design will be used; each participant will complete a 10-week control period followed by a 10-week FT intervention. Weekly 90-min FT sessions will be conducted in groups of 6-10 in local nature reserves. Validated tools will measure self-report QoL and biopsychosocial wellbeing pre- and post-control and intervention periods, and 5-week follow-up. Blood pressure and heart rate will be measured pre- and post-FT sessions. Hypothesised outcomes include improvements in QoL and biopsychosocial wellbeing. This study is the first to assess SP FT, and may provide evidence for a novel, scalable mental illness intervention.

Thomas|Tamsin|T| Baker|James|J| Massey|Debbie|D| D'Appio|Daniel|D| Aggar|Christina|C|0000-0002-0137-7796

quality of life
mindfulness
community services
loneliness
mental disorders
nature therapy
social isolation
social support


Single-cell transcriptome analysis of endometrial tissue.

Abstract:
STUDY QUESTION
How can we study the full transcriptome of endometrial stromal and epithelial cells at the single-cell level?

SUMMARY ANSWER
By compiling and developing novel analytical tools for biopsy, tissue cryopreservation and disaggregation, single-cell sorting, library preparation, RNA sequencing (RNA-seq) and statistical data analysis.

WHAT IS KNOWN ALREADY
Although single-cell transcriptome analyses from various biopsied tissues have been published recently, corresponding protocols for human endometrium have not been described.

STUDY DESIGN, SIZE, DURATION
The frozen-thawed endometrial biopsies were fluorescence-activated cell sorted (FACS) to distinguish CD13-positive stromal and CD9-positive epithelial cells and single-cell transcriptome analysis performed from biopsied tissues without culturing the cells. We studied gene transcription, applying a modern and efficient RNA-seq protocol. In parallel, endometrial stromal cells were cultured and global expression profiles were compared with uncultured cells.

PARTICIPANTS/MATERIALS, SETTING, METHODS
For method validation, we used two endometrial biopsies, one from mid-secretory phase (Day 21, LH+8) and another from late-secretory phase (Day 25). The samples underwent single-cell FACS sorting, single-cell RNA-seq library preparation and Illumina sequencing.

MAIN RESULTS AND THE ROLE OF CHANCE
Here we present a complete pipeline for single-cell gene-expression studies, from clinical sampling to statistical data analysis. Tissue manipulation, starting from disaggregation and cell-type-specific labelling and ending with single-cell automated sorting, is managed within 90 min at low temperature to minimize changes in the gene expression profile. The single living stromal and epithelial cells were sorted using CD13- and CD9-specific antibodies, respectively. Of the 8622 detected genes, 2661 were more active in cultured stromal cells than in biopsy cells. In the comparison of biopsy versus cultured cells, 5603 commonly expressed genes were detected, with 241 significantly differentially expressed genes. Of these, 231 genes were up- and 10 down-regulated in cultured cells, respectively. In addition, we performed a gene ontology analysis of the differentially expressed genes and found that these genes are mainly related to cell cycle, translational processes and metabolism.

LIMITATIONS, REASONS FOR CAUTION
Although CD9-positive single epithelial cells sorting was successfully established in our laboratory, the amount of transcriptome data per individual epithelial cell was low, complicating further analysis. This step most likely failed due to the high dose of RNases that are released by the cells' natural processes, or due to rapid turnaround time or the apoptotic conditions in freezing- or single-cell solutions. Since only the cells from the late-secretory phase were subject to more focused analysis, further studies including larger sample size from the different time-points of the natural menstrual cycle are needed. The methodology also needs further optimization to examine different cell types at high quality.

WIDER IMPLICATIONS OF THE FINDINGS
The symbiosis between clinical biopsy and the sophisticated laboratory and bioinformatic protocols described here brings together clinical diagnostic needs and modern laboratory and bioinformatic solutions, enabling us to implement a precise analytical toolbox for studying the endometrial tissue even at the single-cell level.

Krjutškov|K|K| Katayama|S|S| Saare|M|M| Vera-Rodriguez|M|M| Lubenets|D|D| Samuel|K|K| Laisk-Podar|T|T| Teder|H|H| Einarsdottir|E|E| Salumets|A|A| Kere|J|J|

endometrial biopsy
single-cell FACS
clinical sampling
biopsy cryopreservation
endometrial receptivity


Association of Faecal Calprotectin Level and Combined Endoscopic and Radiological Healing in Patients With Crohn's Disease Receiving Anti-tumour Necrosis Factor Therapy.

Abstract:
BACKGROUND AND AIMS
Combined endoscopic and radiological healing, or deep healing, is associated with favourable outcomes in patients with Crohn's disease; thus, a non-invasive biomarker for predicting deep healing would be invaluable. We evaluated the usefulness of faecal calprotectin for predicting deep healing in patients with Crohn's disease receiving anti-tumour necrosis factor [TNF] therapy.

METHODS
We analysed the records of patients with Crohn's disease who received anti-tumour necrosis factor therapy and underwent endoscopic evaluation, radiological evaluation, and faecal calprotectin measurement within a period of 3 months between August 2017 and November 2018. Results of endoscopic and radiological studies were independently reviewed by two gastrointestinal endoscopists and a gastrointestinal radiologist, respectively. Serum C-reactive protein and albumin were also measured.

RESULTS
Out of 268 patients analysed, 77 [28.7%] had deep healing, 36 [13.4%] had endoscopic healing only, 36 [13.4%] had radiological healing only, and 119 [44.4%] had neither. The median duration of anti-TNF treatment was 40.0 months. The deep healing group had the lowest median faecal calprotectin level [56.5 mg/kg] among the four groups [p <0.001]. The faecal calprotectin cutoff level of 81.1 mg/kg showed a sensitivity of 0.623 and a specificity of 0.817 in predicting deep healing (area under the receiver operating characteristic curve [AUROC], 0.767; 95% confidence interval, 0.702-0.832). Adding serum C-reactive protein and serum albumin to faecal calprotectin further increased the AUROC to 0.805 [95% confidence interval, 0.752-0.858].

CONCLUSIONS
Faecal calprotectin, when combined with serum C-reactive protein and albumin, showed acceptable performance in predicting deep healing in patients with Crohn's disease.

Noh|Soo Min|SM|
Oh|Eun Hye|EH|
Park|Seong Ho|SH|
Lee|Jung Bok|JB|
Kim|Jin Yong|JY|
Park|Jae Cheol|JC|
Kim|Jeongseok|J|
Ham|Nam Seok|NS|
Hwang|Sung Wook|SW|
Park|Sang Hyoung|SH|
Yang|Dong-Hoon|DH|
Byeon|Jeong-Sik|JS|
Myung|Seung-Jae|SJ|
Yang|Suk-Kyun|SK|
Ye|Beyong Duk|BD|

D000079424:Tumor Necrosis Factor Inhibitors

faecal calprotectin
Crohn’s disease
disease monitoring


Production Losses Associated with Alcohol-Attributable Mortality in the European Union.

Abstract: The economic aspects of alcohol misuse are attracting increasing attention from policy makers and researchers but the evidence on the economic burden of this substance is hardly comparable internationally. This study aims to overcome this problem by estimating production losses (indirect costs) associated with alcohol-attributable mortality in 28 European Union (EU) countries in the year 2016. This study applies the prevalence-based top-down approach, societal perspective and human capital method to sex- and age-specific data on alcohol-related mortality at working age. The alcohol-attributable mortality data was taken from estimates based on the Global Burden of Disease Study 2016. Uniform data on labor and economic measures from the Eurostat database was used. The total production losses associated with alcohol-related deaths in the EU in 2016 were €32.1 billion. The per capita costs (share of costs in gross domestic product (GDP)) were €62.88 (0.215%) for the whole EU and ranged from €17.29 (0.062%) in Malta to €192.93 (0.875%) in Lithuania. On average, 81% of the losses were associated with male deaths and mortality among those aged 50-54 years generated the highest burden. Because alcohol is a major avoidable factor for mortality, public health community actions aimed at limiting this substance misuse might not only decrease the health burden but also contribute to the economic welfare of European societies.

production losses
European Union
indirect costs
human capital method
alcohol mortality


Escherichia coli spheroplasts in a Croatian patient misclassified by two urine sediment analysers as erythrocytes: case report.

Abstract:
Introduction
It has already been reported that subinhibitory concentrations of β-lactam antibiotics can cause abnormal changes of bacterial forms, such as spheroplasts. Herein we report a case of Croatian male patient with Escherichia coli spheroplasts present in urine after treatment with tazobactam, on the tenth day of hospitalization. The aim of this report is to emphasize the inability of imaging based automated urine analysers to recognize some relatively uncommon forms of bacterial presentation in urine sediment.

Materials and methods
During routine urine analysis, unusual particles were observed in patient urine. Urine sediment was examined by two urine analysers: Atellica 1500 (Siemens, Germany) and Iris iQ200 (Beckman Coulter, USA). Additionally, urine was sent for culture testing to Microbiology department.

Results
Both urine analysers didn't indicate presence of bacteria in urine sediment. Unusual particles observed on the tenth day were classified as erythrocytes by both instruments. Dipstick test showed blood trace and microscopic analysis revealed bacteria in urine. Urine culture was positive for Escherichia coli. Careful examination of urine sediment has confirmed that shapes present in urine were abnormal bacterial forms called spheroplasts.

Conclusions
Imaging based automated urine analysers are not able to recognize bacterial spheroplasts in urine sediment misclassifying it as erythrocytes. Microscopic examination remains the gold standard for urines with blood trace or negative blood, in which erythrocytes are reported by urine analyser in urine sediment. Failure to identify and follow up such cases may lead to inaccurate treatment decisions and puts patient safety at risk.

Nikler|Ana|A|
Radišić Biljak|Vanja|V|
Čičak|Helena|H|
Marić|Nikolina|N|
Bejuk|Danijela|D|
Poloni|Jose Antonio Tesser|JAT|
Simundic|Ana-Maria|AM|

spheroplasts
bacterial forms
misclassification
urinalysis


Antifungal susceptibility testing of dermatophytes: Development and evaluation of an optimised broth microdilution method.

Abstract:
BACKGROUND
Dermatophytosis is one of the most common infections affecting 3%-17% of the population. Resistance to antifungals so far was not of concern in the therapeutic management. However, recent reports of terbinafine-resistant strains in several countries are worrisome making antifungal susceptibility testing inevitable.

OBJECTIVES
We aimed to develop and evaluate an optimised broth microdilution assay for antifungal drug susceptibility testing of dermatophytes.

METHODS
We first studied the effect of different inocula, incubation temperatures and incubation times to establish an optimised assay. Subsequently, we tested 79 clinical strains of 11 dermatophyte species with 13 antifungals.

RESULTS
We found inoculating with 0.5-5 × 104 colony forming units (CFU) and incubating at 29°C ± 1°C for 4 days to be appropriate. Terbinafine was the most active antifungal agent with minimum inhibitory concentration (MIC) values ≤ 0.06 µg/mL, expect for one resistant T mentagrophytes strain, which was isolated from an Indian patient. Also, a majority of MICs of other antifungals that are commonly used to treat dermatophytosis were low, except those of fluconazole. Fluconazole MICs do not correlate with the good efficacy in the clinical management.

CONCLUSIONS
Our assay enables fast and reliable susceptibility testing of dermatophytes with a large panel of different antifungals. This helps to improve the therapeutic management of dermatophytosis by detecting resistant strains.

antifungal susceptibility testing
susceptibility tests
dermatophytes
broth microdilution
dermatophytosis
terbinafine resistance


Adaptive Doppler analysis for robust handheld optical coherence elastography.

Abstract: Optical coherence tomography (OCT) allows structural and functional imaging of biological tissue with high resolution and high speed. Optical coherence elastography (OCE), a functional extension of OCT, has been used to perform mechanical characterization. A handheld fiber-optic OCE instrument allows high sensitivity virtual palpation of tissue with great convenience and flexibility and can be used in a wide range of clinical settings. Moreover, fiber-optic OCE instruments can be integrated into a needle device to access deep tissue. However, the major challenge in the development of handheld OCE instrument is non-constant motion within the tissue. In this study, a simple and effective method for temporally and spatially adaptive Doppler analysis is investigated. The adaptive Doppler analysis method strategically chooses the time interval (δt) between signals involved in Doppler analysis, to track the motion speed v(z,t) that varies as time (t) and depth (z) in a deformed sample volume under manual compression. The aim is to use an optimal time interval to achieve a large yet artifact free Doppler phase shift for motion tracking.

Zaki|Farzana|F| Wang|Yahui|Y| Wang|Chizhong|C| Liu|Xuan|X|

Doppler
Optical coherence elastography
Optical coherence tomography
Optical sensing and sensors
Tissue characterization


How quantifiers influence the conceptual representation of plurals.

Abstract: This paper reports the results of two experiments that investigate the nature of plural conceptual representations that are created during sentence comprehension. Previous work has found that comprehenders seem to represent both a singular object and a plural set of objects during the comprehension of plural nouns. The activation of the singular object has been attributed to the pragmatic processing involved in understanding the plural (Patson, Journal of Experimental Psychology: Learning, Memory and Cognition, 42, 1140-1153, 2016a). The goal of the current study was to further investigate this hypothesis. Experiment 1 used a picture-matching paradigm to investigate how comprehenders conceptualize plural nouns quantified with many, which renders the scalar implicature unnecessary. Consistent with the pragmatic processing hypothesis, comprehenders did not activate a singular form when the plural was quantified with many. Experiment 2 was designed to further investigate whether all quantifiers block activation of the singular form. The same picture-matching paradigm was used with numerical quantifiers that specify numbers either within or above the subitization range. When the number was within the subitization range, comprehenders' conceptual representations contained exactly that number of objects, and importantly did not contain a singular object. When number was above the subitization range, comprehenders' conceptual representations did not contain an exact number of objects and seemed to activate a singular object. These data are consistent with constraints on how many objects can be represented in visual working memory. Taken together, the results of these two experiments suggest that the plural's conceptual representation emerged as a result of grammatical processing as well as limits on the visual processing system.

Quantifiers
Plural
Language comprehension
Referential processing


Training and retaining mental health professionals: The Romanian experience in the European Union.

Abstract:
BACKGROUND
Romania has been a member of the European Union since 2007. According to the World Health Organization, the national burden of mental disorders is high, with 2743.69 disability-adjusted life years per 100.000 population. Moreover, in a country of 19 million people, Romania's mental health system is currently functioning at capacity, with 5.66 adult psychiatrists/100.000 population and only 0.56 child and adolescent psychiatry (CAP) doctors per 100.000 population.

METHOD
we conducted a simple narrative review of the current literature on the topic of training of psychiatry trainees in Romania.

RESULTS
Undergraduate training consists of only 4 weeks of clinical and theoretical work for adult and CAP. Psychiatry postgraduate training lasts 5 years and is still duration-oriented. Psychiatric trainees mostly spend their clinical work in inpatient units due to the scarcity of other services or the lack of integration of training programs in the existing psychiatric services. Theoretical training is not nationally formalized, and, during training, yearly assessments tend to be neglected. An ongoing challenge in Romania has been retaining young career psychiatrists.

CONCLUSION
Although in a trend toward improvement of health services, "brain drain" has been and continues to be a massive phenomenon among Romanian psychiatrists, mainly driven to Western-European countries due to financial reasons, various shortcomings in overall infrastructure, and because of the lack of continuous professional and personal development opportunities. As the world is currently facing an unprecedented mental health crisis, steps must be taken to improve psychiatric training, retain psychiatrists in Romania, and provide better national mental health services.

mental health
undergraduate
postgraduate
education
psychiatry training