The Role of PI3K/Akt and ERK in Neurodegenerative Disorders

Abstract

Disruption of Akt and Erk-mediated signal transduction significantly contributes in the pathogenesis of various neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's diseases, Huntington's disease, and many others. These regulatory proteins serve as the regulator of cell survival, motility, transcription, metabolism, and progression of the cell cycle. Therefore, targeting Akt and Erk pathway has been proposed as a reasonable approach to suppress ND progression. This review has emphasized on involvement of Akt/Erk cascade in the neurodegeneration. Akt has been reported to regulate neuronal toxicity through its various substrates like FOXos, GSK3β, and caspase-9 etc. Akt is also involved with PI3K in signaling pathway to mediate neuronal survival. ERK is another kinase which also regulates proliferation, differentiation, and survival of the neural cell. There has also been much progress in developing a therapeutic molecule targeting Akt and Erk signaling. Therefore, improved understanding of the molecular mechanism behind the regulatory aspect of Akt and Erk networks can make strong impact on exploration of the neurodegenerative disease pathogenesis.

http://bit.ly/2BcLvCz

Reply to the Letter to the Editor of Fei Jia et al. concerning “Comparison of combined anterior–posterior approach versus posterior-only approach in neuromuscular scoliosis: a systematic review and meta-analysis” by Shao ZX, et al. [Eur Spine J; (2018) 27(9): 2213–2222]

http://bit.ly/2sYmZAj

TiO 2 nanotube arrays modified with nanoparticles of platinum group metals (Pt, Pd, Ru): enhancement on photoelectrochemical performance

Abstract

Highly ordered TiO₂ nanotube arrays (TiO₂ NTs) were synthesized by anodization method using a titanium foil and further modified with nanoparticles (Ø = 2~10 nm) of three platinum group metals (that is, platinum, palladium, and ruthenium) through potentiostatic pulsed electrodeposition method to obtain the composite material. Compared with pure TiO₂ NTs, all the three composite samples (M-TiO₂ NTs, M = Pt, Pd, Ru) showed different enhancement effects on the light responses, as well as different photoelectrochemical performances. In this study, the performance of M-TiO₂ NTs, which worked as photoanode and cathode, was investigated. Ru-TiO₂ exhibited the best degradation yield (~ 85.8%) when applied as photoanode under visible light illumination, which indicated the platinum group metal could also be induced under visible irradiation, not just served as the co-catalyst. M-TiO₂ NTs as cathode were evaluated under the hydrogen evolution reaction (HER). The three M-TiO₂ NT electrodes showed an improved efficiency over pure TiO₂ NTs, while Pt-TiO₂ NTs performed even better (without any sacrificial agent) with higher Faradic efficiency than platinum electrode in the photoelectrocatalytic hydrogen production, which could be explained by the uniform and fine metal nanoparticles on the surface of TiO₂ NTs to offer abundant active sites for the reaction.

Graphical abstract

In this paper, TiO2 nanotube arrays loaded with nanoparticles of platinum group metals have been explored on their enhancement of photoelectrocatalytic activity. Platinum group metals served as co-catalyst in the surface of TiO2 nanotubes and show great variations in different reactions.

http://bit.ly/2Gds9Ap

Verification of image quality and quantification in whole-body positron emission tomography with continuous bed motion

Abstract

Objective

Whole-body dynamic imaging using positron emission tomography (PET) facilitates the quantification of tracer kinetics. It is potentially valuable for the differential diagnosis of tumors and for the evaluation of therapeutic efficacy. In whole-body dynamic PET with continuous bed motion (CBM) (WBDCBM-PET), the pass number and bed velocity are key considerations. In the present study, we aimed to investigate the effect of a combination of pass number and bed velocity on the quantitative accuracy and quality of WBDCBM-PET images.

Methods

In this study, WBDCBM-PET imaging was performed at a body phantom using seven bed velocity settings in combination with pass numbers. The resulting image quality was evaluated. For comparing different acquisition settings, the dynamic index (DI) was obtained using the following formula: [P/S], where P represents the pass number, and S represents the bed velocity (mm/s). The following physical parameters were evaluated: noise equivalent count at phantom (NEC_phantom), percent background variability (N_10 mm), percent contrast of the 10 mm hot sphere (Q_{H, 10 mm}), the Q_{H, 10 mm}/N_10 mm ratio, and the maximum standardized uptake value (SUV_max). Furthermore, visual evaluation was performed.

Results

The NEC_phantom was equivalent for the same DI settings regardless of the bed velocity. The N_10 mm exhibited an inverse correlation (r < − 0.89) with the DI. Q_H,10 mm was not affected by DI, and a correlation between Q_H,10 mm/N_10 mm ratio and DI was found at all the velocities (r > 0.93). The SUV_max of the spheres was not influenced by the DI. The coefficient of variations caused by bed velocity decreased in larger spheres. There was no significant difference between the bed velocities on visual evaluation.

Conclusion

The quantitative accuracy and image quality achieved with WBDCBM-PET was comparable to that achieved with non-dynamic CBM, regardless of the pass number and bed velocity used during imaging for a given acquisition time.

http://bit.ly/2G2JvAQ

The impact of body mass index on perioperative outcomes after robotic liver resection

Abstract

High body mass index (BMI) is associated with other multiple comorbidities such as non-alcoholic fatty liver disease, steatohepatitis, liver cirrhosis, and cardiopulmonary diseases, which can impact the perioperative outcomes following liver resection. We aimed to study the impact of BMI on perioperative outcomes after robotic liver resection. All the patients undergoing robotic liver resection between 2013 and 2017 were prospectively followed. The patients were divided into three groups (BMI < 25, BMI 25–35, BMI > 35 kg/m²) for illustrative purposes. Demographic and perioperative outcome data were compared. Data are presented as median (mean ± SD). Thirty-eight patients underwent robotic hepatectomy, 73% were women, age was 58 (57 ± 17.6) years, and ASA class was 3 (3 ± 0.5). Indications for surgery were neoplastic lesions in 34 patients (89%), hemangioma in two patients (6%), fibrous mass in one patient (2.5%), and focal nodular hyperplasia in one patient (2.5%). 32% of the patients underwent right or left hemihepatectomy, 21% underwent sectionectomy, 5% underwent central hepatectomy and the reminder underwent non-anatomical liver resection. Operative time was 261 (254.6 ± 94.3) min. Estimated blood loss was 175 (276 ± 294.8) ml. Length of hospital stay was 3 (5 ± 4.9) days. By regression analysis of the three BMI groups, estimated blood loss, rate of postoperative complication, rate of conversion, need for transfusion, length of ICU stay, and length of hospital stay did not have a significant relationship with BMI. A total of five patients (13%) experience complications. Four patients had complications that were nonspecific to liver resection, including acute renal injury, respiratory failure, and enterocutaneous fistula. One patient had bile leak, treated with ERCP stenting. No mortality was seen in this study. Obesity should not dissuade surgeons from utilizing minimally invasive robotic approach for liver resection. Robotic technique is a safe and feasible in patients with high BMI. The impact of BMI on outcomes is insignificant.

http://bit.ly/2MJUMGG

MiR-5571-3p and miR-135b-5p, derived from analyses of microRNA profile sequencing, correlate with increased disease risk and activity of rheumatoid arthritis

Abstract

Objectives

This study aimed to investigate microRNA (miRNA) expression profiles in synovium tissues of rheumatoid arthritis (RA) patients by RNA sequencing and to evaluate the values of dysregulated miRNAs in RA diagnosis and monitoring.

Methods

Thirty RA patients who underwent knee arthroscopy and 30 controls with knee trauma who underwent surgery were consecutively recruited, and synovium tissue samples of both groups were obtained during surgeries. In the exploration part, miRNA and mRNA expression profiles of 3 RA samples and 3 control samples were detected using RNA sequencing then followed by bioinformatic analyses. In the validation part, 5 candidate miRNA levels were detected by quantitative polymerase chain reaction (qPCR) in 30 RA patients and 30 control patients.

Results

In the exploration part, 78 miRNAs and 1582 mRNAs were upregulated while 40 miRNAs and 1295 mRNAs were downregulated in synovium tissue samples of RA patients compared with those of controls. Furthermore, enrichment analyses revealed that these dysregulated miRNAs and mRNAs were mainly implicated in immune activities and inflammatory diseases such as leukocyte migration, complement activation, and RA. In the validation part, qPCR assay revealed that miR-5571-3p and miR-135b-5p expressions were increased in RA patients compared with those in controls and disclosed good predictive values for RA risk with high area under the curves (AUCs). Besides, both miR-5571-3p and miR-135b-5p levels were positively correlated with disease activity and inflammation level of RA.

Conclusions

Analyses of miRNA expression profiles by sequencing indicate that miR-5571-3p and miR-135b-5p correlate with increased RA risk and activity.

http://bit.ly/2G2oZjx

A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature

Abstract

Autosomal recessive primary microcephaly (MCPH) is a group of rare neurodevelopmental diseases with severe microcephaly at birth. One type of the disorder, MCPH2, is caused by biallelic mutations in the WDR62 gene, which encodes the WD repeat–containing protein 62. Patients with WDR62 mutation may have a wide range of malformations of cortical development in addition to congenital microcephaly. We describe two patients, a boy and a girl, with severe congenital microcephaly, global developmental delay, epilepsy, and failure to thrive. MRI showed hemispherical asymmetry, diffuse pachygyria, thick gray matter, indistinct gray-white matter junction, and corpus callosum and white matter hypoplasia. Whole exome sequencing revealed the same novel homozygous missense mutation, c.668T>C, p.Phe223Ser in exon 6 of the WDR62 gene. The healthy parents were heterozygous for this mutation. The mutation affects a highly conserved region in one of the WD repeats of the WDR62 protein. Haplotype analysis showed genetic relatedness between the families of the patients. Our findings expand the spectrum of mutations randomly distributed in the WDR62 gene. A review is also provided of the brain malformations described in WDR62 mutations in association with congenital microcephaly.

http://bit.ly/2CZFqct

Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines

Summary

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and sensitizes glioblastoma cells to temozolomide cytotoxicity. Herein, we report in vitro activity of three semi-synthetic ingenol compounds derived from E. tirucalli, IngA (ingenol-3-trans-cinnamate), IngB (ingenol-3-hexanoate) and IngC (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Antineoplastic effects of the three semi-synthetic compounds were assessed using MTS assays on 70 cancer cell lines from a wide array of solid tumors. Additionally, their antitumor potential was compared with known compounds of the same class, namely ingenol-3-angelate (Picato®) and ingenol 3,20-dibenzoate and in combination with standard chemotherapeutic agents. We observed that IngA, B, and C exhibited dose-dependent cytotoxic effects. Amongst the semi-synthetic compounds, IngC displayed the best activity across the tumor cell lines. In comparison with ingenol-3-angelate and ingenol 3,20-dibenzoate, IngC showed a mean of 6.6 and 3.6-fold higher efficacy, respectively, against esophageal cancer cell lines. Besides, IngC sensitized esophageal cancer cells to paclitaxel treatment. In conclusion, the semi-synthetic ingenol compounds, in particular, IngC, demonstrated a potent antitumor activity on all cancer cell lines evaluated. Although the underlying mechanisms of action of IngC are not elucidated, our results provide insights for further studies suggesting IngC as a putative therapy for cancer treatment.

http://bit.ly/2MHZULh

Transgenic versus conventional corn: fate of fumonisins during industrial dry milling

Abstract

The aim of this study was to compare the fate of fumonisins in transgenic and non-transgenic corn during industrial dry milling. For this purpose, whole corn samples and their fractions (germ, pericarp, endosperm, corn meal, and grits) were collected from one of the major Brazilian milling plants, totaling 480 samples. There was no significant difference (p > 0.05) between mean fumonisin (FB₁ + FB₂) levels in transgenic (1130 μg/kg) and non-transgenic (920 μg/kg) whole corn. However, in non-transgenic germ, endosperm and corn meal fraction fumonisin levels were higher (2940 μg/kg, 250 μg/kg and 190 μg/kg, respectively) than in transgenic fractions (2180 μg/kg, 130 μg/kg and 85.0 μg/kg, respectively). Furthermore, the highest percentages of fumonisins were distributed in the germ, corresponding to about 87 and 76% of the total fumonisins present in the whole corn from non-transgenic and transgenic hybrids, respectively. Concerning the endosperm from non-transgenic and transgenic corn, approximately, 23% and 13% of the total fumonisins were retained after the dry milling. Further processing in corn meal (300 to 420 μm particle size) and grits (590 to 1190 μm) decreased the percentages of remaining fumonisins to 4% and 2% (transgenic) and 10% and 3% (non-transgenic corn), respectively. These results suggested that fumonisin concentration was higher in outer and inner non-transgenic fractions when compared to transgenic ones and that the fate of fumonisins during the industrial dry milling could be affected by the transgenic status. However, it was not possible to conclude that the difference was exclusively due to this variable.

http://bit.ly/2SgBT3s

First report of Fusarium foetens as a mycotoxin producer

Abstract

Fusarium foetens, a pathogen of Begonia plants, has been recently described as a new fungal species. This Fusarium species causes a destructive vascular wilt disease which leads to the death of the plant. Moreover, Fusarium species are known to produce a huge variety of secondary metabolites such as mycotoxins and phytotoxins. Here, we studied the toxicogenic profile of one F. foetens strain, isolated from maize, employing two methods based on the use of ultra-performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight detection. The mycotoxins beauvericin and fusaric acid were detected in a pure culture of F. foetens. In addition, four fusaric acid analogs (10,11-dihidroxyfusaric acid, hydroxyfusaric acid, dehydrofusaric acid, and a hydroxylated unsaturated fusaric acid analog) were tentatively identified on the basis of their accurate mass and fragmentation patterns. Therefore, these preliminary data indicate that F. foetens isolated from maize is able to produce Fusarium mycotoxins including beauvericin and fusaric acid.

http://bit.ly/2GeP2U6

Modified ingenol semi-synthetic derivatives from Euphorbia tirucalli induce cytotoxicity on a large panel of human cancer cell lines

Summary

The latex from Euphorbia tirucalli is used in Brazil as a folk medicine for several diseases, including cancer. Recently, we showed a cytotoxic activity of E. tirucalli euphol in a wide range of cancer cell lines. Moreover, we showed that euphol inhibits proliferation, motility and colony formation in pancreatic cancer cells, induces autophagy and sensitizes glioblastoma cells to temozolomide cytotoxicity. Herein, we report in vitro activity of three semi-synthetic ingenol compounds derived from E. tirucalli, IngA (ingenol-3-trans-cinnamate), IngB (ingenol-3-hexanoate) and IngC (ingenol-3-dodecanoate), against a large panel of human cancer cell lines. Antineoplastic effects of the three semi-synthetic compounds were assessed using MTS assays on 70 cancer cell lines from a wide array of solid tumors. Additionally, their antitumor potential was compared with known compounds of the same class, namely ingenol-3-angelate (Picato®) and ingenol 3,20-dibenzoate and in combination with standard chemotherapeutic agents. We observed that IngA, B, and C exhibited dose-dependent cytotoxic effects. Amongst the semi-synthetic compounds, IngC displayed the best activity across the tumor cell lines. In comparison with ingenol-3-angelate and ingenol 3,20-dibenzoate, IngC showed a mean of 6.6 and 3.6-fold higher efficacy, respectively, against esophageal cancer cell lines. Besides, IngC sensitized esophageal cancer cells to paclitaxel treatment. In conclusion, the semi-synthetic ingenol compounds, in particular, IngC, demonstrated a potent antitumor activity on all cancer cell lines evaluated. Although the underlying mechanisms of action of IngC are not elucidated, our results provide insights for further studies suggesting IngC as a putative therapy for cancer treatment.

http://bit.ly/2MHZULh

De-Hankelization of singular spectrum analysis matrices via L 1 norm criterion

Abstract

This paper proposes to employ the L₁ norm criterion to perform the de-Hankelization in the singular spectrum analysis (SSA). In particular, the represented values of the off-diagonals in the two-dimensional SSA matrices are found via minimizing the L₁ norm errors of the vectors defining as the absolute differences between the off-diagonal vectors and the vectors with all their elements being the represented values. This results to reduce the total number of the large-valued elements in the error vectors. Also, this paper guarantees to achieve the exact perfect reconstruction of the original signal. As the formulated problem is a standard linear programming problem, the solution could be efficiently found via the simplex method. The computer numerical simulations verify the results.

http://bit.ly/2S1RQv3

Pediatric nodular fasciitis at the roof of the optic canal causing decreased vision: case report and review of the literature

Abstract

We present a 3-year-old girl with decreased visual acuity of the left eye. Radiological studies revealed a mass lesion at the roof of the left optic canal with bony erosion, which compressed the left optic nerve. Gross total resection of the mass and decompression of the optic canal were performed. Histopathological study was consistent with nodular fasciitis. This is the first report of nodular fasciitis at the roof of the optic canal in a young child. Nodular fasciitis compressing the optic nerve should be included in differential diagnoses of optic neuropathy in young children.

http://bit.ly/2UxjKeV

Antibacterial effects of iron oxide (Fe 3 O 4 ) nanoparticles: distinguishing concentration-dependent effects with different bacterial cells growth and membrane-associated mechanisms

Abstract

Nowadays, the influence of nanoparticles (NPs) on microorganisms attracts a great deal of attention as an alternative to antibiotics. Iron oxide (Fe₃O₄) NPs' effects on Gram-negative Escherichia coli BW 25113 and Gram-positive Enterococcus hirae ATCC 9790 growth and membrane-associated mechanisms have been investigated in this study. Growth specific rate of E. coli was decreased, indicating the bactericidal effect of Fe₃O₄ NPs. This inhibitory effect of NPs had a concentration-dependent manner. The reactive oxygen species together with superoxide radicals and singlet oxygen formed by Fe₃O₄ NPs could be the inhibition cause. Fe₃O₄ NPs showed opposite effects on E. hirae: the growth stimulation or inhibition was observed depending on NPs concentration used. Addition of NPs altered redox potential kinetics and inhibited H₂ yield in E. coli; no change in intracellular pH was determined. Fe₃O₄ NPs decreased H⁺-fluxes through bacterial membrane more in E. coli than in E. hirae even in the presence of DCCD and increased ATPase activity more in E. hirae than in E. coli. Our results showed that the Fe₃O₄ NPs demonstrate differentiating effects on Gram-negative and Gram-positive bacteria likely due to the differences in bacterial cell wall structure and metabolic peculiarities. Fe₃O₄ NPs of different concentrations have no hemolytic (cytotoxic) activity against erythrocytes. Therefore, they can be proposed as antibacterial agents in biomedicine, biotechnology, and pharmaceutics.

http://bit.ly/2t2uztG

Enhanced production and identification of antioxidants in in vitro cultures of the cacti Mammillaria candida and Turbinicarpus laui

Abstract

Cacti are an important source of metabolites but present limitations for their commercial exploitation, like slow growth and a decrease of wild populations. An alternative to obtain their biocompounds without affecting the natural environment are the in vitro culture techniques. We established in vitro cultures from Mammillaria candida Scheidweiler and Turbinicarpus laui Glass and Foster and used different stresses to increase metabolites and antioxidant activity. The cultures were exposed to 1.25% polyethylene glycol to induce a moderate drought stress, 50 g L⁻¹ sucrose to generate an osmotic stress, chitosan (1.25 to 5 mg mL⁻¹) to simulate a biotic attack, or to UV light. Chitosan was the best elicitor improving 1.5 times the concentration of phenolics, 9 to 10 times the content of flavonoids and betalains, and 16% the antioxidant activity in M. candida suspensions. In T. laui suspensions, this elicitor duplicates the flavonoids content and antioxidant activity. The antioxidant levels in elicited suspensions increased 5 to 10 times in relation to plant tubercles. Eleven compounds were identified in M. candida suspensions being digalloyl rhamnoside and epicatequin gallate the most abundant; in the T. laui suspensions, 16 compounds were detected and the most abundant were 17-decarboxi neobetanin and derivatives of luteolin. Thus, cacti in vitro culture is an efficient system to obtain high level of metabolites of biological interest.

http://bit.ly/2MKQEWI

Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial

Summary

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Twelve patients with advanced lung adenocarcinoma were enrolled, the primary endpoint was safety. Two doses of apatinib, 250 mg/day (level 1) and 500 mg/day (level 2), were evaluated in combination with 60 mg/m² doxetacel every 3 weeks. Six patients have been treated at levels 1 and 2, respectively. Optimal dose of apatinib was determined by dose-limiting toxicity (DLT). Results Six patients have been treated at levels 1 and 2. At level 1, one of six patients experienced grade 3 acneiform rash as DLTs. At level 2, two patients experienced grade 3 hypertension and one experienced grade 3 nasal bleeding. MTD and recommended dose for phase II study was 250 mg/day. Most frequent adverse events of any grade were bilirubin elevation, hypertension, alanine aminotransferase elevation, transglutaminase elevation, hand foot syndrome and fatigue. The median progression-free survival was 2.76 month. Moreover, three patients had developed progressive disease and the mean duration of response was 2.79 months. Conclusion Apatinib plus docetaxel was well tolerated and showed promising efficacy in advanced lung adenocarcinoma. This combination therapy may represent a potent therapeutic option for advanced lung adenocarcinoma patients with wild-type EGFR.

http://bit.ly/2UyJHuN

Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo

Summary

We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.

http://bit.ly/2sZ68NO

Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo

Summary

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3⁺ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

http://bit.ly/2UyJAPT

Evaluation des Zungengrunds bei OSAS unter elektrischer Stimulationstherapie des N. hypoglossus

Zusammenfassung

Hintergrund

Die nächtliche elektrische Stimulationstherapie des Nervus hypoglossus von Patienten mit obstruktivem Schlafapnoesyndrom (OSAS) ist eine vergleichsweise junge Therapieform. Verlaufsdaten zu Auswirkungen auf die Zungengrundmorphologie unter langfristiger Stimulationstherapie liegen nicht vor.

Fragestellung

Im Rahmen dieser Studie erfolgte die sonografische Evaluation der Zunge bei Patienten mit OSAS vor und nach der Implantation eines Hypoglossusstimulationssystems. Ziel war es, die Durchführbarkeit der Methode zu zeigen sowie erste Hinweise auf Veränderungen der Zungengrundmorphologie unter Therapie zu erhalten.

Material und Methoden

Bei sieben Patienten mit OSAS (m = 5, w = 2, 60,14 ± 12,5 J, Zeit unter Stimulationstherapie 296,43 ± 92,04 Tage) wurden vor und 12 Monate nach Implantation eines einseitigen Stimulationssystems des N. hypoglossus (ImThera Aura 6000™) mittels Ultraschall (GE Vivid S6, 4 MHz, Konvexsonde) die Zunge und der Zungengrund vermessen.

Ergebnisse

12 Monate nach Implantation hatte sich die gemessene Distanz zwischen beiden Aa. linguales an ihrer Eintrittsstelle in den Zungengrund verringert (MW vor Implantation 3,844 ± 0,397 cm; MW nach 12 Monaten 3,591 ± 0,302; p = 0,037). Alle anderen Parameter wiesen keine statistisch auffällige Veränderung auf.

Diskussion

Ultraschall kann ein sinnvolles Hilfsmittel bei der Evaluation von Patienten mit OSAS sein. Die klinische Bedeutung der beobachteten Messwerte ist noch unklar. Eine langfristige Verkleinerung des Zungengrunddurchmessers durch die Stimulationstherapie scheint möglich zu sein.

http://bit.ly/2GdZ6g2

Apatinib, a novel VEGFR inhibitor plus docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR: a phase I trial

Summary

Background This phase I trial was primarily conducted to determine the maximum tolerated dose (MTD) of apatinib combined with docetaxel in advanced lung adenocarcinoma patients with wild-type EGFR who have failed to first-line platinum-based chemotherapy, and to evaluate the safety and tolerability of apatinib plus docetaxel. Methods This was a single-center, open-label, dose-escalating phase I trial. The study used a standard 3 + 3 dose escalation design with the primary aim of determining the MTD. Twelve patients with advanced lung adenocarcinoma were enrolled, the primary endpoint was safety. Two doses of apatinib, 250 mg/day (level 1) and 500 mg/day (level 2), were evaluated in combination with 60 mg/m² doxetacel every 3 weeks. Six patients have been treated at levels 1 and 2, respectively. Optimal dose of apatinib was determined by dose-limiting toxicity (DLT). Results Six patients have been treated at levels 1 and 2. At level 1, one of six patients experienced grade 3 acneiform rash as DLTs. At level 2, two patients experienced grade 3 hypertension and one experienced grade 3 nasal bleeding. MTD and recommended dose for phase II study was 250 mg/day. Most frequent adverse events of any grade were bilirubin elevation, hypertension, alanine aminotransferase elevation, transglutaminase elevation, hand foot syndrome and fatigue. The median progression-free survival was 2.76 month. Moreover, three patients had developed progressive disease and the mean duration of response was 2.79 months. Conclusion Apatinib plus docetaxel was well tolerated and showed promising efficacy in advanced lung adenocarcinoma. This combination therapy may represent a potent therapeutic option for advanced lung adenocarcinoma patients with wild-type EGFR.

http://bit.ly/2UyJHuN

Lopinavir-NO, a nitric oxide-releasing HIV protease inhibitor, suppresses the growth of melanoma cells in vitro and in vivo

Summary

We generated a nitric oxide (NO)-releasing derivative of the anti-HIV protease inhibitor lopinavir by linking the NO moiety to the parental drug. We investigated the effects of lopinavir and its derivative lopinavir-NO on melanoma cell lines in vitro and in vivo. Lopinavir-NO exhibited a twofold stronger anticancer action than lopinavir in vitro. These results were successfully translated into syngeneic models of melanoma in vivo, where a significant reduction in tumour volume was observed only in animals treated with lopinavir-NO. Both lopinavir and lopinavir-NO inhibited cell proliferation and induced the trans-differentiation of melanoma cells to Schwann-like cells. In melanoma cancer cell lines, both lopinavir and lopinavir-NO induced morphological changes, minor apoptosis and reactive oxygen species (ROS) production. However, caspase activation and autophagy were detected only in B16 cells, indicating a cell line-specific treatment response. Lopinavir-NO released NO intracellularly, and NO neutralization restored cell viability. Treatment with lopinavir-NO induced only a transient activation of Akt and inhibition of P70S6 kinase. The results of this study identify lopinavir-NO as a promising candidate for further clinical trials in melanoma and possibly other solid tumours.

http://bit.ly/2sZ68NO

Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo

Summary

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3⁺ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

http://bit.ly/2UyJAPT

Quality Assurance in Interventional Radiology: Post-procedural Care

Abstract

Purpose of Review

To review best practices to improve the quality of patient service in the field of interventional radiology after performing the procedure.

Recent Findings

The aim of this paper is to highlight aspects of post-procedural care such as effective communication, post-procedural management of the patient, handling of obtained specimens, post-procedural follow-up, tracking outcomes, and education to assist the interventionalist in providing comprehensive quality post-procedural care.

Summary

Post-procedural communication, follow-up, and outcome tracking are essential elements in the quality assurance of an Interventional Radiology service.

http://bit.ly/2HK9izo

Quality Assurance in Interventional Radiology: Preprocedural Care

Abstract

Purpose of Review

To review best practices to improve the quality of patient service in the field of interventional radiology prior to performing the procedure.

Recent Findings

We highlight a checklist of elements that have a potential for improvement and contribution to overall quality of patient care from the time of taking the consult, until the time of the procedure. Our check list includes establishing appropriateness of the procedure, reducing waiting times, patient-centered care, patient education, shared decision making, establishing expectations, informed consent, managing the patient's medication list, preprocedure diet, prevention of CIN, prevention of contrast reactions, pain control and sedation, and coagulation status and hemostasis risk. Several consensus guidelines are referenced in this chapter. However, individual patients and clinical scenario vary and determine which guideline to follow or modify based in clinical judgment.

Summary

The clinic is a key component of success in any Interventional Radiology practice, as it provides the space for consultation, patient education, and preprocedural planning.

http://bit.ly/2t0AY8N

The role of lamin A/C in mesenchymal stem cell differentiation

Abstract

Lamin A/C is the major architectural protein of cell nucleus in charge of the nuclear mechanosensing. By integrating extracellular mechanical and biochemical signals, lamin A/C regulates multiple intracellular events including mesenchymal stem cell (MSC) fate determination. Herein, we review the recent findings about the effects and mechanisms of lamin A/C in governing MSC lineage commitment, with a special focus on osteogenesis and adipogenesis. Better understanding of MSC differentiation regulated by lamin A/C could provide insights into pathogenesis of age-related osteoporosis.

http://bit.ly/2BbxVPK

The perceptual flow of phonetic information

Abstract

Over a long and distinguished career, Randy Diehl has elucidated the brain mechanisms underlying spoken language processing. The present study touches on two of Randy's central interests, phonetic features and Bayesian statistics. How does the brain go from sound to meaning? Traditional approaches to the study of speech intelligibility and word recognition are unlikely to provide a definitive answer. A finer-grained, Bayesian-inspired approach may help. In this study, listeners identified 11 Danish consonants spoken in a Consonant + Vowel + [l] environment. Each syllable was filtered so that only a portion of the original audio spectrum was presented. Three-quarter-octave bands of speech, centered at 750, 1,500, and 3,000 Hz, were presented individually and in combination. The conditional, posterior probabilities associated with decoding the phonetic-features Voicing, Manner, and Place of Articulation were computed from confusion matrices to delineate the perceptual flow of phonetic information processing. Analysis of the conditional probabilities associated with both correct and incorrect feature decoding suggest that Manner of articulation is linked to the decoding of Voicing (but not vice-versa), and that decoding of Place of articulation is associated with decoding of Manner of articulation (but not the converse). Such feature-decoding asymmetries may reflect processing strategies in which the decoding of lower-level features, such as Voicing and Manner, is leveraged to enhance the recognition of more complex linguistic elements (e.g., phonetic segments, syllables, and words), especially in adverse listening conditions. Such asymmetric feature decoding patterns are consistent with a hierarchical, perceptual flow model of phonetic processing.

http://bit.ly/2Soyb81

HDAC2-mediated upregulation of IL-6 triggers the migration of osteosarcoma cells

Abstract

Understanding the mechanisms of advanced metastasis in osteosarcoma (OS) cell is important for the targeted treatment and drug development. Emerging evidence shows that epigenetic factors such as histone deacetylases (HDACs) are involved in the progression and chemoresistance of OS, while their roles are largely unknown. Our data showed that the expression of HDAC2, while not HDAC1, 4, or 8, was significantly increased in OS cells and tissues. OS patients with increased expression of HDAC2 showed reduced overall survival with p value of 0.0001. Targeted inhibition of HDAC2 suppressed the in vitro migration and invasion of OS cells. Our data showed that the inhibition of HDAC2 can decrease the expression and transcription of interleukin-6 (IL-6) in OS cells. Overexpression of IL-6 can reverse si-HDAC2-induced suppression of cell migration. Mechanistical studies showed that inhibition of HDAC2 decreased the phosphorylation and nuclear accumulation of p65, the key factor of NF-κB complex responsible for the transcription of IL-6. This was due to that HDAC2 can activate the transcription of IKK-β in OS cells. Collectively, our data showed that HDAC2-activated NF-κB can increase the expression of IL-6 in OS cells, which resulted in the promotion of cell migration. It suggested that targeted inhibition of HDAC2/NF-κB/IL-6 might be a potential approach for OS therapy.

http://bit.ly/2G1LKnZ

Surgical Anatomy of the Lumbar Plexus (2018) Editors: R.Shane Tubbs, Marios Loukas, Amgad S. Hanna, Rod J. Oskouian 220 pp, 130 illustrations, Hardback ISBN: 9781626238893 Thieme Publishers New York/Stuttgart.

http://bit.ly/2TpZFan

The evolution of structure and performance in copolyether-ester fibers with different heat-treatment process

Abstract

The changes in performance characteristics, such as tenacity and elastic recovery, of copolyether-ester fibers were compared for different post-heat treatments (with or without tension). The differences in the mechanical behaviour were linked to changes in the microstructure which are obtained from wide angle X-ray scattering (WAXS), small X-ray scattering (SAXS) and birefringence techniques. The obtained results showed that the performance of the fibers is strongly dependent on the heat-treatment conditions. The treatment with tension proved to be an effective and viable approach for comprehensively improving the performance characteristics of the fibers, such as tenacity, elasticity and stability. A clear distinction is observed for the treatment without tension, which increases the elasticity but lowers the tenacity of the fibers. Heat treatments without tension lead to small crystal formations and partial crystal fusion between some small crystalline regions within the fibers. The lower molecular orientation during this process leads to the loss of tenacity. When heat treated with tension, a small amount of amorphous hard segments began to crystallize under the tensile stress, resulting in larger phase separation, and part of the amorphous region became oriented, improving the tenacity and elastic recovery of the fibers.

http://bit.ly/2ShaZbt

p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Abstract

Microvascular and macrovascular diseases are the main causes of morbidity in type 2 diabetes patients through chronic hyperglycaemic condition via oxidative stress and inflammation. Reactive oxygen species (ROS) activate p38 MAPK phosphorylation and inflammation which enhances protein modification by carbonylation. The use of metformin and a p38 MAPK inhibitor is hypothesised to reduce ROS production and inflammation but effects of metformin and p38 MAPK inhibitor (SB203580) on ROS production and inflammation in vascular type 2 diabetes mellitus non-obese (T2DM) have not been investigated. The Goto-Kakizaki rat T2DM model was divided into three groups as T2DM, T2DM treated with 15 mg/kg bw metformin and T2DM treated with 2 mg/kg bw SB203580 for 4 weeks. Rat aortas were isolated and protein carbonyl (PC) contents were measured by spectrophotometric DNPH assay. Aortic IL-1ß level was determined by ELISA. Results showed that aortic PC contents in the T2DM group were significantly higher than in non-diabetic rats. Treatment with metformin or SB203580 significantly reduced PC contents while only metformin significantly reduced IL-1ß levels. Findings indicated that metformin reduced ROS production and inflammation in diabetic vessels and possibly reduce vascular complications in non-obese T2DM.

http://bit.ly/2G0htpF

Bazedoxifene protects cerebral autoregulation after traumatic brain injury and attenuates impairments in blood–brain barrier damage: involvement of anti-inflammatory pathways by blocking MAPK signaling

Abstract

Objective

Traumatic brain injury (TBI) is a significant cause of death and long-term deficits in motor and cognitive functions for which there are currently no effective chemotherapeutic drugs. Bazedoxifene (BZA) is a third-generation selective estrogen receptor modulator (SERM) and has been investigated as a treatment for postmenopausal osteoporosis. It is generally safe and well tolerated, with favorable endometrial and breast safety profiles. Recent findings have shown that SERMs may have therapeutic benefits; however, the role of BZA in the treatment of TBI and its molecular and cellular mechanisms remain poorly understood. The aim of the present study was to examine the neuroprotective effects of BZA on early TBI in rats and to explore the underlying mechanisms of these effects.

Materials and methods

TBI was induced using a modified weight-drop method. Neurological deficits were evaluated according to the neurological severity score (NSS). Morris water maze and open-field behavioral tests were used to test cognitive functions. Brain edema was measured by brain water content, and impairments in the blood–brain barrier (BBB) were evaluated by expression analysis of tight junction-associated proteins, such as occludin and zonula occludens-1 (ZO-1). Neuronal injury was assessed by hematoxylin and eosin (H&E) staining. LC–MS/MS analysis was performed to determine the ability of BZA to cross the BBB.

Results

Our results indicated that BZA attenuated the impaired cognitive functions and the increased BBB permeability of rats subjected to TBI through activation of inflammatory cascades. In vivo experiments further revealed that BZA provided this neuroprotection by suppressing TBI-induced activation of the MAPK/NF-κB signaling pathway. Thus, mechanically, the anti-inflammatory effects of BZA in TBI may be partially mediated by blocking the MAPK signaling pathway.

Conclusions

These findings suggest that BZA might attenuate neurological deficits and BBB damage to protect against TBI by blocking the MAPK/NF-κB signaling pathway.

http://bit.ly/2TnfdvB

The Effect of Stimulus Polarity on the Relation Between Pitch Ranking and ECAP Spread of Excitation in Cochlear Implant Users

Abstract

Although modern cochlear implants (CIs) use cathodic-leading symmetrical biphasic pulses to stimulate the auditory nerve, a growing body of evidence suggests that anodic-leading pulses may be more effective. The positive polarity has been shown to produce larger electrically evoked compound action potential (ECAP) amplitudes, steeper slope of the amplitude growth function, and broader spread of excitation (SOE) patterns. Polarity has also been shown to influence pitch perception. It remains unclear how polarity affects the relation between physiological SOE and psychophysical pitch perception. Using a within-subject design, we examined the correlation between performance on a pitch-ranking task and spatial separation between SOE patterns for anodic and cathodic-leading symmetric biphasic pulses for 14 CI ears. Overall, there was no effect of polarity on either ECAP SOE patterns, pitch ranking performance, or the relation between the two. This result is likely due the use of symmetric biphasic pulses, which may have reduced the size of the effect previously observed for pseudomonophasic pulses. Further research is needed to determine if a pseudomonophasic stimulus might further improve the relation between physiology and pitch perception.

http://bit.ly/2TpFoBN

Dried blood spot testing for estimation of renal function and analysis of metformin and sitagliptin concentrations in diabetic patients: a cross-sectional study

Abstract

Purpose

Dried blot spot (DBS) analysis of drugs or clinical parameters offers many advantages. We investigated the feasibility of using DBS for analysis of anti-diabetic drugs concomitantly with the estimated creatinine clearance (Cl_crea).

Methods

The cross-sectional study involved physicians in an enabling analysis with 70 diabetic patients and community pharmacists in a field investigation with 84 participants. All 154 DBS samples were analyzed for creatinine, metformin, and sitagliptin.

Results

The diabetic patients revealed of a wide range of age (32–88 years), BMI values (19.8–54.7 kg/m²), and extent of polypharmacotherapy (1–21 drugs). A correlation factor to convert capillary blood creatinine from DBS into plasma concentrations was determined. Patients' Cl_crea ranged from 21.6–155.9 mL/min. The results indicated statistically significant correlations (p < 0.05) between the use of two or three particular drug classes (diuretics, NSAIDs, renin-angiotensin system blockers) and a decreased renal function. DBS concentrations of metformin ranged between 0.23–4.99 μg/mL. The estimated elimination half-life (t ½) of metformin was 11.9 h in patients with a Cl_Crea higher than 60 mL/min and 18.5 h for diabetics with lower Cl_Crea. Sitagliptin capillary blood concentrations ranged between 11.12–995.6 ng/mL. Calculated t ½ of sitagliptin were 8.4 h and 13.0 h in patients with a Cl_Crea above and below 60 mL/min, respectively.

Conclusions

DBS allow for the analysis of concentrations of predominantly renally eliminated drugs and community pharmacists can provide a valuable contribution to DBS sampling.

http://bit.ly/2G538ID

Frequency of functional gastrointestinal disorders in children with familial Mediterranean fever

Abstract

Introduction

Familial Mediterranean fever (FMF) is characterized by self-limiting fever episodes usually accompanied by serositis, arthralgia, and arthritis. Functional gastrointestinal disorders (FGIDs) are diseases in which brain-gut axis and low-grade inflammation take part in pathogenesis. We aimed to study the FGIDs frequencies and possible risk factors for FGIDs in children with FMF.

Method

This case-control study included 103 children with FMF followed up between July 2016 and July 2018 and 100 healthy controls. Age, gender, disease characteristics, and MEFV gene results were recorded retrospectively. Laboratory parameters were obtained at the time of study enrollment. Diagnosis of FGIDs was assessed with Rome IV criteria.

Results

The mean age at study enrollment was 12.58 ± 3.79 and 9.71 ± 3.59 years in FMF and healthy control groups, respectively. Overall FGID frequency was 39.8% (n = 41) in FMF patients and 19% (n = 19) in the control group. Functional dyspepsia and irritable bowel syndrome (particularly constipation predominant subtype) rates were statistically higher in the FMF group. In detail, genotype, age at onset, symptoms, colchicine duration, and colchicine responses did not differ between FMF patients in regard to having FGIDs.

Conclusions

This study showed that children with FMF may predispose to pain predominant FGIDs. We also suggest that FGIDs should be considered in FMF patients suffering recurrent abdominal pain episodes unaccompanied by APR elevation, which can be also named as incomplete FMF attacks.

http://bit.ly/2DNTjfP

Bilingual Children with Hearing Loss Learn Words Better with Bilingual Instruction

A new study conducted by a team from Vanderbilt University found that bilingual children with hearing loss learned new vocabulary better when taught using bilingual instruction. The researchers evaluated the effectiveness of bilingual and monolingual teaching practices to identify which method would work best with these children who face unique but under-investigated challenges in language learning.

The idea for the study was sparked when Ana Soares, a teacher of the deaf, and Andrea Vargas, a speech-language pathologist, from Mama Lere Hearing School at Vanderbilt noticed challenges that affected Spanish-speaking families when helping their children with hearing loss learn a language. 

“There are many different ideas on how to teach children learning more than one language, and this debate includes children with hearing loss who are bilingual,” explained the study’s lead author Jena C. McDaniel. “An ongoing difference in opinion is whether new vocabulary should be taught in the native language, the new language, or both. More importantly, some have argued that teaching in the native language harms the ability to learn words in the new language.”

Surprised with the dearth of research into this important issue, the team set out to investigate for themselves. “We recognized the need for more evidence on how to meet the language needs of children with hearing loss who are bilingual, including the language used for intervention and instruction, and wanted to be a part of generating and disseminating that knowledge,” McDaniel told The Hearing Journal. “Thus, we created a clinician-researcher team with the goal of optimizing intervention services and language outcomes for children with hearing loss who are bilingual.” 

The study, which involved giving alternating bilingual or monolingual language instructions to three Spanish–English-speaking children with hearing loss, provided evidence that put to question a prevalent belief in language teaching.

“When we counted words said in both languages (i.e., conceptual vocabulary), bilingual children with hearing loss showed more effective word learning when they received instruction in Spanish and English compared with being taught in English alone. We did not find any evidence of an inhibitory effect of instruction in Spanish on the children’s word learning in English,” noted McDaniel. “That is, there was no harmful effect when children were taught in their native language.”

“These findings do not support the widespread, but understudied, recommendation to teach bilingual children with hearing loss or other disabilities exclusively in English,” she added. “Our data suggest that there is no benefit to decreasing these learning opportunities by recommending that these children be taught the new language exclusively (i.e., English only).”     

This study also helps the case of families who want to stay connected with their culture and native language. McDaniel noted, “We believe these findings are important because teaching children with hearing loss in their native language maximizes opportunities to learn new words from parents, siblings, and other community members who speak the child’s native language.”

Moving forward, the team hopes to replicate the study with participants with more diverse hearing loss profiles and language levels. “We would also like to focus on conceptual vocabulary as the primary dependent variable, vary the details of the bilingual intervention systematically to optimize its effectiveness, and target language skills other than vocabulary,” shared McDaniel.

Published: 1/30/2019 11:09:00 AM

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Hearing Loss Research Five Times More Likely to Address Children than Older Adults

​The volume of hearing loss research on older adults lags significantly behind that on children even though hearing loss is three times as prevalent in the geriatric population, a new study found (JAMA Otolaryngol Head Neck Surg. 2019 Jan 17. doi: 10.1001/jamaoto.2018.3889. [Epub ahead of print]). Researchers from the Icahn School of Medicine at Mount Sinai and the Johns Hopkins School of Medicine conducted an advanced literature search on PubMed databases to quantify studies on hearing loss in older adults and children from 1946 to 2017 using specific keywords. They found that publications were five times more likely to address hearing loss in children (9.743) than older adults (1,880). Approximately 137 articles on children and 26 articles on older adults were published per year over 71 years. The number of publications for both groups increased throughout the study period, but more so for the young. The greatest discrepancy in publication by age was for articles related to cochlear implants and language, which were 22 times and 15 times more likely in children than older adults, respectively. The study authors said their hope in describing these disparities is not to discourage hearing loss research in children but to call attention to areas in which significant progress can be made in older adults. 

Published: 1/25/2019 8:55:00 AM

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via IFTTT

New Study Suggests Memory Loss Could be Linked to Hearing Problems, Not Alzheimer’s

Findings of a new study suggest that older adults being evaluated for memory and cognitive issues including Alzheimer's disease should also get a hearing test. After examining patients between 41 and 88 years old at Baycrest's neuropsychology clinic, researchers found that majority had mild to severe hearing loss but only about 20 percent used hearing aids

Hearing loss, the third most common chronic health condition in older adults, has been linked with cognitive issues. This study makes a case for addressing hearing loss, which often seems like a memory issue in this patient population.

When asked about the motivation behind the study, lead author Kate Dupuis, PhD, explained that the research team has been well aware of the growing literature highlighting the key role of hearing loss in the development of dementia. In fact, members of the team were studying the connection between hearing loss and cognition in individuals living with mild cognitive impairment and dementia.

"Of particular interest was how/whether the neuropsychologists at Baycrest Health Sciences were taking hearing loss into account when working with their clients," Dr. Dupuis told The Hearing Journal.

"The Hearing Services team had previously conducted an analogous study in which they investigated how aware audiologists were of a client's cognitive status, and whether they considered conditions such as memory loss or attentional difficulties when recommending interventions. This research project capitalized on the close existing relationship between Baycrest Hearing Services and the hospital's Neuropsychology and Cognitive Health program."

Admittedly, hearing status is not always addressed in neuropsychology evaluations, noted study co-author Susan Vandermorris, PhD, in a press release. In the study, the neuropsychologists were not aware of the participants' hearing test results at the initial assessment and later modified their clinical recommendations to address hearing concerns.

Recognizing hearing loss as a modifiable risk factor for dementia, Dr. Dupuis stressed the role of interdisciplinary health care teams in promoting awareness and management of hearing-related issues among older adults.

"Neuropsychologists and physicians can improve patient care by including standardized questions about hearing loss and hearing care into their interview/assessment techniques with all older clients," she noted. "It may be particularly important to also ask questions of the loved ones/caregivers who accompany the clients, as there can often be a high level of denial on the part of the clients about the existence of hearing loss. Educational materials about the strong connection between hearing loss and brain health should be provided, and recommendations and/or referrals for hearing assessment should be made as part of standard practice when working with an older population." 

Published: 1/22/2019 3:56:00 PM

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via IFTTT

Bilingual Children with Hearing Loss Learn Words Better with Bilingual Instruction

A new study conducted by a team from Vanderbilt University found that bilingual children with hearing loss learned new vocabulary better when taught using bilingual instruction. The researchers evaluated the effectiveness of bilingual and monolingual teaching practices to identify which method would work best with these children who face unique but under-investigated challenges in language learning.

The idea for the study was sparked when Ana Soares, a teacher of the deaf, and Andrea Vargas, a speech-language pathologist, from Mama Lere Hearing School at Vanderbilt noticed challenges that affected Spanish-speaking families when helping their children with hearing loss learn a language. 

"There are many different ideas on how to teach children learning more than one language, and this debate includes children with hearing loss who are bilingual," explained the study's lead author Jena C. McDaniel. "An ongoing difference in opinion is whether new vocabulary should be taught in the native language, the new language, or both. More importantly, some have argued that teaching in the native language harms the ability to learn words in the new language."

Surprised with the dearth of research into this important issue, the team set out to investigate for themselves. "We recognized the need for more evidence on how to meet the language needs of children with hearing loss who are bilingual, including the language used for intervention and instruction, and wanted to be a part of generating and disseminating that knowledge," McDaniel told The Hearing Journal. "Thus, we created a clinician-researcher team with the goal of optimizing intervention services and language outcomes for children with hearing loss who are bilingual." 

The study, which involved giving alternating bilingual or monolingual language instructions to three Spanish–English-speaking children with hearing loss, provided evidence that put to question a prevalent belief in language teaching.

"When we counted words said in both languages (i.e., conceptual vocabulary), bilingual children with hearing loss showed more effective word learning when they received instruction in Spanish and English compared with being taught in English alone. We did not find any evidence of an inhibitory effect of instruction in Spanish on the children's word learning in English," noted McDaniel. "That is, there was no harmful effect when children were taught in their native language."

"These findings do not support the widespread, but understudied, recommendation to teach bilingual children with hearing loss or other disabilities exclusively in English," she added. "Our data suggest that there is no benefit to decreasing these learning opportunities by recommending that these children be taught the new language exclusively (i.e., English only)."     

This study also helps the case of families who want to stay connected with their culture and native language. McDaniel noted, "We believe these findings are important because teaching children with hearing loss in their native language maximizes opportunities to learn new words from parents, siblings, and other community members who speak the child's native language."

Moving forward, the team hopes to replicate the study with participants with more diverse hearing loss profiles and language levels. "We would also like to focus on conceptual vocabulary as the primary dependent variable, vary the details of the bilingual intervention systematically to optimize its effectiveness, and target language skills other than vocabulary," shared McDaniel.

Published: 1/30/2019 11:09:00 AM

from #Audiology via ola Kala on Inoreader http://bit.ly/2G1tMC3

Hearing Loss Research Five Times More Likely to Address Children than Older Adults

​The volume of hearing loss research on older adults lags significantly behind that on children even though hearing loss is three times as prevalent in the geriatric population, a new study found (JAMA Otolaryngol Head Neck Surg. 2019 Jan 17. doi: 10.1001/jamaoto.2018.3889. [Epub ahead of print]). Researchers from the Icahn School of Medicine at Mount Sinai and the Johns Hopkins School of Medicine conducted an advanced literature search on PubMed databases to quantify studies on hearing loss in older adults and children from 1946 to 2017 using specific keywords. They found that publications were five times more likely to address hearing loss in children (9.743) than older adults (1,880). Approximately 137 articles on children and 26 articles on older adults were published per year over 71 years. The number of publications for both groups increased throughout the study period, but more so for the young. The greatest discrepancy in publication by age was for articles related to cochlear implants and language, which were 22 times and 15 times more likely in children than older adults, respectively. The study authors said their hope in describing these disparities is not to discourage hearing loss research in children but to call attention to areas in which significant progress can be made in older adults. 

Published: 1/25/2019 8:55:00 AM

from #Audiology via ola Kala on Inoreader http://bit.ly/2GdETa7

New Study Suggests Memory Loss Could be Linked to Hearing Problems, Not Alzheimer’s

Findings of a new study suggest that older adults being evaluated for memory and cognitive issues including Alzheimer's disease should also get a hearing test. After examining patients between 41 and 88 years old at Baycrest's neuropsychology clinic, researchers found that majority had mild to severe hearing loss but only about 20 percent used hearing aids

Hearing loss, the third most common chronic health condition in older adults, has been linked with cognitive issues. This study makes a case for addressing hearing loss, which often seems like a memory issue in this patient population.

When asked about the motivation behind the study, lead author Kate Dupuis, PhD, explained that the research team has been well aware of the growing literature highlighting the key role of hearing loss in the development of dementia. In fact, members of the team were studying the connection between hearing loss and cognition in individuals living with mild cognitive impairment and dementia.

"Of particular interest was how/whether the neuropsychologists at Baycrest Health Sciences were taking hearing loss into account when working with their clients," Dr. Dupuis told The Hearing Journal.

"The Hearing Services team had previously conducted an analogous study in which they investigated how aware audiologists were of a client's cognitive status, and whether they considered conditions such as memory loss or attentional difficulties when recommending interventions. This research project capitalized on the close existing relationship between Baycrest Hearing Services and the hospital's Neuropsychology and Cognitive Health program."

Admittedly, hearing status is not always addressed in neuropsychology evaluations, noted study co-author Susan Vandermorris, PhD, in a press release. In the study, the neuropsychologists were not aware of the participants' hearing test results at the initial assessment and later modified their clinical recommendations to address hearing concerns.

Recognizing hearing loss as a modifiable risk factor for dementia, Dr. Dupuis stressed the role of interdisciplinary health care teams in promoting awareness and management of hearing-related issues among older adults.

"Neuropsychologists and physicians can improve patient care by including standardized questions about hearing loss and hearing care into their interview/assessment techniques with all older clients," she noted. "It may be particularly important to also ask questions of the loved ones/caregivers who accompany the clients, as there can often be a high level of denial on the part of the clients about the existence of hearing loss. Educational materials about the strong connection between hearing loss and brain health should be provided, and recommendations and/or referrals for hearing assessment should be made as part of standard practice when working with an older population." 

Published: 1/22/2019 3:56:00 PM

from #Audiology via ola Kala on Inoreader http://bit.ly/2FXbPV2

Bilingual Children with Hearing Loss Learn Words Better with Bilingual Instruction

A new study conducted by a team from Vanderbilt University found that bilingual children with hearing loss learned new vocabulary better when taught using bilingual instruction. The researchers evaluated the effectiveness of bilingual and monolingual teaching practices to identify which method would work best with these children who face unique but under-investigated challenges in language learning.

The idea for the study was sparked when Ana Soares, a teacher of the deaf, and Andrea Vargas, a speech-language pathologist, from Mama Lere Hearing School at Vanderbilt noticed challenges that affected Spanish-speaking families when helping their children with hearing loss learn a language. 

“There are many different ideas on how to teach children learning more than one language, and this debate includes children with hearing loss who are bilingual,” explained the study’s lead author Jena C. McDaniel. “An ongoing difference in opinion is whether new vocabulary should be taught in the native language, the new language, or both. More importantly, some have argued that teaching in the native language harms the ability to learn words in the new language.”

Surprised with the dearth of research into this important issue, the team set out to investigate for themselves. “We recognized the need for more evidence on how to meet the language needs of children with hearing loss who are bilingual, including the language used for intervention and instruction, and wanted to be a part of generating and disseminating that knowledge,” McDaniel told The Hearing Journal. “Thus, we created a clinician-researcher team with the goal of optimizing intervention services and language outcomes for children with hearing loss who are bilingual.” 

The study, which involved giving alternating bilingual or monolingual language instructions to three Spanish–English-speaking children with hearing loss, provided evidence that put to question a prevalent belief in language teaching.

“When we counted words said in both languages (i.e., conceptual vocabulary), bilingual children with hearing loss showed more effective word learning when they received instruction in Spanish and English compared with being taught in English alone. We did not find any evidence of an inhibitory effect of instruction in Spanish on the children’s word learning in English,” noted McDaniel. “That is, there was no harmful effect when children were taught in their native language.”

“These findings do not support the widespread, but understudied, recommendation to teach bilingual children with hearing loss or other disabilities exclusively in English,” she added. “Our data suggest that there is no benefit to decreasing these learning opportunities by recommending that these children be taught the new language exclusively (i.e., English only).”     

This study also helps the case of families who want to stay connected with their culture and native language. McDaniel noted, “We believe these findings are important because teaching children with hearing loss in their native language maximizes opportunities to learn new words from parents, siblings, and other community members who speak the child’s native language.”

Moving forward, the team hopes to replicate the study with participants with more diverse hearing loss profiles and language levels. “We would also like to focus on conceptual vocabulary as the primary dependent variable, vary the details of the bilingual intervention systematically to optimize its effectiveness, and target language skills other than vocabulary,” shared McDaniel.

Published: 1/30/2019 11:09:00 AM

from #Audiology via ola Kala on Inoreader http://bit.ly/2G1tMC3
via IFTTT

Hearing Loss Research Five Times More Likely to Address Children than Older Adults

​The volume of hearing loss research on older adults lags significantly behind that on children even though hearing loss is three times as prevalent in the geriatric population, a new study found (JAMA Otolaryngol Head Neck Surg. 2019 Jan 17. doi: 10.1001/jamaoto.2018.3889. [Epub ahead of print]). Researchers from the Icahn School of Medicine at Mount Sinai and the Johns Hopkins School of Medicine conducted an advanced literature search on PubMed databases to quantify studies on hearing loss in older adults and children from 1946 to 2017 using specific keywords. They found that publications were five times more likely to address hearing loss in children (9.743) than older adults (1,880). Approximately 137 articles on children and 26 articles on older adults were published per year over 71 years. The number of publications for both groups increased throughout the study period, but more so for the young. The greatest discrepancy in publication by age was for articles related to cochlear implants and language, which were 22 times and 15 times more likely in children than older adults, respectively. The study authors said their hope in describing these disparities is not to discourage hearing loss research in children but to call attention to areas in which significant progress can be made in older adults. 

Published: 1/25/2019 8:55:00 AM

from #Audiology via ola Kala on Inoreader http://bit.ly/2GdETa7
via IFTTT

New Study Suggests Memory Loss Could be Linked to Hearing Problems, Not Alzheimer’s

Findings of a new study suggest that older adults being evaluated for memory and cognitive issues including Alzheimer's disease should also get a hearing test. After examining patients between 41 and 88 years old at Baycrest's neuropsychology clinic, researchers found that majority had mild to severe hearing loss but only about 20 percent used hearing aids

Hearing loss, the third most common chronic health condition in older adults, has been linked with cognitive issues. This study makes a case for addressing hearing loss, which often seems like a memory issue in this patient population.

When asked about the motivation behind the study, lead author Kate Dupuis, PhD, explained that the research team has been well aware of the growing literature highlighting the key role of hearing loss in the development of dementia. In fact, members of the team were studying the connection between hearing loss and cognition in individuals living with mild cognitive impairment and dementia.

"Of particular interest was how/whether the neuropsychologists at Baycrest Health Sciences were taking hearing loss into account when working with their clients," Dr. Dupuis told The Hearing Journal.

"The Hearing Services team had previously conducted an analogous study in which they investigated how aware audiologists were of a client's cognitive status, and whether they considered conditions such as memory loss or attentional difficulties when recommending interventions. This research project capitalized on the close existing relationship between Baycrest Hearing Services and the hospital's Neuropsychology and Cognitive Health program."

Admittedly, hearing status is not always addressed in neuropsychology evaluations, noted study co-author Susan Vandermorris, PhD, in a press release. In the study, the neuropsychologists were not aware of the participants' hearing test results at the initial assessment and later modified their clinical recommendations to address hearing concerns.

Recognizing hearing loss as a modifiable risk factor for dementia, Dr. Dupuis stressed the role of interdisciplinary health care teams in promoting awareness and management of hearing-related issues among older adults.

"Neuropsychologists and physicians can improve patient care by including standardized questions about hearing loss and hearing care into their interview/assessment techniques with all older clients," she noted. "It may be particularly important to also ask questions of the loved ones/caregivers who accompany the clients, as there can often be a high level of denial on the part of the clients about the existence of hearing loss. Educational materials about the strong connection between hearing loss and brain health should be provided, and recommendations and/or referrals for hearing assessment should be made as part of standard practice when working with an older population." 

Published: 1/22/2019 3:56:00 PM

from #Audiology via ola Kala on Inoreader http://bit.ly/2FXbPV2
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Down-regulation of miR-377 suppresses high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells by direct up-regulation of target gene SIRT1

Abstract

Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes mellitus, which is the main cause of blindness in diabetic patients. Angiogenesis plays an important role in retinal detachment and retinal microvascular inflammation throughout the whole development of DR. This study aimed to investigate the regulatory effect and the potential mechanism of miR-377 on high glucose and hypoxia-induced angiogenesis and inflammation in human retinal endothelial cells, and found that the miR-377 level was significantly increased after high glucose and hypoxia-mimetic agent to simulate the DR milieu. Moreover, miR-377 was confirmed to directly decrease target SIRT1 gene, further aggravated proliferation, cell cycle transition, migration and angiogenesis, pro-inflammatory molecules release induced by high glucose and hypoxia in vitro. Conversely, down-regulation of miR-377 enhanced expression of SIRT1 and in turn alleviated high glucose and hypoxia-induced angiogenesis and inflammation in vitro. Additionally, Western blot results showed that down-regulation of miR-377 restrained high glucose and hypoxia-induced protein expressions of p-IκBα, nuclear P65 and p-P65. Conversely, up-regulation of miR-377 presented opposite results. Conclusively, down-regulation of miR-377 could partially suppress high glucose and hypoxia-induced angiogenic functions, restrain pro-inflammatory cytokines release, and its mechanism may though inhibition of NF-κB pathway by direct up-regulation of target gene SIRT1 expression. Our study suggests that miR-377 may be used as a potential novel target for prevention strategy for DR.

http://bit.ly/2RwbMkk

Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics

Abstract

Introduction

Intra-articular (IA) corticosteroids are used extensively for the treatment of patients with knee osteoarthritis pain. In clinical practice, local anesthetics are frequently combined with corticosteroids prior to IA injection to provide rapid-onset analgesia. From this common practice there is no evidence to suggest that the addition of local anesthetics to corticosteroid preparations, including triamcinolone acetonide (TA), alters the physical properties or efficacy of the corticosteroid. Triamcinolone acetonide extended-release (TA-ER, formerly FX006) is a novel, microsphere-based TA formulation that demonstrated analgesic efficacy in phase 2 and 3 randomized controlled trials.

Methods

The current study assessed the compatibility of TA-ER and lidocaine, ropivacaine, and/or bupivacaine in vitro. The TA-ER and local anesthetic mixtures were assayed for changes in syringeability, pH, particle size, percentage free drug, purity, and appearance compared with TA-ER alone.

Results

By these measures, the combination of local anesthetics with TA-ER did not negatively impact the chemical or physical properties of TA-ER when compared to TA-ER controls.

Conclusion

These results demonstrate that lidocaine, bupivacaine, and ropivacaine are physically and chemically compatible with TA-ER, suggesting that local anesthetic solutions can be added to TA-ER preparations in clinical practice without adversely affecting TA-ER in vitro product characteristics.

Funding

Flexion Therapeutics, Inc.

http://bit.ly/2sWyclb

Comment on: “Equity in Physical Activity: A Misguided Goal”

http://bit.ly/2Uw7MlT

Reply to Williams et al.: Comment on: “Equity in Physical Activity: A Misguided Goal”

http://bit.ly/2DNFDBr

Musculoskeletal pains and cardiovascular autonomic function in the general Northern Finnish population

Abstract

Background

Heart rate variability (HRV) and baroreflex sensitivity (BRS) measurements provide means for the objective assessment of cardiovascular autonomic function. As previous studies have associated chronic pain with abnormal autonomic function, we aimed to characterize the relationship between the number of musculoskeletal pain sites (NPS), pain intensity, and cardiovascular autonomic function among the population-based Northern Finland Birth Cohort 1966.

Methods

At the age of 46, cohort members self-reported their musculoskeletal pains (enabling the determination of NPS [0–8] and pain intensity [Numerical Rating Scale, NRS, 0–10]) and underwent clinical assessments of cardiovascular autonomic function in seated and standing positions (HRV variables: heart rate [HR] and root mean square of successive differences in beat-to-beat intervals [rMSSD] for the entire cohort; BRS variables: low-frequency systolic blood pressure variability [SBPV] and cross-spectral baroreflex sensitivity [BRS] for those attending the examination in Oulu, Finland). Extensive confounder data were also collected (body mass index, physical activity, smoking, Hopkins Symptom Checklist-25, comorbidities, and medications). The full samples included 4186 and 2031 individuals (HRV and BRS samples, respectively). Three subanalyses focused on individuals with intense and frequent pain, individuals with symptoms of depression and anxiety, and the relationship between pain intensity and autonomic parameters.

Results

Linear regression models showed varying associations between NPS, pain intensity, and cardiovascular autonomic parameters. However, after all adjustments NPS was only associated with one outcome among women (BRS, standing: beta = − 0.015, p = 0.048) and two among men (HR, seated: beta = − 0.902, p = 0.003; HR, standing: beta = − 0.843, p = 0.014). Pain intensity was not associated with any outcome after full adjustments. Significant sex*pain interactions were found in the data.

Conclusions

Our data suggest that musculoskeletal pain has, at most, a limited independent association with cardiovascular autonomic function. Future studies should carefully account for the potential confounders and sex interactions that this study revealed.

http://bit.ly/2G0r5Rg

Distal femoral reconstruction following failed total knee arthroplasty is accompanied with risk for complication and reduced joint function

Abstract

Background

Substantial bone loss following failed total knee arthroplasty (TKA) represents a major challenge in revision arthroplasty, that can require distal femoral reconstruction (DFR). In this study, we aimed to assess the clinical outcome and the complication frequencies of individuals who underwent DFR with modular megaprostheses. Additionally, we aimed to compare functional outcome measures after DFR in these sophisticated cases to an age-matched control group of total knee prostheses to quantify the potential loss of function.

Methods

A retrospective chart review of 30 consecutive patients after DFR from 1997 to 2017 with a mean age of 74.38 years (± 10.1) was performed. Complications were classified according to the Henderson classification. Knee Society Score (KSS) was calculated and range of motion (ROM) was assessed.

Results

Thirteen (43.3%) patients had at least one complication requiring revision surgery. Revision-free survival was 74.8% at one year, 62.5% at three and 40.9% at 10 years post-op. Soft-tissue failure complications were found in three (10.0%) patients, aseptic loosening in four (13.3%) patients, structural failure in one (3.3%) patient and infection in eight (26.6%) patients. Of those with infection, five (16.6%) experienced ongoing prosthetic joint infection and three (10.0%) developed new infection after distal femur reconstruction. Patients with DFR achieved 69.3% of KSS pain score, 23.1% KSS function score and 76.2% of ROM compared to patients with primary TKA.

Conclusions

DFR after failed TKA represents a treatment procedure with high risk for complication in this particular group. Despite the prospect of rapid postoperative mobilization, reduced functionality, range of motion and mobilization have to be considered when choosing this treatment option.

http://bit.ly/2GeYTte

Evaluation of health-related quality of life after total hip arthroplasty: a case-control study in the Iranian population

Abstract

Background

As the total hip arthroplasty (THA) mainly aims to improve the quality of life of the patients, study of health-related quality of life (HRQoL) after THA has attracted much attention. Yet, the results considerably vary between studies. Here, we evaluate the HRQoL of the patient after THA, for the first time in the Iranian population.

Methods

In a case-control study, HRQoL was assessed in 217 patients after THA and compared with a matched reference population. The 36-item short-form health survey (SF-36) was used for the evaluation of HRQoL. A multiple linear regression model was used to investigate the influence of sociodemographic and clinical characteristics of the patients on the HRQOL.

Results

The mean follow-up of the patients was 27 ± 18 months. The mean total SF-36 score was 41.4 ± 22.2 in the case and 67.3 ± 26.6 in the control group (p = 0.001). The mean physical component score, but not the mental component score, was significantly lower in the patient group (p = 0.001). Except for the vitality and emotional role, all other SF-36 subscales were significantly lower in the case group. Male sex (B = 4.52, p = 0.023), number of comorbidities (B = − 4.82, p = 0.011), body mass index (B = − 1.18, p = 0.044), number of post-operative complications (B = − 6.57, p = 0.001), and adherence to physiotherapy protocol (B = 2.09, p = 0.014) were associated with HRQoL after THA.

Conclusion

Although THA is considered as one of the most successful orthopedic practices, it is associated with remarkable reduced HRQoL in Iranian population when compared with the reference population. A variety of patients-associated factors influence the HRQoL after THA.

http://bit.ly/2FZhnOV

Analysis of patellofemoral arthrokinematic motion quality in open and closed kinetic chains using vibroarthrography

Abstract

Background

Knee movements performed in open (OKC) and closed (CKC) kinetic chains generate various patterns of muscle activities and especially distinct contact stresses in the patellofemoral joint (PFJ). In contrast to these features, the arthrokinematic motion quality (AMQ) of the PFJ has not been compared between mentioned conditions. In this study we performed vibroarthrographic analysis of AMQ in movements performed in OKC and CKC, in healthy subjects and individuals with chondromalacia patellae, to assess which of the test conditions is more efficient in differentiation between healthy and deteriorated joints. Moreover, our analysis will broaden the knowledge related to behavior of normal and pathological synovial joints during motion with and without weight bearing. It is an essential issue, due to the recently observed significant interest in comparing potential benefits and limitations of CKC and OKC exercises as they relate to lower extremity rehabilitation.

Methods

100 subjects (62 healthy controls and 38 subjects with PFJ chondromalacia) were enrolled. During repeated knee flexion/extension motions performed in OKC (in a sitting position) and CKC (sit-to-stand movements), the vibroarthrographic signals were collected using an accelerometer and described by variability (VMS), amplitude (R4), and spectral power in 50–250 Hz (P1) and 250–450 Hz (P2) bands.

Results

Significant differences in VMS [V], R4 [V], P1 [V²/Hz] and P2 [V²/Hz] between OKC and CKC were found (0.0001, 0.969. 0.800 0.041 vs 0.013, 3.973, 6.790, 0.768, respectively, P < 0.001). Moreover, in both analyzed load-related conditions the subjects with chondromalacia were characterized by significantly higher values of all parameters, when compared to controls (P < 0.001), with effect size values over 0.6.

Conclusions

We showed that motion of the physiological, unloaded PFJ articular surfaces in OKC is nearly vibrationless, which corresponds with optimal AMQ of PFJ, while loaded movements in CKC are characterized by a higher vibroacoustic emission level. Moreover, chondral lesions should be considered as an increased friction-related, aggravating factor of AMQ, which is critical in CKC movements under load. Nonetheless, OKC and CKC conditions are characterized by large effect sizes, and provide an efficient test frame for differentiating physiological knees and joints with chondral lesions.

http://bit.ly/2GcpXZT

Biomechanics following skip-level cervical disc arthroplasty versus skip-level cervical discectomy and fusion: a finite element-based study

Abstract

Background

Moderately increased motion at the intermediate segment (IS) after skip-level fusion may accelerate disc degeneration. However, limited biomechanical data are available that examine the effects on the IS following cervical disc arthroplasty (CDA). The purpose of this study is to investigate the biomechanical changes in the IS of the cervical spine after skip-level fusion or skip-level arthroplasty.

Methods

A finite element model of a healthy cervical spine (C2-C7) was constructed. Two surgical models were developed: (1) skip-level fusion at C3/4 and C5/6 and (2) skip-level arthroplasty at C3/4 and C5/6. A 75-N follower load and 1.0-N·m moments were applied to the top of the C2 vertebra to produce flexion, extension, lateral bending and axial rotation in the intact model. The end-points in each direction corresponding to the intact model were applied to the surgical models under displacement-control protocols.

Results

The ranges of motion (ROMs) of the fusion model were markedly decreased at the operated levels, while the corresponding ROMs of the arthroplasty model were similar to those of the intact spine in all directions. In the fusion model, the ROMs of the IS (C4/5) were markedly increased in all directions. The ROMs in the arthroplasty model were similar to those in the intact spine, and the ROMs of untreated segments were evenly increased. In the fusion model, the intradiscal pressure and facet contact force at were C4/5 remarkably increased and unevenly distributed among the unfused segments. In the arthroplasty model, the IS did not experience additive stress.

Conclusion

The IS does not experience additive ROM or stress in the intervertebral disc or facet joints after skip-level arthroplasty, which has fewer biomechanical effects on the IS than does skip-level fusion. This study provides a biomechanical rationale for arthroplasty in treating patients with skip-level cervical degenerative disc disease.

http://bit.ly/2G197xV

Mitteilungen der DGMKG

http://bit.ly/2GcmJpf

Die operative Behandlung von Lippen-Kiefer-Gaumen-Spalten – eine interdisziplinäre Aufgabe

http://bit.ly/2G2Mjh6

Synthesis of rGO/TiO 2 /PEDOT nanocomposites, supercapacitor device performances and equivalent electrical circuit models

Abstract

A new nanocomposite electrode incorporating poly(3,4-ethylenedioxythiophene) (PEDOT) within the nanocomposite film of the reduced graphene oxide / Titanium dioxide (TiO₂) was synthesized to be used in supercapacitor devices. We used constant EDOT monomer for in-situ polymerization and different initial monomer concentration ratio of [rGO]_o/[TiO₂]_o = 1/1, ½ and 1/5. The obtained nanocomposites were examined by FTIR-ATR, UV-vis, SEM-EDX, TGA-DTA, BET surface areas and pore distribution, XRD, TEM, AFM, CV, GCD and EIS analyses. The results showed that graphene oxide was successfully reduced to rGO by means of the microwave-assisted method. It was confirmed by the increases in the specific capacitance of (C_sp = 652 F/g) at 1 mV/s for the rGO/TiO₂/PEDOT nanocomposite at [rGO]_o/[TiO₂]_o = 1/5. This was related to the pore size (~33.50 nm) of the material for rGO/TiO₂/PEDOT at [rGO]_o/[TiO₂]_o = 1/5 obtained from BET analysis. The other C_sp values were 475.33 F/g for [rGO]_o/[TiO₂]_o = 1/2, 114.09 F/g for rGO/PEDOT and 48.02 F/g for [rGO]_o/[TiO₂]_o = 1/1. Equivalent circuit model of R_ct(C_dlR_ct) was analyzed via ZSimpWin and TINA programmes. A facile and inexpensive approach for a ternary nanocomposite synthesis of rGO/TiO₂/PEDOT was presented for future supercapacitor applications.

Graphical abstract

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http://bit.ly/2Uyi8lo

Missed opportunities: the absence of climate change in media coverage of forest fire events in Alberta

Abstract

Extreme weather events that may be associated with climate change drivers offer valuable opportunities for public discussion of climate change. Such events tend to draw a high level of public attention, and they represent acute and personal impacts of climate change, unlike most climate-related information to which members of the public are exposed. Media coverage of such extreme events, however, appears to avoid linking such events to climate change. In one of few media analyses of the inclusion of climate change discussion in coverage of extreme events that are linked to climate change, we provide the results of an analysis of media coverage of climate-related threats to forests, including in particular forest fires in the Province of Alberta. This is a region in which forests, which are threatened by the impacts of climate change, are an important contributor to the regional economy, livelihoods, and lifestyles. Newspaper articles were collected from Alberta's two largest regional papers, the Edmonton Journal and the Calgary Herald. Our findings show that coverage of forest issues in the media is dominated by fires, while discussion of pest outbreaks and forest sustainability are far less prevalent. While climate change is a topic that is covered in these newspapers as frequently as forest-related issues, there is very little overlap in this coverage and the articles that do discuss both forests and climate change are not associated with extreme events. In subsequent thematic analysis, we find that forest fire coverage tends to be restricted to discussion of single themes, particularly, risk or the economy, while avoiding discussion of multiple themes and their interactions. Mention of the causes of climate change is rare in coverage of either of these forest-related issues. Possible explanations for avoidance of climate change discussion in forest fire media coverage are discussed.

http://bit.ly/2MMyHaA

Development of conditional cell lysis mutants of Saccharomyces cerevisiae as production hosts by modulating OCH1 and CHS3 expression

Abstract

The traditional yeast Saccharomyces cerevisiae has been widely used as a host for the production of recombinant proteins and metabolites with industrial potential. However, its thick and rigid cell wall presents problems for the effective recovery of products. In this study, we modulated the expression of ScOCH1, encoding the α-1,6-mannosyltransferase responsible for outer chain biosynthesis of N-glycans, and ScCHS3, encoding the chitin synthase III required for synthesis of the majority of cell wall chitin, by exploiting the repressible ScMET3 promoter. The conditional single mutants P_MET3-OCH1 and P_MET3-CHS3 and the double mutant P_MET3-OCH1/P_MET3-CHS3 showed comparable growth to the wild-type strain under normal conditions but exhibited increased sensitivity to temperature and cell wall-disturbing agents in the presence of methionine. Such conditional growth defects were fully recovered by supplementation with 1 M sorbitol. The osmotic lysis of the conditional mutants cultivated with methionine was sufficient to release the intracellularly expressed recombinant protein, nodavirus capsid protein, with up to 60% efficiency, compared to lysis by glass bead breakage. These mutant strains also showed approximately three-fold-enhanced secretion of a recombinant extracellular glycoprotein, Saccharomycopsis fibuligera β-glucosidase, with markedly reduced hypermannosylation, particularly in the P_MET3-OCH1 mutants. Furthermore, a substantial increase of extracellular glutathione production, up to four-fold, was achieved with the conditional mutant yeast cells. Together, our data support that the conditional cell wall lysis mutants constructed based on the modulation of ScOCH1 and ScCHS3 expression would likely be useful hosts for the improved recovery of proteins and metabolites with industrial application.

http://bit.ly/2S0ttOl

Correction to: Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes

Page 7, Section 4.1, third paragraph, which previously read:

http://bit.ly/2BeCZTA

l -Ornithine l -Aspartate (LOLA) for Hepatic Encephalopathy in Cirrhosis: Results of Randomized Controlled Trials and Meta-Analyses

Abstract

This manuscript represents an appraisal of the evidence in support of l-ornithine-l-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.

http://bit.ly/2UBuIQX