Tear meniscus volume changes in dacryocystorhinostomy evaluated with quantitative measurement using anterior segment optical coherence tomography.

Abstract:
PURPOSE
To evaluate tear meniscus (TM) changes in external dacryocystorhinostomy (ex-DCR) with quantitative measurement of tear meniscus height (TMH), area (TMA), and volume (TMV) using anterior segment optical coherence tomography (AS-OCT).

METHODS
Twenty-five eyes from 21 patients (11 males and 10 females) with primary acquired nasolacrimal duct obstruction (PANDO) who received ex-DCR from May 2010 to April 2011 were evaluated prospectively on their TMH, TMA, and TMV changes by AS-OCT. Measurements were performed before surgery (Pre) and 2 weeks (2W), 2 months (2M), and 6 months (6M) after surgery. Data were analyzed using Kruskal-Wallis test, Wilcoxon signed-rank test with Bonferroni adjustment, and Spearman's rank correlation coefficient.

RESULTS
All patients had a good clinical course, and there were significant differences in the values of each TM parameter before and after surgery (P < 0.0001). The median values of TMH (mm) throughout the observation period were 0.707 (Pre), 0.334 (2W), 0.278 (2M), and 0.277 (6M). The TMA median values (mm(2)) were 0.1097 (Pre), 0.0483 (2W), 0.0255 (2M), and 0.0224 (6M). The TMV median values (mm(3)) were 0.7799 (Pre), 0.1614 (2W), 0.1071 (2M), and 0.1553 (6M). There were significant differences in TMH, TMA, and TMV reduction at each postoperative visit as compared to preoperative values (P < 0.001). In addition, TMH change 6 months after ex-DCR showed a significant positive correlation with age (r = 0.4434, P = 0.0264).

CONCLUSIONS
The perioperative TM changes in ex-DCR can be evaluated noninvasively and quantitatively by using AS-OCT.

Ohtomo|Kazuyoshi|K| Ueta|Takashi|T| Fukuda|Reina|R| Usui|Tomohiko|T| Miyai|Takashi|T| Shirakawa|Rika|R| Amano|Shiro|S| Nagahara|Miyuki|M|


Availability of Palliative Care in Long-Term Acute Care Hospitals.

Abstract:
OBJECTIVE
To determine the availability of palliative care programs in long-term acute care hospitals (LTACHs) DESIGN: Cross-sectional analysis using the 2016 American Hospital Association (AHA) Annual Survey.

SETTING AND PARTICIPANTS
LTACHs in the United States.

METHOD
We used descriptive analyses to compare the prevalence of palliative care programs in LTACHs across the United States in 2016. For LTACHs without a program, we also examined palliative care physician capacity in regions where those LTACHs resided to evaluate if expertise existed in those regions.

RESULTS
One-third (36.5%) of 405 LTACHs (50.6% response rate) self-reported having a palliative care program. Among LTACHs without palliative care, 42.4% were in regions with the highest palliative care physician capacity nationwide.

CONCLUSIONS AND IMPLICATIONS
LTACHs care for patients with serious and prolonged illnesses, many of whom would benefit from palliative care. Despite this, our study finds that specialty palliative care is limited in LTACHs. The limited palliative care availability in LTACHs is mismatched with the needs of this seriously ill population. Greater focus on increasing palliative care in LTACHs is essential and may be feasible as 40% of LTACHs without a palliative care program were located in regions with the highest palliative care physician capacity.

Sumarsono|Nathan|N|
Sudore|Rebecca L|RL|
Smith|Alexander K|AK|
Pantilat|Steven Z|SZ|
Anderson|Wendy G|WG|
Makam|Anil N|AN|

D003430:Cross-Sectional Studies
D006268:Health Facilities
D006761:Hospitals
D006801:Humans
D008134:Long-Term Care
D010166:Palliative Care
D014481:United States

palliative care
Long-term acute care
LTACH
health policy
health services


Ternary toxicological interactions of insecticides, herbicides, and a heavy metal on the earthworm Eisenia fetida.

Abstract: The combined toxicities of five insecticides (chlorpyrifos, avermectin, imidacloprid, λ-cyhalothrin, and phoxim), two herbicides (atrazine and butachlor), and a heavy metal (cadmium) have been examined using the acute toxicity test on the earthworm. With a concentration of 2.75 mg/kg being lethal for 50% of the organisms, imidacloprid exhibited the highest acute toxicity toward the earthworm Eisenia fetida. Toxicological interactions of these chemicals in ternary mixtures were studied using the combination-index (CI) equation method. Twenty-one ternary mixtures exhibited various interactive effects, in which 11 combinations showed synergistic effects, four led to dual synergistic/additive behaviors, one exhibited an additive effect, and five showed increasing antagonism within the entire range of effects. The CI method was compared with the classical models of concentration addition and independent action, and it was found that the CI method could accurately predict combined toxicity of the chemicals studied. The predicted synergism in the majority of the mixtures, especially at low-effect levels, might have implications in the real terrestrial environment.

Wang|Yanhua|Y| Chen|Chen|C| Qian|Yongzhong|Y| Zhao|Xueping|X| Wang|Qiang|Q|

Insecticide
Herbicide
Heavy metal
Eisenia fetida
Acute mixture toxicity
Combination index


The objectives, design and implementation of the INTERGROWTH-21st Project.

Abstract: INTERGROWTH-21(st) is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care.

Villar|J|J|
Altman|D G|DG|
Purwar|M|M|
Noble|J A|JA|
Knight|H E|HE|
Ruyan|P|P|
Cheikh Ismail|L|L|
Barros|F C|FC|
Lambert|A|A|
Papageorghiou|A T|AT|
Carvalho|M|M|
Jaffer|Y A|YA|
Bertino|E|E|
Gravett|M G|MG|
Bhutta|Z A|ZA|
Kennedy|S H|SH|
|||

D039401:Prenatal Nutritional Physiological Phenomena

INTERGROWTH-21st growth nutrition standards Fetal newborn preterm


Ion Fluxes through KCa2 (SK) and Cav1 (L-type) Channels Contribute to Chronoselectivity of Adenosine A1 Receptor-Mediated Actions in Spontaneously Beating Rat Atria.

Abstract: Impulse generation in supraventricular tissue is inhibited by adenosine and acetylcholine via the activation of A1 and M2 receptors coupled to inwardly rectifying GIRK/KIR3.1/3.4 channels, respectively. Unlike M2 receptors, bradycardia produced by A1 receptors activation predominates over negative inotropy. Such difference suggests that other ion currents may contribute to adenosine chronoselectivity. In isolated spontaneously beating rat atria, blockade of KCa2/SK channels with apamin and Cav1 (L-type) channels with nifedipine or verapamil, sensitized atria to the negative inotropic action of the A1 agonist, R-PIA, without affecting the nucleoside negative chronotropy. Patch-clamp experiments in the whole-cell configuration mode demonstrate that adenosine, via A1 receptors, activates the inwardly-rectifying GIRK/KIR3.1/KIR3.4 current resulting in hyperpolarization of atrial cardiomyocytes, which may slow down heart rate. Conversely, the nucleoside inactivates a small conductance Ca(2+)-activated KCa2/SK outward current, which eventually reduces the repolarizing force and thereby prolong action potentials duration and Ca(2+) influx into cardiomyocytes. Immunolocalization studies showed that differences in A1 receptors distribution between the sinoatrial node and surrounding cardiomyocytes do not afford a rationale for adenosine chronoselectivity. Immunolabelling of KIR3.1, KCa2.2, KCa2.3, and Cav1 was also observed throughout the right atrium. Functional data indicate that while both A1 and M2 receptors favor the opening of GIRK/KIR3.1/3.4 channels modulating atrial chronotropy, A1 receptors may additionally restrain KCa2/SK activation thereby compensating atrial inotropic depression by increasing the time available for Ca(2+) influx through Cav1 (L-type) channels.

Bragança|Bruno|B|
Oliveira-Monteiro|Nádia|N|
Ferreirinha|Fátima|F|
Lima|Pedro A|PA|
Faria|Miguel|M|
Fontes-Sousa|Ana P|AP|
Correia-de-Sá|Paulo|P|

L-type voltage-sensitive calcium channels


Controversies in Neuroscience: A Literature-Based Course for First Year Undergraduates that Improves Scientific Confidence While Teaching Concepts.

Abstract: Controversies in Neuroscience is a half-semester elective for first year science students at Carnegie Mellon University with an emphasis on discussing primary literature to highlight current research topics and to introduce students to neuroscience. In order to evaluate the effectiveness of teaching first-year students using a literature-only approach, we took advantage of an opportunity to teach the same topics to a traditional textbook-based upper division course as to the first year seminar. Students in both courses took surveys at the beginning and end of the course, and self-reported confidence levels as well as exam scores were compared. At the conclusion of both courses, students reported increased level of comfort with scientific terminology and methodology. In addition, students enrolled in the first-year seminar performed at least as well or better than students involved in the upper division course on exam material. These results suggest that first year students are capable of making great strides in learning and understanding scientific principles strictly through exposure to primary literature, even with little or no access to a standard textbook. Furthermore, introducing students to primary literature-based courses early on in their undergraduate career can increase enthusiasm for learning science and improve confidence with neuroscience concepts and methodology. We therefore conclude that it is valuable to provide students opportunities to critically evaluate scientific literature early in their undergraduate careers.

active learning
hippocampus
introductory course
long-term potentiation (LTP)
neuroscience methodology
pedagogy
scientific papers
synapse


UHPLC-MS/MS analysis of cAMP and cGMP in rat plasma as potential biomarkers of Yin-Yang disharmony in traditional Chinese medicine.

Abstract: Cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) are considered as potential biomarkers for Yin-Yang disharmony in traditional Chinese medicine. However, phosphodiesterase-mediated ex vivo degradation of these molecules in biological samples may result in their underestimation. In the present study, a ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for determination of cAMP and cGMP in rat plasma, with special consideration of their stability ex vivo. Following precipitation of proteins from plasma samples with 0.4 M perchloric acid, the analytes were chromatographed on a Shimadzu Shim-pack-XR-ODS II column with 2.5 mM ammonium acetate and methanol in gradient mode. The MS/MS detection was performed using multiple reaction monitoring in the positive electrospray ionization mode. The lower limit of quantification was 0.27 ng/mL for cAMP and 0.37 ng/mL for cGMP. The method was used to determine the plasma cAMP and cGMP levels in normal and Yin deficiency diabetic rats treated with or without Rehmannia glutinosa. The developed method may be useful for evaluating the regulatory effects of Chinese herbal medicine on the levels of cAMP and cGMP in the body.

Wang|Xin|X| Du|Yue|Y| Wu|Cuiting|C| Xu|Ming|M| Liu|Youping|Y| Di|Xin|X|

UHPLC-MS/MS
cAMP
cGMP
Plasma
Yin-Yang disharmony


Functional research and cognitive-process research in behavioural science: An unequal but firmly connected pair.

Abstract: Drawing on illustrative examples of the functional and cognitive psychology in contemporary research, the present article emphasizes the primacy of functional relationships, which provide the fundament for all attempts to uncover invisible cognitive processes. Cognitive research is not only inherently more difficult and much more ambitious than functional research. It also suffers from several home-made problems, such as unwarranted inferences from model fitting, the mediation-analysis cult and the failure to take environmental influences into account. However, despite the primacy of functional psychology and the problems associated with the ambitious goals of cognitive research, the two partners in this unequal pair are firmly connected and jointly responsible for the most impressive examples of progress in behavioural science.

Inductive cognition
Methodology
Social cognition


A Pan-Cancer Analysis of the Oncogenic and Immunogenic Role of m6Am Methyltransferase PCIF1.

Abstract:
Background
Phosphorylated CTD-interacting factor 1 (PCIF1) is identified as the only known methyltransferase of N6,2'-O-dimethyladenosine (m6Am) in mRNA. However, its oncogenic and immunogenic role in cancer research is at an initial stage.

Methods
Herein, we carried out a pan-cancer analysis of PCIF1, with a series of datasets (e.g., TIMER2.0, GEPIA2, cBioPortal).

Results
PCIF1 expression was higher in most cancers than normal tissues and was discrepant across pathological stages. Highly expressed PCIF1 was positively correlated with overall survival (OS) or disease-free survival (DFS) of some tumors. PCIF1 expression had a positive correlation with CD4+ T-cell infiltration in kidney renal clear cell carcinoma (KIRC), CD8+ T cells, macrophages, and B cells in thyroid carcinoma (THCA), and immune checkpoint genes (ICGs) in LIHC but a negative correlation with CD4+ T cells, neutrophils, myeloid dendritic cells, and ICGs in THCA. It also affected tumor mutational burden (TMB) and microsatellite instability (MSI) of most tumors.

Conclusion
PCIF1 expression was correlated with cancer prognosis and immune infiltration, suggesting it to be a potential target for cancer therapy.

Jin|Ming-Zhu|MZ| Zhang|Yi-Gan|YG| Jin|Wei-Lin|WL| Wang|Xi-Peng|XP|

pan-cancer analysis
PCIF1
immune checkpoint genes (ICGs)
N6,2′-O-dimethyladenosine (m6Am)
posttranslational modification


Evaluation of the scars' vascularization using computer processing of the digital images.

Abstract:
BACKGROUND
The application of new techniques of the scars' correction requires the objective evaluation of their vascularization.

OBJECTIVE
To evaluate the effectiveness of digital program ImageJ in assessing neovascularization of pathologic scars.

MATERIAL AND METHODS
In this cross-sectional study, a total of 25 patients with pathologic scars were enrolled. Vessel selection in the first set of digital images of their scars was performed by computer processing started from thresholding with subsequent manual correction. In the second set of the same pictures, Vessel Analysis plugin was used. Comparison of both approaches was performed by three independent investigators. The time required for images processing was measured.

RESULTS
The average time that image processing and calculation have taken in the first group (753.3 ± 88.02 seconds) was statistically longer (P < 0.0001) than in the second one (358.1 ± 105.91 seconds). Independent investigators scored the precision of vessel selection in the first group as 80.4 ± 9.82, in the second group as 72.6 ± 10.53 (P < 0.0001). Kolmogorov-Smirnov test demonstrated higher precision of vessel selection by method that involves manual correction (P < 0.001). The results of Vascular Density measurements were obviously overestimated in the second group. More expedient looks calculation of the Vascular Length Density: ratio of skeletonized vasculature area to total area. Skeletonization avoids overestimation of Vascular Density, but the density of the vessel mesh can be determined.

CONCLUSIONS
Computer processing of the scars' digital photographs using ImageJ software gives cheap, technically easy and not cumbersome way of superficial scars' vascularization objectifying. Vessel selection with subsequent manual correction has advantage of higher precision.

scar
digital imaging
ImageJ
neovascularization
computerized evaluation
telangiectasia


Effect of sterilization on structural and material properties of 3-D silk fibroin scaffolds.

Abstract: The development of porous scaffolds for tissue engineering applications requires the careful choice of properties, as these influence cell adhesion, proliferation and differentiation. Sterilization of scaffolds is a prerequisite for in vitro culture as well as for subsequent in vivo implantation. The variety of methods used to provide sterility is as diverse as the possible effects they can have on the structural and material properties of the three-dimensional (3-D) porous structure, especially in polymeric or proteinous scaffold materials. Silk fibroin (SF) has previously been demonstrated to offer exceptional benefits over conventional synthetic and natural biomaterials in generating scaffolds for tissue replacements. This study sought to determine the effect of sterilization methods, such as autoclaving, heat-, ethylene oxide-, ethanol- or antibiotic-antimycotic treatment, on porous 3-D SF scaffolds. In terms of scaffold morphology, topography, crystallinity and short-term cell viability, the different sterilization methods showed only few effects. Nevertheless, mechanical properties were significantly decreased by a factor of two by all methods except for dry autoclaving, which seemed not to affect mechanical properties compared to the native control group. These data suggest that SF scaffolds are in general highly resistant to various sterilization treatments. Nevertheless, care should be taken if initial mechanical properties are of interest.

Hofmann|Sandra|S|
Stok|Kathryn S|KS|
Kohler|Thomas|T|
Meinel|Anne J|AJ|
Müller|Ralph|R|

D017550:Spectroscopy, Fourier Transform Infrared

Sterilization
Silk fibroin
Scaffold
Tissue engineering


Naringenin, a dietary flavanone, enhances insulin-like growth factor 1 receptor-mediated antioxidant defense and attenuates methylglyoxal-induced neurite damage and apoptotic death.

Abstract: Objectives: Recent studies revealed the neuroprotective effects of naringenin (NGEN), a common dietary bioflavonoid contained in citrus fruits. However, there are limited data on its protection against methylglyoxal (MG), the most potent precursor of advanced glycation end-products. The present study was to investigate the protection of NGEN on MG-induced neurotoxicity and the involvement of insulin-like growth factor 1 receptor (IGF-1R) signaling. Methods: NSC34 motor neuron-like cells was used. Cell viability was measured by MTT assay. Protein expressions were analyzed by western blots. Morphological changes of neurites were observed by an inverted microscope. Reactive oxygen species (ROS) production and apoptotic cell numbers were measured by flow cytometer. Glutathione (GSH) level and superoxide dismutase (SOD) activity were measured by ELISA. Results: >NGEN attenuated ROS production and increased GSH level, SOD activity and nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear expression in MG-treated NSC34 cells. NGEN also increased neurite length and enhanced IGF-1R and p-Akt in MG-treated NSC34 cells. Furthermore, NGEN attenuated MG-induced apoptotic death accompanied with down-regulation of cleaved-poly (ADP-ribose) polymerase (PARP) and up-regulation of B-cell lymphoma-2 (Bcl-2). However, AG1024, an IGF-1R antagonist, attenuated the anti-oxidative and anti-apoptotic effects of NGEN in MG-treated cells. Discussion: The present results demonstrated that NGEN decreased neuronal apoptosis and improved antioxidant defense in MG-treated NSC34 cells. Moreover, IGF-1R-mediated antioxidant defense plays an important role in this protective mechanism. These findings suggest the potential benefits of NGEN on the prevention of MG-induced or diabetes/hyperglycemia-related neurotoxicity. In vivo studies are needed for further confirmation on NGEN-mediated neuroprotection.

Tseng|Yu-Ting|YT| Hsu|Hung-Te|HT| Lee|Tzu-Ying|TY| Chang|Wan-Hsuan|WH| Lo|Yi-Ching|YC|

Naringenin
insulin-like growth factor 1
antioxidant defense
methylglyoxal
anti-apoptosis
glucose neurotoxicity
motor neurons


Adapting clinical practice guidelines for diabetic retinopathy in Kenya: process and outputs.

Abstract:
BACKGROUND
The use of clinical practice guidelines envisages augmenting quality and best practice in clinical outcomes. Generic guidelines that are not adapted for local use often fail to produce these outcomes. Adaptation is a systematic and rigorous process that should maintain the quality and validity of the guideline, while making it more usable by the targeted users. Diverse skills are required for the task of adaptation. Although adapting a guideline is not a guarantee that it will be implemented, adaptation may improve acceptance and adherence to its recommendations.

METHODS
We describe the process used to adapt clinical guidelines for diabetic retinopathy in Kenya, using validated tools and manuals. A technical working group consisting of volunteers provided leadership.

RESULTS
The process was intensive and required more time than anticipated. Flexibility in the process and concurrent health system activities contributed to the success of the adaptation. The outputs from the adaptation include the guidelines in different formats, point of care instruments, as well as tools for training, monitoring, quality assurance and patient education.

CONCLUSION
Guideline adaptation is applicable and feasible at the national level in Kenya. However, it is labor- and time -intensive. It presents a valuable opportunity to develop several additional outputs that are useful at the point of care.

Mwangi|Nyawira|N|0000-0002-8236-470X
Gachago|Muchai|M|
Gichangi|Michael|M|
Gichuhi|Stephen|S|
Githeko|Kibata|K|
Jalango|Atieno|A|
Karimurio|Jefitha|J|
Kibachio|Joseph|J|
Muthami|Lawrence|L|
Ngugi|Nancy|N|
Nduri|Carmichael|C|
Nyaga|Patrick|P|
Nyamori|Joseph|J|
Zindamoyen|Alain Nazaire Mbongo|ANM|
Bascaran|Covadonga|C|
Foster|Allen|A|

Clinical practice guidelines
Diabetic retinopathy
Kenya
Guideline adaptation
Diabetes mellitus
Guideline development


Metformin Use and Vitamin B12 Deficiency: Untangling the Association.

Abstract:
BACKGROUND
Current evidence linking vitamin B12 deficiency with metformin use is inconsistent. Hence, there is uncertainty regarding the diagnostic approach in this scenario. Furthermore, this possible association has not been studied in the complete spectrum of patients with diabetes.

MATERIALS AND METHODS
We conducted a cross-sectional, controlled study with the objective of assessing differences in serum vitamin B12 levels among patients with and without diabetes with different metformin-treatment regimens. A total of 150 participants were recruited: patients with diabetes (group 1: metformin alone ≥850mg/day, group 2: patients with type 2 diabetes naive to treatment and group 3: metformin ≥850mg/day, in addition to any other oral glucose lowering agent or insulin, or both) and without diabetes (group 4: polycystic ovary syndrome or group 5: healthy individuals). Serum vitamin B12, folate levels and complete blood counts were obtained for the entire population. Methylmalonic acid and homocysteine were obtained for patients when vitamin B12 levels were found to be borderline or low.

RESULTS
When patients with or without diabetes were compared, no significant difference was found in relation to their vitamin B12 levels (517.62 versus 433.83; P = 0.072). No difference in vitamin B12 levels was found among participants with metformin use and metformin naive participants (503.4 versus 462.3; P = 0.380).

CONCLUSIONS
Irrespective of metformin use, no significant difference in the serum levels of vitamin B12 was observed, both in patients with and without diabetes. In the light of the body of evidence and the results of this study, a universal recommendation for vitamin B12 deficiency screening cannot be made.

Rodríguez-Gutiérrez|René|R|
Montes-Villarreal|Juan|J|
Rodríguez-Velver|Karla Victoria|KV|
González-Velázquez|Camilo|C|
Salcido-Montenegro|Alejandro|A|
Elizondo-Plazas|Anasofia|A|
González-González|José Gerardo|JG|

Metformin
Vitamin B12 deficiency
Type 2 diabetes
Cyanocobalamin-deficiency


The LQT-associated calmodulin mutant E141G induces disturbed Ca2+-dependent binding and a flickering gating mode of the CaV1.2 channel.

Abstract: Calmodulin (CaM) mutations are associated with congenital long QT (LQT) syndrome (LQTS), which may be related to the dysregulation of the cardiac-predominant Ca2+ channel isoform CaV1.2. Among various mutants, CaM-E141G was identified as a critical missense variant. However, the interaction of this CaM mutant with the CaV1.2 channel has not been determined. In this study, by utilizing a semiquantitative pull-down assay, we explored the interaction of CaM-E141G with CaM-binding peptide fragments of the CaV1.2 channel. Using the patch-clamp technique, we also investigated the electrophysiological effects of the mutant on CaV1.2 channel activity. We found that the maximum binding (Bmax) of CaM-E141G to the proximal COOH-terminal region, PreIQ-IQ, PreIQ, IQ, and NT (an NH2-terminal peptide) was decreased (by 17.71-59.26%) compared with that of wild-type CaM (CaM-WT). In particular, the Ca2+-dependent increase in Bmax became slower with the combination of CaM-E141G + PreIQ and IQ but faster in the case of NT. Functionally, CaM-WT and CaM-E141G at 500 nM Ca2+ decreased CaV1.2 channel activity to 24.88% and 55.99%, respectively, compared with 100 nM Ca2+, showing that the inhibitory effect was attenuated in CaM-E141G. The mean open time of the CaV1.2 channel was increased, and the number of blank traces with no channel opening was significantly decreased. Overall, CaM-E141G exhibits disrupted binding with the CaV1.2 channel and induces a flickering gating mode, which may result in the dysfunction of the CaV1.2 channel and, thus, the development of LQTS. The present study is the first to investigate the detailed binding properties and single-channel gating mode induced by the interaction of CaM-E141G with the CaV1.2 channel.

Su|Jingyang|J| Gao|Qinghua|Q| Yu|Lifeng|L| Sun|Xuanxuan|X| Feng|Rui|R| Shao|Dongxue|D| Yuan|Yuan|Y| Zhu|Zhengnan|Z| Sun|Xuefei|X| Kameyama|Masaki|M| Hao|Liying|L|

calmodulin mutant
CaV1.2 channel
Ca2+-dependent inactivation
long QT syndrome


A randomized controlled trial of auricular acupressure in heart rate variability and quality of life for hypertension.

Abstract:
BACKGROUND
Hypertension is one of the most common chronic diseases. Hypertensive patients who intend to control blood pressure need professional medical assistance. Auricular acupressure is a patient-dependent task, wherein a person does not have to rely on a healthcare professional to self-perform the task.

OBJECTIVE
To evaluate the effects of auricular acupressure on heart rate variability (HRV) and quality of life (QoL) in patients with hypertension.

METHODS
A randomized controlled trial with permuted block randomization was used. In total, 150 participants from a medical teaching hospital were randomly assigned to the experimental group that received auricular acupressure for 10 weeks, and the control group that received only routine care of equal duration. Outcomes were assessed through HRV parameters, heart rate, blood pressure, and QoL before and after the auricular acupressure intervention.

RESULTS
After the adjustment of disease duration and mental health, a significant difference existed between the two groups in body pain (p=.03) and mental health (p=.002) of QoL, but not in HRV parameters, heart rate, blood pressure, and overall QoL (p>.05).

CONCLUSION
Acupressure can be applied at the acupoints of shenmen, sympathesis, kidney, liver, heart, and subcortex to improve physical pain and mental health of QoL for hypertensive patients. Auricular acupressure is acceptable and feasible although it does not support physiological benefits. Further studies are warranted to assure the effects of using auricular acupressure as an adjunctive care for patients with hypertension.

Yeh|Mei-Ling|ML| Chang|Yu-Chun|YC| Huang|Yi-Ying|YY| Lee|Tso-Ying|TY|

Auricular acupressure
Hypertension
Heart rate variability (HRV)
Quality of life (QoL)
Mental health
Pain


Friendship network characteristics and psychological well-being in late adolescence: exploring differences by gender and gender composition.

Abstract:
AIMS
The aim of the present study was to examine the association between friendship networks and psychological well-being among 19-year-olds.

METHODS
The data used was a random sample of Swedish individuals born in 1990 who answered a questionnaire in 2009-2010. Friendship networks were considered in terms of three measures of emotional support. Six statements about the individual's emotional state were used to create a summary measure of psychological well-being. Gender and gender composition were included as potentially moderating factors. The association between friendship networks and psychological well-being was analysed by means of linear regression analysis (n = 1289).

RESULTS
The results indicate that males' and females' friendship networks were similar with regard to quality and trust, whereas males' networks were characterized by less self-disclosure and a stronger preference for same-gender friendships. Gender composition did not matter for the support levels. Emotional support was associated with psychological well-being but there were gender differences: females seemed to benefit more health-wise from having high-quality (and trusting) networks. Moreover, whereas self-disclosure among males was positively linked to well-being, this was not the case among females. None of these associations were moderated by gender composition.

CONCLUSIONS
In sum, friendship networks are beneficial for the psychological well-being among late adolescents, but there are some important differences according to gender.

Almquist|Ylva B|YB|
Östberg|Viveca|V|
Rostila|Mikael|M|
Edling|Christofer|C|
Rydgren|Jens|J|

friendship
psychological well-being
late adolescence
Emotional support
gender differences
social networks


Tumor-associated myeloid cells: new understandings on their metabolic regulation and their influence in cancer immunotherapy.

Abstract: Tumor-associated myeloid cells (TAMCs), mainly represented by tumor-associated macrophages and myeloid-derived suppressor cells, can promote tumor growth directly, by favoring tumor cell proliferation and survival, and indirectly, by creating an immunosuppressive microenvironment. Myeloid cells are characterized by an extreme phenotypical and functional plasticity. Immunometabolism is now emerging as a crucial aspect of TAMCs skewing toward pro-tumoral activities. The metabolic re-education of myeloid cells is a new strategy to boost their antitumor effector functions. Several anticancer therapies targeting TAMCs are already under investigation. Nowadays, the hot topic of cancer immunotherapy is represented by immune checkpoint inhibitors. These drugs unrestrain T-cell-mediated tumor elimination by removing suppressive signals delivered by tumor-associated cells. The efficacy of immune checkpoint blockade can be enhanced using coordinated strategies to counteract the TAMCs-dependent impairment of immune adaptive responses. In the first part of the review, we will describe the association between metabolic reprogramming and TAMCs biological activities. In the second part, we will illustrate the potential of combination therapies associating TAMC-targeting drugs with immune checkpoint inhibitors.

tumor-associated macrophages
myeloid-derived suppressor cells
immunometabolism
checkpoint inhibitors
tumor microenvironment


Impacts of contracted endodontic cavities compared to traditional endodontic cavities in premolars.

Abstract:
BACKGROUND
This study aims to compare the percentage of dentin removed, instrumentation efficacy, root canal filling and load at fracture between contracted endodontic cavities, and traditional endodontic cavities on root canal therapy in premolars.

METHODS
Forty extracted intact human first premolars were imaged with micro-CT and randomly assigned to the contracted endodontic cavity (CEC) or traditional endodontic cavity (TEC) groups. CEC was prepared with the aid of a 3D-printed template, canals were prepared with a 0.04 taper M-Two rotary instrument, and cavities were restored with resin. Specimens were loaded to fracture in an Instron Universal Testing Machine after a fatigue phase. The data were analyzed by the independent samples T test and Mann-Whitney U test, appropriate post hoc tests.

RESULTS
In the premolars tested in vitro, the percentage of dentin removed in the premolars with two dental roots in the CEC group (3.85% ± 0.42%) was significantly smaller (P < 0.05) than in the TEC group (4.94% ± 0.5%). The untouched canal wall (UCW) after instrumentation for TECs (16.43% ± 6.56%) was significantly lower (P < .05) than the UCW (24.42% ± 9.19%) for CECs in single-rooted premolars. No significant differences were observed in the increased canal volume and surface areas in premolars between the TEC and CEC groups (P > 0.05). CECs conserved coronal dentin in premolars with two dental roots but no impact on the instrument efficacy. There were no differences between the CEC groups and the TEC groups in the percentage of filling material and voids (P > 0.05). In addition, the mean load at failure of premolars did not significantly differ between the CEC and TEC groups and there was no significant difference in the type of fracture (P > 0.05).

CONCLUSION
The results of this study suggest that CEC could not improve the fracture resistance of the endodontically treated premolars. The instrumentation efficacy and the percentage of filling material did not significantly differ between CECs and TECs in premolars.

Xia|Juan|J| Wang|Weidong|W| Li|Zhengmao|Z| Lin|Bingpeng|B| Zhang|Qian|Q| Jiang|Qianzhou|Q| Yang|Xuechao|X|

Contracted endodontic cavities
Instrumentation efficacy
Root canal filling
3D-printed template
Fracture resistance


Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm.

Abstract: Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice.

stress testing
coronary artery disease.
CT angiography
cardiac CT


Disparities in Access and Mortality of Patients With ST-Segment-Elevation Myocardial Infarction Using the Brazilian Public Healthcare System: VICTIM Register.

Abstract: Background There is a scarcity of knowledge as to whether rates of myocardial reperfusion use and 30-day mortality for patients with ST-segment-elevation myocardial infarction are similar among patients using the Brazilian Public Health System (SUS) and those using the private healthcare system. Methods and Results A total of 707 patients were analyzed using the VICTIM (Via Crucis for the Treatment of Myocardial Infarction) register database; 589 patients from the SUS and 118 from the private network with ST-segment-elevation myocardial infarction, who attended hospitals with the capacity to perform primary percutaneous coronary intervention (PCI) were investigated. The timeline, rates of use of PCI, and the 30-day probability of death were investigated, comparing the SUS patients to those in the private system. The mean time between symptom onset and arrival at the PCI hospital was higher for SUS patients compared with users of the private system (25.4±36.5 versus 9.0±21 hours; P<0.001, respectively). Rates of primary PCI were low in both groups, but significantly lower for the SUS patients (45% versus 78%; P<0.001). The 30-day mortality rate of SUS patients was 11.9% and of private patients was 5.9% (P=0.04). In the fully adjusted model, the odds ratio for 30-day mortality for the SUS patients was higher (odds ratio, 2.96; 95% CI, 1.15-7.61; P=0.02). Conclusions The delay in reaching a PCI hospital was almost 3 times higher for the SUS patients. Primary PCI was underused in both groups, especially in the SUS patients. The SUS patients were more likely to die during the 30-day follow-up.

Oliveira|Jussiely Cunha|JC|
Almeida-Santos|Marcos Antonio|MA|
Cunha-Oliveira|Jeferson|J|
Oliveira|Laís Costa Souza|LCS|
de Carvalho Barreto|Ikaro Daniel|ID|
Clair RemacreMunareto Lima|Ticiane|T|
Andreline Maia Arcelino|Larissa|L|
Andrade Prado|Luís Flávio|LF|
Serra Silveira|Fábio|F|
Augusto da Silva Nascimento|Thiago|T|
Pereira Ferreira|Eduardo José|EJ|
Vasconcelos Barreto|Rafael|R|
Vieira Moraes|Enilson|E|
Teles de Mendonça|José|J|
Sousa|Antonio Carlos Sobral|ACS|
Barreto-Filho|José Augusto|JA|
|||

D000072657:ST Elevation Myocardial Infarction

acute myocardial infarction
health disparities
health policy and outcomes research
health services coverage


Oocyte vitrification offers more space for a tailored surgical management of endometriosis.

Abstract: Oocyte vitrification is an attractive and efficient option in the long-term management of endometriosis patients. Which women would benefit from banked oocytes when pregnancy is attempted, and whether oocyte vitrification should be carried out before or after the surgical management of endometriosis, is still debated. On the basis of recent data, and in the absence of cost-effective modelling, a personalized strategy should assess crucial variables, such as type of surgery, effect on oocyte yield and the huge heterogeneity of the clinical scenarios possibly requiring surgery. Research into a more tailored approach to maximize the result of each available intervention, e.g. hormones, surgery, assisted reproductive technology or their combination to prevent infertility and reduce the actual burden of personal and societal cost of the disease, is recommended.

Endometriosis
Surgery
Fertility preservation
Oocyte cryopreservation


Towards reassigning the rare AGG codon in Escherichia coli.

Abstract: The rare AGG codon in Escherichia coli has been reassigned to code non-canonical amino acids (ncAAs) by using the PylRS-tRNA(Pyl)(CCU) pair. When N(ε) -alloc-lysine was used as a PylRS substrate, almost quantitative occupancy of N(ε) -alloc-lysine at an AGG codon site was achieved in minimal medium. ncAAs can be potentially incorporated at the AGG codon with varying efficiencies, depending on their activities towards corresponding enzymes. As AGG is a sense codon, the approach reported here resolves the typical low ncAA incorporation issue that has been associated with ncAA mutagenesis and therefore allows bulk preparation of proteins with site-selectively incorporated ncAAs for applications such as therapeutic protein production.

D000596:Amino Acids
D000604:Amino Acyl-tRNA Synthetases
D003062:Codon
D004926:Escherichia coli
D008968:Molecular Conformation

AGG codon
non-canonical amino acids
AGGA codon
genetic code expansion
sense codon reassignment


Frontier Orbital Energy-Customized Ionomer-Based Polymer Electrolyte for High-Voltage Lithium Metal Batteries.

Abstract: The development of gel polymer electrolytes (GPEs) is considered to be an effective strategy to drive practical applications of high-voltage lithium metal batteries (HLMBs). However, rare GPEs that can satisfy the demands of HLMBs have been developed because of the limited compatibility with lithium anodes and high-voltage cathodes simultaneously. Herein, a novel strategy for constructing polymer matrixes with a customized frontier orbital energy for GPEs is proposed. The as-investigated polymer matrix (P(CUMA-NPF6))-based GPE (P(CUMA-NPF6)-GPE) obtained via in situ random polymerization delivers a wide voltage window (0-5.6 V vs Li+/Li), large lithium-ion transference number (tLi+, 0.61), and superior electrode/electrolyte interface compatibility. It is to be noted that such a tLi+ of P(CUMA-NPF6)-GPE, which is one of the largest tLi+ among high-voltage GPEs in a fair comparison, results from the high dissociation of lithium salts and effective anion immobilization abilities of P(CUMA-NPF6). Ultimately, the as-assembled HLMB delivers more enhanced cycle performance than its counterpart of commercial liquid electrolytes. It is also demonstrated that P(CUMA-NPF6) can scavenge the active PF5 intermediate generated in the electrolyte at the anode side, thus suppressing the PF5-mediated decomposition reaction of carbonates. This work will enlighten the rational structure design of GPEs for HLMBs.

customized frontier orbital energy level


Siderophore-Mediated Interactions Determine the Disease Suppressiveness of Microbial Consortia.

Abstract: Interactions between plant pathogens and root-associated microbes play an important role in determining disease outcomes. While several studies have suggested that steering these interactions may improve plant health, such approaches have remained challenging in practice. Because of low iron availability in most soils, competition for iron via secreted siderophore molecules might influence microbial interaction outcomes. Here, we tested if bacterial interactions mediated by iron-scavenging siderophores can be used to predict the disease suppressiveness of microbial consortia against soilborne Ralstonia solanacearum, a bacterial pathogen in the tomato rhizosphere. Iron availability significantly affected the interactions within inoculated consortia and between the consortia and the pathogen. We observed contrasting effects of siderophores and other nonsiderophore metabolites on the pathogen growth, while the siderophore effects were relatively much stronger. Specifically, disease incidence was reduced in vivo when the inoculated consortia produced siderophores that the pathogen could not use for its own growth. Employing siderophore-mediated interactions to engineer functionally robust microbial inoculants shows promise in protecting plants from soilborne pathogens.IMPORTANCE Soil-borne pathogens cause high losses in crop yields globally. The development of environmentally friendly approaches is urgently needed, but is often constrained by complex interactions between root-associated microbes and pathogens. Here, we demonstrate that the interactions within microbial consortia mediated by iron-scavenging siderophores play an important role in reducing pathogen infection and enhancing plant health. This study provides a promising and novel research direction for dealing with a wide range of microbial infections through iron exploitation, which is important for the colonization and infection of both plant and human hosts by pathogens.

Gu|Shaohua|S| Yang|Tianjie|T| Shao|Zhengying|Z| Wang|Tao|T| Cao|Kehao|K| Jousset|Alexandre|A| Friman|Ville-Petri|VP| Mallon|Cyrus|C| Mei|Xinlan|X| Wei|Zhong|Z| Xu|Yangchun|Y| Shen|Qirong|Q| Pommier|Thomas|T|

plant pathogens
plant health
Siderophore
microbial interactions
soil microbiology


No Decrease in Muscle Strength after Botulinum Neurotoxin-A Injection in Children with Cerebral Palsy.

Abstract: Spasticity and muscle weakness is common in children with cerebral palsy (CP). Spasticity can be treated with botulinum neurotoxin-A (BoNT-A), but this drug has also been reported to induce muscle weakness. Our purpose was to describe the effect on muscle strength in the lower extremities after BoNT-A injections in children with CP. A secondary aim was to relate the effect of BoNT-A to gait pattern and range of motion. Twenty children with spastic CP were included in the study, 8 girls and 12 boys (mean age 7.7 years). All were able to walk without support, but with increased muscle tone interfering with motor function and gait pattern. Sixteen children had unilateral spastic CP and four bilateral spastic CP. Twenty-four legs received injections with BoNT-A in the plantar flexor muscles. The children were tested before treatment, around 6 weeks after at the peak effect of BoNT-A, and at 6 months after treatment, with measurement of muscle strength, gait analysis, and range of motion. There were no differences in muscle strength in plantar flexors of treated legs at peak effect compared to baseline. Six months after treatment, there was still no change in untreated plantar flexor muscles, but an increasing trend in plantar flexor strength in legs treated with BoNT-A. Parents reported positive effects in all children, graded as: small in three children, moderate in eight, and large in nine children. The gait analysis showed a small improvement in knee extension at initial contact, and there was a small increase in passive range of motion for ankle dorsiflexion. Two children had a period with transient weakness and pain. We found that voluntary force production in plantar flexor muscles did not decrease after BoNT-A, instead there was a trend to increased muscle strength at follow-up. The increase may be explained as an effect of the blocking of involuntary nerve impulses, leading to an opportunity to using and training the muscles with voluntary control. Adequate muscle strength is important for maintaining the ability to walk and knowledge of how a treatment affects muscle strength is useful when selecting interventions.

muscle strength
children
cerebral palsy
spasticity
botulinum toxin


Identification of a Novel Inhibitor against Middle East Respiratory Syndrome Coronavirus.

Abstract: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (KD) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC50) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.

Sun|Yaping|Y| Zhang|Huaidong|H| Shi|Jian|J| Zhang|Zhe|Z| Gong|Rui|R|

D065207:Middle East Respiratory Syndrome Coronavirus

MERS-CoV
fusion inhibitor
six-helix bundle
heptad repeat
five-helix bundle


Tubed Supraglottic Laryngeal Closure to Treat Chronic Aspiration After Radiotherapy for Head and Neck Cancer.

Abstract:
OBJECTIVES/HYPOTHESIS
To evaluate the long-term swallowing outcomes after surgical treatment for chronic aspiration in patients treated with radiotherapy for head and neck cancer.

STUDY DESIGN
This was a retrospective study.

METHODS
The data of patients who underwent radiotherapy for head and neck cancer and who subsequently required a laryngectomy or a tubed supraglottic laryngeal closure (TSLC) for recurrent aspiration pneumonia between 2004 and 2017 were retrieved from a tertiary referral hospital dysphagia clinic. The Functional Oral Intake Scale (FOIS) and the Swallowing Performance and Status Scale (SPSS) were used to assess swallowing function.

RESULTS
Of the 17 patients who required surgery for chronic aspiration secondary to radiotherapy for head and neck cancer, two underwent a laryngectomy and 15 a TSLC. During a mean follow-up of 77 months, the FOIS and SPSS scores significantly improved at 12, 24, and 36 months after laryngectomy and TSLC relative to the baseline (P < .05). Both patients who underwent laryngectomy and 11 of the 15 (73.3%) who underwent a TSLC resumed oral feeding. Both laryngectomy patients had episodes of recurrent aspiration pneumonia after surgery due to leakage through the tracheoesophageal puncture or prosthesis, whereas none of the TSLC patients had these episodes.

CONCLUSION
A tubed supraglottic laryngeal closure, which is a reversible procedure that preserves the larynx and allows for natural phonation, should be considered an alternative to laryngectomy for the control of chronic aspiration.

LEVEL OF EVIDENCE
4 Laryngoscope, 131:E1234-E1243, 2021.

aspiration
head and neck
cancer
Dysphagia
surgery


Effectiveness and Comparison of Various Audio Distraction Aids in Management of Anxious Dental Paediatric Patients.

Abstract:
BACKGROUND
Dental anxiety is a widespread phenomenon and a concern for paediatric dentistry. The inability of children to deal with threatening dental stimuli often manifests as behaviour management problems. Nowadays, the use of non-aversive behaviour management techniques is more advocated, which are more acceptable to parents, patients and practitioners. Therefore, this present study was conducted to find out which audio aid was the most effective in the managing anxious children.

AIMS AND OBJECTIVES
The aim of the present study was to compare the efficacy of audio-distraction aids in reducing the anxiety of paediatric patients while undergoing various stressful and invasive dental procedures. The objectives were to ascertain whether audio distraction is an effective means of anxiety management and which type of audio aid is the most effective.

MATERIALS AND METHODS
A total number of 150 children, aged between 6 to 12 years, randomly selected amongst the patients who came for their first dental check-up, were placed in five groups of 30 each. These groups were the control group, the instrumental music group, the musical nursery rhymes group, the movie songs group and the audio stories group. The control group was treated under normal set-up & audio group listened to various audio presentations during treatment. Each child had four visits. In each visit, after the procedures was completed, the anxiety levels of the children were measured by the Venham's Picture Test (VPT), Venham's Clinical Rating Scale (VCRS) and pulse rate measurement with the help of pulse oximeter.

RESULTS
A significant difference was seen between all the groups for the mean pulse rate, with an increase in subsequent visit. However, no significant difference was seen in the VPT & VCRS scores between all the groups. Audio aids in general reduced anxiety in comparison to the control group, and the most significant reduction in anxiety level was observed in the audio stories group.

CONCLUSION
The conclusion derived from the present study was that audio distraction was effective in reducing anxiety and audio-stories were the most effective.

Navit|Saumya|S|
Johri|Nikita|N|
Khan|Suleman Abbas|SA|
Singh|Rahul Kumar|RK|
Chadha|Dheera|D|
Navit|Pragati|P|
Sharma|Anshul|A|
Bahuguna|Rachana|R|

Dental anxiety
Venham’s clinical rating scale
Venham’s picture test


Topical colloidal silver as an anti-biofilm agent in a Staphylococcus aureus chronic rhinosinusitis sheep model.

Abstract:
BACKGROUND
Treatment of recalcitrant chronic rhinosinusitis (CRS) is a challenge with increasing antibiotic resistance, leading to re-emergence of topical therapies. The aim of this study was to assess safety and efficacy of topical colloidal silver solution for the treatment of Staphylococcus aureus biofilms in a sheep model.

METHODS
In the safety study, normal saline (control) and 30-ppm colloidal silver solution (test) was used to flush the frontal sinuses for 14 days in 8 sheep (4 sheep each). In the efficacy study, following frontal sinus infection with Staphylococcus aureus, sheep were treated with either control saline or topical silver solution of varying concentrations (30 ppm/20 ppm/10 ppm/5 ppm) for 5 days, with 4 sheep in each group. Blood silver level, full blood counts, and biochemical parameters were analyzed in both safety and efficacy studies. Sinus tissue was harvested for histological examination and ciliary structure analysis in safety and for biofilm biomass quantification by fluorescence in situ hybridization (FISH) technique and COMSTAT 2 software in the efficacy study. Results were analyzed using appropriate statistical tests.

RESULTS
Sheep treated with silver showed a significant decrease in biofilm biomass (0.004, 0.004, 0.004, and 0.007, in the 4 silver-treated groups, respectively) compared to saline control (0.175), p < 0.001. Although average blood silver levels were higher in the treated groups compared to controls (p < 0.05), blood counts and biochemical parameters were normal. Histology and ciliary structure analysis did not show any difference between control and treatment groups.

CONCLUSION
Topical colloidal silver solution has effective antibiofilm activity in Staphylococcus aureus CRS in a sheep model and appears safe.

Rajiv|Sukanya|S| Drilling|Amanda|A| Bassiouni|Ahmed|A| James|Craig|C| Vreugde|Sarah|S| Wormald|Peter-John|PJ|

colloidal silver
Staphylococcus aureus
chronic rhinosinusitis
sheep
biofilm


Yfiler(®) Plus amplification kit validation and calculation of forensic parameters for two Austrian populations.

Abstract: With the new 6-dye AmpFISTR(®) Yfiler(®) Plus amplification kit (Thermo Fisher Scientific, Waltham, MA, USA) a set of 25 Y-chromosomal short tandem repeat loci (Y-STRs), including seven rapidly mutating Y-STRs (RM Y-STRs), is now available for forensic DNA typing. In this study we present our validation data for the AmpFISTR(®) Yfiler(®) Plus amplification kit and show the results of Y-chromosomal typing of 425 unrelated male individuals from two Austrian populations (Salzburg and Upper Austria) with the AmpFISTR(®) Yfiler(®) Plus amplification kit. Forensic parameters were calculated and compared for four Y-STR marker sets. We also typed five brother pairs to evaluate the power of discrimination for related individuals. The AmpFISTR(®) Yfiler(®) Plus (Yfiler Plus) kit appeared to be unimpaired by typical inhibitors such as hematin and humic acid or by large amounts of female components. An upgrade of analyzed markers resulted in increased discrimination capacity that is crucial for forensic trace analysis.

Pickrahn|Ines|I| Müller|Eva|E| Zahrer|Waltraud|W| Dunkelmann|Bettina|B| Cemper-Kiesslich|Jan|J| Kreindl|Gabriele|G| Neuhuber|Franz|F|

D001317:Austria
D041322:Chromosomes, Human, Y
D016172:DNA Fingerprinting
D053803:Forensic Genetics
D005787:Gene Frequency
D014644:Genetic Variation
D005828:Genetics, Population
D006239:Haplotypes
D006801:Humans
D008297:Male
D018895:Microsatellite Repeats
D016133:Polymerase Chain Reaction
D011933:Reagent Kits, Diagnostic
D015203:Reproducibility of Results

Yfiler
Y-chromosome
Y-STRs
Rapidly mutating Y-STRs (RM Y-STRs)
Yfiler Plus
Haplotype diversity


Activation of the Listeria monocytogenes Stressosome in the Intracellular Eukaryotic Environment.

Abstract: Listeria monocytogenes is a ubiquitous environmental bacterium and intracellular pathogen that responds to stress using predominantly the alternative sigma factor SigB. Stress is sensed by a multiprotein complex, the stressosome, extensively studied in bacteria grown in nutrient media. Following signal perception, the stressosome triggers a phosphorylation cascade that releases SigB from its anti-sigma factor. Whether the stressosome is activated during the intracellular infection is unknown. Here, we analyzed the subcellular distribution of stressosome proteins in L. monocytogenes located inside epithelial cells following their immunodetection in membrane and cytosolic fractions prepared from intracellular bacteria. Unlike bacteria in laboratory media, intracellular bacteria have a large proportion of the core stressosome protein RsbR1 associated with the membrane. However, another core protein, RsbS, is undetectable. Despite the absence of RsbS, a SigB-dependent reporter revealed that SigB activity increases gradually from early (1 h) to late (6 h) postinfection times. We also found that RsbR1 paralogues attenuate the intensity of the SigB response and that the miniprotein Prli42, reported to tether the stressosome to the membrane in response to oxidative stress, plays no role in associating RsbR1 to the membrane of intracellular bacteria. Altogether, these data indicate that, once inside host cells, the L. monocytogenes stressosome may adopt a unique configuration to sense stress and to activate SigB in the intracellular eukaryotic niche. IMPORTANCE The response to stress mediated by the alternative sigma factor SigB has been extensively characterized in Bacillus subtilis and Listeria monocytogenes. These bacteria sense stress using a supramacromolecular complex, the stressosome, which triggers a cascade that releases SigB from its anti-sigma factor. Despite the fact that many structural data on the complex are available and analyses have been performed in mutants lacking components of the stressosome or the signaling cascade, the integration of the stress signal and the dynamics of stressosome proteins following environmental changes remain poorly understood. Our study provides data at the protein level on essential stressosome components and SigB activity when L. monocytogenes, normally a saprophytic bacterium, adapts to an intracellular lifestyle. Our results support activation of the stressosome complex in intracellular bacteria. The apparent loss of the stressosome core protein RsbS in intracellular L. monocytogenes also challenges current models, favoring the idea of a unique stressosome architecture responding to intracellular host cues.

Dessaux|Charlotte|C|
Pucciarelli|M Graciela|MG|
Guerreiro|Duarte N|DN|
O'Byrne|Conor P|CP|
García-Del Portillo|Francisco|F|

D001426:Bacterial Proteins
D002460:Cell Line
D049109:Cell Proliferation
D004847:Epithelial Cells
D005057:Eukaryotic Cells
D006801:Humans
D008089:Listeria monocytogenes
D012808:Sigma Factor
D013312:Stress, Physiological

Listeria stressosome intracellular phosphorylation SigB RsbR1


Toxicity and Genotoxicity of Three Antimicrobials Commonly Used in Veterinary Medicine.

Abstract: The toxicity of chlortetracycline (CTC), oxytetracycline (OTC) and enrofloxacin (ENF) was tested on two green algal species: the international standard Pseudokirchneriella subcapitata and the native Argentine species Ankistrodesmus fusiformis. All three antibiotics inhibited the algal growth. The most sensitive species was P. subcapitata, for which the EC50 for CTC, OTC and ENF were 1.19 ± 0.53, 0.92 ± 0.30 and 5.18 ± 3.80 mg L-1, respectively. The EC50 for A. fusiformis, were 3.23 ± 0.53, 7.15 ± 2.69 and 10.6 ± 1.28 mg L-1, respectively. The genotoxicity of these veterinary antibiotics was also assessed using chromosome aberration (CA) and micronuclei (MN) induction in Allium cepa roots. Three concentrations were tested (0.1, 1 and 10 mg L-1). Only ENF at 1 and 10 mg L-1 showed any significant MN induction. These data revealed that CTC, OTC and ENF could cause toxicity on green algae, whereas ENF could cause genotoxicity on A. cepa plants.

Chlortetracycline
Oxytetracycline
Enrofloxacin
Pseudokirchneriella subcapitata
Allium cepa


Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5).

Abstract: Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2'-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2'-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P=0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly reduced by the knockdown of mIndy, likely mediating a trend to decreased basal rates of endogenous glucose production as well as an increased suppression of hepatic glucose production by 25% during a hyperinsulinemic-euglycemic clamp. Together, these data suggest that inducible liver-selective reduction of mIndy in rats is able to ameliorate hepatic steatosis and insulin resistance, conditions occurring with high calorie diets and during aging.

Pesta|Dominik H|DH|
Perry|Rachel J|RJ|
Guebre-Egziabher|Fitsum|F|
Zhang|Dongyan|D|
Jurczak|Michael|M|
Fischer-Rosinsky|Antje|A|
Daniels|Martin A|MA|
Willmes|Diana M|DM|
Bhanot|Sanjay|S|
Bornstein|Stefan R|SR|
Knauf|Felix|F|
Samuel|Varman T|VT|
Shulman|Gerald I|GI|
Birkenfeld|Andreas L|AL|

hepatic insulin resistance
Slc13a5
Indy
aging
type 2 diabetes


Efficacy and safety of everolimus in Chinese metastatic HR positive, HER2 negative breast cancer patients: a real-world retrospective study.

Abstract:
BACKGROUND
Everolimus combined with endocrine therapy has been proved to be effective among postmenopausal women with hormone receptor-positive human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). We aimed to evaluate the efficacy and safety of everolimus plus endocrine therapy in Chinese real-world practice for the first time, and investigate factors associated with efficacy.

METHODS
Seventy-five HR+/HER2- MBC patients were included in this retrospective study who received everolimus plus endocrine therapy after progression on prior endocrine therapy in Fudan University Shanghai Cancer Center (FUSCC) between June 2013 and February 2016. Main outcome measures are progression free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety profile.

RESULTS
After a median follow up of 10.3 (range: 2.1-32.2) months, median PFS was 5.9 months (95%CI 4.6-7.2), and median OS was not reached. The CBR was 38.8% (95%CI, 26.8-50.8) and ORR was 9.0% (95%CI, 2.0-16.0). Most common all-grade adverse events were stomatitis (57.1%), fatigue (25.7%), infection (24.3%) and hyperglycemia (21.4%). The most common ≥3 grade adverse events were stomatitis (9.3 %) and thrombocytopenia (5.7%). No treatment-related death was documented during and one month after the drug administration.

CONCLUSIONS
The combination of everolimus and endocrine therapy proved to be effective in Chinese population. The safety profiles were similar to previous studies but incidences were lower. In conclusion, everolimus combined with endocrine therapy provides a reasonable option for Chinese HR+/HER2- metastatic breast cancer patients.

Gong|Chengcheng|C| Zhao|Yannan|Y| Wang|Biyun|B| Hu|Xichun|X| Wang|Zhonghua|Z| Zhang|Jian|J| Zhang|Sheng|S|

everolimus
endocrine therapy
metastatic breast cancer
real-world study


Colorectal Cancer Screening Recommendations and Outcomes in Lynch Syndrome.

Abstract: Screening for colorectal cancer (CRC) in Lynch syndrome enables early detection and likely cancer prevention. CRC screening guidelines have evolved from universal to gene-specific recommendations based on lifetime neoplasia risks. Regular screening for Lynch syndrome reduces CRC-related mortality; however, high CRC incidence during regular colonoscopy screening suggests the possibility of nonpolypoid carcinogenesis. Colonoscopy is the primary modality for screening for Lynch syndrome with mixed and emerging data on quality metrics, chromoendoscopy, artificial intelligence, and nonendoscopic modalities. Screening adherence varies across studies. In this review, we present the current state of CRC screening recommendations, outcomes, and modalities in Lynch syndrome.

D003123:Colorectal Neoplasms, Hereditary Nonpolyposis

Colorectal cancer
Screening
Lynch syndrome
Quality
Chromoendoscopy
Artificial intelligence


To branch or to expand?

Abstract: Oscillating protein signals control the branching and expansion of blood vessels.

Bridges|Esther M|EM|
Harris|Adrian L|AL|0000-0003-1376-8409

D048868:Adaptor Proteins, Signal Transducing

D047908:Intracellular Signaling Peptides and Proteins

agent based modelling
angiogenesis
computational biology
developmental biology
human
mouse
neovascularization
signalling dynamics
stem cells
systems biology


Active site-adjacent phosphorylation at Tyr-397 by c-Abl kinase inactivates caspase-9.

Abstract: Caspase-9 (casp-9) is an initiator caspase and plays a central role in activating apoptotic cell death. Control of all caspases is tightly regulated by a series of phosphorylation events enacted by several different kinases. Caspase-9 is the most heavily phosphorylated of all caspases, with phosphorylation of at least 11 distinct residues in all three caspase-9 domains by nine kinases. Caspase-9 phosphorylation by the non-receptor tyrosine kinase c-Abl at Tyr-153 reportedly leads to caspase-9 activation. All other phosphorylation events on caspases have been shown to block proteolytic function by a number of mechanisms, so we sought to unravel the molecular mechanism of the putative caspase-9 activation by phosphorylation. Surprisingly, we observed no evidence for Tyr-153 phosphorylation of caspase-9 in vitro or in cells, suggesting that Tyr-153 is not phosphorylated by c-Abl. Instead, we identified a new site for c-Abl-mediated phosphorylation, Tyr-397. This residue is adjacent to the caspase-9 active site but, as a member of the second shell, not a residue that directly contacts substrate. Our results further indicate that Tyr-397 is the dominant site of c-Abl phosphorylation both in vitro and upon c-Abl activation in cells. Of note, phosphorylation at this site inhibits caspase-9 activity, and the bulk of the added phosphate moiety appeared to directly block substrate binding. c-Abl plays both proapoptotic and prosurvival roles, and our findings suggest that c-Abl's effects on caspase-9 activity promote the prosurvival mode.

Serrano|Banyuhay P|BP|
Szydlo|Hannah S|HS|
Alfandari|Dominique|D|
Hardy|Jeanne A|JA|

caspase
ABL tyrosine kinase
apoptosis
phosphocapture
phosphoenrichment
protease
protein phosphorylation
substrate-binding groove


Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.

Abstract: Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.

Ou|An-Te|AT| Zhang|Jia-Xin|JX| Fang|Yue-Fei|YF| Wang|Rong|R| Tang|Xue-Ping|XP| Zhao|Peng-Fei|PF| Zhao|Yu-Ge|YG| Zhang|Meng|M| Huang|Yong-Zhuo|YZ|

D018746:Systemic Inflammatory Response Syndrome

lactoferrin
sepsis
disulfiram
pyroptosis
ulcerative colitis
inflammation
macrophage-targeting delivery


Effect of resistance exercise intensity on the expression of PGC-1α isoforms and the anabolic and catabolic signaling mediators, IGF-1 and myostatin, in human skeletal muscle.

Abstract: The purpose of this study was to investigate the acute messenger (mRNA) expression of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) isoforms, insulin-like growth factor-1Ea (IGF-1Ea), and myostatin in response to 2 resistance exercise intensities. In a uniform-balanced, crossover design, 10 participants performed 2 separate testing sessions involving a lower body resistance exercise component consisting of a lower intensity (50% of 1-repetition maximum; 1RM) protocol and a higher intensity (80% of 1RM) protocol of equal volumes. Muscle samples were obtained at before exercise, 45 min, 3 h, 24 h, and 48 h postexercise. Resistance exercise did not alter total PGC-1α mRNA expression; however, distinct responses of each PGC-1α isoform were observed. The response of each isoform was consistent between sessions, suggesting no effect of resistance exercise intensity on the complex transcriptional expression of the PGC-1α gene. IGF-1Ea mRNA expression significantly increased following the higher intensity session compared with pre-exercise and the lower intensity session. Myostatin mRNA expression was significantly reduced compared with pre-exercise values at all time points with no difference between exercise intensity. Further research is needed to determine the effects of the various isoforms of PGC-1α in human skeletal muscle on the translational level as well as their relation to the expression of IGF-1 and myostatin.

Schwarz|Neil A|NA|
McKinley-Barnard|Sarah K|SK|
Spillane|Mike B|MB|
Andre|Thomas L|TL|
Gann|Joshua J|JJ|
Willoughby|Darryn S|DS|

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

resistance exercise
exercise intensity
PGC-1α
IGF-1
myostatin
myostatin
skeletal muscle
exercice contre résistance
expression génique
gene expression
intensité de l’exercice
muscle squelettique
myostatine


BoNT-A for Post-Stroke Spasticity: Guidance on Unmet Clinical Needs from a Delphi Panel Approach.

Abstract: There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients' clinical condition. Patients monitoring is needed over time, a follow-up of 4-6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician's perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice.

spasticity
Delphi
botulinum toxin
rehabilitation
stroke


A qualitative study of 'fear' as a regulator of children's independent physical activity in the suburbs.

Abstract: A crisis discourse has developed within the health and physical activity literature that paints a disparaging picture about the decline of children's participation in active play and independent mobility. Fear as a moderator of children's mobility, in this case focused on independent active school travel (IAST), remains a poorly understood construct. Within the popular press and academic literature, middle class parents have been characterised as overly anxious towards culturally reinforced dangers whilst being ignorant of the benefits of IAST during childhood. Fear of strangers, dangers and risk-taking are portrayed as nebulous and irrational anxiety states that are contributing to another great fear, a fear that our children are getting fat. The study draws upon Tudor's, (2003), parameters of fear framework to explore parent negotiations of fear and risk associated with IAST. In depth individual and focus group interviews with parents (N=24) provide insight into meanings, rules and customs that govern the way in which fear is experienced and expressed within a middle class white suburb in Australia. Far from being irrational, and operating purely from drivers at a cultural level, parents were aware of the consequences of their decisions on a range of outcomes. Parents could articulate their own anxieties and in many cases the rational probabilities of anything bad happening. Fear was being constructed through complex relations, negotiated individually and collectively within a specific cultural and environmental context. In the process of their decision-making, there remained a constant negotiation between a desire to allow their child independence and the question 'what if?' Those seeking to mediate increased opportunities for children's IAST are encouraged to remove the rational/irrational focus that was redundant for parents in this study, and consider shifting the message toward the positive side of what is a highly contested decision making space for parents.

Fear
Children
Physical activity
Mobility
Risk


Epipericardial fat necrosis - a rare cause of pleuritic chest pain: case report and review of the literature.

Abstract: Epipericardial fat necrosis (EPFN) is an uncommon cause of chest pain. Typically manifesting as severe acute chest pain, EPFN can be mistaken for a serious disorder, such as pulmonary embolism or myocardial infarction. We report a case of EPFN, diagnosed tentatively based on clinical and radiographic findings, with documented resolution of the lesion on chest CT. According to our literature search, this is only the second case in which chest CT alone was used to both diagnose the lesion and track its resolution. It is the first documented case diagnosed and followed as such in North America.


Paraneoplastic syndrome in Hawai'i: a case of dermatomyositis associated with endometrial cancer.

Abstract: Dermatomyositis as a paraneoplastic consequence of gynecological malignancy has rarely been reported in literature and never been reported in Honolulu. This case report describes a local Honolulu resident who was diagnosed with endometrial adenocarcinoma upon presenting with acute dermatomyositis symptoms.

Wada|Cherisse|C|
Hua|Charles Nc|CN|
Carney|Michael E|ME|

Paraneoplastic
dermatomyositis
endometrial
cancer
gynecological
gynecological
local
adenocarcinoma
Gottron papules
gynecology
heliotrope erythema
myositis
ovarian


Inflammasome components and ADAMTS4 in premature rupture of membranes.

Abstract: Inflammation may be responsible for the development of premature rupture of membranes (PROM) including preterm PROM (PPROM) and mature PROM (MPROM). A total of four classic receptor proteins have been confirmed to assemble inflammasomes: NLR family pyrin domain containing (NLRP)1, NLRP3 and NLR family CARD‑domain containing 4 (NLRC4) and absent in melanoma 2 (AIM2). The activation and expression of these receptor‑modulated inflammasomes in placenta and fetal membrane of PROM pregnancies requires investigation. In addition, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a risk factor for PROM, but whether its expression is associated with inflammasome activation remains to be elucidated. In the present study, the placenta and fetal membrane tissues of patients who had suffered PPROM and MPROM and healthy pregnancies were investigated. Reverse transcription‑quantitative PCR was used to determine the mRNA expression of inflammasomes and ADAMTS4. Western blotting, immunohistochemistry and ELISA were used to investigate the protein expression levels of inflammasomes and ADAMTS4. The results demonstrated that all four inflammasomes were elevated in placenta and fetal membrane of PPROMs as were mRNA and protein expression levels of IL‑18 and IL‑1β (compared with controls). A further increase of inflammasomes and interleukins was observed in MPROMs compared with controls. Similar results were also observed in ADAMTS4 expression in PPROM and MPROM groups. However, immunohistochemistry results revealed no significant difference of inflammasome receptor expression in PPROMs compared with controls. Finally, a general positive correlation between ADAMTS4 and all four inflammasome receptors in placenta and fetal membrane of PPROMs and MPROMs was observed. The present study revealed that NLRP1, NLRP3, AIM2 and NLRC4 inflammasome activation in PROM was increased. Promoted ADAMTS4 level was further observed in PROM group and was significantly correlated with inflammasome expression. Inhibition of inflammasome activation may provide a therapeutic target for clinical PROM treatment.

Zhu|Jinming|J| Ma|Chunling|C| Luan|Xiaomei|X| Li|Juan|J| Peng|Fengyun|F| Huang|Lei|L|

D005322:Fetal Membranes, Premature Rupture

D015971:Gene Expression Regulation, Enzymologic


Effects of Porphyromonas gingivalis lipopolysaccharide on osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling.

Abstract: In bone remodeling, the Eph family is involved in regulating the process of osteoclast and osteoblast coordination in order to maintain bone homeostasis. In this study, the effects of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the osteoblast-osteoclast bidirectional EphB4-EphrinB2 signaling were investigated. An osteoblast-osteoclast co-culture system was achieved successfully. Hence, direct contact and communication between osteoblasts and osteoclasts was permitted. Regarding the protein expression and gene expression of EphB4 and EphrinB2, it was shown that Pg-LPS increased the expression of EphB4 while inhibiting the expression of EphrinB2. Therefore, the results indicate that, when treated with Pg-LPS, the EphB4 receptor on osteoblasts and the EphrinB2 ligand on osteoclasts may generate bidirectional anti-osteoclastogenic and pro-osteoblastogenic signaling into respective cells and potentially facilitate the transition from bone resorption to bone formation. This study may contribute to the control of osteoblast differentiation and bone formation at remodeling, and possibly also modeling, sites.

Zhang|Yi|Y| Wang|Xi-Chao|XC| Bao|Xing-Fu|XF| Hu|Min|M| Yu|Wei-Xian|WX|


The atypical lipopolysaccharide of Francisella.

Abstract: Bacterial lipopolysaccharides (LPSs) are ubiquitous molecules that are prominent components of the outer membranes of most gram-negative bacteria. Genetic and structural characterizations of Francisella LPS have revealed substantial differences when compared to more commonly studied LPSs of the Enterobacteriaceae. This review discusses both the general characteristics and the unusual features of Francisella LPS.


Bone Mineral Density and Cortical-Bone Thickness of the Distal Radius Predict Femoral Stem Subsidence in Postmenopausal Women.

Abstract:
BACKGROUND
The distal radius is an optional site for evaluation of bone quality in postmenopausal women before cementless total hip arthroplasty. We hypothesized that dual-energy X-ray absorptiometry (DXA) and pulse-echo ultrasonometry of the distal radius may help discriminate subjects at high risk of femoral stem subsidence.

METHODS
A prospective cohort of postmenopausal women with primary hip osteoarthritis underwent total hip arthroplasty with implantation of a parallel-sided femoral stem. Postoperative stem migration was measured using radiostereometric analysis. Preoperatively, subjects had multisite DXA measurement of bone mineral density (BMD) and pulse-echo ultrasonometry of the cortical-bone thickness. The diagnostic abilities of these methods to discriminate <2 mm and ≥2 mm femoral stem subsidence were tested.

RESULTS
The accuracy of the distal radius BMD and cortical-bone thickness of the distal radius were moderate (area under the curve, 0.737 and 0.726, respectively) in discriminating between <2 mm and ≥2 mm stem subsidence. Women with low cortical-bone thickness of the radius were more likely (odds ratio = 6.7; P = .002) to develop stem subsidence ≥2 mm. These subjects had lower total hip BMD (P = .007) and reduced thickness of the medial cortex of the proximal femur (P = .048) with lower middle (P < .001) and distal (P = .004) stem-to-canal fill ratios.

CONCLUSION
Femoral stem stability and resistance to subsidence are sensitive to adequate bone stock and unaltered anatomy. DXA and pulse-echo ultrasonometry of the distal radius may help discriminate postmenopausal women at high risk of stem subsidence.

Nazari-Farsani|Sanaz|S|
Vuopio|Mia E|ME|
Aro|Hannu T|HT|

cementless total hip arthroplasty
DXA
pulse-echo ultrasonometry
cortical bone
osteoporosis
radiostereometric analysis (RSA)


2-Aminoethanol Extraction as a Method for Purifying Sc3N@C80 and for Differentiating Classes of Endohedral Fullerenes on the Basis of Reactivity.

Abstract: Extraction with 2-aminoethanol is an inexpensive method for removing empty cage fullerenes from the soluble extract from electric-arc-generated fullerene soot that contains endohedral metallofullerenes of the type Sc3N@C2n (n = 34, 39, 40). Our method of separation exploits the fact that C60, C70, and other larger, empty cage fullerenes are more susceptible to nucleophilic attack than endohedral fullerenes and that these adducts can be readily extracted into 2-aminoethanol. This methodology has also been employed to examine the reactivity of the mixture of soluble endohedral fullerenes that result from doping graphite rods used in the Krätschmer-Huffman electric-arc generator with the oxides of Y, Lu, Dy, Tb, and Gd. For example, with Y2O3, we were able to detect by mass spectrometry several new families of endohedral fullerenes, namely Y3C108 to Y3C126, Y3C107 to Y3C125, Y4C128 to Y4C146, that resisted reactivity with 2-aminoethanol more than the empty cage fullerenes and the mono- and dimetallo fullerenes. The discovery of the family Y3C107 to Y3C125 with odd numbers of carbon atoms is remarkable, since fullerene cages must involve even numbers of carbon atoms. The newly discovered families of endohedral fullerenes with the composition M4C2n (M = Y, Lu, Dy, Tb, and Gd) are unusually resistant to reaction with 2-aminoethanol. Additionally, the individual endohedrals, Y3C112 and M3C102 (M = Lu, Dy, Tb and Gd), were remarkably less reactive toward 2-aminoethanol.

Sarina|Evan A|EA|
Mercado|Brandon Q|BQ|
Franco|Jimmy U|JU|
Thompson|Christopher J|CJ|
Easterling|Michael L|ML|
Olmstead|Marilyn M|MM|
Balch|Alan L|AL|

2-aminoethanol
extraction
endohedral fullerene
mass spectrometry
purification


Genomewide and Enzymatic Analysis Reveals Efficient d-Galacturonic Acid Metabolism in the Basidiomycete Yeast Rhodosporidium toruloides.

Abstract: Biorefining of renewable feedstocks is one of the most promising routes to replace fossil-based products. Since many common fermentation hosts, such as Saccharomyces cerevisiae, are naturally unable to convert many component plant cell wall polysaccharides, the identification of organisms with broad catabolism capabilities represents an opportunity to expand the range of substrates used in fermentation biorefinery approaches. The red basidiomycete yeast Rhodosporidium toruloides is a promising and robust host for lipid- and terpene-derived chemicals. Previous studies demonstrated assimilation of a range of substrates, from C5/C6 sugars to aromatic molecules similar to lignin monomers. In the current study, we analyzed the potential of R. toruloides to assimilate d-galacturonic acid, a major sugar in many pectin-rich agricultural waste streams, including sugar beet pulp and citrus peels. d-Galacturonic acid is not a preferred substrate for many fungi, but its metabolism was found to be on par with those of d-glucose and d-xylose in R. toruloides A genomewide analysis by combined transcriptome sequencing (RNA-seq) and RB-TDNA-seq revealed those genes with high relevance for fitness on d-galacturonic acid. While R. toruloides was found to utilize the nonphosphorylative catabolic pathway known from ascomycetes, the maximal velocities of several enzymes exceeded those previously reported. In addition, an efficient downstream glycerol catabolism and a novel transcription factor were found to be important for d-galacturonic acid utilization. These results set the basis for use of R. toruloides as a potential host for pectin-rich waste conversions and demonstrate its suitability as a model for metabolic studies with basidiomycetes.IMPORTANCE The switch from the traditional fossil-based industry to a green and sustainable bioeconomy demands the complete utilization of renewable feedstocks. Many currently used bioconversion hosts are unable to utilize major components of plant biomass, warranting the identification of microorganisms with broader catabolic capacity and characterization of their unique biochemical pathways. d-Galacturonic acid is a plant component of bioconversion interest and is the major backbone sugar of pectin, a plant cell wall polysaccharide abundant in soft and young plant tissues. The red basidiomycete and oleaginous yeast Rhodosporidium toruloides has been previously shown to utilize a range of sugars and aromatic molecules. Using state-of-the-art functional genomic methods and physiological and biochemical assays, we elucidated the molecular basis underlying the efficient metabolism of d-galacturonic acid. This study identified an efficient pathway for uronic acid conversion to guide future engineering efforts and represents the first detailed metabolic analysis of pectin metabolism in a basidiomycete fungus.

yeasts
Rhodosporidium toruloides
aerobic catabolism
carbon metabolism
galacturonic acid


Outcomes and outcome measures used in evaluation of communication training in oncology - a systematic literature review, an expert workshop, and recommendations for future research.

Abstract:
BACKGROUND
Communication between health care provider and patients in oncology presents challenges. Communication skills training have been frequently developed to address those. Given the complexity of communication training, the choice of outcomes and outcome measures to assess its effectiveness is important. The aim of this paper is to 1) perform a systematic review on outcomes and outcome measures used in evaluations of communication training, 2) discuss specific challenges and 3) provide recommendations for the selection of outcomes in future studies.

METHODS
To identify studies and reviews reporting on the evaluation of communication training for health care professionals in oncology, we searched seven databases (Ovid MEDLINE, CENTRAL, CINAHL, EMBASE, PsychINFO, PsychARTICLES and Web of Science). We extracted outcomes assessed and the respective assessment methods. We held a two-day workshop with experts (n = 16) in communication theory, development and evaluation of generic or cancer-specific communication training and/or outcome measure development to identify and address challenges in the evaluation of communication training in oncology. After the workshop, participants contributed to the development of recommendations addressing those challenges.

RESULTS
Out of 2181 references, we included 96 publications (33 RCTs, 2 RCT protocols, 4 controlled trials, 36 uncontrolled studies, 21 reviews) in the review. Most frequently used outcomes were participants' training evaluation, their communication confidence, observed communication skills and patients' overall satisfaction and anxiety. Outcomes were assessed using questionnaires for participants (57.3%), patients (36.0%) and observations of real (34.7%) and simulated (30.7%) patient encounters. Outcomes and outcome measures varied widely across studies. Experts agreed that outcomes need to be precisely defined and linked with explicit learning objectives of the training. Furthermore, outcomes should be assessed as broadly as possible on different levels (health care professional, patient and interaction level).

CONCLUSIONS
Measuring the effects of training programmes aimed at improving health care professionals' communication skills presents considerable challenges. Outcomes as well as outcome measures differ widely across studies. We recommended to link outcome assessment to specific learning objectives and to assess outcomes as broadly as possible.

Outcome
Evaluation
Communication training
Oncology


Control of noncoding RNA production and histone levels by a 5' tRNA fragment.

Abstract: Small RNAs derived from mature tRNAs, referred to as tRNA fragments or "tRFs," are an emerging class of regulatory RNAs with poorly understood functions. We recently identified a role for one specific tRF-5' tRF-Gly-GCC, or tRF-GG-as a repressor of genes associated with the endogenous retroelement MERVL, but the mechanistic basis for this regulation was unknown. Here, we show that tRF-GG plays a role in production of a wide variety of noncoding RNAs-snoRNAs, scaRNAs, and snRNAs-that are dependent on Cajal bodies for stability and activity. Among these noncoding RNAs, regulation of the U7 snRNA by tRF-GG modulates heterochromatin-mediated transcriptional repression of MERVL elements by supporting an adequate supply of histone proteins. Importantly, the effects of inhibiting tRF-GG on histone mRNA levels, on activity of a histone 3' UTR reporter, and ultimately on MERVL regulation could all be suppressed by manipulating U7 RNA levels. We additionally show that the related RNA-binding proteins hnRNPF and hnRNPH bind directly to tRF-GG, and are required for Cajal body biogenesis, positioning these proteins as strong candidates for effectors of tRF-GG function in vivo. Together, our data reveal a conserved mechanism for 5' tRNA fragment control of noncoding RNA biogenesis and, consequently, global chromatin organization.

Boskovic|Ana|A|
Bing|Xin Yang|XY|
Kaymak|Ebru|E|
Rando|Oliver J|OJ|


A unique case of a discontinuous duplication 3q26.1-3q28 resulting from a segregation error of a maternal complex chromosomal rearrangement involving an insertion and an inversion.

Abstract: Until now, few cases of partial trisomy of 3q due to segregation error of parental balanced translocation and segregation of a duplicated deficient product resulting from parental pericentric inversion have been reported so far. Only five cases of chromosomal insertion malsegregation involving 3q region are available yet, thus making it relatively rare. In this case report, we are presenting a unique case of discontinuous partial trisomy of 3q26.1-q28 region which resulted from a segregation error of two insertions involving 3q26.1 to 3q27.3 and 3q28 regions with ~21Mb and ~2Mb sizes, respectively. The maternally inherited insertion was cytogenetically characterized as der(8)(8pter→8p22::3q26→3q27.3::3q28→3q28::8p22→8qter) and the patient's major clinical features involved Dandy Walker malformation, sub-aortic ventricular septal defect, upslanting palpebral fissures, clinodactyly, hirsutism, and prominent forehead. Besides, a review of the literature involving cases with similar chromosomal imbalances and cases with "3q-duplication syndrome" is also provided.

Rodríguez|Laura|L|
Bhatt|Samarth S|SS|
García-Castro|Mónica|M|
Plasencia|Ana|A|
Fernández-Toral|Joaquín|J|
Abarca|Elena|E|
de Bello Cioffi|Marcelo|M|
Liehr|Thomas|T|

D017404:In Situ Hybridization, Fluorescence

Dandy Walker malformation
ventricular septal defect
3q-duplication syndrome
BAC
DD
DWM
FISH
ID
MCB
Molecular cytogenetics
OFC
P
VSD
array comparative genomic hybridization
array-CGH
bacterial artificial chromosomes
developmental delay
fluorescence in situ hybridization
intellectual disability
multicolor banding technique
occipitofrontal circumference
percentile
subcenM-FISH
subcentromere-specific multicolor FISH

P P P U U U U U U M U U U U U M U M U U U U U U


Adapting STEMI care for the COVID-19 pandemic: The case for low-risk STEMI triage and early discharge.

Abstract: The coronavirus pandemic has resulted in the need for rapid assessment of resource utilization within our hospital systems. Specifically, the overwhelming need for intensive care unit (ICU) beds within epicenters of the pandemic has created a need for consideration as to how acute coronary syndrome cases, and specifically ST-elevation myocardial infarction (STEMI) patients, are managed postprocedure. While most patients in the United States continue to be managed in coronary care units after primary percutaneous coronary intervention, there is a robust literature regarding the ability to triage STEMI patients safely and efficiently with low-risk features to non-ICU beds. We review the various risk scores for STEMI triage and the data supporting their usage. In summary, these findings support an approach to low-risk STEMI triage that does not come at the expense of quality patient care or outcomes, where up to two-thirds of patients with STEMI may be able to be safely managed without ICU-level care.

STEMI
pandemic
acute coronary syndrome
PCI


Infected aortic and iliac aneurysms: Clinical manifestations in the emergency departments of two hospitals in southern Taiwan, China.

Abstract:
BACKGROUND
Accurate diagnosis of infected aortic and iliac aneurysms is often delayed, hampering timely treatment and potentially resulting in a fatal consequence. The aim of this study was to discover useful clinical features that can help physicians to identify these patients.

METHODS
We reviewed the discharge notes from two hospitals and identified all patients who had a diagnosis of infected aneurysms of the thoracoabdominal aorta and iliac arteries between July 2009 and December 2013. Eighteen patients, aged from 41 to 93, were reviewed. Only 6 patients were diagnosed accurately in their first visit to our ED.

RESULTS
Most patients had at least one underlying illness, and it took 1 to 30 (9.9±6.5) days for physicians to diagnose their infected aneurysm. Localized pain and fever were the two most commonly presented symptoms. The majority (92%) of isolated microorganisms were gram-negative bacilli, including Salmonella spp, Klebsiella pneumoniae, and Escherichia coli. Two of the 3 patients who underwent non-operative therapy died, and all of the patients who underwent a combination of medical and operative therapies survived.

CONCLUSION
We suggest that physicians liberally use computed tomography scans on patients with unknown causes of pain and inflammatory processes. A combination of surgical and medical treatments is indicated for all patients with infected aortic and iliac aneurysms.

Clinical manifestation
Emergency department
Infected aneurysm
Salmonella
Misdiagnosis


Exploring perceptions on medical app use in clinical communication among Austrian physicians: Results of a validation study.

Abstract: Physicians increasingly use medical applications to facilitate clinical information management. The respective effect on clinical communication and quality of healthcare provision has not been studied in the Austrian context so far. Thus, the current cross-sectional online study analyzed prevalent medical applications use and views on clinical communication competence in everyday medical practice among Austrian physicians (n = 151) and validated the survey tool. More than half of the participants used medical applications in daily clinical practice. The top three benefits of medical applications use were higher quality of healthcare, location-independent health service access, and higher efficiency in healthcare resource allocation. Moreover, study participants felt that communication competence acquired during medical studies inadequately prepared them for daily clinical practices. Medical applications use certainly affects the therapeutic alliance between patients and physician. This study supports the importance of initiating an open, constructive discussion among healthcare stakeholders and developing according to evidence-based guidelines.

healthcare personnel
online survey
principal component analysis
smartphones
telehealth