In vitro injection of osteoporotic cadaveric femurs with a triphasic calcium-based implant confers immediate biomechanical integrity.

Abstract: Current pharmaceutical therapies can reduce hip fractures by up to 50%, but compliance to treatment is low and therapies take up to 18 months to reduce risk. Thus, alternative or complementary approaches to reduce the risk of hip fracture are needed. The AGN1 local osteo-enhancement procedure (LOEP) is one such alternative approach, as it is designed to locally replace bone lost due to osteoporosis and provide immediate biomechanical benefit. This in vitro study evaluated the initial biomechanical impact of this treatment on human cadaveric femurs. We obtained 45 pairs of cadaveric femurs from women aged 77.8 ± 8.8 years. One femur of each pair was treated, while the contralateral femur served as an untreated control. Treatment included debridement, irrigation/suction, and injection of a triphasic calcium-based implant (AGN1). Mechanical testing of the femora was performed in a sideways fall configuration 24 h after treatment. Of the 45 pairs, 4 had normal, 16 osteopenic, and 25 osteoporotic BMD T-scores. Altogether, treatment increased failure load on average by 20.5% (p < 0.0001). In the subset of osteoporotic femurs, treatment increased failure load by 26% and work to failure by 45% (p < 0.01 for both). Treatment did not significantly affect stiffness in any group. These findings provide evidence that local delivery of the triphasic calcium-based implant in the proximal femur is technically feasible and provides immediate biomechanical benefit. Our results provide strong rationale for additional studies investigating the utility of this approach for reducing the risk of hip fracture. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.

Stroncek|John D|JD|
Shaul|Jonathan L|JL|
Favell|Dominique|D|
Hill|Ronald S|RS|
Huber|Bryan M|BM|
Howe|James G|JG|
Bouxsein|Mary L|ML|

bone mechanics and finite element analysis


Chemical strategies for the covalent modification of filamentous phage.

Abstract: Historically filamentous bacteriophage have been known to be the workhorse of phage display due to their ability to link genotype to phenotype. More recently, the filamentous phage scaffold has proven to be powerful outside the realm of phage display technology in fields such as molecular imaging, cancer research and materials, and vaccine development. The ability of the virion to serve as a platform for a variety of applications heavily relies on the functionalization of the phage coat proteins with a wide variety of functionalities. Genetic modification of the coat proteins has been the most widely used strategy for functionalizing the virion; however, complementary chemical modification strategies can help to diversify the range of materials that can be developed. This review emphasizes the recent advances that have been made in the chemical modification of filamentous phage as well as some of the challenges that are involved in functionalizing the virion.

Bernard|Jenna M L|JM|
Francis|Matthew B|MB|

filamentous phage
chemical modification
bioconjugation
delivery
polymers
protein modification


Socioeconomic outcome of epilepsy surgery: A controlled national study.

Abstract:
PURPOSE
Epilepsy surgery has been a standard treatment for refractory epilepsies that cannot be controlled by standard medical treatment. We aimed to evaluate the health and social consequences of resective surgery relative to controls from a study of national data.

METHODS
Using the Danish National Patient Registry we identified all subjects with an epilepsy diagnosis between 1996 and 2009 and compared them with a group of patients with an epilepsy diagnosis who had had neither epilepsy surgery nor a vagus stimulation diagnosis by the index date, and who were matched by gender, index year for epilepsy diagnosis, and index year for epilepsy surgery. We considered all the health and social information available in the Danish health, medication and social registers. The duration of follow-up was three years.

RESULTS
254 epilepsy patients and 989 controls were analyzed. Surgery patients were more severely affected by their disease as indicated by health care use and social impact before the surgical procedure. Patients who underwent epilepsy surgery had a significantly lower costs associated with the use of medication, outpatient services, inpatient admissions, and accident and emergency visits after surgery. The surgical intervention had no significant effects on social status in terms of occupation and educational level.

CONCLUSION
Although epilepsy surgery was followed by a reduction in inpatient and outpatient health care use, medication and use of accident and emergency facilities, suggesting a positive effect on the epileptic disease, there was no significant effect on social outcome measures.

Jennum|Poul|P| Sabers|Anne|A| Christensen|Jakob|J| Ibsen|Rikke|R| Kjellberg|Jakob|J|

Epilepsy
Controlled
Childhood
Prospective
Welfare costs


Extracellular matrix alterations, accelerated leukocyte infiltration and enhanced axonal sprouting after spinal cord hemisection in tenascin-C-deficient mice.

Abstract: The extracellular matrix glycoprotein tenascin-C has been implicated in wound repair and axonal growth. Its role in mammalian spinal cord injury is largely unknown. In vitro it can be both neurite-outgrowth promoting and repellent. To assess its effects on glial reactions, extracellular matrix formation, and axonal regrowth/sprouting in vivo, 20 tenascin-C-deficient and 20 wild type control mice underwent lumbar spinal cord hemisection. One, three, seven and fourteen days post-surgery, cryostat sections of the spinal cord were examined by conventional histology and by immunohistochemistry using antibodies against F4/80 (microglia/macrophage), GFAP (astroglia), neurofilament, fibronectin, laminin and collagen type IV. Fibronectin immunoreactivity was significantly down-regulated in tenascin-C-deficient mice. Moreover, fourteen days after injury, immunodensity of neurofilament-positive fibers was two orders of magnitude higher along the incision edges of tenascin-C-deficient mice as compared to control mice. In addition, lymphocyte infiltration was seen two days earlier in tenascin-C-deficient mice than in control mice and neutrophil infiltration was increased seven days after injury. The increase in thin neurofilament positive fibers in tenascin-C-deficient mice indicates that lack of tenascin-C alters the inflammatory reaction and extracellular matrix composition in a way that penetration of axonal fibers into spinal cord scar tissue may be facilitated.

Schreiber|Jenny|J|
Schachner|Melitta|M|
Schumacher|Udo|U|
Lorke|Dietrich Ernst|DE|

extracellular matrix
tenascin-C-deficient
tenascin-C
Microglia
GFAP
Neurofilament
Neurofilament
Fibronectin
Laminin
Collagen
Astrocytes
CNS
CST
ECM
H&E
IOD
Mouse
NF
PBS
PFA
TNC
TNC+/+
TNC−/−
U
arbitrary unit
central nervous system
corticospinal tract
glial fibrillary acidic protein
hematoxylin and eosin
integrated optical density
neurofilament
paraformaldehyde
phosphate buffered saline
tenascin-C wild type

P P P P P P P P P P U U U U U U U U U U U U U U U U U M M U P U U R


Ex vivo feasibility study of endoscopic intraductal laser ablation of the breast.

Abstract:
OBJECTIVE
To determine the feasibility and safety of breast endoscopic thulium laser ablation for treatment of intraductal neoplasia.

STUDY DESIGN
Ductoscopy is a minimally invasive endoscopic approach of the milk ducts of the breast via the nipple. Besides diagnosis in women with pathologic nipple discharge (PND), it allows non-invasive removal of intraductal lesions with a stalk like papillomas. Removal, however, is often incomplete and flat lesions cannot be targeted. We therefore developed laser ductoscopy.

METHODS
Dosimetry of laser ductoscopy was assessed in thirteen mastectomy specimens, applying power settings of 1-5 W with 100-1000 ms pulsed exposure to a 375-μm outer diameter thulium fiber laser. Subsequently histology was obtained from the breast tissue that was treated with the Thulium laser.

RESULTS
Endoscopic view was maintained during ductoscopic laser ablation at 1-3 W. Increasing power to 4-5 W caused impaired vision due to shrinkage of the main duct around the ductoscope tip. Histology revealed localized ablation of the duct wall.

CONCLUSION
We show for the first time that laser ductoscopy is technically feasible. The Thulium laser enables a superficial intraductal ablation and is a useful tool for intraductal interventions. An in vivo prospective study is needed to further demonstrate its potential. Lasers Surg. Med. 50:137-142, 2018. © 2017 Wiley Periodicals, Inc.

de Boorder|Tjeerd|T|
Waaijer|Laurien|L|
van Diest|Paul J|PJ|
Witkamp|Arjen J|AJ|

intraductal
ductoscopy
nipple discharge
breast cancer
endoscopy
laser treatment


Enzyme-Responsive Polymeric Vesicles for Bacterial-Strain-Selective Delivery of Antimicrobial Agents.

Abstract: Antimicrobial resistance poses serious public health concerns and antibiotic misuse/abuse further complicates the situation; thus, it remains a considerable challenge to optimize/improve the usage of currently available drugs. We report a general strategy to construct a bacterial strain-selective delivery system for antibiotics based on responsive polymeric vesicles. In response to enzymes including penicillin G amidase (PGA) and β-lactamase (Bla), which are closely associated with drug-resistant bacterial strains, antibiotic-loaded polymeric vesicles undergo self-immolative structural rearrangement and morphological transitions, leading to sustained release of antibiotics. Enhanced stability, reduced side effects, and bacterial strain-selective drug release were achieved. Considering that Bla is the main cause of bacterial resistance to β-lactam antibiotic drugs, as a further validation, we demonstrate methicillin-resistant S. aureus (MRSA)-triggered release of antibiotics from Bla-degradable polymeric vesicles, in vitro inhibition of MRSA growth, and enhanced wound healing in an in vivo murine model.

enzyme-responsive
polymeric vesicles
β-lactamase
antibiotic resistance
block copolymers


The sensitivity of the alternative maximal accumulated oxygen deficit method to discriminate training status.

Abstract: The purpose of the study was to investigate the sensitivity of an alternative maximal accumulated oxygen deficit (MAODALT) method to discriminate the "anaerobic" capacity while comparing: least trained (LT) participants (n = 12), moderately trained (MT) participants (n = 12), endurance trained (ET) participants (n = 16), and rugby (RG) players (n = 11). Participants underwent a graded exercise test on a treadmill and a supramaximal effort for assessing MAODALT. MAODALT was calculated as the sum of oxygen equivalents from the phosphagen and glycolytic metabolic pathways. MAODALT was significantly higher (P < 0.05) in RG (64.4 ± 12.1 mL · kg-1) than in ET (56.8 ± 5.4 mL · kg-1; effect size [ES] = 0.77; +13.5%), MT (53.8 ± 5.3 mL · kg-1; ES = 1.08; +19.8%), and LT (49.9 ± 4.5 mL · kg-1; ES = 1.50; +36.4%). In addition, the magnitude-based inference analysis revealed that MAODALT was likely (LT vs. MT), very likely (MT vs. RG, and ET vs. RG) and most likely (LT vs. ET, and LT vs. RG) different between all groups, except for MT and ET, which presented an unclear difference. In conclusion, MAODALT was sensitive enough to distinguish the "anaerobic" capacity in individuals with different training status, especially for RG players compared with LT participants and MT participants.

excessive post-exercise oxygen consumption


From problem solving to problem definition: scrutinizing the complex nature of clinical practice.

Abstract: In medical education, we have tended to present problems as being singular, stable, and solvable. Problem solving has, therefore, drawn much of medical education researchers' attention. This focus has been important but it is limited in terms of preparing clinicians to deal with the complexity of the 21st century healthcare system in which they will provide team-based care for patients with complex medical illness. In this paper, we use the Soft Systems Engineering principles to introduce the idea that in complex, team-based situations, problems usually involve divergent views and evolve with multiple solution iterations. As such we need to shift the conversation from (1) problem solving to problem definition, and (2) from a problem definition derived exclusively at the level of the individual to a definition derived at the level of the situation in which the problem is manifested. Embracing such a focus on problem definition will enable us to advocate for novel educational practices that will equip trainees to effectively manage the problems they will encounter in complex, team-based healthcare.

Systems Engineering
Interactions
Perspectives


High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus.

Abstract: This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.

D017127:Glycation End Products, Advanced

high protein diet
oxidative stress
cerebral cortex
hypothalamus
oxidative damage


Overexpression of RACK1 enhanced the replication of porcine reproductive and respiratory syndrome virus in Marc-145 cells and promoted the NF-κB activation via upregulating the expression and phosphorylation of TRAF2.

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative pathogen for porcine reproductive and respiratory syndrome (PRRS), which lead to huge loss to porcine industry. RACK1 (receptor of activated protein C kinase 1) was first identified as a receptor for protein kinase C. Mounting evidence demonstrated that RACK1 played diverse roles in NF-κB activation and virus infections. We previously reported that siRNA knockdown of RACK1 inhibited PRRSV replication in Marc-145 cells, abrogated NF-κB activation induced by PRRSV infection and reduced the viral titer. Here we established a Marc-145 cell line which could stably overexpress RACK1 to consolidate our findings. Based on the data from RT-qPCR, western blot, immunofluorescence staining, cytopathic effects and viral titer analysis, we concluded that overexpression of RACK1 could enhance the replication of PRRSV in Marc-145 cells and promote the NF-κB activation via upregulating TRAF2 expression and its phosphorylation. Marc-145 cells overexpressing RACK1exhibited severe cytopathic effects post infection with PRRSV and elevated the viral titer. Taken together, RACK1 plays an essential role for PRRSV replication in Marc-145 cells and NF-κB activation. The results presented here shed more light on the understanding of the molecular mechanisms underlying PRRSV infection and its subsequent NF-κB activation. Therefore, we anticipate RACK1 as a promising target for PRRS control.

Liu|Xiao|X| Bi|Junlong|J| Zhao|Qian|Q| Li|Miao|M| Zuo|Qingwei|Q| Wang|Xiaochun|X| Lan|Rui|R| Li|Xidan|X| Yang|Guishu|G| Liu|Jianping|J| Yin|Gefen|G|

D019316:Porcine respiratory and reproductive syndrome virus

D000075370:Receptors for Activated C Kinase

D047992:TNF Receptor-Associated Factor 2


Designing a Low-Fat Food Packaging: Comparing Consumers' Responses in Virtual and Physical Shopping Environments.

Abstract: This paper aims to test to what extent emotional responses towards a low-fat product presented virtually converge with emotional responses toward this product when presented physically. Second, we want to probe if low-order emotions (physiological/unconscious responses) and high-order emotions (cognitive/conscious responses) converge to explain healthy product choices. To this end, 83 young participants were engaged in our experiment. Two packaging design variables were manipulated with the help of a real company (the color and the message), so that six different packages were created. Two different buying contexts were simulated: A virtual context and a physical context. Physiological responses were continuously recorded in both contexts (heart rates, electro-dermal responses, and eye muscle reactions). At the end, participants provided cognitive responses in a questionnaire concerning the selected package. Our results have demonstrated that low-order emotions remain stable (from a virtual to a physical environments). Virtual simulations elections and real product elections are correlated (X2 = 40.493; p < 0.02). Physiological and cognitive responses do not converge. Correlations between unconscious responses (low-order emotions) and self-reported measures (high-order emotions) was contrary to expectations (negative sign). Only low-order emotions explain product choices. On the contrary, real packaging choice and high-order emotions correlated inversely (the t values were significant but negative).

packaging virtual physical emotions cognition


Genetic Regulation of the 2D to 3D Growth Transition in the Moss Physcomitrella patens.

Abstract: One of the most important events in the history of life on earth was the colonization of land by plants; this transition coincided with and was most likely enabled by the evolution of 3-dimensional (3D) growth. Today, the diverse morphologies exhibited across the terrestrial biosphere arise from the differential regulation of 3D growth processes during development. In many plants, 3D growth is initiated during the first few divisions of the zygote, and therefore, the genetic basis cannot be dissected because mutants do not survive. However, in mosses, which are representatives of the earliest land plants, 3D shoot growth is preceded by a 2D filamentous phase that can be maintained indefinitely. Here, we used the moss Physcomitrella patens to identify genetic regulators of the 2D to 3D transition. Mutant screens yielded individuals that could only grow in 2D, and through an innovative strategy that combined somatic hybridization with bulk segregant analysis and genome sequencing, the causative mutation was identified in one of them. The NO GAMETOPHORES 1 (NOG1) gene, which encodes a ubiquitin-associated protein, is present only in land plant genomes. In mutants that lack PpNOG1 function, transcripts encoding 3D-promoting PpAPB transcription factors [1] are significantly reduced, and apical initial cells specified for 3D growth are not formed. PpNOG1 acts at the earliest identified stage of the 2D to 3D transition, possibly through degradation of proteins that suppress 3D growth. The acquisition of NOG1 function in land plants could thus have enabled the evolution and development of 3D morphology.

Moody|Laura A|LA|
Kelly|Steven|S|
Rabbinowitsch|Ester|E|
Langdale|Jane A|JA|

D018506:Gene Expression Regulation, Plant

somatic hybridization
developmental transitions
land plant evolution
morphogenesis


Reasons for low level of skilled birth attendance in Afar pastoralist community, North East Ethiopia: a qualitative exploration.

Abstract:
Introduction
Ethiopia has expanded the number of health facilities that offer maternal health services during the last two decades. However, the utilization of skilled birth attendants in health facilities is still very low especially among the pastoralist regions of the country. This study explored why women in the pastoralist region of Afar, Ethiopia still prefer to give birth at home.

Methods
A qualitative study approach was used to collect information from October to December 2015. A total of eighteen focus group discussions and twenty-four key informant interviews were conducted. Focus group discussions were separately conducted with mothers and male tribal or religious leaders. Key informant interviews were conducted with heads of Women's Affairs Bureau, district health office heads and traditional birth attendants. Data were coded and categorized using open code software for qualitative data management and analyzed based on a thematic approach.

Results
Women preferred to deliver at home due to lack of awareness about the benefits of maternity health facilities, their nomadic lifestyle, lack of confidence and trust in health workers and their close affinity and easy access to traditional birth attendants. Supply-side barriers included distant health facilities, lack of transportation and poor health care.

Conclusion
Demand and supply related factors were identified as barriers to utilization of skilled birth attendants. Increasing awareness, bringing the service closer, arranging maternity waiting area around health facilities, and creating client-friendly service were found critical. Future research to define and improve services and approaches suitable for pastoralist population is warranted.

Ibrhim|Mohammed Ahmed|MA|
Demissie|Meaza|M|
Medhanyie|Araya Abrha|AA|
Worku|Alemayehu|A|
Berhane|Yemane|Y|

Pastoralist
Ethiopia
Afa
health facility delivery
home delivery


Aortic graft infection with enteric organism after embolization of late type II endoleak.

Abstract: An 82-year-old man with a history of endovascular repair for ruptured abdominal aortic aneurysm 6 years ago presented with a type II endoleak and enlarging sac. He had successful transabdominal direct sac puncture embolization but developed fever 2 days postoperatively. Contrast-enhanced computed tomography showed a rim-enhancing collection, and sac aspiration was positive for enteric organisms, confirming endograft infection. The patient underwent graft explantation and neoaortic reconstruction using superficial femoral veins. Three months postoperatively, computed tomography showed complete resolution of fluid collection and no signs of graft infection. This report illustrates direct puncture embolization complicated by endograft infection from enteric bacteria.

Li|Ben|B|
Tan|Kong Teng|KT|
MacDonald|Mary Elizabeth|ME|
Byrne|John|J|

Graft infection
Abdominal aortic aneurysm
Aortic reconstruction
Endoleak embolization
Endovascular aneurysm repair


A tailored intervention for illness acceptance improves adherence and quality of life in adults with haemophilia using prophylaxis.

Abstract:
INTRODUCTION
Adherence to prophylactic treatment (prophylaxis) in persons with haemophilia is challenging and has been reported at only ±50%. Acceptance problems are one of the main reasons for non-adherence in haemophilia. An evidence-based intervention was developed based on an acceptance and commitment therapy (ACT) approach.

AIM
To evaluate a tailored intervention focused on illness acceptance in adults with haemophilia who were prescribed prophylaxis.

METHODS
A pre-post study was executed in adults with haemophilia who were prescribed prophylaxis. A series of 8 2-hour group trainings were held, including 3-8 participants/series. Adherence (VERITAS-Pro, optimum 0), health-related quality of life (HRQoL, SF-36, optimum 100) and illness perception (BIPQ, optimum 0) were measured at start, after six months and 12 months and analysed using Wilcoxon signed-rank test.

RESULTS
Twenty-four patients (median age 47 years, range 27-74) were included. After 12 months, adherence improved in 68% of patients, quality of life in 48% and illness perception in 31%. Adherence (total score) improved from 35 to 25 (P<0.01). HRQoL showed clinically relevant improvement in domains of social-functioning (P = 0.04), role-emotional, physical-functioning, role-physical and bodily pain. Illness perception improved statistically significant on domains of affect (P = 0.01), concern (P = 0.01) and understanding (P = 0.04). Patients evaluated the training useful, an eye-opener, a personal enrichment and insightful.

CONCLUSION
The tailored group intervention resulted in significant improvement of adherence, quality of life and illness perception. Based on our current experience, we have implemented it in clinical practice and collaborate with the patient association to make it available for all Dutch people with haemophilia.

D064869:Acceptance and Commitment Therapy

intervention
illness acceptance
adherence
quality of life
haemophilia


Comparative multiplex analysis of cytokines, chemokines and growth factors in follicular fluid of normoresponder women undergoing ovum donation with gonadotropin-releasing hormone agonist versus gonadotropin-releasing hormone antagonist protocols.

Abstract:
BACKGROUND
Conflicting results were yielded about the superiority of gonadotropin-releasing hormone agonist (GnRH-a) versus gonadotropin-releasing hormone antagonist (GnRH-ant) protocols used in ovarian stimulation in in vitro fertilization (IVF) set-up. Reports also indicate that any single specific individual marker in follicular fluid collected at the time of oocyte retrieval bears inconclusive value as a predictor of oocyte quality.

AIMS
Simultaneous analyses of large numbers of cytokines, chemokines and growth factors in ovarian follicular fluid and perifollicular vascularity in both protocols for ovarian stimulation in IVF program to address the above mentioned lacunae.

SETTINGS AND DESIGNS
Normoresponder women (n = 45) were subjected to either GnRH-a (Group 1; n = 23) or GnRH-ant (Group 2; n = 22) for ovarian stimulation in IVF clinics.

MATERIALS AND METHODS
The fluid samples of dominant follicles collected at oocyte retrieval from women in Group 1 (GnRH-a; n = 20) and Group 2 (GnRH-ant; n = 16) were used for simultaneous quantitative assays of 48 cytokines. Perifollicular vascularity was assessed by Doppler hemodynamics to assess the ovarian vascular response in all participants in Groups 1 and 2.

RESULTS
Despite demographic and reproductive parameters studied remained comparable, higher follicular fluid concentration of interleukins, IL-3 (P < 0.01), IL12p70 (P < 0.05) and vascular endothelial growth factor (P < 0.01), P4 (P < 0.05) and pulsatility index (P < 0.04) along with a lower number of oocytes in metaphase II stage (P < 0.03) was observed in Group 2 compared with Group 1. GnRH-a protocol appeared to be superior to GnRH-ant protocol for ovarian stimulation in normoresponder women.

Malhotra|Neena|N| Srivastava|Akhilesh|A| Rana|Harpal|H| Bahadur|Anupama|A| Sengupta|Jayasree|J| Ghosh|Debabrata|D|

multiplex analysis
Cytokines
follicular fluid
ovarian stimulation
perifollicular hemodynamics


Performance of the coronary calcium score in an outpatient chest pain clinic and strategies for risk stratification.

Abstract:
BACKGROUND
Coronary artery calcium score (CAC) is an objective marker of atherosclerosis. The primary aim is to assess CAC as a risk classifier in stable coronary artery disease (CAD).

HYPOTHESIS
CAC improves CAD risk prediction, compared to conventional risk scoring, even in the absence of cardiovascular risk factor inputs.

METHODS
Outpatients presenting to a cardiology clinic (n = 3518) were divided into two cohorts: derivation (n = 2344 patients) and validation (n = 1174 patients). Adding logarithmic transformation of CAC, we built two logistic regression models: Model 1 with chest pain history and risk factors and Model 2 including chest pain history only without risk factors simulating patients with undiagnosed comorbidities. The CAD I Consortium Score (CCS) was the conventional reference risk score used. The primary outcome was the presence of coronary artery disease defined as any epicardial artery stenosis≥50% on CT coronary angiogram.

RESULTS
Area under curve (AUC) of CCS in our validation cohort was 0.80. The AUC of Models 1 and 2 were significantly improved at 0.88 (95%CI 0.86-0.91) and 0.87 (95%CI 0.84-0.90), respectively. Integrated discriminant improvement was >15% for both models. At a pre-specified cut-off of ≤10% for excluding coronary artery disease, the sensitivity and specificity were 89.3% and 74.7% for Model 1, and 88.1% and 71.8% for Model 2.

CONCLUSION
CAC helps improve risk classification in patients with chest pain, even in the absence of prior risk factor screening.

D002118:Calcium
D002637:Chest Pain
D017023:Coronary Angiography
D003324:Coronary Artery Disease
D006801:Humans
D010045:Outpatients
D018710:Pain Clinics
D011237:Predictive Value of Tests
D018570:Risk Assessment
D012307:Risk Factors

chest pain
coronary artery calcium
coronary artery disease
risk score


Binding interaction of SGLT with sugar and thiosugar by the molecular dynamics simulation.

Abstract: The human sodium-glucose co-transporter 2 (hSGLT2) is a transporter responsible for reabsorption of glucose in the proximal convoluted tubule of the kidney. hSGLT2 inhibitors, including luseogliflozin, have been developed as drugs for type 2 diabetes mellitus. Only luseogliflozin contains a thiosugar ring in its chemical structure, while other hSGLT2 inhibitors contain glucose rings. Consequently, we focused on the binding interactions of hSGLT2 with sugars and thiosugars. We first revealed that the binding affinities of thiosugars are stronger than those of sugars through molecular dynamics simulations of Vibrio parahaemolyticus, sodium-galactose co-transporter, and human hSGLT2. We then demonstrated that Na(+) dissociates from the protein to the cytoplasmic solution more slowly in the thiosugar system than in the sugar system. These differences between sugars and thiosugars are discussed on the basis of the different binding modes due to the atom at the 5-position of the sugar and thiosugar rings. Finally, as a result of Na(+) dissociation, we suggest that the dissociation of thiosugars is slower than that of sugars.

Tamura|Yunoshin|Y| Miyagawa|Hiroh|H| Yoshida|Tatsusada|T| Chuman|Hiroshi|H|

Molecular dynamics
Co-transporter
Luseogliflozin
Bennett's acceptance ratio method
Binding free energy


Altered mu-rhythm suppression in Borderline Personality Disorder.

Abstract: Borderline Personality Disorder (BPD) is characterized, among other symptoms, by interpersonal dysfunction and difficulties in empathizing. According to Simulation Theory empathy is linked to the activity of the mirror neuron system (MNS). Mu-rhythm desynchronization, as reflected in a suppression of electroencephalographic alpha-frequency bands (8-13Hz) provides a non-invasive electrophysiological window into MNS function. Here, we analyzed mu-desynchronization in twenty-two patients with BPD and twenty-three matched healthy controls in a reward and punishment-sensitive action observation task. In addition, we examined empathy using the Interpersonal Reactivity Index. BPD patients and controls did not differ with regard to mu-desynchronization when the entire time course was compared. However, differences in mu-suppression between groups occurred after the goal of the action became discernible. Correlations between mu-suppression and empathy ratings emerged only in controls, but not in the patient group. These findings suggest that BPD patients do not have a generalized impairment in MNS activity, though associations with contextual factors seem plausible.

Martin|Franziska|F|
Flasbeck|Vera|V|
Brown|Elliot C|EC|
Brüne|Martin|M|

Borderline Personality Disorder
Simulation Theory
Empathy
Mirror neurons
Mu oscillations


Factors Influencing Sleep Difficulty and Sleep Quantity in the Citizen Pscientist Psoriatic Cohort.

Abstract:
INTRODUCTION
Sleep is essential for overall health and well-being, yet more than one-third of adults report inadequate sleep. The prevalence is higher among people with psoriasis, with up to 85.4% of the psoriatic population reporting sleep disruption. Poor sleep among psoriasis patients is particularly concerning because psoriasis is independently associated with many of the same comorbidities as sleep dysfunction, including cardiovascular disease, obesity, and depression. Given the high prevalence and serious consequences of disordered sleep in psoriasis, it is vital to understand the nature of sleep disturbance in this population. This study was designed to help meet this need by using survey data from Citizen Pscientist, an online patient portal developed by the National Psoriasis Foundation.

METHODS
Our analysis included 3118 participants who identified as having a diagnosis by a physician of psoriasis alone or psoriasis with psoriatic arthritis. Demographic information, psoriasis severity and duration, sleep apnea status, smoking and alcohol consumption, itch timing, and sleep characteristics were included. Two separate multivariate logistic regression models in STATA were used to determine whether the presence of psoriatic arthritis, age, gender, body mass index, comorbid sleep apnea, psoriasis severity, timing of worst itch, smoking status, or high-risk alcohol consumption were associated with sleep difficulty or low sleep quantity, defined by the American Academy of Sleep Medicine as less than 7 h of sleep per night on average.

RESULTS
Results from the multivariate logistic regressions found that sleep difficulty was associated with psoriatic arthritis (OR 2.15, 95% CI [1.79-2.58]), female gender (2.03 [1.67-2.46]), obese body mass index (BMI ≥ 30) (1.25 [1.00-1.56]), sleep apnea (1.41 [1.07-1.86]), psoriasis severity of moderate (1.59 [1.30-1.94]) or severe (2.40 [1.87-3.08]), and smoking (1.60 [1.26-2.02]). Low sleep quantity was associated with obese BMI (1.62 [1.29-2.03]), sleep apnea (1.30 [1.01-1.68]), psoriasis severity of moderate (1.41 [1.16-1.72]) or severe (1.40 [1.11-1.76]), and smoking (1.62 [1.31-2.00]). Sleep difficulty and low sleep quantity were not associated with age, alcohol consumption, or timing of worst itch.

CONCLUSION
These results are potentially meaningful in several aspects. We identify an important distinction between sleep difficulty and sleep quantity in psoriatic disease, whereby having psoriatic arthritis and being female are each associated with sleep difficulty despite no association with low sleep quantity. Furthermore, there is conflicting evidence from prior studies as to whether psoriasis severity is associated with sleep difficulty, but this well-powered, large study revealed a strong, graded relationship between psoriasis severity and both sleep difficulty and low sleep quantity. Overall, our results show that both sleep difficulty and low sleep quantity were associated with multiple factors in this analysis of a large psoriatic cohort. These findings suggest that dermatologists may gather clinically useful information by screening psoriatic patients for trouble sleeping and low sleep quantity to identify potential comorbidities and to more effectively guide disease management.

Smith|Mary Patricia|MP|
Ly|Karen|K|
Thibodeaux|Quinn|Q|
Weerasinghe|Thulasi|T|
Beck|Kristen|K|
Shankle|Lindsey|L|
Armstrong|April W|AW|
Boas|Marc|M|
Bridges|Alisha|A|
Doris|Frank|F|
Gelfand|Joel M|JM|
Lafoy|Brian|B|
Orbai|Ana-Maria|AM|
Takeshita|Junko|J|
Truman|Sarah|S|
Wan|Marilyn T|MT|
Wu|Jashin J|JJ|
Siegel|Michael P|MP|
Bell|Stacie J|SJ|
Bhutani|Tina|T|
Liao|Wilson|W|

Sleep
Psoriasis
Comorbidities
Survey research


Effect of 3-Dimensional Central Stimuli on Near Point of Convergence.

Abstract:
AIM
Since an interaction between binocular disparity and the vergence system takes place in order to reduce retinal disparity, it is likely that vergence control, as measured with the near point of convergence (NPC), will be better if the target used for measurement has 3-dimensional (3-D) features in its most central parts. The aim of the present study was therefore to investigate if the NPC would give a better result using a fixation target with centrally placed 3-D features when compared with a two-dimensional (2-D) target.

METHODS
Twenty-three asymptomatic subjects (2 men, 21 women; average age 30.0 years ± 7.36 SD) who experienced diplopia when a fixation target was brought close to the eyes had their break point NPC measured using a modified RAF-ruler. A metal cube and a printed image of the cube were used as a 3-D and 2-D stimuli. The measurements were repeated 3 times in each subject for each test condition, for a total of 6 randomized NPC measurements.

RESULTS
On average a significant difference in NPC (p = 0.0172) was found for break point NPC with a 3-D stimuli (mean: 7.27 cm ± 2.37 SD), giving the better result as compared with a 2-D stimuli (mean: 8.02 cm ± 2.82 SD). Comparing the most remote recorded NPC values of the 3 repeated measurements under each stimulus condition, a significant difference was found (p = 0.0159, t = 2.612) with 3-D stimuli giving the better result.

CONCLUSION
The results of this study demonstrate the influence of binocular disparity stimuli on the vergence control as NPC was better if the target used for measurement had 3-D features in its most central parts.

Glimne|Susanne A M|SA|
Öqvist Seimyr|Gustaf|G|
Brautaset|Rune L|RL|

vergence control
2-dimensional object
3-dimensional drive
Binocular vision
stereoscopic vision


Biofilm-Resistant Nanocoatings Based on ZnO Nanoparticles and Linalool.

Abstract: Biofilms represent an increasing challenge in the medical practice worldwide, imposing a serious threat to public health. As bacterial strains have developed antibiotic resistance, researcher's attention has been extensively focused on developing more efficient antimicrobial strategies. In this context, the present study reports the synthesis, physicochemical characterization, ex vivo biodistribution, and in vitro evaluation of the capacity of nanostructured surfaces based on zinc oxide (ZnO) and biologically active molecules to modulate clinically relevant microbial biofilms. ZnO nanoparticles (NPs) were synthesized through a co-precipitation method without thermal treatment. The matrix-assisted pulsed laser evaporation (MAPLE) was applied for preparing nanostructured coatings based on ZnO NPs surface modified with linalool that were further characterized by X-ray diffraction (XRD), thermogravimetric analysis with differential scanning calorimetry (TGA-DSC), scanning electron microscopy (SEM), transmission electron microscopy with selected area electron diffraction (TEM-SAED), Fourier-transform infrared spectroscopy (FT-IR), and infrared microscopy (IRM). Histological analyses carried out at 7 days and 14 days after the intraperitoneal administration of linalool modified ZnO NPs revealed the absence of the latter from the brain, kidney, liver, lung, myocardium, and pancreas. Through in vitro assays on prokaryotic cells, it was proven that ZnO coatings hinder microbial biofilm formation of both Gram-positive and Gram-negative bacteria strains.


Anomalous Size Effect of Pt Ultrathin Nanowires on Oxygen Reduction Reaction.

Abstract: The classical size effect of Pt particles on oxygen reduction reaction (ORR) suggests that the activity and durability would decrease with reducing the particle size, self-limiting the effectiveness in maximizing the Pt utilization efficiency with the particle-size-reduction strategy. Herein, we discover an anomalous size effect based on Pt nanowires (NWs) with tunable diameters, where the monotonically increasing activity and durability for ORR were observed with decreasing the diameter from 2.4 to 1.1 nm. Our results reveal that the dominant role of increased compressive strain induced by decreasing the diameter of NWs in weakening the adsorption and suppressing the Pt dissolution accounts for this anomalous size effect, where the reduced low-coordinated sites on NWs, the intrinsic structural advantage, is the root. Our findings not only expand the knowledge to the classical size effect but also provide new implications to break through the size limit in the design of Pt-based ORR catalysts.

anomalous size effect
oxygen reduction
strain
diameter-dependent
platinum


How empathic is your healthcare practitioner? A systematic review and meta-analysis of patient surveys.

Abstract:
BACKGROUND
A growing body of evidence suggests that healthcare practitioners who enhance how they express empathy can improve patient health, and reduce medico-legal risk. However we do not know how consistently healthcare practitioners express adequate empathy. In this study, we addressed this gap by investigating patient rankings of practitioner empathy.

METHODS
We conducted a systematic review and meta-analysis of studies that asked patients to rate their practitioners' empathy using the Consultation and Relational Empathy (CARE) measure. CARE is emerging as the most common and best-validated patient rating of practitioner empathy. We searched: MEDLINE, Embase, PsycINFO, Cinahl, Science & Social Science Citation Indexes, the Cochrane Library and PubMed from database inception to March 2016. We excluded studies that did not use the CARE measure. Two reviewers independently screened titles and extracted data on average CARE scores, demographic data for patients and practitioners, and type of healthcare practitioners.

RESULTS
Sixty-four independent studies within 51 publications had sufficient data to pool. The average CARE score was 40.48 (95% CI, 39.24 to 41.72). This rank s in the bottom 5th percentile in comparison with scores collected by CARE developers. Longer consultations (n = 13) scored 15% higher (42.60, 95% CI 40.66 to 44.54) than shorter (n = 9) consultations (34.93, 95% CI 32.63 to 37.24). Studies with mostly (>50%) female practitioners (n = 6) showed 16% higher empathy scores (42.77, 95% CI 38.98 to 46.56) than those with mostly (>50%) male (n = 6) practitioners (34.84, 95% CI 30.98 to 38.71). There were statistically significant (P = 0.032) differences between types of providers (allied health professionals, medical students, physicians, and traditional Chinese doctors). Allied Health Professionals (n = 6) scored the highest (45.29, 95% CI 41.38 to 49.20), and physicians (n = 39) scored the lowest (39.68, 95% CI 38.29 to 41.08). Patients in Australia, the USA, and the UK reported highest empathy ratings (>43 average CARE), with lowest scores (<35 average CARE scores) in Hong Kong.

CONCLUSIONS
Patient rankings of practitioner empathy are highly variable, with female practitioners expressing empathy to patients more effectively than male practitioners. The high variability of patient rating of practitioner empathy is likely to be associated with variable patient health outcomes. Limitations included frequent failure to report response rates introducing a risk of response bias. Future work is warranted to investigate ways to reduce the variability in practitioner empathy.

D004645:Empathy
D019538:Health Care Surveys
D006801:Humans
D010358:Patient Participation
D017060:Patient Satisfaction
D018802:Patient-Centered Care
D010817:Physician-Patient Relations
D012017:Referral and Consultation
D017678:Sex Distribution
D012938:Social Perception

Practitioner Empathy Consultation Communication Expectations


Epigenetic consequences of interploidal hybridisation in synthetic and natural interspecific potato hybrids.

Abstract: Interploidal hybridisation can generate changes in plant chromosome numbers, which might exert effects additional to the expected due to genome merger per se (that is genetic, epigenetic and phenotypic novelties). Wild potatoes are suitable to address this question in an evolutionary context. To this end, we performed genetic (AFLP and single sequence repeart (SSR)), epigenetic (MSAP), and cytological comparisons in: (1) natural populations of the diploid cytotype of the hybrid taxonomic species Solanum × rechei (2n = 2×, 3×) and its parental species, the triploid cytotype of Solanum microdontum (2n = 2×, 3×) and Solanum kurtzianum (2n = 2×); and (2) newly synthesised intraploidal (2× × 2×) and interploidal (3× × 2×) S. microdontum × S. kurtzianum hybrids. Aneuploidy was detected in S. × rechei and the synthetic interploidal progeny; this phenomenon might have originated the significantly higher number of methylation changes observed in the interploidal vs the intraploidal hybrids. The wide epigenetic variability induced by interploidal hybridisation is consistent with the novel epigenetic pattern established in S. × rechei compared to its parental species in nature. These results suggest that aneuploid potato lineages can persist throughout the short term, and possibly medium term, and that differences in parental ploidy resulting in aneuploidy are an additional source of epigenetic variation.

D054458:Amplified Fragment Length Polymorphism Analysis

Solanum × rechei
Solanum microdontum
Solanum kurtzianum
aneuploidy
DNA methylation
Solanum section Petota
crop wild relatives
introgression


Assessing genetic counselors' graduate school education and training in congenital heart defects.

Abstract: Genetic counselors are one of the many providers involved in caring for patients with congenital heart defects (CHDs); however, little is known about the cardiovascular genetics training they receive by their graduate programs. To explore the recalled education experiences regarding CHDs by practicing genetic counselors, we surveyed graduates of programs primarily accredited by the American Council on Genetic Counseling (ACGC) about their graduate training in this area, the depth of CHD-specific education they received, and whether CHDs are a substantial referral indication in their current practice. Genetic counselors were recruited from the National Society of Genetic Counselors and Twitter (n = 112), and participants reflecting multiple specialties and 35 graduate programs completed an online survey which included questions about fieldwork placements and lectures in cardiovascular genetics, exposure to classification schemes regarding cardiac embryology, and education in counseling strategies for CHDs and CHD-related topics during their graduate training. When asked whether CHDs are a substantial referral indication seen in their current practice, 55% (62/112) responded yes. Most participants (79%, 88/112) recalled receiving some education about CHDs, but 91% (80/88) reported receiving little to no education regarding embryologic classification of CHDs and how to apply classification schemes to their counseling. Both participating prenatal and pediatric GCs reported that CHDs can be a common referral indication, yet they reported receiving limited education on teratogens associated with CHDs, family screening recommendations, and recurrence risk counseling for CHDs. Based on participant responses, the majority of respondents reported receiving sufficient education on syndromes with CHDs which can be beneficial in specialties such as pediatrics. This exploratory study provides insight into opportunities to further support genetic counseling educational opportunities for CHDs. These findings suggest genetic counseling graduate programs could consider implementing education on CHD counseling strategies as a standardized component of the curriculum and that practicing genetic counselors could benefit from educational opportunities and resources with updated information on this topic.

education
genetic counseling
comprehension
congenital heart disease


Aerodynamic and acoustic effects of ventricular gap.

Abstract:
PURPOSE
Supraglottic compression is frequently observed in individuals with dysphonia. It is commonly interpreted as an indication of excessive circumlaryngeal muscular tension and ventricular medialization. The purpose of this study was to describe the aerodynamic and acoustic impact of varying ventricular medialization in a canine model.

METHODS
Subglottal air pressure, glottal airflow, electroglottograph, acoustic signals, and high-speed video images were recorded in seven excised canine larynges mounted in vitro for laryngeal vibratory experimentation. The degree of gap between the ventricular folds was adjusted and measured using sutures and weights. Data were recorded during phonation when the ventricular gap was narrow, neutral, and large. Glottal resistance was estimated by measures of subglottal pressure and glottal flow.

RESULTS
Glottal resistance increased systematically as ventricular gap became smaller. Wide ventricular gaps were associated with increases in fundamental frequency and decreases in glottal resistance. Sound pressure level did not appear to be impacted by the adjustments in ventricular gap used in this research.

CONCLUSIONS
Increases in supraglottic compression and associated reduced ventricular width may be observed in a variety of disorders that affect voice quality. Ventricular compression may interact with true vocal fold posture and vibration resulting in predictable changes in aerodynamic, physiological, acoustic, and perceptual measures of phonation. The data from this report supports the theory that narrow ventricular gaps may be associated with disordered phonation. In vitro and in vivo human data are needed to further test this association.

Ventricular gap
Ventricular fold
Excised canine larynx
Glottal flow resistance
Medial compression


Integrating thin film microfluidics in developing a concise synthesis of DGJNAc: A potent inhibitor of α-N-acetylgalctosaminidases.

Abstract: A simple synthesis, which utilizes a thin film microfluidic reactor for a problematic step, of a potent inhibitor of α-N-acetylhexosaminidases, DGJNAc, has been developed.

Wills|Siobhán S|SS|
Raston|Colin L|CL|
Stubbs|Keith A|KA|

Thin film microfluidics
Inhibitors
Flow chemistry
Glycosidases
Iminosugars


Decrease in glucose transporter 1 levels and translocation of glucose transporter 3 in the dentate gyrus of C57BL/6 mice and gerbils with aging.

Abstract: In the present study, we compared the cell-specific expression and changes protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in the mouse and gerbil brains using immunohistochemistry and Western blot analysis. In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the subgranular zone and the molecular layer of the dentate gyrus. GLUT1-immunoreactivity in blood vessels and GLUT1 protein levels were significantly decreased with age in the mice and gerbils, respectively. In addition, few GLUT3-immunoreactive cells were found in the subgranular zone in aged mice and gerbils, but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double immunofluorescence study, GLUT3-immunoreactive structures in gerbils were localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the dentate gyrus. Western blot analysis showed that GLUT3 expression in the hippocampal homogenates was slightly, although not significantly, decreased with age in mice and gerbils, respectively. These results indicate that the reduction in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone of dentate gyrus may be associated with the decrease in uptake of glucose into brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3 in the astrocytes in polymorphic layer of dentate gyrus may be associated with metabolic changes in glucose in aged hippocampus.

Lee|Kwon Young|KY|
Yoo|Dae Young|DY|
Jung|Hyo Young|HY|
Baek|Loktam|L|
Lee|Hangyul|H|
Kwon|Hyun Jung|HJ|
Chung|Jin Young|JY|
Kang|Seok Hoon|SH|
Kim|Dae Won|DW|
Hwang|In Koo|IK|
Choi|Jung Hoon|JH|

Glucose transporter
dentate gyrus
aging
blood vessels
astrocytes
neuroblasts


Prokaryotic NavMs channel as a structural and functional model for eukaryotic sodium channel antagonism.

Abstract: Voltage-gated sodium channels are important targets for the development of pharmaceutical drugs, because mutations in different human sodium channel isoforms have causal relationships with a range of neurological and cardiovascular diseases. In this study, functional electrophysiological studies show that the prokaryotic sodium channel from Magnetococcus marinus (NavMs) binds and is inhibited by eukaryotic sodium channel blockers in a manner similar to the human Nav1.1 channel, despite millions of years of divergent evolution between the two types of channels. Crystal complexes of the NavMs pore with several brominated blocker compounds depict a common antagonist binding site in the cavity, adjacent to lipid-facing fenestrations proposed to be the portals for drug entry. In silico docking studies indicate the full extent of the blocker binding site, and electrophysiology studies of NavMs channels with mutations at adjacent residues validate the location. These results suggest that the NavMs channel can be a valuable tool for screening and rational design of human drugs.

Bagnéris|Claire|C|
DeCaen|Paul G|PG|
Naylor|Claire E|CE|
Pryde|David C|DC|
Nobeli|Irene|I|
Clapham|David E|DE|
Wallace|B A|BA|

D062550:NAV1.1 Voltage-Gated Sodium Channel


Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance.

Abstract: Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

Meng|Yibin|Y| Hao|Dingjun|D| Huang|Yunfei|Y| Jia|Shuaijun|S| Zhang|Jianan|J| He|Xirui|X| Sun|Liang|L| Liu|Deyin|D|

D015972:Gene Expression Regulation, Neoplastic


Early mitochondrial dysfunction in glycolytic muscle, but not oxidative muscle, of the fructose-fed insulin-resistant rat.

Abstract: Although evidence that type 2 diabetes mellitus (T2DM) is accompanied by mitochondrial dysfunction in skeletal muscle has been accumulating, a causal link between mitochondrial dysfunction and the pathogenesis of the disease remains unclear. Our study focuses on an early stage of the disease to determine whether mitochondrial dysfunction contributes to the development of T2DM. The fructose-fed (FF) rat was used as an animal model of early T2DM. Mitochondrial respiration and acylcarnitine species were measured in oxidative (soleus) and glycolytic [extensor digitorum longus (EDL)] muscle. Although FF rats displayed characteristic signs of T2DM, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, mitochondrial content was preserved in both muscles from FF rats. The EDL muscle had reduced complex I and complex I and II respiration in the presence of pyruvate but not glutamate. The decrease in pyruvate-supported respiration was due to a decrease in pyruvate dehydrogenase activity. Accumulation of C14:1 and C14:2 acylcarnitine species and a decrease in respiration supported by long-chain acylcarnitines but not acetylcarnitine indicated dysfunctional β-oxidation in the EDL muscle. In contrast, the soleus muscle showed preserved mitochondrial respiration, pyruvate dehydrogenase activity, and increased fatty acid oxidation, as evidenced by overall reduced acylcarnitine levels. Aconitase activity, a sensitive index of reactive oxygen species production in mitochondria, was reduced exclusively in EDL muscle, which showed lower levels of the antioxidant enzymes thioredoxin reductase and glutathione peroxidase. Here, we show that the glycolytic EDL muscle is more prone to an imbalance between energy supply and oxidation caused by insulin resistance than the oxidative soleus muscle.

Warren|Blair E|BE|
Lou|Phing-How|PH|
Lucchinetti|Eliana|E|
Zhang|Liyan|L|
Clanachan|Alexander S|AS|
Affolter|Andreas|A|
Hersberger|Martin|M|
Zaugg|Michael|M|
Lemieux|Hélène|H|

D000154:Aconitate Hydratase
D000818:Animals
D002331:Carnitine
D003924:Diabetes Mellitus, Type 2
D004040:Dietary Carbohydrates
D018450:Disease Progression
D004734:Energy Metabolism
D005227:Fatty Acids
D005632:Fructose
D018698:Glutamic Acid
D006019:Glycolysis
D007333:Insulin Resistance
D008297:Male
D008931:Mitochondria, Muscle
D018482:Muscle, Skeletal
D010085:Oxidative Phosphorylation
D011236:Prediabetic State
D011768:Pyruvate Dehydrogenase Complex
D019289:Pyruvic Acid
D051381:Rats
D017207:Rats, Sprague-Dawley
D017382:Reactive Oxygen Species

mitochondrial dysfunction
type 2 diabetes
skeletal muscle
fatty acid oxidation
aconitase
insulin resistance
sirtuin-3


Proniosomal Telmisartan Tablets: Formulation, in vitro Evaluation and in vivo Comparative Pharmacokinetic Study in Rabbits.

Abstract:
Objective
The purpose of this study was to prepare proniosomal vesicles of Telmisartan (TEL) to be compressed into tablets which will be further evaluated in vitro and in vivo.

Materials and Methods
An experimental design was adopted using surfactants of different HLB values (span 40-brij 35), different cholesterol ratios (20-50%) and different phospholipid types (egg yolk-soyabean). Different responses were measured followed by tablet manufacturing. The highest EE was shown in F3 (85%) while the lowest value was obtained in F7 (8.4%). Finally, zeta potential results were in the range of -0.67 to -27.6 mv. Compressibility percent revealed that F5 showed an excellent flowability characteristic with a value of 9.74±1.61 while F3 and F6 showed good flowability characteristics. By the end of the release, F6 showed approximately 90% drug release.

Results
F6 was selected for the in vivo study; Cmax was increased by 1.5-fold while AUC0-∞ also increased significantly by 3-fold when compared with commercial tablet and finally, tmax was increased by 3-fold indicating sustained release pattern. The relative bioavailability was also increased by 3.2-fold.

Conclusion
The results of this study suggested that the formulation of compressed tablets containing more stable proniosomal powder extended the release of TEL and increased its bioavailability as well.

telmisartan
TEL
EE
bioavailability
entrapment efficiency
multifactorial design
proniosomal-derived niosomes
sustained-release tablet


Determination and pharmacokinetic analysis of ticarcillin disodium-clavulanate potassium for injection in rat plasma by UPLC-ESI-MS/MS.

Abstract:
OBJECTIVE
To establish a specific and rapid ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method for measuring ticarcillin and clavulanate levels in rat plasma.

METHODS
A Waters ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 μm) and SCIEX QTRAP® LC-MS/MS System were used. Analyses were conducted to optimize the chromatographic and MS conditions, and the pharmacokinetic parameters of ticarcillin and clavulanate were assessed.

RESULTS
Linear relationships were observed in the ranges of 10 to 10,000 ng/mL for ticarcillin R (r2 = 0.9967) 30 to 10,000 ng/mL for ticarcillin S (r2 = 0.9961), and 30 to 10,000 ng/mL for clavulanate (r2 = 0.9981). The average extraction recoveries of all compounds ranged from 86.9% to 96.4%. The pharmacokinetic parameters of the ticarcillin R and S isomers in rats were distinctive. The ticarcillin R and S isomers and clavulanate were rapidly absorbed in vivo. Ticarcillin S and clavulanate had similar elimination rates, whereas that of ticarcillin R was slower.

CONCLUSION
A UPLC-ESI-MS/MS method was developed and validated for the determination of ticarcillin and clavulanate in rat plasma.

D000284:Administration, Oral
D000818:Animals
D002853:Chromatography, Liquid
D019818:Clavulanic Acid
D051381:Rats
D017207:Rats, Sprague-Dawley
D015203:Reproducibility of Results
D053719:Tandem Mass Spectrometry
D013982:Ticarcillin


Validated computed cleansing score for video capsule endoscopy.

Abstract:
BACKGROUND AND AIM
Diagnostic yield of video capsule endoscopy may be hampered by intestinal content or air bubbles. A major limitation in video capsule-related study is the lack of a validated objective score for bowel preparation quality. We aimed to design and validate a computed small bowel preparation score for research and clinical use.

METHODS
Two experienced physicians reached a consensus regarding bowel preparation quality based on known criteria used in previous studies and their confidence of an accurate medical interpretation of the procedure. A computed algorithm based on the pixels in the color bar was created and validated. Concordance between the gastroenterologists' agreement (gold standard) and the computed analysis was assessed.

RESULTS
Of 85 videos studied, 44 (52%), 13 (15%) and 28 (33%) had adequate, borderline and inadequate bowel preparation, respectively, according to the gastroenterologists' agreement. Computer analysis restricted to adequate and inadequate cases yielded accurate classification of bowel preparation in 65/72 cases (90% agreement, sensitivity 95%, specificity 82%, total accuracy 90%, Kappa 0.79). When adding the borderline definition, the computer analysis correctly classified 71/85 of the cases, yielding an overall agreement of 84% (Kappa 0.72). Minute-by-minute analysis of 10 cases also yielded an agreement of 91.4%.

CONCLUSION
The present study introduces a user-friendly computer analysis-based small bowel preparation score, which demonstrated excellent concordance with the physician's assessment. This score holds promise as a standardization tool in research and clinical practice of video capsule endoscopy. Further validation is warranted.

Klein|Amir|A|
Gizbar|Moshe|M|
Bourke|Michael J|MJ|
Ahlenstiel|Golo|G|

cleansing score
capsule endoscopy
diagnostic yield
small bowel
polyethylene Glycol


Quercetin ameliorates liver injury induced with Tripterygium glycosides by reducing oxidative stress and inflammation.

Abstract: Quercetin (Que) is one of main compounds in Lysimachia christinae Hance (Christina loosestrife), and has both medicinal and nutritional value. Glycosides from Tripterygium wilfordii Hook.f. (léi gōng téng [the thunder duke vine]; TG) have diverse and broad bioactivities but with a high incidence of liver injury. Our previous study reported on the hepatoprotective properties of an ethanol extract from L. christinae against TG-induced liver injury in mice. This research is designed to observe, for the first time, the possible protective properties of the compound Que against TG-induced liver injury, and the underlying mechanisms that are involved in oxidative stress and anti-inflammation. The results indicated that TG caused excessive elevation in serum levels of alanine/aspartate transaminase (ALT/AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), and pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), as well as hepatic lipid peroxidation (all P < 0.01). On the other hand, following TG exposure, we observed significantly reduced levels of biomarkers, including hepatic glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and the anti-inflammatory cytokine interleukin (IL)-10, as well as the enzyme activity and mRNA expression of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) (all P < 0.01). Nevertheless, all of these alterations were reversed by the pre-administration of Que or the drug bifendate (positive control) for 7 consecutive days. Therefore, this study suggests that Que ameliorates TG-induced acute liver injury, probably through its ability to reduce oxidative stress and its anti-inflammatory properties.

Wang|Junming|J| Miao|Mingsan|M| Zhang|Yueyue|Y| Liu|Ruixin|R| Li|Xaobing|X| Cui|Ying|Y| Qu|Lingbo|L|

D056486:Chemical and Drug Induced Liver Injury

oxidative stress
hepatoprotection
pro-inflammatory cytokines
anti-inflammatory cytokines
antioxidant enzymes
cytokines anti-inflammatoires
cytokines pro-inflammatoires
enzymes antioxydantes
hépatoprotection
stress oxydant


Prevention of pressure injuries in critically ill children: A preliminary evaluation.

Abstract:
AIMS
To evaluate a prevention strategy implemented to reduce incidence and severity of positioning related pressure injuries affecting pediatric patients in a pediatric critical care unit. Secondary objective was to evaluate compliance with preventive recommendations.

BACKGROUND
The skin in infants or children has important physiological and anatomical differences compared with adults. Further, factors such as the immaturity of the skin and limited activity and mobility in pediatric critical care unit, along with the pressure exerted by medical devices, increases the risk of pressure ulcers in infants and children. The most effective preventive measures specific to this intensive care population need to be evaluated.

MATERIAL AND METHODS
Quasi-experimental before-after study with consecutive sampling. The effectiveness of the care bundle implementation was evaluated based on the latest evidence (intervention group) versus the application of non-standardized care (control group). Pediatric patients up to 14 years old at risk of suffering from pressure injuries and who were admitted more than 48 h in a pediatric intensive care unit (level III) participated. For the collection of data, two computer programs and the hospital clinical records of each participant were consulted. The data collection period was 6 months per group (pre and post intervention).

RESULTS
A sample of 110 patients was obtained (50 control group and 60 intervention group). The cumulative incidence in pediatric patients exposed to the risk of pressure injuries was reduced from 16% to 13.3%; and in the subgroup of patients with prolonged stay (≥28 days), the incidence was reduced from 55.55% to 20%. In the intervention group, category III and IV pressure ulcers were completely reduced. In addition, the total number of pressure injuries decreased by 21.43%. The care bandle recommendations with the highest level of adhesion recorded were: skin inspection, application of hyperoxygenated fatty acids and use of a special support surface. The main risk factor found during the study was the prone position (p < 0.05).

CONCLUSIONS
The application of a care bundle for prevention can be an effective solution to reduce the number and severity of LPPs in an intensive care unit. The most vulnerable subgroup of patients may benefit from the application of these resources.

Bargos-Munárriz|Marta|M|
Bermúdez-Pérez|Montserrat|M|
Martínez-Alonso|Ana María|AM|
García-Molina|Pablo|P|
Orts-Cortés|María Isabel|MI|

Pressure injury
Pediatrics
Intensive care unit
Support surfaces
Evidence-based nursing
Pressure ulcer/ prevention & control


O2 sensing, mitochondria and ROS signaling: The fog is lifting.

Abstract: Mitochondria are responsible for the majority of oxygen consumption in cells, and thus represent a conceptually appealing site for cellular oxygen sensing. Over the past 40 years, a number of mechanisms to explain how mitochondria participate in oxygen sensing have been proposed. However, no consensus has been reached regarding how mitochondria could regulate transcriptional and post-translational responses to hypoxia. Nevertheless, a growing body of data continues to implicate a role for increased reactive oxygen species (ROS) signals from the electron transport chain (ETC) in triggering responses to hypoxia in diverse cell types. The present article reviews our progress in understanding this field and considers recent advances that provide new insight, helping to lift the fog from this complex topic.

Waypa|Gregory B|GB|
Smith|Kimberly A|KA|
Schumacker|Paul T|PT|

Hypoxia
electron transport chain
metabolism
oxidant signaling


Lyophilized platelets versus cryopreserved platelets for management of bleeding in thrombocytopenic dogs: A multicenter randomized clinical trial.

Abstract:
BACKGROUND
Thrombocytopenia in dogs is common in critical care medicine, but availability of fresh platelet concentrates in veterinary medicine can be limiting. Lyophilized platelets have long shelf-lives and can be easily transported, stored, and administered in various settings.

OBJECTIVE
To evaluate the efficacy and safety of a novel trehalose-stabilized canine lyophilized platelet product in thrombocytopenic dogs with clinically-evident bleeding.

ANIMALS
Eighty-eight dogs with platelet counts <50 × 103 /μL and a standardized bleeding assessment tool (DOGiBAT) score ≥2.

METHODS
Multicenter, randomized, non-blinded, non-inferiority clinical trial comparing dimethyl sulfoxide (DMSO)-stabilized cryopreserved platelet concentrates (CPP) with trehalose-stabilized lyophilized platelets (LP) for control of bleeding in thrombocytopenic dogs. Dogs were randomized to receive 3 × 109 platelets/kg of LP or CPP. Primary outcome measures were change in DOGiBAT score, platelet count, need for additional red cell transfusion and all-cause mortality.

RESULTS
Fifty dogs received LP and 38 received CPP. Baseline demographics and clinical characteristics of both groups were comparable. At 1-hour post-transfusion, LP were superior for change in DOGiBAT score, and non-inferior at 24-hours post-transfusion. The LP were non-inferior to CPP for change in platelet count, need for additional red blood cell units, and survival to discharge. The LP were superior for change in hematocrit at 1-hour post-transfusion, and non-inferior at 24-hours. No adverse effects were noted in either group.

CONCLUSIONS AND CLINICAL IMPORTANCE
A novel trehalose-stabilized canine LP product appears to be logistically superior and is clinically non-inferior to DMSO-stabilized canine CPP for management of bleeding in thrombocytopenic dogs.

canine
transfusion
hemorrhage
immune thrombocytopenia
trehalose


Alternative Devices for Heart Rate Variability Measures: A Comparative Test-Retest Reliability Study.

Abstract: Using healthy adult participants, seven measures of heart rate variability were obtained simultaneously from four devices in five behavioral conditions. Two devices were ECG-based and two utilized photoplethysmography. The 140 numerical values (measure, condition, device) are presented. The comparative operational reliability of the four devices was assessed, and it was found that the two ECG-base devices were more reliable than the photoplethysmographic devices. The interchangeability of devices was assessed by determining the between-device Limits of Agreement. Intraclass correlation coefficients were determined and used to calculate the standard error of measurement and the Minimal Detectable Difference. The Minimal Detectable Difference, MDD, quantifies the smallest statistically significant change in a measure and is therefore critical when HRV measures are used longitudinally to assess treatment response or disease progression.

Killian|Jacquelin M|JM|
Radin|Rachel M|RM|
Gardner|Cubby L|CL|0000-0003-0197-7692
Kasuske|Lalon|L|
Bashirelahi|Kylee|K|
Nathan|Dominic|D|
Keyser|David O|DO|
Cellucci|Christopher J|CJ|
Darmon|David|D|
Rapp|Paul E|PE|0000-0001-8045-9740

heart rate variability
photoplethysmography
intraclass correlation coefficients
HRV
portable heart rate monitor
test–retest reliability


Insights into the methodology of radiography science.

Abstract:
INTRODUCTION
The aim of this article is to give an insight into radiography as a science and a discipline from the viewpoints of knowledge interest and methodological approach and design.

METHODS
Original articles published in Radiography (n = 184) and the Journal of Clinical Radiography and Radiotherapy (n = 10) at the timeline 2015 to 3/2017 were reviewed for research focus and the methodology used. To abstract the results, thematisation analysis was used.

RESULTS
Out of 194 studies analysed, 99 (50%) were found to have a technical, 80 (42%) a practical and 15 (8%) a critical interest of knowledge. The research methodologies used did not rigorously fit into the methodological approach expected on the basis of the interest of knowledge.

CONCLUSION
Radiography as a science seems to have mostly a technical and practical interest of knowledge, but somewhat critical research is also being made. It seems to be a remarkably open and flexible science when it comes to the use of research methodologies. More discussion and research on the science name and paradigm is needed in order to strengthen the scientific status of radiography.

Radiography science
Discipline
Thematisation analysis
Interest of knowledge


Whole mitochondrial genome sequencing and analysis for chronic obstructive pulmonary disease rat strain.

Abstract: Mitochondrial genome plays a central role in aging, cancer, apoptosis and metabolism. We sequenced a complete mitochondrial genome sequence of a rat chronic obstructive pulmonary disease rat strain for the first time. The total length of the mitochondrial genome was 16,310 bp and coding 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes. This genome describing information will supply the potential use of mtDNA mutations as markers in cancer.

Jiang|Zhi-Ming|ZM| Zhao|Qing-Sheng|QS| Xu|Yong-Qing|YQ| Li|Tao|T| Jie|Jian|J| Zhang|Zhong-Hui|ZH|

D029424:Pulmonary Disease, Chronic Obstructive

mitochondrial genome
chronic obstructive pulmonary disease
Cancer


Preparation and Electrochemical Characterization of Organic-Inorganic Hybrid Poly(Vinylidene Fluoride)-SiO2 Cation-Exchange Membranes by the Sol-Gel Method Using 3-Mercapto-Propyl-Triethoxyl-Silane.

Abstract: A new synthesis method for organic-inorganic hybrid Poly(vinylidene fluoride)-SiO2 cation-change membranes (CEMs) is proposed. This method involves mixing tetraethyl orthosilicate (TEOS) and 3-mercapto-propyl-triethoxy-silane (MPTES) into a polyvinylidene fluoride (PVDF) sol-gel solution. The resulting slurry was used to prepare films, which were immersed in 0.01 M HCl, which caused hydrolysis and polycondensation between the MPTES and TEOS. The resulting Si-O-Si polymers chains intertwined and/or penetrated the PVDF skeleton, significantly improving the mechanical strength of the resulting hybrid PVDF-SiO2 CEMs. The -SH functional groups of MPTES oxidized to-SO3H, which contributed to the excellent permeability of these CEMs. The surface morphology, hybrid structure, oxidative stability, and physicochemical properties (IEC, water uptake, membrane resistance, membrane potential, transport number, and selective permittivity) of the CEMs obtained in this work were characterized using scanning electron microscope and Fourier transform infrared spectroscopy, as well as electrochemical testing. Tests to analyze the oxidative stability, water uptake, membrane potential, and selective permeability were also performed. Our organic-inorganic hybrid PVDF-SiO2 CEMs demonstrated higher oxidative stability and lower resistance than commercial Ionsep-HC-C membranes with a hydrocarbon structure. Thus, the synthesis method described in this work is very promising for the production of very efficient CEMs. In addition, the physical and electrochemical properties of the PVDF-SiO2 CEMs are comparable to the Ionsep-HC-C membranes. The electrolysis of the concentrated CoCl2 solution performed using PVDF-SiO2-6 and Ionsep-HC-C CEMs showed that at the same current density, Co2+ production, and current efficiency of the PVDF-SiO2-6 CEM membrane were slightly higher than those obtained using the Ionsep-HC-C membrane. Therefore, our novel membrane might be suitable for the recovery of cobalt from concentrated CoCl2 solutions.

Li|Yanhong|Y| Li|Zhiwei|Z| Li|Yanjuan|Y| Guan|Wenxue|W| Zheng|Yangyang|Y| Zhang|Xuemin|X| Wang|Sanfan|S|

cation-exchange membrane
polyvinylidene fluoride
oxidative stability
membrane resistance


Modulating and restoring inter-muscular coordination in stroke patients using two-dimensional myoelectric computer interface: a cross-sectional and longitudinal study.

Abstract:
OBJECTIVE
Traditional trainings focus on the improvement of motor function at limb or joint level, while inter-muscular coordination plays an important role in fine motor control and is often ignored. The purpose of this study is to investigate the changes of inter-muscular coordination induced by myoelectric-controlled interface (MCI) and the therapeutic effects of MCI-based inter-muscular coordination training in the stroke patients.

APPROACH
11 stroke patients, 20 young subjects and 13 age-match subjects were recruited to investigate the dimensionality effect of MCI on inter-muscular coordination in evaluation test. A stroke patient participated in 20-day training to test the therapeutic effects as a case study analysis in training test. In both tests, all subjects performed tracking tasks by flexing/extending their elbow according to biofeedback from MCI, and electromyography (EMG) and functional near infrared spectroscopy (fNIRS) were used to simultaneously record the muscle and cortical activations, respectively.

MAIN RESULTS
The significant decreasing activation in antagonist and increasing activation involvement in prefrontal cortex (PFC) and primary motor cortex (M1) were found in all groups with increasing MCI dimensionality. The significant reduction in muscle activation and increase in cortical activation were found in the stroke patient, which was due to a progressive normalization for the patient following training.

SIGNIFICANCE
These findings suggested that two-dimensional MCI should be an effective tool for the stroke patients in directly modulating inter-muscular coordination. Inter-muscular coordination training may restore the ability to coordinate agonist-antagonist muscle for stroke patient and this improvement was accompanied by cortical reorganization.

Jian|Chuyao|C| Deng|Linchuan|L| Liu|Huihua|H| Yan|Tiebin|T| Wang|Xiaoyun|X| Song|Rong|R|0000-0003-3662-116X

inter-muscular coordination
EMG
fNIRS
cortical reorganization
stroke rehabilitation
upper limb


Modulation of Cas9 level for efficient CRISPR-Cas9-mediated chromosomal and plasmid gene deletion in Bacillus thuringiensis.

Abstract:
OBJECTIVES
To set up an efficient gene editing system in Bacillus thuringiensis (Bt) using CRISPR-Cas9 by demonstrating deletion of chromosomal and plasmid genes.

RESULTS
CRISPR-Cas9 from Streptococcus pyogenes was found to function in Bt cells, resulting in DNA cleavage that is lethal to the cells. The system was assessed for its ability to mediate gene editing by knock-out of the protease genes nprA (neutral protease A) and aprA (alkaline protease A). Gene editing was not detected when the Bacillus-derived pBCX was used to carry CRISPR-Cas9 elements and a DNA repair template. When the Cas9 promoter was replaced with the sporulation-specific promoter cyt2A, a Bt ∆nprA clone was obtained, but this plasmid construct did not give reproducible results. Bt ∆nprA ∆aprA and Bt ∆aprA deletion mutants were finally generated when the Lactobacillus plantarum-derived plasmid pLPPR9 was used, likely due to its lower copy number reducing Cas9 toxicity. Only three to four clones each needed to be screened to identify the desired gene-modified mutants. Conversely, efficient editing of the plasmid vip3A gene required the use of pBCX and longer homology sequences for the repair template.

CONCLUSIONS
Capitalizing on the differential impact of plasmid copy number and homology arm length, we devised distinct yet simple and efficient approaches to chromosomal and plasmid gene deletion for Bt that condense the screening process, minimize screening, and facilitate multiple consecutive gene editing steps.

D001413:Bacillus thuringiensis
D001426:Bacterial Proteins
D000076987:CRISPR-Associated Protein 9
D064113:CRISPR-Cas Systems
D002876:Chromosomes, Bacterial
D017353:Gene Deletion
D000072669:Gene Editing
D010957:Plasmids
D011401:Promoter Regions, Genetic
D013297:Streptococcus pyogenes

Plasmid
Gene deletion
Bacillus thuringiensis
Gene editing
CRISPR-Cas9


Laparoscopic-thoracoscopic esophageal resection in the treatment of giant epiphrenic esophageal diverticulum (Ivor Lewis operation): Case report.

Abstract:
INTRODUCTION
Complicated esophageal diverticulum is an extremely rare disease. The most widespread surgical tactic in such cases is drainage of the mediastinum and the position of a feeding gastrostomy or enterostomy. Our objective was to demonstrate the possibility of performing a one-step operation in case of giant esophageal diverticulum with necrotic diverticulitis and sepsis on the background of dilatation of the esophagus.

PRESENTATION OF CASE
A 57-year-old woman complained of persistent nagging epigastric pain, heartburn, belching, daily vomiting of eaten food and liquid, impaired swallowing, fever up to 39° C. EGD revealed large pouch of the right esophageal wall in middle and lower third of the esophagus with signs of inflammation, ulceration and necrosis and retained food in the pouch. Barium esophagogram demonstrated 50 × 100 mm epiphrenic diverticulum on the right side and in the lower third of the esophagus which contained food. CBC revealed leukocytosis along with "left upper shift" and ESR.

DISCUSSION
The laparoscopic-thoracoscopic esophageal resection with gastric tube plasty (Ivor Lewis operation) might be the method of choice in cases of giant epiphrenic esophageal diverticula, when esophageal resection is connected with the high risk of anastomotic dehiscence due to esophageal wall necrosis.

CONCLUSION
We have established that in case of necrobiotic changes in the esophageal wall in the area of the diverticulum, this tactic is completely justified because of the greater patient safety and the less risk of the stapler suture line dehiscence.

Khitaryan|Аlexander|А| Golovina|Anastasiya|A| Mezhunts|Arut|A| Veliev|Kamil|K| Zavgorodnyaya|Raisa|R| Orekhov|Аlexey|А|


Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring.

Abstract:
BACKGROUND
Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR.

METHODS
Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured.

DISCUSSION
Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR.

TRIAL REGISTRATION
This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

Kilovoltage intrafraction monitoring
Hepatocellular carcinoma
LARK trial
Liver Cancer
Oligometastases
Stereotactic radiotherapy


Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients.

Abstract:
BACKGROUND
Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod.

METHODS
In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab (n = 135) or fingolimod (n = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated.

RESULTS
NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod (p < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy.

CONCLUSION
We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.

relapsing-remitting type of multiple sclerosis


The impact of COVID-19 on different population subgroups: ethnic, gender and age-related disadvantage.

Abstract: Against a background of stalling UK life expectancy, the COVID-19 pandemic is a major crisis for public health with impacts differing markedly by ethnicity, gender, and age. Direct health impacts include mortality and long-term harms among survivors. Social disruption and lockdown measures arising from uncontrolled infection have destabilised healthcare and other essential services. The economic crisis resulting from the pandemic is already triggering job losses, which will in turn have their own adverse health effects. These myriad impacts of the pandemic are not affecting everyone equally. Ethnic minorities, men and older people have disproportionately suffered from COVID-19, including their risk of mortality. However, some indirect impacts - including those on mental health and employment - are more likely to affect women and younger people. The health consequences of the pandemic will affect the lives of people in the UK for decades.

Katikireddi|Srinivasa Vittal|SV|
Hainey|Kirsten Jane|KJ|
Beale|Sarah|S|

COVID-19
ethnicity
gender
age
healthcare inequalities


Role of ROCK/NF‑κB/AQP8 signaling in ethanol‑induced intestinal epithelial barrier dysfunction.

Abstract: The present study aimed to investigate the signaling pathways and the underlying molecular mechanisms involved in ethanol‑induced intestinal epithelial barrier (IEB) dysfunction. Therefore, an in vitro experimental model of IEB was established using an ethanol‑treated Caco‑2 intestinal epithelial cell monolayer. The results confirmed that Rho‑associated kinases (ROCKs), namely ROCK1 and ROCK2, were involved in the underlying pathway of ethanol‑induced IEB dysfunction. Ethanol exposure significantly increased the expression of both ROCK isoforms and the activity of nuclear factor κB (NF‑κB). Furthermore, ROCK1‑ and ROCK2‑specific small interfering RNAs (siRNAs), and the NF‑κB inhibitor ammonium pyrrolidine dithiocarbamate partially inhibited transepithelial electrical resistance in Caco‑2 cells in an in vitro IEB model. In addition, ROCK1‑ and ROCK2‑specific siRNAs inhibited the activity of NF‑κB, thereby downregulating the expression of aquaporin 8 (AQP8). Taken together, the results of the present study suggested that ROCK1/ROCK2‑mediated activation of NF‑κB and upregulation of AQP8 expression levels may represent a novel mechanism of ethanol‑induced impairment of IEB function.


Sucrose-based biosynthetic process for chain-length-defined α-glucan and functional sweetener by Bifidobacterium amylosucrase.

Abstract: A unique thermostable amylosucrase from Bifidobacterium thermophilum was produced as a recombinant protein with the half-life of 577 h at 50 °C. By adding 1.0 M fructose, turanose yield was improved from 22.7% to 43.3% with 1.0 M sucrose, and from 23.7% to 39.4% with 1.5 M sucrose. Sucrose consumption rate was greatest at 55 °C, but the lowest amount of turanose was produced. Thus, turanose yield from sucrose biomass was inversely proportional to reaction temperature and was highly dependent on [fructose]. Meanwhile, insoluble α-glucan yield was clearly reduced as [fructose] increased. With 1.0 M fructose + 1.0 M sucrose, glucan byproduct yield significantly decreased from 29.4% to 1.1%. Molecular weights of linear glucans were almost identical among various [sucrose]s and were homogenous with very low polydispersity. This unique dual reaction patterns of amylosucrase enzyme would be very useful for massive productions of two different biomaterials simply by changing sucrose biomass concentration.

α-Glucan
Amylosucrase
Bifidobacterium thermophilum
Turanose
Sucrose
Biocatalysis


The Structure and Parameterization of the Breast Cancer Transition Model Among Chinese Women.

Abstract:
OBJECTIVES
Markov model simulation based on the natural history of disease is commonly employed for the comparative research of health interventions. The present study aims to simulate the natural progression of breast cancer and parameterize the initial and transition probabilities of multiple states of breast cancer development among Chinese women.

METHODS
The age-specific incidence, mortality, and clinical stage distribution of breast cancer; and relapse rate of each clinical stage were collected from China's cancer registry yearbooks and clinical epidemiological studies to simulate the process from full health to breast cancer to death among Chinese women aged 30 to 80 through a Markov cohort study. The validity analysis was conducted to evaluate the accuracy of the model estimation.

RESULTS
A Markov transition model with 7 states (no breast cancer, clinical stages 0-IV breast cancer, and death) was constructed for Chinese women. The age-specific incidence, mortality, and clinical stage distribution of breast cancer estimated by the initial and transition probabilities among different Markov states were highly consistent with the registered data and observed studies.

CONCLUSION
A breast cancer transition model for Chinese women has been established with validity. It could be a point of reference for further economic evaluations and breast cancer screening policy formulation.

Huang|Yuan|Y| Li|Qin|Q| Torres-Rueda|Sergio|S| Li|Jiayuan|J|

breast cancer
Markov model
transition probability
validity analysis
disease transition model


Synthetic pheromone exposure increases calling and reduces subsequent mating in female Contarinia nasturtii (Diptera: Cecidomyiidae).

Abstract:
BACKGROUND
Pheromone-mediated mating disruption, which uses large amounts of synthetic female pheromones to interrupt insect reproductive behavior, has been successful for managing important agricultural pests. While multiple mechanisms have been discovered explaining how synthetic pheromone treatments prevent males from finding females, it is less clear how unnaturally large doses of synthetic sex pheromone impact the behavior of female insects, particularly nonlepidopteran females. In some species, 'autodetecting' females possess pheromone receptors and respond to ambient pheromones by altering their mating behavior. Here, we test whether exposure to stereospecific and racemic synthetic pheromones influences calling and subsequent propensity to mate in female swede midge (Contarinia nasturtii Kieffer; Diptera: Cecidomyiidae), a pest of Brassica crops.

RESULTS
In both laboratory and field settings, females exposed to stereospecific and racemic three-component pheromone blends called significantly more frequently and for longer durations than midges in control treatments. In the field, midges were twice as likely to call in pheromone-treated plots versus nontreated plots. Additionally, pheromone pre-exposure reduced subsequent mating: while 68% of female midges mated following control conditions, only 42% and 35% of females pre-exposed to stereospecific and racemic three-component blends mated, respectively.

CONCLUSION
While more frequent calling within pheromone-treated backgrounds may increase the likelihood that females are detected by males, a reduction in female propensity to mate would increase the efficacy of a pheromone-mediated mating disruption system. Our work presents the first known investigation of autodetection behavior in Cecidomyiidae. Additional research is necessary to understand the implications of female autodetection for swede midge management.

mating
pheromone-mediated mating disruption
autodetection
insect behavior
invasive pest
pest management


Corroboration of Height Velocity Prediction Markers for rhGH With an Oral GH Secretagogue Treatment in Children With GHD.

Abstract:
Context
Recombinant human growth hormone (rhGH) is approved for treatment of pediatric growth hormone deficiency (GHD), with greatest growth responses observed in those with severe GHD. Orally administered GH secretagogues (GHS) may be useful treatment in patients with moderate GHD. Distinguishing children with severe vs moderate GHD could identify children who would be better treated with rhGH or GHS.

Objectives
Evaluate baseline insulin-like growth factor-I (IGF-I) and stimulated peak GH response as predictors of 12-month height velocity (HV) in children with GHD.

Design
Data on children with GHD were analyzed in a legacy data base (GeNeSIS data).

Participants
514 naïve to rhGH-treatment, prepubertal children with idiopathic isolated GHD for whom stimulated GH, baseline serum IGF-I, and first-year HV during rhGH treatment data are available.

Outcome Measures
Children with severe or moderate GHD were categorized based on GH and IGF-I data and evaluated based on baseline auxologic and hormone profiles and first-year growth response to rhGH.

Results
Cohorts of severe and moderate GHD were 81/514 (15.8%) and 433/514 (84.2%). Cohorts differed significantly with regard to indicators of GHD [eg, baseline height SD score (SDS), height SDS minus target height SDS, HV, HV SDS, and change in height SDS during rhGH treatment]. Multiple regression analysis showed IGF-I and stimulated GH were significant predictors of HV independent of other known variables. Expected first-year HV in moderate GHD was 8.3 cm/y.

Conclusions
The combination of peak GH to GH stimulation testing and baseline IGF-I concentration are predictive enrichment markers for annualized HV responses to rhGH therapy.

rhGH
GHD
recombinant human growth hormone
insulin-like growth factor-I
IGF-I
GeNeSIS
GH deficiency


Dilation of cortical capillaries is not related to astrocyte calcium signaling.

Abstract: The brain requires an adequate supply of oxygen and nutrients to maintain proper function as neuronal activity varies. This is achieved, in part, through neurovascular coupling mechanisms that mediate local increases in blood flow through the dilation of arterioles and capillaries. The role of astrocytes in mediating this functional hyperemia response is controversial. Specifically, the function of astrocyte Ca2+ signaling is unclear. Cortical arterioles dilate in the absence of astrocyte Ca2+ signaling, but previous work suggests that Ca2+ increases are necessary for capillary dilation. This question has not been fully addressed in vivo, however, and we have reexamined the role of astrocyte Ca2+ signaling in vessel dilation in the barrel cortex of awake, behaving mice. We recorded evoked vessel dilations and astrocyte Ca2+ signaling in response to whisker stimulation. Experiments were carried out on WT and IP3R2 KO mice, a transgenic model where astrocyte Ca2+ signaling is substantially reduced. Compared to WT mice at rest, Ca2+ signaling in astrocyte endfeet contacting capillaries increased by 240% when whisker stimulation evoked running. In contrast, Ca2+ signaling was reduced to 9% of WT values in IP3R2 KO mice. In all three conditions, however, the amplitude of capillary dilation was largely unchanged. In addition, the latency to the onset of astrocyte Ca2+ signaling lagged behind dilation onset in most trials, although a subset of rapid onset Ca2+ events with latencies as short as 0.15 s occurred. In summary, we found that whisker stimulation-evoked capillary dilations occurred independent of astrocyte Ca2+ increases in the cerebral cortex.

astrocyte
calcium signaling
capillary dilation
IP3R2 KO
endfeet
awake mouse
cerebral blood flow
processes


Strontium Insertion in Methylammonium Lead Iodide: Long Charge Carrier Lifetime and High Fill-Factor Solar Cells.

Abstract: The addition of Sr2+ in CH3 NH3 PbI3 perovskite films enhances the charge carrier collection efficiency of solar cells leading to very high fill factors, up to 85%. The charge carrier lifetime of Sr2+ -containing perovskites is in excess of 40 μs, longer than those reported for perovskite single crystals.

Pérez-Del-Rey|Daniel|D|
Forgács|Dávid|D|
Hutter|Eline M|EM|
Savenije|Tom J|TJ|
Nordlund|Dennis|D|
Schulz|Philip|P|
Berry|Joseph J|JJ|
Sessolo|Michele|M|
Bolink|Henk J|HJ|

strontium
lifetime
solar cells
perovskites
doping