Evolution of Generalists by Phenotypic Plasticity.

Abstract: Adapting organisms face a tension between specializing their phenotypes for certain ecological tasks and developing generalist strategies that permit persistence in multiple environmental conditions. Understanding when and how generalists or specialists evolve is an important question in evolutionary dynamics. Here, we study the evolution of bacterial range expansions by selecting Escherichia coli for faster migration through porous media containing one of four different sugars supporting growth and chemotaxis. We find that selection in any one sugar drives the evolution of faster migration in all sugars. Measurements of growth and motility of all evolved lineages in all nutrient conditions reveal that the ubiquitous evolution of fast migration arises via phenotypic plasticity. Phenotypic plasticity permits evolved strains to exploit distinct strategies to achieve fast migration in each environment, irrespective of the environment in which they were evolved. Therefore, selection in a homogeneous environment drives phenotypic plasticity that improves performance in other environments.

Fraebel|David T|DT|
Gowda|Karna|K|
Mani|Madhav|M|
Kuehn|Seppe|S|

Evolutionary Biology
Evolutionary Mechanisms
Microbiology


A grounded theory study on midwifery managers' views and experiences of implementing and sustaining continuity of carer models within the UK maternity system.

Abstract:
BACKGROUND
Current UK health policy recommends the transition of maternity services towards provision of Midwifery Continuity of Carer (MCoCer) models. Quality of healthcare is correlated with the quality of leadership and management yet there is little evidence available to identify what is required from midwifery managers when implementing and sustaining MCoCer.

AIM
To develop a theoretical framework that represents midwifery managers' experiences of implementing and sustaining MCoCer models within the UK's National Health Service (NHS).

METHODS
Charmaz's grounded theory approach was used for this study. Five experienced UK based midwifery managers were interviewed to elicit views and understanding of the social processes underlying the implementation and sustaining of MCoCer. Interviews were transcribed and analysed and focus codes developed into theoretical codes resulting in an emergent core category.

FINDINGS
The theoretical framework illustrates the core category 'Leading Meaningful Midwifery'. To manage MCoCer models midwifery managers require a trust and belief in woman centred philosophy of care. They need the skills to focus on non-hierarchical transformational leadership and the courage to assimilate alternative models of care into the NHS. Promoting and protecting the MCoCer model within current services is essential whilst forming a culture based on high quality, safe MCoCer.

DISCUSSION
MCoCer models that have sustained within the NHS have had supportive leadership from midwifery managers who have the necessary skills, attitudes, aptitudes and behaviours identified within the findings. Sustainable implementation of MCoCer is achieved through development of a values-based recruitment and retention policy within all areas of midwifery and encouraging midwives with previous experience in MCoCer or supportive philosophies towards it, to manage the model.

CONCLUSION
Providing the appropriate support for MCoCer is time consuming and personally demanding for midwifery managers, however, implementing and sustaining MCoCer was shown by participants who valued MCoCer models to be rewarding, bringing meaning to their midwifery leadership.

Grounded theory
Midwifery management
Midwifery continuity of carer
Leadership
Meaningful midwifery


Improved Ventricular Function after TEE-guided Cardioversion of Atrial Arrhythmias in Patients after the Fontan Operation.

Abstract:
OBJECTIVE
Atrial tachyarrhythmias frequently develop after the Fontan operation. Patients with Fontan physiology rely on atrial contribution to cardiac output, and thus control of atrial arrhythmias is important. Outcomes after cardioversion in patients after Fontan have not been reported. We sought to determine if cardioversion results in improved echocardiographic parameters or clinical symptomatology; and, discern risk factors for arrhythmia recurrence.

DESIGN
We retrospectively analyzed the Mayo Clinic echocardiographic database to capture patients after the Fontan operation who underwent transesophageal echocardiography-guided electrical cardioversion from 2000-2015. Clinical and echocardiographic data were collected and compared at baseline and follow-up.

RESULTS
Eight hundred ninety patients with prior Fontan operation underwent echocardiographic evaluation; 341 (38%) developed atrial arrhythmias. Thirty-six patients [20 males, median age 29 (12-51)] underwent transesophageal echocardiography-guided cardioversion of atrial arrhythmias [atrial flutter/intraatrial reentrant tachycardia (75%); atrial fibrillation (25%)]. At follow-up, improvements were noted in ejection fraction by 10% (P < .0001); atrioventricular valve regurgitation grade (39%) (P = .002); New York Heart Association (NYHA) class (61%) (P < .001); and resolution of spontaneous echo contrast in the Fontan circuit (65%) (P < .01). No embolic events occurred following cardioversion. Eighteen patients (50%) developed recurrent atrial arrhythmias at 15 (3-36) months after cardioversion. Five-year freedom from arrhythmia recurrence was 61%. Significant univariate predictors of arrhythmia recurrence were atrial flutter/intraatrial reentrant tachycardia (HR = 4.3, P = .02); NYHA ≥ II (HR = 4.1, P = .03); systemic right ventricle (HR = 5.2; P = .02); and ejection fraction ≤ 40% (HR = 2.8; P = .04). On multivariate analysis, only systemic right ventricle (HR = 3.7; P = .02) remained an independent predictor of arrhythmia recurrence.

CONCLUSION
After the Fontan operation, cardioversion of atrial arrhythmias improves ventricular function, atrioventricular valve regurgitation grade, and NYHA class. Arrhythmia recurrence was common and patients with atrial flutter/intraatrial reentrant tachycardia, systemic right ventricle, or reduced ventricular function may be at risk of arrhythmia recurrence. Further studies are required to identify additional risk factors and protective factors for arrhythmia recurrence.

Poterucha|Joseph T|JT|
Egbe|Alexander C|AC|
Johnson|Jonathan N|JN|
Niaz|Talha|T|
Wackel|Phillip L|PL|
Cannon|Bryan C|BC|
Eidem|Benjamin W|BW|
Cetta|Frank|F|

Cardioversion
Atrial Arrhythmias
Fontan
Adult Congenital Heart Disease
Transesophageal Echocardiography


Controversies and prospects about microglia in maternal immune activation models for neurodevelopmental disorders.

Abstract: Activation of the maternal immune system during pregnancy is a well-established risk factor for neuropsychiatric disease in the offspring, yet, the underlying mechanisms leading to altered brain function remain largely undefined. Microglia, the resident immune cells of the brain, are key to adequate development of the central nervous system (CNS), and are prime candidates to mediate maternal immune activation (MIA)-induced brain abnormalities. As such, the effects of MIA on the immunological phenotype of microglia has been widely investigated. However, contradicting results due to differences in read-out and methodological approaches impede final conclusions on MIA-induced microglial alterations. The aim of this review is to critically discuss the evidence for an activated microglial phenotype upon MIA.

Smolders|Silke|S|
Notter|Tina|T|
Smolders|Sophie M T|SMT|
Rigo|Jean-Michel|JM|
Brône|Bert|B|

D011297:Prenatal Exposure Delayed Effects

Microglia
Maternal immune activation
Neurodevelopmental disorders
LPS
Poly(I:C)


Maternal Nutrition and Neurodevelopment: A Scoping Review.

Abstract: In this scoping review, we examined the association between maternal nutrition during pregnancy and neurodevelopment in offspring. We searched the Pubmed and ScienceDirect databases for articles published from 2000 to 2020 on inadequate intake of vitamins (B12, folate, vitamin D, vitamin A, vitamin E, vitamin K), micronutrients (cooper, iron, creatine, choline, zinc, iodine), macronutrients (fatty acids, proteins), high fat diets, ketogenic diets, hypercaloric diets, and maternal undernutrition. Some older relevant articles were included. The search produced a total of 3590 articles, and 84 studies were included in the qualitative synthesis. Data were extracted and analyzed using charts and the frequency of terms used. We concluded that inadequate nutrient intake during pregnancy was associated with brain defects (diminished cerebral volume, spina bifida, alteration of hypothalamic and hippocampal pathways), an increased risk of abnormal behavior, neuropsychiatric disorders (ASD, ADHD, schizophrenia, anxiety, depression), altered cognition, visual impairment, and motor deficits. Future studies should establish and quantify the benefits of maternal nutrition during pregnancy on neurodevelopment and recommend adequate supplementation.

D039382:Maternal Nutritional Physiological Phenomena

maternal nutrition
neurodevelopment
nutrients
neuropsychiatric disorders
cognitive abilities


Somatosensory-motor cortex interactions measured using dual-site transcranial magnetic stimulation.

Abstract:
BACKGROUND
Dual-site transcranial magnetic stimulation (ds-TMS) is a neurophysiological technique to measure functional connectivity between cortical areas.

OBJECTIVE/HYPOTHESIS
To date, no study has used ds-TMS to investigate short intra-hemispheric interactions between the somatosensory areas and primary motor cortex (M1).

METHODS
We examined somatosensory-M1 interactions in the left hemisphere in six experiments using ds-TMS. In Experiment 1 (n = 16), the effects of different conditioning stimulus (CS) intensities on somatosensory-M1 interactions were measured with 1 and 2.5 ms inter-stimulus intervals (ISIs). In Experiment 2 (n = 16), the time-course of somatosensoy-M1 interactions was studied using supra-threshold CS intensity at 6 different ISIs. In Experiment 3 (n = 16), the time-course of short-interval cortical inhibition (SICI) and effects of different CS intensities on SICI were measured similar to Experiments 1 and 2. Experiment 4 (n = 13) examined the effects of active contraction on SICI and somatosensory-M1 inhibition. Experiments 5 and 6 (n = 10) examined the interactions between SAI with either 1 ms SICI or somatosensory-M1 inhibition.

RESULTS
Experiments 1 and 2 revealed reduced MEP amplitudes when applying somatosensory CS 1 ms prior to M1 TS with 140 and 160% CS intensities. Experiment 3 demonstrated that SICI at 1 and 2.5 ms did not correlate with somatosensory-M1 inhibition. Experiment 4 found that SICI but not somatosensory-M1 inhibition was abolished with active contraction. The results of Experiments 5-6 showed SAI was disinhibited in presence of somatosensory-M1 while SAI was increased in presence of SICI.

CONCLUSION
Collectively, the results support the notion that the somatosensory areas inhibit the ipsilateral M1 at very short latencies.

Brown|Matt J N|MJN|
Weissbach|Anne|A|
Pauly|Martje G|MG|
Vesia|Michael|M|
Gunraj|Carolyn|C|
Baarbé|Julianne|J|
Münchau|Alexander|A|
Bäumer|Tobias|T|
Chen|Robert|R|

Somatosensory
Motor
Dual-site TMS
Paired-pulse TMS
Sensorimotor control
TMS


Determinants of disability using count-based approaches to ICF-based definition of neurological disability.

Abstract:
INTRODUCTION
The aim of this study was to explore the most relevant determinants of severe disability in a heterogeneous sample of patients with neurological conditions.

OBJECTIVES
We used data from previous studies on patients with myasthenia gravis (MG), migraine, Parkinson's disease (PD), multiple sclerosis, traumatic brain injury (TBI), stroke and epilepsy (349 patients, aged 18-74 years; mean 48.0, SD 11.7). We calculated count-based extension indexes to address severe disability, and hierarchical logistic regression to assess the association between severe disability, sociodemographic and health status information.

CONCLUSIONS
Results show that sociodemographic variables played a minor role, while health state information was a stronger determinant of severe disability. Compared to the reference value of TBI patients, those with MG, PD and epilepsy had higher odds to have severe difficulties undertaking daily activities despite the presence of environmental factors. Our results contrast with those of previous studies, mostly derived from general populations, showing the different impact of clinical and sociodemographic variables.

Raggi|A|A| Covelli|V|V| Leonardi|M|M| Meucci|P|P| Scaratti|C|C| Schiavolin|S|S| Willems|M|M| Sattin|D|D|

D064702:International Classification of Functioning, Disability and Health

Disability
ICF classification
barriers
mental functions
mobility


ZBP-89 function in colonic stem cells and during butyrate-induced senescence.

Abstract: ZBP-89 (Zfp148, ZNF148) is a Kruppel-type zinc-finger family transcription factor that binds to GC-rich DNA elements. Earlier studies in cell lines demonstrated that ZBP-89 cooperates with Wnt β-catenin signaling by inducing β-catenin gene expression. Since β-catenin levels are normally highest at the crypt base, we examined whether ZBP-89 is required for stem cell maintenance. Lineage-tracing using a Zfp148Cre transgenic line demonstrated expression in both intestine and colonic stem cells. Deleting the Zfp148 locus in the colon using the Cdx2NLSCre transgene, reduced the size and number of polyps formed in the Apc-deleted mice. Since colon polyps form in the presence of butyrate, a short chain fatty acid that suppresses cell growth, we examined the direct effect of butyrate on colon organoid survival. Butyrate induced senescence of colon organoids carrying the Apc deletion, only when Zfp148 was deleted. Using quantitative PCR and chromatin immunoprecipitation, we determined that butyrate treatment of colon cell lines suppressed ZNF148 gene expression, inducing CDKN2a (p16 ) gene expression. Collectively, Zfp148 mRNA is expressed in CBCs, and is required for stem cell maintenance and colonic transformation. Butyrate induces colonic cell senescence in part through suppression of ZBP-89 gene expression and its subsequent occupancy of the CDKN2A promoter.

Ocadiz-Ruiz|Ramon|R|
Photenhauer|Amanda L|AL|
Hayes|Michael M|MM|
Ding|Lin|L|
Fearon|Eric R|ER|
Merchant|Juanita L|JL|


HIV testing experiences in Nairobi slums: the good, the bad and the ugly.

Abstract:
BACKGROUND
HIV testing is an integral component of HIV prevention, treatment and care and, therefore, is crucial in achieving UNAIDS 90-90-90 targets. HIV testing in Kenya follows both the voluntary counselling and testing (VCT) and provider initiated testing and counselling (PITC) models. However, little is known about the individual experiences of undergoing an HIV test in the two testing models. This study provides experiential evidence of undergoing an HIV test in a resource poor urban slum setting.

METHODS
The study explored testing experiences and challenges faced in respect to ensuring the 3 Cs (consent, counselling and confidentiality), using in-depth interviews (N = 41) with HIV-infected men and women in two slum settlements of Nairobi City. The in-depth interview respondents were aged above 18 years with 56% being females. All interviews were audio-recorded, transcribed and then translated into English. The transcribed data were analysed using thematic analysis method.

RESULTS
The respondent HIV-testing experiences were varied and greatly shaped by circumstances and motivation for HIV testing. The findings show both positive and negative experiences, with sporadic adherence to the 3Cs principle in both HIV testing models. Although some respondents were satisfied with the HIV testing process, a number of them raised a number of concerns, with instances of coercion and testing without consent being reported.

CONCLUSION
The 3Cs (consent, counselling and confidentiality) principle must underlie HIV testing and counselling practices in order to achieve positive testing outcomes. The study concludes that adherence to the 3Cs during HIV testing contributes to both the individual and public health good - irrespective of whether testing is initiated by the individual or by the health provider.

HIV testing
Slums
Kenya
VCT
PITC
PLWHA
sub-Saharan Africa


Tracking natural and anthropogenic origins of dissolved arsenic during surface and groundwater interaction in a post-closure mining context: Isotopic constraints.

Abstract: Arsenic contamination of stream waters and groundwater is a real issue in Au-As mine environments. At the Salsigne Au-As mine, southern France, arsenic contamination persists after closure and remediation of the site. In this study, natural and anthropogenic arsenic inputs in surface water and groundwater are identified based on (87)Sr/(86)Sr, and δ(18)O and δ(2)H isotopic composition of water. In the wet season, downstream of the remediated zone, the arsenic contents in stream water and alluvial aquifer groundwater are high, with values in the order of 36 μg/L and 40 μg/L respectively, while upstream natural background average concentrations are around 4 μg/L. Locally down-gradient of the reclaimed area, arsenic concentrations in stream water showed 2 peaks, one during an important rainy event (101 mm) in the wet season in May, and a longer one over the dry period, reaching 120 and 110 μg/L respectively. The temporal variations in arsenic content in stream water can be explained i) during the dry season, by release of arsenic stored in the alluvial sediments through increased contribution from base flow and decreased stream flow and ii) during major rainy events, by mobilization of arsenic associated with important surface runoff. The (87)Sr/(86)Sr ratios associated with increasing arsenic content in stream waters downstream of the reclaimed area are significantly lower than that of the natural Sr inherited from Variscan formations. These low (87)Sr/(86)Sr ratios are likely to be associated with the decontaminating water treatment processes, used in the past and still at present, where CaO, produced from marine limestone and therefore showing a low (87)Sr/(86)Sr ratios, is used to precipitate Ca3(AsO4)2. The low Sr isotope signatures will then impact on the Sr isotope ratio of (1) the Ca-arsenate stored in tailing dams, (2) effluent currently produced by water treatment process and (3) groundwater draining from the overall site. Furthermore, Δ(2)H shows that the low (87)Sr/(86)Sr ratio, arsenic rich water is characterized by an evaporated signature suggesting a potential influence of water impacted by evaporation during storage in decantation lagoons. This study shows the suitability of Sr and stable isotopes of water as tracers to differentiate natural and anthropogenic sources of arsenic release or other trace elements from mining context where CaO is used for water treatment.

Khaska|Mahmoud|M|
Le Gal La Salle|Corinne|C|
Verdoux|Patrick|P|
Boutin|René|R|

D052918:Environmental Restoration and Remediation

Stream water
(87)Sr/(86)Sr
δ(18)O and δ(2)H
Tailing dams
Arsenic pollution
Surface water–groundwater interaction


Effect of high flow arteriovenous fistula on cardiac function in hemodialysis patients.

Abstract:
Background
Vascular access for hemodialysis (HD) with an inappropriately high flow may underlie the onset of high output heart failure (HOHF).The aim of this study was to determine the prevalence of high flow access (HFA) in chronic HD patients, and to determine its effects on cardiac functions.

Methods
This cross sectional study was conducted on 100 chronic hemodialysis patients through arteriovenous fistula (AVF). The study cohort was subdivided into 2 groups based on AVF flow: Group A (Non-HFA group with Qa < 2000 ml/min), and Group B (HFA group with Qa ≥ 2000 ml/min). AVF flow (Qa) was assessed using Color Doppler ultrasonography. Transthoracic echocardiography was performed for all patients to assess cardiac dimensions and functions.

Results
Prevalence of HFA among study population was 24%. Mean AVF Qa was 958.63 ± 487.35 and 3430.13 ± 1256.28 ml/min, for group A and B respectively. The HFA group demonstrated a significant dilatation in LV dimensions and volumes and significantly larger LA volume as compared to non-HFA group. A significantly lower LV ejection fraction [EF] was also observed in group B with a mean value of 57.32 ± 6.19% versus 62.90 ± 5.76%. A significant association between HFA group and high Qa/cardiac output (CO) ratio (≥20%) was also observed.

Conclusion
HFA is a prevalent hemodialysis vascular access problem. HFA was associated with dilated LV dimensions, impaired LV systolic function. High Qa/CO ratio (≥20%) was an independent predictor of high output heart failure (HOHF) in our study population.

Saleh|Mohamed Ayman|MA|
El Kilany|Wael Mahmoud|WM|
Keddis|Viola William|VW|
El Said|Tamer Wahid|TW|

Hemodialysis
Vascular access
High output heart failure
High flow access


Protein Glycosylation Investigated by Mass Spectrometry: An Overview.

Abstract: The protein glycosylation is a post-translational modification of crucial importance for its involvement in molecular recognition, protein trafficking, regulation, and inflammation. Indeed, abnormalities in protein glycosylation are correlated with several disease states such as cancer, inflammatory diseases, and congenial disorders. The understanding of cellular mechanisms through the elucidation of glycan composition encourages researchers to find analytical solutions for their detection. Actually, the multiplicity and diversity of glycan structures bond to the proteins, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies make their detection much trickier than other kinds of biopolymers. An overview of the most prominent techniques based on mass spectrometry (MS) for protein glycosylation (glycoproteomics) studies is here presented. The tricks and pre-treatments of samples are discussed as a crucial step prodromal to the MS analysis to improve the glycan ionization efficiency. Therefore, the different instrumental MS mode is also explored for the qualitative and quantitative analysis of glycopeptides and the glycans structural composition, thus contributing to the elucidation of biological mechanisms.

Illiano|Anna|A| Pinto|Gabriella|G| Melchiorre|Chiara|C| Carpentieri|Andrea|A| Faraco|Vincenza|V| Amoresano|Angela|A|

post-translational modifications (PTM), mass spectrometry


Acute pain management in patients with drug dependence syndrome.

Abstract: Managing patients with dependence requires knowledge of pharmacology; an understanding of the diagnosis of dependence and recognition of withdrawal; skills in communication and collaborative working; and a nonjudgmental, empathic attitude.

acute pain
addiction
analgesics
behavior
opioid
opioid substitution therapy


Neural crest emigration: From start to stop.

Abstract: Within the dynamic context of a developing embryo, the multicellular patterns formed are extraordinarily precise. Through cell-cell communication, neighboring progenitors coordinate their activities, sequentially generating distinct tissues. The development of the dorsal neural tube remarkably illustrates this principle. It first generates neural crest (NC) cells, precursors of most of the peripheral nervous system, and then becomes the roof plate (RP) of the central nervous system. While the molecular network regulating emigration of NC progenitors has been extensively studied, the mechanisms by which dorsal neural tube precursors transit from an initial NC fate to a definitive RP identity remain widely open to investigation. Critical differences exist between premigratory NC and RP cells. Whereas the former extensively proliferate and undergo an epithelial-to-mesenchymal transition that generates cellular migrations, the latter progressively exit the cell cycle and regain epithelial traits including apico-basal polarity and regeneration of a laminin-containing basement membrane. To understand this transition, the nature of the cross-talk between these two sequentially forming progenitor subsets should be unraveled, including the identity and mode of action of signals that, on the one hand, induce the arrest of NC emigration, and, on the other hand, promote formation of a definitive RP.

D018507:Gene Expression Regulation, Developmental

neural tube
roof plate
epithelial-to-mesenchymal transition
BMP
cell fate
cell proliferation


Survivin regulates chromosome segregation by modulating the phosphorylation of Aurora B during porcine oocyte meiosis.

Abstract: SURVIVIN is an essential chromosomal passenger complex (CPC) subunit and participates in cell division. In this study, we used porcine oocyte as a model to investigate the roles of Survivin during porcine oocyte maturation. Survivin was highly expressed in germinal vesicle (GV) and germinal vesicle breakdown (GVBD) stages oocytes, mainly localized in the GV at GV stage and on the chromosomes after GVBD. We have used RNA interference to specifically deplete Survivin in oocytes during in vitro maturation (IVM). Immunofluorescence assay showed that Survivin-depleted oocytes failed to produce polar body in meiosisⅠ (failed to complete cytokinesis), and they were arrested in metaphaseⅠwith misaligned chromosomes. The homologous chromosomes in Survivin-depleted oocytes could not be separated normally. Moreover, both the phosphorylation levels of Aurora B and the mRNA level of Mad2L1 related to spindle assembly checkpoint (SAC) was decreased in Survivin-depleted oocytes, which thus inhibited the degradation of Cyclin B1 (CCNB1) to complete meiosis. Taken together, we conclude that Survivin is an important mediator of centromere and midbody docking of Aurora-B as well as its activity and regulates SAC and MPF activity during meiosis in porcine oocytes.

Chen|Li|L| Yin|Tailang|T| Nie|Zheng-Wen|ZW| Wang|Tao|T| Gao|Ying-Ying|YY| Yin|Shu-Yuan|SY| Huo|Li-Jun|LJ| Zhang|Xia|X| Yang|Jing|J| Miao|Yi-Liang|YL|

Survivin
chromosomes
oocyte
spindle assembly checkpoint
metaphase I
pig


Self-stigma among Korean patients with diabetes: A concept analysis.

Abstract:
AIMS AND OBJECTIVES
To conduct a concept analysis of self-stigma among patients with diabetes and introduce an operational definition of self-stigma.

BACKGROUND
Due to fears of being monitored, patients with diabetes often conceal their disease and/or withdraw from social relationships. These behaviours negatively affect patients' self-care and socialisation.

DESIGN
A concept analysis was conducted using a three-phase (theoretical phase, fieldwork phase and final analysis phase) hybrid method by Schwartz-Barcott and Kim (Nursing research methodology: Issues and implementations, 1986, Rockville, MD: Aspen).

METHODS
During the theoretical phase, a literature search was conducted using PubMed and CINAHL. Using COREQ guidelines, in the fieldwork phase, in-depth interviews were conducted with nine participants with diabetes. The recorded data were analysed using a grounded theory approach. Results from both were included in the analytic phase.

RESULTS
In the fieldwork phase, nine patients with diabetes (four men and five women; mean age = 57.00 ± 21.93 years) participated in the interview. The mean duration of diabetes was 21.44 ± 12.39 years. The self-stigma concept included three categories with nine attributes: affective (negative feelings and feeling sorry for others who have concerns about me), cognitive (low self-esteem and self-efficacy, perceived weakness, low expectations for the future, worry for children and disease burden) and behavioural factors (social withdrawal and avoiding disease disclosure). The nine attributes included 23 indicators.

CONCLUSIONS
Self-stigma among patients with diabetes is defined as a state in which patients develop negative self-feelings as they deal with the disease. This can cause diminished self-esteem and self-efficacy, as well as a tendency to avoid disclosing the illness along with social withdrawal.

RELEVANCE TO CLINICAL PRACTICE
Based on this self-stigma concept analysis, we clarified the attributes of diabetes self-stigma and distinguished it from social stigma in nurse professionals during patient education and clinical assessment.

nursing
social stigma
concept formation
diabetes mellitus


Qualitative methods in the development of a parent survey of children's oral health status.

Abstract:
Background
Parents' perceptions of their 8-17-year-old children's oral health status were assessed using a sample from diverse dental clinics in Greater Los Angeles County to identify constructs for a survey instrument.

Methods
Focus groups with 29 parents or guardians were conducted to identify themes that informed development of survey items. The draft items were administered to a different group of 32 parents or guardians in cognitive interviews, and revised for subsequent field-testing.

Results
Thematic and narrative analyses were performed after the focus groups and key lay-oriented dimensions were uncovered, notably the relationship between oral health, systemic health and the life course. In the cognitive interviews, parents entered multiple responses to questions related to the look of their child's teeth, and their overall perception of tooth color. Parents also assessed their child's fear or discomfort with the dental experience, and other social and psychological concerns related to oral health status. The temporal dimensions of certain items were specified; for example, oral pain and mood items were revised to include duration of the symptom or mood state. As parents tended to confuse oral health maintenance and prevention, these two related concepts were separated into two items. Based on the qualitative work, we revised items in preparation for a field test.

Conclusions
As a PRO measurement study, qualitative research informed a field test survey to assess factors associated with oral health status and the individual's perceptions and subjective views of these constructs for eventual item development for epidemiological and clinical use.

Maida|Carl A|CA|
Marcus|Marvin|M|
Hays|Ron D|RD|
Coulter|Ian D|ID|
Ramos-Gomez|Francisco|F|
Lee|Steve Y|SY|
McClory|Patricia S|PS|
Van|Laura V|LV|
Wang|Yan|Y|
Shen|Jie|J|
Lau|Bryant|B|
Spolsky|Vladimir W|VW|
Crall|James J|JJ|
Liu|Honghu|H|

Qualitative research
Child and adolescent oral health
Outcomes
Psychosocial aspects of oral health


Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease.

Abstract:
AIM
To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients.

METHODS
A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale - Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale - Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function.

RESULTS
Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group.

CONCLUSIONS
The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.

Tang|Hongmei|H| Huang|Jing|J| Nie|Kun|K| Gan|Rong|R| Wang|Limin|L| Zhao|Jiehao|J| Huang|Zhiheng|Z| Zhang|Yuhu|Y| Wang|Lijuan|L|

Parkinson's disease
early-onset Parkinson's disease (EOPD)
late-onset Parkinson's disease (LOPD)
cognitive function
age of onset


In rape trauma PTSD, patient characteristics indicate which trauma-focused treatment they are most likely to complete.

Abstract:
BACKGROUND
Dropout rates for effective therapies for posttraumatic stress disorder (PTSD) can be high, especially in practice settings. Although clinicians have intuitions regarding what treatment patients may complete, there are few systematic data to drive those judgments.

METHODS
A multivariable model of dropout risk was constructed with randomized clinical trial data (n = 160) comparing prolonged exposure (PE) and cognitive processing therapy (CPT) for rape-induced PTSD. A two-step bootstrapped variable selection algorithm was applied to identify moderators of dropout as a function of treatment condition. Employing identified moderators in a model, fivefold cross-validation yielded estimates of dropout probability for each patient in each condition. Dropout rates between patients who did and did not receive their model-indicated treatment were compared.

RESULTS
Despite equivalent dropout rates across treatments, patients assigned to their model-indicated treatment were significantly less likely to drop out relative to patients who did not (relative risk = 0.49 [95% CI: 0.29-0.82]). Moderators included in the model were: childhood physical abuse, current relationship conflict, anger, and being a racial minority, all of which were associated with higher likelihood of dropout in PE than CPT.

CONCLUSIONS
Individual differences among patients affect the likelihood they will complete a particular treatment, and clinicians can consider these moderators in treatment planning. In the future, treatment selection models could be used to increase the percentage of patients who will receive a full course of treatment, but replication and extension of such models, and consideration of how best to integrate them into routine practice, are needed.

Keefe|John R|JR|0000-0001-7250-8960
Wiltsey Stirman|Shannon|S|
Cohen|Zachary D|ZD|
DeRubeis|Robert J|RJ|
Smith|Brian N|BN|
Resick|Patricia A|PA|

trauma
treatment
clinical trials
CBT/cognitive behavior therapy
PTSD/posttraumatic stress disorder
behavior therapy
empirical supported treatments


Genetic and morphological characterization of Thysaniezia tapeworms from cattle and sheep in Senegal.

Abstract: Genetic and morphological diversity of Thysaniezia tapeworms from cattle and sheep in Senegal was investigated using light and scanning microscopic observations and molecular analysis based on mitochondrial cytochrome c oxidase subunit 1 (cox1) and nuclear small subunit ribosomal RNA gene (SSU rDNA). A total of 52 adult tapeworms were collected from sheep and cattle. Although the tapeworms of the two hosts were morphologically very close, phylogenetic analysis based on cox1 and SSU rDNA gene sequences showed that they were divided into two clades corresponding each to a host. The maximum pairwise divergence between the clades were 12.1% in cox1 and 2.9% in SSU rDNA, indicating they are distinct species. The tapeworms collected from sheep were morphologically identified as Thysaniezia ovilla, a cosmopolitan species in domestic ruminants. Detailed morphological observations revealed a consistent difference between the tapeworms obtained from sheep and those from cattle. The latter were identified as Thysaniezia connochaeti. The present study highlights presence of two species of Thysaniezia among domestic ruminants in Senegal: T. ovilla specific to sheep and T. connochaeti specific to cattle. Our work is the first report of T. connochaeti from domestic animals.

Ndom|Mallé|M|
Yanagida|Tetsuya|T|
Diop|Gora|G|
Quilichini|Yann|Y|
Ba|Aïssatou|A|
Sako|Yasuhito|Y|
Nakao|Minoru|M|
Marchand|Bernard|B|
Dieye|Alioune|A|
Ba|Cheikh Tidiane|CT|
Ito|Akira|A|

Thysaniezia
Senegal
Ruminants
Cestoda
Genetic diversity


Defining corneal chemical burns: A novel exact and adjustable ocular model.

Abstract:
Introduction
Live-animal-free ocular toxicity models and tests are a necessity in multiple branches of medicine, industry and science. Corneal models with adjustable ranges of injury severities do not exist. In this work, a novel and precise and dose - response method to induce and observe ex vivo corneal chemical burns has been established.

Methods
The EVEIT (Ex Vivo Eye Irritation Test) is based on an ex vivo corneal organ model for rabbit corneas from food industry. Further, a highly precise three - axis workstation has been employed to apply liquid corrosive, sodium hydroxide (NaOH), droplets in a nanolitre (nL) range onto the corneal surface. Optical Coherence Tomography (OCT) has been used to observe and quantify the elicited changes in the corneal layers.

Results
The speed and intervals of single nanodroplet application played a crucial role in the extent of the corneal changes. Similar total volumes applied at low frequencies elicited deep and extensive changes in the corneal layers whereas high application frequencies elicited comparatively superficial changes. Increasing NaOH concentrations effected measurably increasing corneal changes. Increasing the volume of applied NaOH also showed an increase in corneal changes.

Conclusions
OCT imaging proved to be effective in observing, documenting and quantifying the changes in the corneal layers. The ex vivo model, in conjunction with the novel application method was able to induce and display distinctive and consistent correlations between NaOH volume, concentration and elicited corneal changes. This ex vivo ocular chemical burn model provides a consistent in vitro basis for pharmaceutical and toxicological experiments and investigations into corneal chemical burn mechanisms and treatment.

Glaudo|Markus|M|
Panfil|Claudia|C|
Schrage|Norbert F|NF|

EVEIT
Cornea
OCT imaging
3R
EVEIT, Ex Vivo Eye Irritation Test
Ex vivo organ culture
Live animal free toxicological test
Ocular corrosion model


Multiple dipole source localization of EEG measurements using particle filter with partial stratified resampling.

Abstract: Tracking and detection of neural activity has numerous applications in the medical research field. By considering neural sources, it can be monitored by electroencephalography (EEG). In this paper, we focus primarily on developing advanced signal processing methods for locating neural sources. Due to its high performance in state estimation and tracking, particle filter was used to locate neural sources. However, particle degeneracy limits the performance of particle filters in the most utmost situations. A few resampling methods were subsequently proposed to ease this issue. These resampling methods, however, take on heavy computational costs. In this article, we aim to investigate the Partial Stratified Resampling algorithm which is time-efficient that can be used to locate neural sources and compare them to conventional resampling algorithms. This work is aimed at reflecting on the capabilities of various resampling algorithms and estimating the performance of locating neural sources. Simulated data and real EEG data are used to conduct evaluation and comparison experiments.

Localization
EEG
Particle filter
Resampling
Inverse problems


eHealth for patients with rare diseases: the eHealth Working Group of the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN).

Abstract:
BACKGROUND
The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) was launched in 2017 and involves, to date, 35 highly specialised multidisciplinary expert centres (from the 30 full Healthcare Provider members) coming from 11 countries and more than 70 patient organizations from 16 countries. The eHealth Working Group (WG) of VASCERN was set up to develop practical, patient-centred solutions and strategies for effective use of eHealth tools to answer the needs of patients with multisystemic vascular rare diseases.

THE EHEALTH WG
Following the identified patients' needs and following the guiding principles of collaboration and patient-centredness, the eHealth WG was created with the following aims: to develop a mobile app to help patients find expert centres and patient organizations, and to develop resources (Pills of Knowledge, PoK) for training and education via digital platforms (eLearning). The mobile app includes, to date, functionalities that allow users to find expert centres and patient organizations across Europe in the area of rare multisystemic vascular diseases. Discussed app developments include personalized digital patient passports, educational material, emergency management guidelines and remote consultations. Regarding training and education, a variety of PoK have been developed. The PoK cover several topics, target several user groups, and are delivered in various formats so that they are easy-to-use, easy-to-understand, informative, and viable for delivery and sharing through digital platforms (eLearning) including, e.g., the VASCERN YouTube™ channel.

CONCLUSION
Overall, the work carried out by the eHealth WG of VASCERN can be seen as a pilot experience that may serve as a basis to for collaborative development of patient-centred eHealth tools that answer the needs of patients with various rare diseases, not limited to rare multisystemic vascular diseases. By expanding the multidisciplinary approach here described, clinical and research networks can take advantage of eHealth services and use them as strategic assets in achieving the ultimate goal of ensuring equity of access to prevention programs, timely and accurate diagnosis and specialized care for patients with rare diseases throughout Europe.

Paglialonga|Alessia|A|
Gaetano|Raffaella|R|
Robert|Leema|L|
Hurard|Marine|M|
Botella|Luisa Maria|LM|
Barr|Natasha|N|
Jondeau|Guillaume|G|
Pini|Alessandro|A|0000-0002-8325-6057

European commission 3rd health programme


Characterizing breast cancer treatment pathways in Kumasi, Ghana from onset of symptoms to final outcome: outlook towards cancer control.

Abstract:
BACKGROUND
Cancer rates are increasing in Africa, including Ghana. Breast cancer is the second most common cancer in incidence and mortality in Ghana.

OBJECTIVE
We outlined both breast cancer patient characteristics and management at the Komfo Anokye Teaching Hospital (KATH), the main cancer management hospital in central Ghana. Moreover, we identified the treatment interventions predictive of patient outcome.

METHODS
Medical records of 597 breast cancer patients seen in 2008-2011 were abstracted to investigate management and treatment patterns. Abstracted variables included type and extent of surgery, number and cycles of chemotherapy and radiotherapy, as well as the course of treatment completed.

RESULTS
Late stage at diagnosis was common, treatment plans of the study hospital were relatively standardized according to disease severity, and defaulting/interrupting treatment in the records was also common. Patients diagnosed with late stage cancer who received adjuvant therapy and patients with hormone status evaluation were more likely to have complied with treatment guidelines and continued oncotherapy at the study hospital than those who never had hormone status requested or reported.

CONCLUSIONS
Our study lends support to improving patient outcomes in low- and middle-income countries through raising knowledge and reporting of tumor hormonal status and providing appropriately tailored treatment. Achieving improved outcomes should also consider enhancing public understanding of the importance of early detection and completion of treatment.

Scherber|Samuel|S|
Soliman|Amr S|AS|
Awuah|Baffour|B|
Osei-Bonsu|Ernest|E|
Adjei|Ernest|E|
Abantanga|Frank|F|
Merajver|Sofia D|SD|

D010342:Patient Acceptance of Health Care

Breast cancer
Ghana
developing countries (LMIC)
health systems navigation


Accounting for strain variations and resistance mutations in the characterization of hepatitis C NS3 protease inhibitors.

Abstract:
CONTEXT
Natural strain variation and rapid resistance development makes development of broad spectrum hepatitis C virus (HCV) drugs very challenging and evaluation of inhibitor selectivity and resistance must account for differences in the catalytic properties of enzyme variants.

OBJECTIVE
To understand how to study selectivity and relationships between efficacy and genotype or resistant mutants for NS3 protease inhibitors.

MATERIALS AND METHODS
The catalytic properties of NS3 protease from genotypes 1a, 1b and 3a, and their sensitivities to four structurally and mechanistically different NS3 protease inhibitors have been analysed under different experimental conditions.

RESULTS
The optimisation of buffer conditions for each protease variant enabled the comparison of their catalytic properties and sensitivities to the inhibitors. All inhibitors were most effective against genotype 1a protease, with VX-950 having the broadest selectivity.

DISCUSSION AND CONCLUSION
A new strategy for evaluation of inhibitors relevant for the discovery of broad spectrum HCV drugs was established.

Ehrenberg|Angelica E|AE|
Schmuck|Benjamin|B|
Anwar|Muhammad Ikram|MI|
Gustafsson|Sofia Svahn|SS|
Stenberg|Gun|G|
Danielson|U Helena|UH|

HCV
Experimental conditions
inhibition
optimization
vitality value


Risks and benefits of late onset hypogonadism treatment: an expert opinion.

Abstract: Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized association with sexual and reproductive failure. LOH is frequently associated with chronic conditions including cardiovascular diseases (CVD), obesity, osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases. Despite this evidence, in patients with these conditions, LOH is still only rarely investigated and testosterone replacement therapy (TRT) rarely considered. In this paper, we critically reviewed the available evidence on LOH treatment focusing on possible risks and benefits. Medical therapy of LOH should be individualized depending on the etiology of the disease and the patient's expectations. The fear of prostate cancer and the risk of erythrocytosis probably represent the main limitations of TRT in aging men. However, TRT in healthy older men in near physiological doses does not appear to incur serious adverse events, although regular monitoring of prostate-specific antigen and hematocrit levels is required. Available evidence also suggests that TRT might ameliorate central obesity and glycometabolic control in patients with metabolic syndrome and type 2 diabetes. In addition, TRT has been associated with an increase in bone mineral density in men with osteoporosis, with an improvement in lean body mass in subjects with human immunodeficiency virus infection or chronic obstructive pulmonary disease, as well as with peripheral oxygenation in patients with chronic kidney diseases. Despite this evidence, however, it should be recognized that the results of these trials were heterogeneous and limited by small sample sizes. Hence, further research is required regarding the long-term benefits and adverse effects of TRT in LOH.

Corona|Giovanni|G| Vignozzi|Linda|L| Sforza|Alessandra|A| Maggi|Mario|M|

Hypogonadism
Testosterone
Prostate
Diabetes mellitus
Erectile dysfunction


Sex differences in distribution, management and outcomes of combined ischemic-bleeding risk following acute coronary syndrome.

Abstract:
BACKGROUND
Risk factors for further bleeding and ischemic events after acute coronary syndrome (ACS) often overlap. Little is known about sex-based differences in the management and outcomes of ACS patients according to their combined bleeding-ischemic risk.

METHODS
All ACS hospitalizations in the United Kingdom (2010-2017) were retrospectively analyzed, stratified by sex and bleeding-ischemic risk combination (using CRUSADE and GRACE scores). Multivariable logistic regression was performed to examine association between risk-groups and 1) receipt of guideline-recommended management and 2) in-hospital outcomes.

RESULTS
Of 584,360 patients, a third of males (32.3%) and females (32.6%) were in the dual high-risk group (High CRUSADE- High GRACE). In comparison to the dual low-risk group (Low CRUSADE-Low GRACE), the dual high-risk patients of both sexes were 59-83% less likely to receive inpatient revascularisation (PCI or CABG) and 50% less likely to receive dual antiplatelet therapy (DAPT) on discharge, with a significant increase in odds of MACE (~8 to 9-fold), all-cause and cardiac mortality (25 to 35-fold), and bleeding (78-91%). The greatest difference in management and clinical outcomes between sexes was found in the dual-high risk group where females were less likely to receive guideline-recommended therapy (revascularisation and DAPT), compared to males, and were more likely to experience MACE, all-cause and cardiac mortality.

CONCLUSION
ACS patients with dual high-risk for bleeding and recurrent ischemia, especially females, are less likely to receive guideline-recommended therapy and experience significantly worse outcomes. Novel strategies are needed to effectively manage this highly prevalent, complex patient group and address the under-treatment of females.

Mohamed|Mohamed O|MO|
Rashid|Muhammad|M|
Timmis|Adam|A|
Clarke|Sarah|S|
Lawson|Claire|C|
Michos|Erin D|ED|
Kwok|Chun Shing|CS|
De Belder|Mark|M|
Valgimigli|Marco|M|
Mamas|Mamas A|MA|

Sex
Management
Outcomes
CRUSADE
GRACE
Risk scores


Treatment of carbon monoxide poisoning: high-flow nasal cannula versus non-rebreather face mask.

Abstract:
OBJECTIVE
In this study, the aim was to compare the rate of decrease in carboxyhemoglobin (COHb) values at consecutive time points and calculate the half-life of COHb (COHb t½) in patients admitted to the emergency department (ED) with carbon monoxide (CO) poisoning and treated with either high flow nasal cannula oxygen therapy (HFNC) or non-rebreather face mask (NRFM).

METHODS
This retrospective, cohort study with historical controls was performed over a 2-year period and included adult patients with CO poisoning, whose COHb values were checked. The HFNC group consisted of patients admitted to the ED with CO poisoning when HFNC was available in the hospital, while the NRFM group consisted of patients who presented to the ED with CO poisoning before the availability of HFNC. The primary outcome of the study was to detect the COHb t½.

RESULTS
A total of 71 patients were enrolled in the study. While 35 patients received oxygen with NRFM, 36 patients received HFNC. The mean COHb t½ in the HFNC group was 41.1 min (95% CI: 31.0-58.4) and 64.0 min (95% CI: 43.5-114.4) in the NRFM group. We did not find a significant difference in the COHb t½ between the HFNC group and NRFM group (p = 0.099). COHb levels between treatment arms at serial time points showed a statistically significant difference at 60 min (p = 0.048). We compared the decay constant and half-life of COHb between groups according to gender. In both genders, COHb t½ was significantly different between groups, and COHb t½ was lower in the patients treated with HFNC.

CONCLUSION
HFNC was effective in reducing the half-life of COHb values in patients with carbon monoxide poisoning. Prospective studies to be conducted in larger groups are needed to fully understand the effect of HFNC on carbon monoxide poisoning.

Carbon monoxide poisoning
non-rebreather face mask
high-flow nasal cannula oxygen therapy


Intrasellar cavernous hemangiomas: A case report with a comprehensive review of the literature.

Abstract:
Background
Extra-axial cerebral cavernous hemangiomas particularly those found in the sellar region, are extremely rare. Their clinical manifestations and imaging characteristics can mimic those of a pituitary adenoma thus making preoperative diagnosis difficult. Few cases are reported in the literature. We present a case, along with a comprehensive review of the literature regarding specific aspects of diagnosis and management of all similarly reported rare cases.

Case Description
We present the clinical, radiological, and operative data of a rare case of a large intrasellar cavernous hemangioma in a 49-year-old female patient presented with headache and diminution of vision, which was diagnosed intraoperatively during an endonasal endoscopic transsphenoidal approach. Subtotal debulking was performed with immediate postoperative clinical improvement. The patient was then referred for radiotherapy and maintained her clinical improvement since then.

Conclusion
Neurosurgeons should consider this rare pathology in the preoperative differential diagnosis of sellar tumors. Bright hyperintense T2 signal with or without signal voids associated with centripetal delayed contrast enhancement in magnetic resonance imaging images might raise the suspicion which can be further confirmed intraoperatively with frozen sections. Due the reported high vascularity and intraoperative profuse bleeding leading to high operative morbidities, piecemeal subtotal resection followed by radiosurgery may be considered today as the safest and most effective strategy.

Al-Saiari|Sultan|S| Al-Orabi|Khalid|K| Farag|Ahmed|A| Brinji|Zaina|Z| Azzouz|Azza|A| Mohammed|Tahira|T| Mushtaq|Deepa|D| Hamouda|Waeel|W|

Cavernous hemangioma
Sellar
Transsphenoidal
Radiosurgery


Alternatives to opioid protocols in Colorado emergency departments reduce opioid use without changing reported pain.

Abstract:
Objective
The objective of this study was to determine whether instituting an alternative to opioids (ALTO) protocol significantly reduced opioid use in emergency departments (EDs). The secondary objective was to determine whether patient-reported pain and satisfaction were affected.

Methods
Electronic health records for 10 EDs in Colorado were retrospectively examined for the 6 months before the intervention and for the same 6 months the following year after the intervention, which consisted of systemic and educational initiatives in line with the Colorado American College of Emergency Physicians 2017 Opioid Prescribing and Treatment Guidelines.

Results
Of the total preintervention and postintervention unique patient visits, 47.2% received 1 of the drugs of interest, an opioid or ALTO, while in the ED. In aggregate, the EDs decreased opioid usage, measured in morphine equivalent units per 1000 ED visits, by 37.4% (95% confidence interval, 33.6%-76.2%; P < 0.0001) after the intervention. Statistically significant decreases were seen in every type of opioid. Statistically significant increases in ALTO usage were also noted across all study hospitals. There were no significant changes observed in Hospital Consumer Assessment of Healthcare Providers and Systems patient satisfaction scores before and after the intervention in the hospitals with Hospital Consumer Assessment of Healthcare Providers and Systems data (preintervention mean, 3.74; postintervention mean, 3.74; P = 0.637), and there was a small but statistically significant improvement in pain scores (preintervention mean, 3.62; postintervention mean, 3.66; P = 0.002). In a subgroup analysis of patients presenting with chief complaints of long bone fractures and malignant neoplasms, there were no significant reductions in opioid use.

Conclusions
This study demonstrated the feasibility and effectiveness of implementing ALTO protocols to reduce opioid use in the ED setting without an overall reduction in patient perception of pain or satisfaction with care.

Stader|Donald|D|
Wald|Heidi|H|
Rossi MacKay|Diane|D|
Mannerings|Alexandra|A|
Valuck|Robert|R|
Kuljis|Dominick|D|
Brady|Mark F|MF|

opioids
emergency department
pain
ALTO
opioid reduction


Randomised controlled trials as part of clinical care: A seven-step routinisation framework proposal.

Abstract: Evidence translation in wound care relies on the need for evidence generation. Clinical practice may generate evidence only if evidence-generating research projects, such as randomised controlled trials (RCTs), became routinised in clinical settings. The aim of this study was to identify optimal trial-related practices to routinise trial-related activities in Melbourne-located wound clinics as reported by clinicians and researchers. We conducted a secondary analysis of the available data on how to routinise RCTs in clinical care, with a focus on enablers and suggestions provided by the participants during face-to-face and telephone interviews. Data were obtained from a qualitative observational study nested within a randomised, double-blinded, placebo-controlled trial on clinical effectiveness of aspirin as an adjunct to compression therapy in healing chronic venous leg ulcers (ASPiVLU). We developed a seven-step Routinisation of Trials in Clinical Care Framework. These steps include: (1) pre-trial clinical site assessment, (2) optimising pre-recruitment arrangements, (3) developing and updating trial-related skills, (4) embedding RCT recruitment as part of routine clinical care, (5) promoting teamwork and trial-related collaboration, (6) addressing trial-related financial issues, and (7) communicating trial results to clinicians.

D016032:Randomized Controlled Trials as Topic

wound care
venous leg ulcers
evidence-based practice
evidence-generating practice
routinisation of RCTs


The Content of Dietary Fibre and Polyphenols in Morphological Parts of Buckwheat (Fagopyrum tataricum).

Abstract: In this report, we presented the profile of polyphenolic substances in flowers, leaves, stalk and roots of Fagopyrum tataricum estimated by using RP-UHPLC-ESI-MS equipment (reversed-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry). The neutral detergent fibre, acid detergent fibre, acid detergent lignin, cellulose and hemicellulose were also determined. Flowers, leaves, stalk and roots showed varying levels of dietary fibre and polyphenols. The highest content of neutral and acid detergent fibre were found in the roots (63.92 and 45.45% d.m., respectively) while the most rich in phenolic compounds were flowers (4.8 mg/1 g d.m.). Root and stalk contained the highest level of cellulose, 38.70 and 25.57% d.m., respectively. Among the investigated polyphenolic substances such as: 2,6-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 4-hydrobenzoic acid, caffeic acid, catechin, chlorogenic acid, fagopyrin, ferulic acid, myricetin, gallic acid, isovanilic acid, isovitexin, kaempferol, luteolin, p-coumaric acid, procyanidin B2, quercetin, quercetin 3-D galactoside, rutin, syringic acid and vitexin, we observed that the contents of rutin and chlorogenic acid were the highest. We found some correlation between dietary fibre fractions and individual phenolic substances. The levels of acid detergent fibre (ADF), cellulose and hemicellulose were negatively correlated with isovitexin, kaempferol, vitexin, fagopyrin, caffeic acid and procyanidin B2 content. In this investigation, two solvents (water and methanol) were estimated regarding their extraction efficiency of phenolic compounds. Taking these results into consideration, we recommend using methanol as the extractor to isolate chlorogenic acid, fagopyrin, kaempferol, procyanidin B2, quercetin, quercetin 3-D-galactoside, rutin, vitexin, and water for other investigated polyphenolic substances obtained from Fagopyrum tataricum.

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

Dietary fibre
Methanol extract
Phenolic substances profile
Tartary buckwheat
Water extract


Isolation and identification of N-butyl-tetrahydro-5-oxofuran-2-carboxamide produced by Bacillus sp. L60 and its antifungal activity.

Abstract: Rhizoctonia solani is the cause of substantial economic loss in many crops. The aim of this study is to investigate biocontrol potential of Bacillus sp. L60 against R. solani and to purify an antifungal compound. In this study, Bacillus sp. L60 demonstrated significant antagonism toward R. solani with the dual culture assay. The antifungal compound was extracted from Bacillus sp. L60 culture supernatant with n-butanol, and identified as N-butyl-tetrahydro-5-oxofuran-2-carboxamide (BT-5O-2C) having molecular weights of 185.1052 Da with the formula C9 H15 NO3 using NMR and HR-ESI-MS analysis. The minimum inhibitory concentration (MIC) value of the antifungal compound was 256 µg ml-1 against R. solani. Therefore, our results clearly demonstrated BT-5O-2C as well as Bacillus sp. L60 as potential biological control agents for the management of R. solani.

Lee|Yong-Seong|YS| Cho|Jeong-Yong|JY| Moon|Jae-Hak|JH| Kim|Kil-Yong|KY|


Patient-controlled oral analgesia for acute abdominal pain: A before-and-after intervention study on pain intensity and use of analgesics.

Abstract:
AIM
To compare the use of patient-controlled oral analgesia with nurse-controlled analgesia for patients admitted to hospital with acute abdominal pain. The primary outcome measure was pain intensity. The secondary outcome measures were the use of analgesics and antiemetics.

BACKGROUND
Inadequate pain management of patients with acute abdominal pain can occur during hospital admission. Unrelieved acute pain can result in chronic pain, stroke, bleeding and myocardial ischemia.

METHODS
A before-and-after intervention study was conducted in an emergency department and a surgical department with three subunits. Data were collected from medical charts and analyzed using chi-squared and Kruskal-Wallis tests.

RESULTS
A total of 170 patients were included. The median pain intensity score, using the numeric ranking scale, was 2.5 and 2 on Day 2 (p = 0.10), 2 and 2 on Day 3 (p = 0,40), 2.5 and 0 on Day 4 (p = 0.10), 2 and 0 on Day 5 (p = 0.045) in the control and intervention group, respectively. The percentage of patients receiving analgesics was 93 and 86 on Day 2 (p = 0.20), 91 and 75 on Day 3 (p = 0.02), 89 and 67 on Day 4 (p = 0.009) and 80 and 63 on Day 5 (p = 0.39). The use of antiemetics was similar in the two groups.

CONCLUSION
Patient-controlled oral analgesia significantly reduced the numerical ranking pain scale score on Day 5 and the consumption of analgesics on Days 3 and 4 after hospital admission. Patient-controlled oral analgesia is feasible as pain management for patients, but only with minor impact on experienced pain intensity and use of analgesics.

Madsen|Sandra Bruun|SB|
Qvist|Niels|N|
Möller|Sören|S|
Schultz|Helen|H|

Pain management
Acute pain
Patient involvement
Patient-centered care
Self-administered medication


Seizures in autoimmune encephalitis: specific features based on a systematic comparative study.

Abstract:
OBJECTIVE
To highlight specific characteristics of seizure semiology and EEG features associated with different subtypes of autoimmune encephalitis (AE).

METHODS
We systematically reviewed the seizure semiology and all the EEG recordings from patients with AE managed in a tertiary referral centre for epilepsy and a neuro-intensive care unit. Each characteristic across the different subtypes of AE was compared by post hoc analysis.

RESULTS
We identified 66 patients with anti-neuronal antibody-mediated AE or Rasmussen's encephalitis (RE) experiencing seizures, which were the most frequent symptom at onset. Anti-NMDAR and anti-LGI1 AE accounted for the majority of patients; 41% and 24%, respectively. We isolated specific semiological features, such as early tonic-clonic seizures (TCS) in anti-NMDAR AE, early mesial temporal lobe seizures with emotional symptoms in anti-GAD AE, somatosensory seizures in RE, and a lower frequency of TCS in anti-LGI1 AE. EEG analysis also provided additional insights into distinguishing the subtypes based on: (1) generalized rhythmic delta activity, which was more sensitive than extreme delta brush in identifying anti-NMDAR AE among all subtypes; and (2) temporal interictal epileptiform activity and temporal seizures on EEG in anti-GAD AE. We identified a new EEG pattern consisting of temporal low-voltage and periodic spikes associated with ipsilateral hippocampal abnormalities on MRI, which could be a sign of inflammatory mesial temporal involvement.

SIGNIFICANCE
Specific clinical and EEG features can be useful in guiding the diagnosis of a subtype of AE with acute symptomatic seizures, particularly before the results of anti-neuronal antibody testing are available.

Cousyn|Louis|L| Lambrecq|Virginie|V| Houot|Marion|M| Shor|Natalia|N| Nguyen-Michel|Vi-Huong|VH| Frazzini|Valerio|V| Dupont|Sophie|S| Demeret|Sophie|S| Navarro|Vincent|V|

epilepsy
anti-neuronal antibodies
autoimmune diseases
electroencephalography


Contamination of polychlorinated biphenyls in honey from the Brazilian state of Rio Grande do Sul.

Abstract: Persistent organic pollutants are characterised by their chemical structure, environmental persistence and toxicity to human and wildlife populations. The production of these chemicals is regulated and restricted. However, they continue to be detected in the environment. In this study, the occurrence of 11 congeners of polychlorinated biphenyls (PCBs 28, 52, 77, 81, 101, 118, 126, 138, 153, 169, and 180) was investigated in 90 honey samples produced in the Brazilian state of Rio Grande do Sul. The samples were from different municipalities, production systems and floral origins. Extraction was performed using the modified QuEChERS method (Quick, Easy, Cheap, Effective, Rugged and Safe) followed by gas chromatography with micro-electron capture detector. The results showed the presence of four congeners (PCBs 28, 77, 81, 101) in 15 honey samples confirming the environmental contamination in Southern Brazil. Among the contaminated samples, no significant differences were identified regarding the production system and floral origin.

Dos Santos|Mariele|M|
Vareli|Catiucia S|CS|
Janisch|Bárbara|B|
Pizzutti|Ionara R|IR|
Fortes|Juciane|J|
Sautter|Cláudia Kaehler|CK|
Costabeber|Ijoni H|IH|

persistent organic pollutants
Environmental pollution
bioindicators
food quality
organic production


Biofilm biodiversity in French and Swiss show caves using the metabarcoding approach: First data.

Abstract: In recent decades, show caves have begun to suffer from microorganism proliferation due to artificial lighting installations for touristic activity. In addition to the aesthetic problem, light encourages microorganisms that are responsible for physical and chemical degradation of limestone walls, speleothems and prehistoric paintings of cultural value. Microorganisms have previously been described by microscopy or culture-dependent methods, but data provided by new generation sequencing are rare. The authors identified, for the first time, microorganisms proliferating in one Swiss and in four French show caves using three different primers. The results showed that both photosynthetic and non-photosynthetic bacteria were the dominant taxa present in biofilms. Microalgae were heavily represented by the Trebouxiophyceae, Eustigmatophyceae and Chlorophyceae groups. Twelve diatoms were also recorded, with dominance of Syntrichia sp. (96.1%). Fungi were predominantly represented by Ascomycota, Zygomycota and Basidiomycota, fully half of the sampled biofilms where Fungi were detected. Comparing microbial communities from bleach-treated caves to those in untreated caves showed no significant difference except for a low-level change in the abundance of certain taxa. These findings provided by Illumina sequencing reveal a complex community structure in the 5 caves based on the assembly of bacteria, cyanobacteria, algae, diatoms, fungi and mosses.

Pfendler|Stéphane|S| Karimi|Battle|B| Maron|Pierre-Alain|PA| Ciadamidaro|Lisa|L| Valot|Benoît|B| Bousta|Faisl|F| Alaoui-Sosse|Laurence|L| Alaoui-Sosse|Badr|B| Aleya|Lotfi|L|

Biodiversity
Caves
Metabarcoding
Conservation
Microorganism communities


Exercise training provides cardioprotection by activating and coupling endothelial nitric oxide synthase via a β3-adrenergic receptor-AMP-activated protein kinase signaling pathway.

Abstract: Exercise training confers sustainable protection against ischemia/reperfusion injury. However, the mechanism by which this process occurs is not fully understood. Previously, it was shown that β3-adrenergic receptors (β3-ARs) play a critical role in regulating the activation of endothelial nitric oxide synthase (eNOS) in response to exercise and play a critical role in exercise-mediated cardioprotection. Intriguingly, a deficiency in β3-ARs led to increased myocardial injury following exercise training. The purpose of the current study was to determine mechanisms by which β3-ARs are linked to eNOS activation and to determine the mechanism responsible for the exacerbated ischemia/reperfusion injury displayed by β3-AR deficient (β3-AR KO) mice after exercise training. Wild-type (n = 37) and β3-AR KO (n = 40) mice were subjected to voluntary wheel running for 4 weeks. Western blot analysis revealed that neither protein kinase B nor protein kinase A linked β3-ARs to eNOS following exercise training. However, analysis revealed a role for AMP-activated protein kinase (AMPK). Specifically, exercise training increased the phosphorylation of AMPK in the hearts of wild-type mice, but failed to do so in the hearts of β3-AR KO mice. Additional studies revealed that exercise training rendered eNOS less coupled and increased NOS-dependent superoxide levels in β3-AR KO mice. Finally, supplementing β3-AR KO mice with the eNOS coupler, tetrahydrobiopterin, during the final week of exercise training reduced myocardial infarction. These findings provide important information that exercise training protects the heart in the setting of myocardial ischemia/reperfusion injury by activating and coupling eNOS via the stimulation of a β3-AR-AMPK signaling pathway.

Barr|Larry A|LA|
Lambert|Jonathan P|JP|
Shimizu|Yuuki|Y|
Barouch|Lili A|LA|
Naqvi|Nawazish|N|
Calvert|John W|JW|0000-0001-6858-6042

exercise
endothelial nitric oxide synthase
nitric oxide
β3-adrenergic receptors
AMP-activated protein kinase
heart
infarction
myocardial ischemia/reperfusion injury


Clinical course and long-term outcome following venoarterial extracorporeal life support-facilitated interhospital transfer of patients with circulatory failure.

Abstract:
BACKGROUND
Interhospital transfer of patients experiencing circulatory failure and shock has a significant risk of cardiovascular deterioration and death. Extracorporeal life support (ECLS) is a rescue tool for hemodynamic stabilization that makes patient transportation much safer.

METHODS
Demographic data, clinical course, and outcome data were reviewed for patients who underwent placement of a venoarterial ECLS in a remote hospital and were transported to our tertiary care facility.

RESULTS
68 patients were transported to our center with ECLS. The majority of these patients (79%) underwent cardiopulmonary resuscitation during or immediately prior to ECLS initiation. The mean patient age was 52 years, and 53 patients were male. The most common underlying diagnosis was acute coronary syndrome (60%). Overall, 23 patients underwent consecutive cardiosurgical procedures, including coronary artery bypass grafting in 12, and left ventricular assist device and biventricular assist device implantation in 11. The median duration of ECLS was 5 days. None of the patients died during transportation. Twelve of the surgically treated patients survived, as well as 21 patients with non-surgical treatment, which resulted in an overall survival of 33 patients (48.5%).

CONCLUSION
ECLS-facilitated patient transfer enables safe interhospital transfer of critically ill patients. In this study, a relevant percentage of patients were in need of a cardiosurgical intervention. The long-term survival rate of these patients supports the further use of this time-, cost- and personnel-demanding strategy.

Schopka|Simon|S| Philipp|Alois|A| Hilker|Michael|M| Müller|Thomas|T| Zimmermann|Markus|M| Arlt|Matthias|M| Rupprecht|Leopold|L| Schmid|Christof|C| Lunz|Dirk|D|

D010043:Outcome and Process Assessment, Health Care

Shock
Cardiopulmonary resuscitation
Extracorporeal circulation
Heart arrest


Method of evaluation of process of red blood cell sedimentation based on photometry of droplet samples.

Abstract: The paper focuses on research aimed at creating and testing a new approach to evaluate the processes of aggregation and sedimentation of red blood cells for purpose of its use in clinical laboratory diagnostics. The proposed method is based on photometric analysis of blood sample formed as a sessile drop. The results of clinical approbation of this method are given in the paper. Analysis of the processes occurring in the sample in the form of sessile drop during the process of blood cells sedimentation is described. The results of experimental studies to evaluate the effect of the droplet sample focusing properties on light radiation transmittance are presented. It is shown that this method significantly reduces the sample volume and provides sufficiently high sensitivity to the studied processes.

Blood
Photometry
Aggregation
Erythrocyte sedimentation rate


Bubble-Sheet-Like Interface Design with an Ultrastable Solid Electrolyte Layer for High-Performance Dual-Ion Batteries.

Abstract: In this work, a bubble-sheet-like hollow interface design on Al foil anode to improve the cycling stability and rate performance of aluminum anode based dual-ion battery is reported, in which, a carbon-coated hollow aluminum anode is used as both anode materials and current collector. This anode structure can guide the alloying position inside the hollow nanospheres, and also confine the alloy sizes within the hollow nanospheres, resulting in significantly restricted volumetric expansion and ultrastable solid electrolyte interface (SEI). As a result, the battery demonstrates an excellent long-term cycling stability within 1500 cycles with ≈99% capacity retention at 2 C. Moreover, this cell displays an energy density of 169 Wh kg-1 even at high power density of 2113 W kg-1 (10 C, charge and discharge within 6 min), which is much higher than most of conventional lithium ion batteries. The interfacial engineering strategy shown in this work to stabilize SEI layer and control the alloy forming position could be generalized to promote the research development of metal anodes based battery systems.

Qin|Panpan|P| Wang|Meng|M| Li|Na|N| Zhu|Haili|H| Ding|Xuan|X| Tang|Yongbing|Y|

dual-ion batteries
aluminum anodes
solid electrolyte interfaces
hollow nanostructures


Supramolecular Interactions and Morphology of Self-Assembling Peptide Amphiphile Nanostructures.

Abstract: The morphology of supramolecular peptide nanostructures is difficult to predict given their complex energy landscapes. We investigated peptide amphiphiles containing β-sheet forming domains that form twisted nanoribbons in water. We explained the morphology based on a balance between the energetically favorable packing of molecules in the center of the nanostructures, the unfavorable packing at the edges, and the deformations due to packing of twisted β-sheets. We find that morphological polydispersity of PA nanostructures is determined by peptide sequences, and the twisting of their internal β-sheets. We also observed a change in the supramolecular chirality of the nanostructures as the peptide sequence was modified, although only amino acids with l-configuration were used. Upon increasing charge repulsion between molecules, we observed a change in morphology to long cylinders and then rodlike fragments and spherical micelles. Understanding the self-assembly mechanisms of peptide amphiphiles into nanostructures should be useful to optimize their well-known functions.

self-assembly
peptide amphiphile
nanostructure
supramolecular chirality


Is robotic hepatectomy cost-effective? In view of patient-reported outcomes.

Abstract:
BACKGROUND
Robotic hepatectomy has been accepted as an alternative for patients needing surgery. However, few reports addressed the patient-reported outcomes and long-term quality of life (QoL) of patients having undergone robotic liver surgery.

METHODS
This study presented the QoL and cost-effectiveness associated with robotic and open hepatectomy by performing a comparative survey using two standardized questionnaires (Short Form-36 and Gastrointestinal Quality of Life Index).

RESULTS
One hundred patients completed the study. The robotic group tended to experienced longer operation time but shorter length of hospital stay compared to open group. Moreover, the robotic group had faster return to daily activities, less need of patient-controlled anesthesia, and less wound-related complaints in long-term follow-up. The robotic group incurred higher peri-operative expenses; however, the cost of inpatient care was lower.

CONCLUSIONS
Our study suggested that robotic hepatectomy provided good post-operative QoL and recovery of daily activity. However, efforts for lowering the financial burden of medical care by reducing the cost of robotic surgery is necessary for further application.

Wu|Chao-Ying|CY| Chen|Po-Da|PD| Chou|Wei-Han|WH| Liang|Jin-Tung|JT| Huang|Chiun-Sheng|CS| Wu|Yao-Ming|YM|

Robotic hepatectomy
Cost-effectiveness
Patient-reported outcome
Quality of life


Abstract: Multiple clinical studies have shown that bardoxolone methyl, a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2), is effective in increasing glomerular filtration rate in patients with chronic kidney disease. However, whether an Nrf2 activator can protect tubules from proteinuria-induced tubular damage via anti-inflammatory and antioxidative stress mechanisms is unknown. Using an Institute of Cancer Research-derived glomerulonephritis (ICGN) mouse model of nephrosis, we examined the effects of dihydro-CDDO-trifluoroethyl amide (dh404), a rodent-tolerable bardoxolone methyl analog, in protecting the tubulointerstitium; dh404 markedly suppressed tubular epithelial cell damage in the renal interstitium of ICGN mice. The tubular epithelial cells of ICGN mice showed a decrease in the size and number of mitochondria, as well as the breakdown of the crista structure, whereas the number and ultrastructure of mitochondria were maintained by the dh404 treatment. To further determine the effect of dh404 on mitochondrial function, we used human proximal tubular cells in vitro. Stimulation with albumin and free fatty acid increased mitochondrial reactive oxygen species (ROS). However, dh404 administration diminished mitochondrial ROS. Our data show that dh404 significantly reduced proteinuria-induced tubular cell mitochondrial damage, suggesting that improved redox balance and mitochondrial function and suppression of inflammation underlie the cytoprotective mechanism of Nrf2 activators, including bardoxolone methyl, in diabetic kidney disease.-Nagasu, H., Sogawa, Y., Kidokoro, K., Itano, S., Yamamoto, T., Satoh, M., Sasaki, T., Suzuki, T., Yamamoto, M., Wigley, W. C., Proksch, J. W., Meyer, C. J., Kashihara, N. Bardoxolone methyl analog attenuates proteinuria-induced tubular damage by modulating mitochondrial function.

Nagasu|Hajime|H|
Sogawa|Yuji|Y|
Kidokoro|Kengo|K|
Itano|Seiji|S|
Yamamoto|Toshiya|T|
Satoh|Minoru|M|
Sasaki|Tamaki|T|
Suzuki|Takafumi|T|
Yamamoto|Masayuki|M|
Wigley|W Christian|WC|
Proksch|Joel W|JW|
Meyer|Colin J|CJ|
Kashihara|Naoki|N|


A cancer cell-specific fluorescent probe for imaging Cu2+ in living cancer cells.

Abstract: Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2+ in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2+, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581nm in response to Cu2+. The probe exhibited excellent sensitivity and high selectivity for Cu2+ over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2+ in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

Wang|Chao|C| Dong|Baoli|B| Kong|Xiuqi|X| Song|Xuezhen|X| Zhang|Nan|N| Lin|Weiying|W|

Fluorescent probe
Cancer cell
Copper
Fluorescence imaging


An unusual presentation of Listeria monocytogenes rhombencephalitis.

Abstract: We describe a case of 52-year-old woman with a medical history of Crohn's disease presented abrupt fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem. The patient was initially diagnosed with ischaemic stroke, because of acute clinical course and results of neuroimaging. Cerebrospinal fluid analysis revealed mild infection with negative Gram staining and culture. Final diagnosis of Listeria monocytogenes brainstem infection (rhombencephalitis) was set up on the basis of further clinical course and positive blood cultures. Listerial rhombencephalitis should be kept in mind in immunocompromised adult patients who develop fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem even without typical neuroimaging, cerebrospinal fluid findings and negative cultures. Early diagnosis and adequate antibiotic treatment is of crucial importance.

Acewicz|Albert|A| Witkowski|Grzegorz|G| Rola|Rafal|R| Ryglewicz|Danuta|D| Sienkiewicz-Jarosz|Halina|H|

D038524:Diffusion Magnetic Resonance Imaging

Listeria monocytogenes
Rhombencephalitis
Brain infection
Stroke mimics


miRNAs as Potential Biomarkers for Viral Hepatitis B and C.

Abstract: Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.

Loureiro|Dimitri|D|
Tout|Issam|I|
Narguet|Stéphanie|S|
Benazzouz|Sabrina Menasria|SM|
Mansouri|Abdellah|A|0000-0003-3856-5771
Asselah|Tarik|T|

liver
chronic hepatitis
anti-fibrogenic
chronic liver diseases
diagnosis
fibrosis markers
inflammation
pro-fibrogenic


A humidity sensitive two-dimensional tunable amorphous photonic structure in the outer layer of bivalve ligament from Sunset Siliqua.

Abstract: A humidity sensitive two-dimensional tunable amorphous photonic structure (2D TAPS) in the outer layer of bivalve ligament from Sunset Siliqua (OLLS) was reported in this paper. The structural color and microstructure of OLLS were investigated by reflection spectra and scanning electron microscopy, respectively. The results indicate that the reflection peak wavelength of the wet OLLS blue-shifts from 454 nm to 392 nm with the increasing of air drying time from 0 to 40 min, while the reflectivity decreases gradually and vanishes at last, relevant color changes from blue to black background color. The structural color in the OLLS is produced by a two-dimensional amorphous photonic structure consisting of aligned protein fibers, in which the diameter of protein fiber and the inter-fiber spacing are 101 ± 12 nm. Water can reversibly tune the reflection peak wavelength and reflectivity of this photonic structure, and the regulation achieved through dynamically tuning the interaction between inter-fiber spacing and average refractive index.

Humidity sensitive
Bivalve ligament
Structural color
2D tunable photonic structure


Rotavirus A infection in children under five years old with a double health problem: undernutrition and diarrhoea - a cross-sectional study in four provinces of Mozambique.

Abstract:
BACKGROUND
Mozambique has a high burden of group A rotavirus (RVA) infection and chronic undernutrition. This study aimed to determine the frequency and potential risk factors for RVA infection in undernourished children under 5 years old with diarrhoea in Mozambique.

METHODS
The analysis was conducted using data from March 2015 to December 2017, regarding children under 5 years old with at least one type of undernutrition. Anthropometric measures were used to calculate indices of weight-for-age, weight-for-height and height-for-age through the Z-Scores. RVA results were extracted from the National Diarrhoea Surveillance database. Descriptive statistics, chi-square test was used for qualitative variables and organized in contingency tables and 95% Confidence Intervals (CI) were considered for the calculation of RVA infection proportion and in the multiple logistic regression models to estimate the adjusted odds ratios (AOR).

RESULTS
Of the 842 undernourished children included in the analysis, 27.2% (95% CI: 24.3-30.3%) were positive for RVA. The rate of RVA infection was 42.7% (95% CI: 38.0-47.5%) in the pre-vaccine period, with great reduction to 12.2% (95% CI: 9.4-15.6%) in the post-vaccine period. Most of the RVA undernourished children had severe wasting (33.3%) and severe stunting (32.0%). The risk of infection was significantly high in children from 0 to 11 months (p-value < 0.001) when compared to the age group of 24-59 months. A higher proportion of RVA infection was detected in households with five or more members (p-value = 0.029). Similar proportions of RVA were observed in children fed only by breast milk (34.9%) and breast milk with formula (35.6%). A higher proportion of undernourished HIV-positive children co-infected with RVA (7.4%) was observed.

CONCLUSIONS
The frequency of RVA infection in undernourished children declined following the introduction of the vaccine in Mozambique. Beyond the temporal variation, Maputo province, age and crowded households were also associated to RVA infection. A high proportion of RVA infection was observed in children with severe wasting and a triple burden of disease: undernutrition, RVA and HIV, highlighting the need to conduct follow-up studies to understand the long-term impact of these conditions on children's development.

Rotavirus A
Undernutrition
Diarrhoea
Mozambique
Risk factors


The pulmonary and autonomic effects of high-intensity and low-intensity exercise in diesel exhaust.

Abstract:
BACKGROUND
Exposure to air pollution impairs aspects of pulmonary and autonomic function and causes pulmonary inflammation. However, how exercising in air pollution affects these indices is poorly understood. Therefore, the purpose of this study was to determine the effects of low-intensity and high-intensity cycling with diesel exhaust (DE) exposure on pulmonary function, heart rate variability (HRV), fraction of exhaled nitric oxide (FeNO), norepinephrine and symptoms.

METHODS
Eighteen males performed 30-min trials of low-intensity or high-intensity cycling (30 and 60% of power at VO2peak) or a resting control condition. For each subject, each trial was performed once breathing filtered air (FA) and once breathing DE (300μg/m3 of PM2.5, six trials in total). Pulmonary function, FeNO, HRV, norepinephrine and symptoms were measured prior to, immediately post, 1 h and 2 h post-exposure. Data were analyzed using repeated-measures ANOVA.

RESULTS
Throat and chest symptoms were significantly greater immediately following DE exposure than following FA (p < 0.05). FeNO significantly increased 1 h following high-intensity exercise in DE (21.9 (2.4) vs. 19.3 (2.2) ppb) and FA (22.7 (1.7) vs. 19.9 (1.4)); however, there were no differences between the exposure conditions. All HRV indices significantly decreased following high-intensity exercise (p < 0.05) in DE and FA. The exception to this pattern was LF (nu) and LF/HF ratio, which significantly increased following high-intensity exercise (p < 0.05). Plasma norepinephrine (NE) significantly increased following high-intensity exercise in DE and FA, and this increase was greater than following rest and low-intensity exercise (p < 0.05). DE exposure did not modify any effects of exercise intensity on HRV or norepinephrine.

CONCLUSIONS
Healthy individuals may not experience greater acute pulmonary and autonomic effects from exercising in DE compared to FA; therefore, it is unclear if such individuals will benefit from reducing vigorous activity on days with high concentrations on particulate matter.

Giles|Luisa V|LV|
Carlsten|Christopher|C|
Koehle|Michael S|MS|

Exercise
Air pollution
Pulmonary function
FeNO
Norepinephrine
Exercise intensity


Bitter Rot of Apple in the Mid-Atlantic United States: Causal Species and Evaluation of the Impacts of Regional Weather Patterns and Cultivar Susceptibility.

Abstract: Apple growers in the Mid-Atlantic region of the United States have been reporting an increase in losses to bitter rot of apple and are requesting up-to-date management recommendations. Management is complicated by variations in apple cultivar susceptibility, temperature, rainfall, and biology of the Colletotrichum spp. that cause bitter rot. Over 500 apple fruit with bitter rot were obtained from 38 orchards across the Mid-Atlantic and the causal species were identified as Colletotrichum fioriniae and C. nymphaeae of the C. acutatum species complex and C. chrysophilum, C. noveboracense, C. siamense, C. fructicola, C. henanense, and C. gloeosporioides sensu stricto of the C. gloeosporioides species complex, the latter two being first reports. Species with faster in vitro growth rates at higher temperatures were more abundant in warmer regions of the Mid-Atlantic, while those with slower growth rates at higher temperatures were more abundant in cooler regions. Regional bloom dates are earlier and weather data show a gradual warming trend that likely influenced but was not necessarily the main cause of the recent increase in bitter rot in the region. A grower survey of apple cultivar susceptibility showed high variation, with the increase in acres planted to the highly susceptible cultivar Honeycrisp broadly corresponding to the increase in reports of bitter rot. These results form a basis for future studies on the biology and ecology of the Colletotrichum spp. responsible, and suggest that integrated bitter rot management must begin with selection of less-susceptible apple cultivars.

Martin|Phillip L|PL|0000-0002-0967-826X
Krawczyk|Teresa|T|
Khodadadi|Fatemeh|F|
Aćimović|Srđan G|SG|
Peter|Kari A|KA|

C. nymphaeae
C. noveboracense
C. siamense
C. fructicola
C. henanense
C. gloeosporioides sensu stricto
C. fioriniae
Colletotrichum chrysophilum
climate change
disease control and pest management
fungal pathogens
population biology


Anterior internal impingement of the shoulder in rugby players and other overhead athletes.

Abstract:
Background/Objective
Impingement syndromes are a common cause of shoulder pain in overhead athletes. Anterior internal impingement is a recently suggested mechanism for activity-related pain of the shoulder. Impingement syndromes were initially described to occur due to repetitive or excessive contact between the rotator cuff and other structures in the shoulder.

Methods
This is a retrospective, clinical case study reporting 54 consecutive cases of anterior internal impingement in overhead athletes, of which 28 (51.2%) cases were of rugby players. All had undergone physiotherapy without relief of the symptoms. Of 54, there were 45 male and 9 female patients with an average age of 27 years (range, 17-51). The mean duration from injury to surgery was 40.7 weeks (range, 5-364). Of the 54 patients, 29 (53.7%) were full-time professional and 25 (46.3%) were semiprofessional or recreational athletes. The players associated the onset of pain occurred following an injury in 29/54 cases (53.4%), whereas in the remaining 25 cases (46.2%), a gradual onset of symptoms was described. All 54 patients could demonstrate a "functional impingement sign" in positioning their arm and provoke pain.

Result
On examination, the examiner could reproduce the same pain in 38/54 (70.3%) patients only. Of the 54 patients, "SLAP tests" including O'Brien's test, Palm up test, and compression rotation test were positive in shoulders of 39 (72.2 %) patients, Jobe's test in 27 (50%), Gerber's lift off test in 6 (11%), and Hawkin's test in 6 (11%) patients. During arthroscopic assessment, impinging flap tears were found in 44 (81.4%) patients from the SLAP, whereas undersurface rotator cuff flap tears were found in 24 (44.4%), flap tears from the anterior or inferior labrum were found in 16 (29.6%), and distal subscapularis flap tears were found in 10 (18.5%) patients. Only in 12/54 patients (22.2%) was an isolated pathology found, in all cases SLAP tears. Treatment included vaporisation and excision of the impinging flaps. In 15/54 (27.7%) patients, repair of an unstable SLAP tear was undertaken using absorbable suture anchors and fibre wires. All athletes returned to their previous activity level within 17.2 weeks (range, 6-36) from surgery and were discharged when they claimed that they were symptom free.

Conclusion
This series of anterior internal impingement, which we believe is the largest in the literature to date, demonstrates the value of an to assess and successfully treat overhead athletes with anterior impingement syndrome.

Shah|Siddharth R|SR|
Horsley|Ian|I|
Rolf|Christer G|CG|

SLAP tear
anterior shoulder impingement
posterior shoulder impingement
rugby shoulder pain
shoulder arthroscopy


The xanthine oxidase inhibitor oxypurinol reduces cancer cachexia-induced cardiomyopathy.

Abstract:
BACKGROUND
Cachexia is a common complication of cancer and may be responsible for 22% of all cancer-related deaths. The exact cause of death in cancer cachexia patients is unknown. Recently, atrophy of the heart has been described in cancer cachexia animal models, which resulted in impaired cardiac function and is likely to contribute to mortality. In cancer patients hyperuricaemia independent of tumour lysis syndrome is often associated with a worse prognosis. Xanthine oxidase (XO) metabolizes purines to uric acid and its inhibition has been shown to improve clinical outcome in patients with chronic heart failure.

METHODS
The rat Yoshida AH-130 hepatoma cancer cachexia model was used in this study. Rats were treated with 4 or 40 mg/kg/d oxypurinol or placebo starting one day after tumour-inoculation for maximal 15 days. Cardiac function was analyzed by echocardiography on day 11.

RESULTS
Here we show that inhibition of XO by oxypurinol significantly reduces wasting of the heart and preserves cardiac function. LVEF was higher in tumour-bearing rats treated with 4 mg/kg/d (61±4%) or 40 mg/kg/d (64±5%) oxypurinol vs placebo (51±3%, both p<0.05). Fractional shortening was improved by 4 mg/kg/d (43±3%) oxypurinol vs placebo (30±2, p<0.05), while 40 mg/kg/d oxypurinol (41±5%) did not reach statistical significance. Cardiac output was increased in the 4 mg/kg/d dose only (71±11 mL/min vs placebo 38±4 mL/min, p<0.01).

CONCLUSION
Inhibition of XO with oxypurinol has beneficial effects on cardiac mass and function in a rat model of severe cancer cachexia, suggesting that XO might be a viable drug target in cancer cachexia.

Springer|Jochen|J|
Tschirner|Anika|A|
Hartman|Kai|K|
von Haehling|Stephan|S|
Anker|Stefan D|SD|
Doehner|Wolfram|W|

Xanthine oxidase
Oxypurinol
Cancer cachexia
Heart
Cardiac function
Uric acid


Identification of a new clade of hepatitis B virus genotype F.

Abstract: Hepatitis B virus (HBV) is classified into eight main genotypes (A-H) and several subgenotypes. Here, three new genotype F complete genome sequences isolated from patients from Buenos Aires city are reported. The new sequences form a separate monophyletic group from the previously known subgenotype F4 strains. Based on results of phylogenetic, genetic distance and evolutionary analyses, the name F4b is proposed for these isolates and F4a for the formerly known as F4. The identification of new clusters allows deepening the knowledge about the diversification process and evolutionary history of HBV.

Mojsiejczuk|Laura Noelia|LN|
Torres|Carolina|C|
Fainboin|Hugo Alberto|HA|
Galdame|Omar Andres|OA|
Campos|Rodolfo Hector|RH|
Flichman|Diego Martin|DM|

D016000:Cluster Analysis
D016384:Consensus Sequence
D014644:Genetic Variation
D005838:Genotype
D006509:Hepatitis B
D006515:Hepatitis B virus
D006801:Humans
D017720:Molecular Epidemiology
D010802:Phylogeny
D017422:Sequence Analysis, DNA

Hepatitis B virus
Phylogenetics
Diversity
Evolution
HBV genotype F