Tuesday, December 1, 2020

Influence of exogenous and endogenous estrogen on thermoregulatory responses to mild heat and the interaction with light and dark phases

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Abstract

The present study aimed to determine the influence of estradiol (E2) and the interaction with circadian phases on thermoregulatory responses to mild heat in female rats. Heat loss and production during 3-h exposure to the environment at an ambient temperature of 28–34 °C were assessed by measuring abdominal temperature (Tabd), tail skin temperature, and oxygen consumption in ovariectomized rats with and without E2 replacement (OVX + E2 and OVX, respectively) and in control rats in the proestrus (P) and diestrus (D) phases. In the light phase, Tabd remained unchanged in all groups. Tabd increased in the dark phase, but was lower in the OVX + E2 and P groups than in the OVX and D groups. Oxygen consumption decreased at 34 °C, but to a lesser extent in the OVX + E2 group than in the OVX group. These results suggest that E2 activates thermoregulation in mild heat in the dark phase.

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Visual imagery influences attentional guidance during visual search: Behavioral and electrophysiological evidence

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Abstract

Recent behavioral studies have shown that color imagery can benefit visual search when it is congruent with an upcoming target. In the present study we investigated whether this color imagery benefit was due to the processes underlying attentional guidance, as indicated by the electrophysiological marker known as the N2pc component. Participants were instructed to imagine a color prior to each trial of a singleton search task. On some trials, the imagined color was congruent with the target, and on other trials, it was congruent with the distractors. The analyses revealed that the N2pc was present when color imagery was congruent with the search target, and absent when it was congruent with the distractors. Further, there was preliminary evidence that attentional guidance depended on the vividness of color imagery and the frequency at which participants implemented the imagery instruction. Overall, the results of the present study indicate that color imagery can influence the attentional guidance processes underlying visual search.

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General Characteristics of Microbubble-Adenovirus Vectors Carrying Genes

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Abstract

Introduction

Transferring genes safely, targeting cells and achieving efficient transfection are urgent problems in gene therapy that need to be solved. Combining microbubbles (MBs) and viruses to construct double vectors has become a promising approach for gene delivery. Understanding the characteristic performance of MBs that carry genes is key to promoting effective gene transfer. Therefore, in this study, we constructed MB-adenovirus vectors and discussed their general characteristics.

Methods

We constructed MB-adenovirus vectors carrying the chemokine (C-X-C motif) ligand 12 (Cxcl12) and bone morphogenetic protein-2 (Bmp2) genes (pAd-Cxcl12 and pAd-Bmp2, respectively) to explore the general characteristics of double vectors carrying genes.

Results

The MB-adenovirus vectors had stable physical properties, and no significant differences in diameter, concentration, or pH were noted compared with naked MBs (p > 0.05). Flow cytometry and RT-PCR were used to detect the gene-loading capacity of MBs. The gene-loading efficiency of MBs increased with increasing virus amounts and was highest (91%) when 10.0 µL of virus was added. Beyond 10.0 µL of added virus, the gene-loading efficiency of MBs decreased with the continuous addition of virus. The maximum amounts of pAd-Cxcl12 and pAd-Bmp2 in 100 µL of MBs were approximately 14 and 10 µL, respectively.

Conclusions

This study indicates that addition of an inappropriate viral load will result in low MB loading efficiency, and the maximum amount of genes loaded by MBs may differ based on the genes carried by the virus.

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Transitional nystagmus in a Bow Hunter’s Syndrome case report

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Abstract

Background

Bow Hunter's Syndrome (BHS) is known as one of cervical diseases which causes vertigo, but the details of its vertigo, especially nystagmus and eye movement, are still incompletely understood. This time, we reported the first case of BHS with a nystagmus chart with video record of transitional nystagmus.

Case presentation

The patient, a 47-year-old female, complained of vertigo caused by head rotation. When she turned her head leftward, leftward nystagmus appeared, and this was followed by dullness of the right arm. After her head was returned to the central position, downbeat nystagmus appeared, which changed to rightward nystagmus. She was diagnosed with BHS by her symptoms and images. We recorded a nystagmus video and nystagmus chart of this transitional nystagmus including downbeat nystagmus. Her vertigo was cured by the modification of a prescription for her past medical history: hypertension.

Conclusion

The vertigo of BHS accompanies nystagmus. In this present case, the transitional nystagmus was observed, and it occurred toward the healthy side. Then the nystagmus direction was changed to the affected side via downbeat nystagmus. This is the first report with both a nystagmus chart with video of BHS. Nowadays, various kinds of vertigo induced by neck movement are known. BHS is a rare disease among vertigo diseases, but we should consider it as a different diagnosis of vertigo patients. A precise interview and proper examination are required to make the final diagnosis.

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Enablers and Barriers to Identifying Children at Risk of Developmental Delay: A Pilot Study of Australian Maternal and Child Health Services

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Abstract

Background

Twenty per cent of Australian children enter primary school with at least one area of developmental vulnerability (Commonwealth of Australia. (2018). Australian early development census [AEDC]. Retrieved from https://www.aedc.gov.au/.). This statistic is in the context of Maternal and Child Health (MCH) services offering regular developmental screening up to 8 times between 2 weeks and 3.5 years of age.

Objectives

This study investigated: (1) enablers and barriers influencing MCH nurses in identifying children from birth to school age at risk of developmental delay. This focused on their experience, knowledge, attitudes and skills regarding the use of developmental screening tools. And (2) strategies to support MCH nurses and parents to identify children at risk of delay.

Method

This mixed-methods study combined an online questionnaire and three focus groups and participants were MCH Nurses (N = 19) from one Australian municipality.

Results

MCH nurses surveyed (N = 19) reported more confidence in screening older children compared to children younger than 12 months. 15 of 19 nurses did not have accurate knowledge and skill in using PEDS and Brigance screens. In the focus group interviews (N = 16), time restraints, language used in developmental screening tools, and excessive waiting time for referral were raised as key barriers to identifying children at risk.

Limitations

While the study provides rich insight, caution needs to be exercised when making generalisations from the findings given the small number of participants from one municipality.

Conclusion

Recommendations for practice, service management, and further research are provided to improve the process of early detection.

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In Silico Ventilation Within the Dose-Volume is Predictive of Lung Function Post-radiation Therapy in Patients with Lung Cancer

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Abstract

Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = − 0.61). Patients wit h higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT.

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Analyzing Liver Surface Indentation for In Vivo Refinement of Tumor Location in Minimally Invasive Surgery

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Abstract

Manual palpation to update the position of subsurface tumor(s) is a normal practice in open surgery, but is not possible through the small incisions of minimally invasive surgery (MIS). This paper proposes a method that has the potential to use a simple constant-force indenter and the existing laparoscopic camera for tumor location refinement in MIS. The indenter floats with organ movement to generate a static surface deformation on the soft tissue, resolving problems of previous studies that require complicated measurement of force and displacement during indentation. By analyzing the deformation profile, we can intraoperatively update the tumor's location in real-time. Indentation experiments were conducted on healthy and "diseased" porcine liver specimens to obtain the deformation surrounding the indenter site. An inverse finite element (FE) algorithm was developed to determine the optimal material parameters of the healthy liver tissue. With these param eters, a computational model of tumorous tissue was constructed to quantitatively evaluate the effects of the tumor location on the induced deformation. By relating the experimental data from the "diseased" liver specimen to the computational results, we estimated the radial distance between the tumor and the indenter, as well as the angular position of the tumor relative to the indenter.

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Brain Strain: Computational Model-Based Metrics for Head Impact Exposure and Injury Correlation

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Abstract

Athletes participating in contact sports are exposed to repetitive subconcussive head impacts that may have long-term neurological consequences. To better understand these impacts and their effects, head impacts are often measured during football to characterize head impact exposure and estimate injury risk. Despite widespread use of kinematic-based metrics, it remains unclear whether any single metric derived from head kinematics is well-correlated with measurable changes in the brain. This shortcoming has motivated the increasing use of finite element (FE)-based metrics, which quantify local brain deformations. Additionally, quantifying cumulative exposure is of increased interest to examine the relationship to brain changes over time. The current study uses the atlas-based brain model (ABM) to predict the strain response to impacts sustained by 116 youth football athletes and proposes 36 new, or derivative, cumulative strain-based metrics that quantify the com bined burden of head impacts over the course of a season. The strain-based metrics developed and evaluated for FE modeling and presented in the current study present potential for improved analytics over existing kinematically-based and cumulative metrics. Additionally, the findings highlight the importance of accounting for directional dependence and expand the techniques to explore spatial distribution of the strain response throughout the brain.

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The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome

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Abstract

Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer's disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably, the reduction of O-GlcNAcylated proteins involves also tau and APP, thus promoting their aberrant phosphorylation in AD brain and the onset of AD pathological markers. Down syndrome (DS) individuals are characterized by the early development of AD by the age of 60 and, although the two conditions present the same pathological hallmarks and share the alteration of many molecular mechanisms driving brain degeneration, no evidence has been sought on the implication of O-GlcNAcylation in DS pathology. Our study aimed to unravel for the first time the role of protein O-GlcNacylation in DS brain alterations positing the attention of potential trisomy-related mechanisms triggering the aberrant regulation of OGT/OGA cycle. We demonstrate the disruption of O-GlcNAcylation homeostasis, as an effect of altered OGT and OGA regulatory mechanism, and confirm the relevance of O-GlcNAcylation in the appearance of AD hallmarks in the brain of a murine model of DS. Furthermore, we provide evidence for the neuroprotective effects of brain-targeted OGA inhibition. Indeed, the rescue of OGA activity was able to restore protein O-GlcNAcylation, and reduce AD-related hallmarks and decreased protein nitration, possibly as effect of induced autophagy.

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Discovery of Isoform p53 Protein in Failed Cases of ChronicLymphocytic Leukemia by Elisa Method

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Aurelian Udristioiu, Manole Cojocaru and Delia NicaBadea
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Tumor stiffness measured by shear wave elastography correlates with tumor hypoxia as well as histologic biomarkers in breast cancer

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Abstract

Background

Shear wave elastography (SWE) is an ultrasound technique for the noninvasive quantification of tissue stiffness. The hypoxic tumor microenvironment promotes tumor stiffness and is associated with poor prognosis in cancer. We aimed to investigate the correlation between tumor hypoxia and histologic biomarkers and tumor stiffness measured by SWE in breast cancer.

Methods

From June 2016 to January 2018, 82 women with invasive breast cancer who underwent SWE before treatment were enrolled. Average tumor elasticity (Eaverage) and tumor-to-fat elasticity ratio (Eratio) were extracted from SWE. Immunohistochemical staining of glucose transporter 1 (GLUT1) was used to assess tumor hypoxia in breast cancer tissues and automated digital image analysis was performed to assess GLUT1 activities. Spearman correlation and logistic regression analyses were performed to identify associations between GLUT1 expression and SWE values, histologic biomarkers, and molecular subtypes. The Mann–Whitney U test, t test, or Kruskal–Wallis test was used to compare SWE values and histologic features according to the GLUT1 expression (≤the median vs > median).

Results

Eaverage (r = 0.676) and Eratio (r = 0.411) correlated significantly with GLUT1 expression (both p <  0.001). Eaverage was significantly higher in cancers with estrogen receptor (ER)–, progesterone receptor (PR)–, Ki67+, and high-grade (p <  0.05). Eratio was higher in cancers with Ki67+, lymph node metastasis, and high-grade (p <  0.05). Cancers with high GLUT1 expression (>median) had higher Eaverage (mean, 85.4 kPa vs 125.5 kPa) and Eratio (mean, 11.7 vs 17.9), and more frequent ER– (21.7% vs 78.3%), PR– (26.4% vs 73.1%), Ki67+ (31.7%% vs 68.3%), human epidermal growth factor receptor 2 (HER2) + (25.0% vs 75.0%), high-grade (28.6% vs 71.4%), and HER2-overexpressing (25.0% vs 75.0%) and triple-negative (23.1% vs 76.9%) subtypes (p <  0.05). Multivariable analysis sh owed that Eaverage was independently associated with GLUT1 expression (p <  0.001).

Conclusions

Tumor stiffness on SWE is significantly correlated with tumor hypoxia as well as histologic biomarkers. In particular, Eaverage on SWE has independent prognostic significance for tumor hypoxia in the multivariable analysis and can potentially be used as a noninvasive imaging biomarker to predict prognosis and pretreatment risk stratification in breast cancer patients.

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Evaluating the Tubridge™ flow diverter for large cavernous carotid artery aneurysms

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Abstract

Background

The Tubridge™ flow diverter (TFD) was recently developed in China; however, its safety and efficacy in treating large cavernous carotid artery aneurysms (LCCAs) are unclear. Our objective was to evaluate the safety and efficacy of the TFD in patients receiving TFDs to treat LCCAs (10–25 mm).

Methods

Between June 2013 and May 2014, seven patients with LCCAs were enrolled in our study, and all seven patients underwent TFD implantation combined with coils.

Results

Angiographic follow-up images were available for all seven patients at a median of 57.5 ± 16.7 (range, 6–69) months. Seven patients obtained favorable angiographic results defined as O'Kelly–Marotta Scale C and D. Clinical follow-up data were available for all seven patients at a median of 73.32 ± 3.6 (range, 66–78) months. No patients developed new neurological deficits. Six patients achieved a modified Rankin scale score of 0, and diplopia improved in the remaining patient.

Conclusions

The results were excellent for the aneurysms treated with TFDs in our patients with LCCAs. TFDs are feasible for the treatment of LCCAs, but a multicenter, controlled clinical trial is needed to evaluate the long-term safety and efficacy of the TFD to treat LCCAs.

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