CDK4/6 inhibition in early and metastatic breast cancer: a review

Publication date: Available online 20 September 2017
Source:Cancer Treatment Reviews
Author(s): A.F. de Groot, C.J. Kuijpers, J.R. Kroep
Breast cancer (BC) is responsible for 14% of cancer-related deaths in women. [1] Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of selective drugs, offering an effective and tolerable treatment. CDK 4/6 inhibitors induce cell cycle arrest in the G1 phase, and may thereby prevent tumour progression. Three CDK 4/6 inhibitors have been tested in clinical BC trials: palbociclib, ribociclib, and abemaciclib. The Food and Drug Administration (FDA) and European Commission (EMA) have approved palbociclib for the treatment of patients HR+ HER2- locally advanced or metastatic BC (aBC) in combination with an aromatase inhibitor as initial therapy in postmenopausal women or in combination with fulvestrant in women who have received prior endocrine therapy. Ribociclib has been approved by the FDA in combination with an aromatase inhibitor as initial therapy for postmenopausal women with HR+ HER2- aBC. Moreover, CDK 4/6 inhibitors have shown promising results in the (neo)adjuvant setting. In this review, the principal completed and ongoing clinical trials in aBC are reviewed for both the metastatic as (neo)adjuvant setting. Tables will provide a complete overview of the ongoing clinical trials. At last, the future perspectives of these CDK4/6 inhibitors are discussed.



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Evaluation of Beauveria bassiana infection in the hemolymph serum proteins of the housefly, Musca domestica L. (Diptera: Muscidae)

Abstract

Beauveria bassiana plays a prominent role in biocontrol of houseflies, Musca domestica (L.). Thus, a deeper insight into immune response of M. domestica during B. bassiana infection was warranted to assist the production of more efficient mycoinsecticides. The present study investigates changes in protein profile of M. domestica hemolymph serum post B. bassiana infection using two-dimensional difference gel electrophoresis (2D-DIGE) followed by identification of selected proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The non-infected or control group of flies showed an expression of 54 proteins, while M. domestica infected with B. bassiana expressed a total of 68 hemolymph serum proteins. Thirty three proteins were expressed in both groups of houseflies, whereas 35 proteins were exclusively expressed in infected flies and 21 proteins were exclusively expressed in control flies. Among the 33 proteins which were expressed in both groups of houseflies, 17 proteins showed downregulation, while16 proteins were upregulated in the infected flies compared to the non-infected ones. The results from this study are expected to facilitate better understanding of insect's immune response mechanism.

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An assessment of the potential use of compost filled plastic void forming units to serve as vents on historic landfills and related sites

Abstract

Much of the solid municipal waste generated by society is sent to landfill, where biodegrading processes result in the release of methane, a major contributor to climate change. This work examined the possibility of installing a type of biofilter within paved areas of the landfill site, making use of modified pervious paving, both to allow the escape of ground gas and to avoid contamination of groundwater, using specially designed test models with provision for gas sampling in various chambers. It proposes the incorporation of an active layer within a void forming box with a view to making dual use of the pervious pavement to provide both a drainage feature and a ground gas vent, whilst providing an active layer for the oxidation of methane by microbial action. The methane removal was observed to have been effected by microbial oxidation and as such offers great promise as a method of methane removal to allow for development of landfills.

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Compound-specific isotopic and congener-specific analyses of polychlorinated biphenyl in the heat medium and rice oil of the Yusho incident

Abstract

Compound-specific isotope analysis (CSIA) can be used to examine the source and transformation processes of organic pollutants in the environment. We performed a carbon stable isotope analysis of polychlorinated biphenyl (PCB) congeners in the PCB heat-transfer medium (heat medium) and the original Kanechlor-400 (KC-400, a commercial brand of PCBs) involved in the Yusho incident. The main purpose is to investigate whether isotope fractionation occurred in the rice oil deodorization process that caused the incident. The carbon isotope ratios (δ¹³C values) of the targeted PCB congeners ranged from − 29.39 to − 27.00‰ in the heat medium and from − 28.77 to − 27.05‰ in the original KC-400. No significant differences were found in the δ¹³C values, suggesting carbon isotope fractionation did not occur for the targeted PCB congeners in the heat medium when deodorization of rice oil occurred at temperatures above 200 °C. Furthermore, we also conducted a congener-specific analysis of 64 PCB congeners found in the heat medium and rice oil contaminated by it. The total PCB congener concentrations were 503 mg/g in the heat medium and 81 μg/g in the rice oil. The concentrations of the highly chlorinated congeners were significantly lower in the heat medium than in the original KC-400, and the compositional ratios of the lowly chlorinated congeners were relatively lower in the rice oil than in the heat medium. These results suggest that the PCB congener patterns gradually changed from that of the original KC-400 in the deodorization process and subsequent contamination into the rice oil. Thus, a combination of CSIA and congener-specific analysis is a new approach for investigating the changing PCB congener profiles in samples from the Yusho incident.

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The effectiveness and safety of the Impella ventricular assist device for high-risk percutaneous coronary interventions: A systematic review

Abstract

Background

Small randomized controlled trials (RCTs) and observational studies have examined the effectiveness and safety of the Impella device, a percutaneous left ventricular assist device, in the setting of high-risk percutaneous coronary intervention (PCI). However, data are sparse and results are conflicting. Our objective was to evaluate the effectiveness and safety of the Impella device in high-risk patients undergoing PCI via a systematic review of the literature.

Methods

We searched Medline, EMBASE, and the Cochrane Library for RCTs and observational studies that evaluated the Impella device in high-risk patients undergoing PCI. Inclusion was restricted to studies in which ≥10 patients received the Impella device; both uncontrolled and controlled (versus intra-aortic-balloon pump [IABP]) studies were included.

Results

A total of 20 studies (4 RCTs, 2 controlled observational studies, and 14 uncontrolled observational studies; 1,287 patients) were included, with follow-up ranging from 1 to 42 months. The use of Impella resulted in improved procedural and hemodynamic characteristics in controlled and uncontrolled studies. In controlled studies, the 30-day rates of all-cause mortality and MACE were similar across groups. In most uncontrolled studies, the 30-day rates of all-cause mortality were generally low (range: 3.7%–10%), though rates of MACE were slightly higher (range: 5%–20%).

Conclusion

The Impella device was found to improve procedural and hemodynamic parameters, but only limited randomized data are available regarding clinical outcomes associated with its use. Large, multicenter RCTs are needed to definitively establish the effectiveness of the Impella device among high-risk PCI patients.

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Guidewire electrosurgery-assisted trans-septal puncture

Abstract

Objectives

Electrifying a coronary guidewire may be a simple escalation strategy when trans-septal needle puncture is unsuccessful.

Background

Radiofrequency energy to facilitate trans-septal puncture through a dedicated device is costly and directly through a trans-septal needle may be less safe. Our technique overcomes these limitations.

Methods

The technique was used in patients when trans-septal needle penetration failed despite excessive force or tenting of the atrial septum. A coronary guidewire, connected to an electrosurgery pencil, was advanced through the trans-septal needle, dilator, and sheath to perforate the interatrial septum during a short burst of radiofrequency energy. With the guidewire tip no longer "active," the dilator and sheath were advanced safely over the wire into the left atrium.

In posthoc validation, radiofrequency assisted Brockenbrough needle and coronary guidewire punctures were made in freshly explanted pig hearts and compared under microscopy.

Results

Eight patients who required trans-septal access for structural intervention were escalated to a guidewire electrosurgery strategy. Six patients had thickened fibrotic septum and two had prior surgical patch repair. Crossing was successful in all patients with no procedure related complications.

The size of punctures (1.11 ± 0.40 mm vs 0.37 ± 0.08 mm, P = .009) and blanched penumbra (3.62 ± 1.23 mm vs 0.72 ± 0.29 mm, P = .003) in pig atrial septum were larger with an electrified needle than electrified guidewire. The hole generated by the electrified guidewire was smaller than by the nonelectrified needle.

Conclusions

When conventional trans-septal puncture fails, a coronary guidewire can be used to deliver brief radiofrequency energy safely and effectively. This technique is inexpensive and accessible to operators.

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A comparison of the fully repositionable and retrievable Boston Lotus and direct flow medical valves for the treatment of severe aortic stenosis: A single center experience

Abstract

Background

Second generation transcatheter aortic valve implantation (TAVI) devices have been designed to reduce the rate of paravalvular leak (PVL) and other complications. An important technological advancement has been the ability to fully reposition devices to facilitate optimal implantation depth and position to reduce the likelihood of PVL.

Objectives

To compare procedural and 30-day outcomes according to the Valve Academic Research Consortium (VARC)-2 criteria following TAVI with the fully repositionable and retrievable Lotus and DFM devices.

Methods and Results

175 patients with severe aortic stenosis underwent transfemoral TAVI with the Lotus (n = 60) and DFM (n = 115) valve. Baseline clinical characteristics did not differ between the two groups. All devices were successfully implanted, with one case of valve embolization in the Lotus group. Device success (95 vs. 98.2%, P = 0.89), VARC-defined combined safety (90 vs. 93%, P = 0.48), and clinical efficacy (86.7 vs. 90.4%, P = 0.65) rates at 30-days were similar between Lotus and DFM groups. There was no severe PVL; one patient in both Lotus and DFM group developed moderate PVL after the procedure. The Lotus valve was associated with a higher rate of new pacemaker implantation (37.3 vs. 11.2%, P < 0.001) and a lower mean aortic gradient (9.4 ± 5 vs. 12.3 ± 5, P < 0.001) at 30-days as compared with the DFM valve.

Conclusions

In this single-center, retrospective analysis, both Lotus and DFM devices demonstrated excellent device success, safety and efficacy at 30-day follow-up. The DFM valve was associated with minimally higher transvalvular gradients but lower new pacemaker implantation rates when compared to the Lotus valve.

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Real-time optical coherence tomography coregistration with angiography in percutaneous coronary intervention–impact on physician decision-making: The OPTICO-integration study

Abstract

Aims

Intracoronary optical coherence tomography (OCT) imaging allows for high-resolution characterization of coronary lesions. Difficulties in matching cross-sectional OCT-images with angiographic lesion localization may limit optimal clinical utilization. We sought to prospectively assess the impact of a novel system of real-time OCT coregistration with angiography (ACR) on physician decision-making during percutaneous coronary interventions (PCI).

Methods and Results

Strategy for PCI (stent - length, - diameter, - strategy, landing zone) and PCI-optimization (stent-malappostion, -underexpansion, edge-dissections, geographical mismatch) was prospectively assessed in 50 patients with 58 coronary lesions after (I) angiography, (II) OCT imaging, and (III) ACR.

Preprocedural OCT imaging altered stent-length (58.9%), diameter (33.9%), and PCI-strategy (12.5%) in 40 (71.4%) lesions. The use of ACR resulted in additional changes in PCI strategy in 40.7% of mostly complex lesions in comparison to OCT imaging alone and involved mainly device landing zone (24.1%) and stent length (22.2%). Postprocedural OCT imaging revealed the need for PCI optimization in 52.2% of the lesions, whereas post-procedural ACR had no further impact.

Conclusions

Real-time OCT ACR had significant impact on PCI strategy, favoring mainly complete lesion coverage especially in complex lesions.

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Preferential Reduction of Circulating Innate Lymphoid Cells Type 2 in Patients with Common Variable Immunodeficiency with Secondary Complications Is Part of a Broader Immune Dysregulation

Abstract

Purpose

Over a third of patients with common variable immunodeficiency (CVID) suffer from secondary complications like inflammatory organ disease, autoimmune manifestations, or lymphoproliferation contributing to increased morbidity and mortality in affected patients. Innate lymphoid cells (ILCs) have emerging roles in setting the milieu for physiological, but also pathological, immune responses and inflammation. We therefore sought to correlate the recently identified disturbed homeostasis of ILCs with alterations of the adaptive immune system in complex CVID patients (CVIDc).

Methods

We quantified peripheral blood ILC and T helper cell subsets of 58 CVID patients by flow cytometry and compared the results to the clinical and immunological phenotype.

Results

Total ILCs were significantly reduced in peripheral blood of CVIDc patients compared to healthy individuals, but not to CVID patients who suffered only from infections (CVIDio). This reduction was mainly due to a decrease in ILC2s, while ILC3s were relatively increased in CVIDc compared to CVIDio patients. This alteration in ILC phenotype was more prominent in patients with an expansion of CD21^low B cells, but we could not detect an association of the altered ILC phenotype with a T_H1-shift among circulating CD4 T cells, which was also prominent in CVIDc patients.

Conclusion

We confirm a relative shift in ILCs of CVIDc patients towards ILC3s which was associated with the expansion of CD21^low B cells, but not overtly with the relative expansion of T_H1-like T cells. Given the relative abundance of T_H1-like T cells compared to ILCs, these probably represent a more prominent source of the observed IFNγ-signature in CVIDc patients.

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Advances in Craniofacial Trauma

The epidemiology of craniofacial injury has changed significantly due to influences such as the advent of airbags and an increase in the sophistication of civilian weaponization. The emergency management of severe trauma has also evolved, leading to the survival of injuries that would have previously proved fatal. Together, these forces have had a notable impact on the challenges that surgeons treating craniofacial trauma now face.

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Effect of ingredients on the quality characteristics of gluten free snacks

Abstract

Grain-based fabricated snacks from non-wheat grains (amaranth, finger millet, sorghum and black gram) were used to prepare puffed snacks employing the method of hot air toasting. The functional characteristics and sensory attributes of the snack were determined by varying the moisture content and time of toasting. The quality attributes of the snacks like the instrumental color parameters, peak force and puff thickness of the snack correlated well with the sensory attributes (appearance/color, texture and overall acceptability). A snack made from amaranth showed a bright reddish brown colour at a moisture content of 20–40%; the product had a good puffing and high overall acceptability. The moisture content of all the snacks was around 3% and had a fat content of 1–2%; protein and dietary fiber contents were in the ranges of 22–23 and 10–11%, respectively. The principal component analysis (PCA) accounted for a total of 89.6% variation. The PCA biplot showed that sensory appearance, sensory texture and sensory overall acceptability were closely related to the puff thickness. The microstructure of the snack indicated the presence of air cells to offer a porous structure. On toasting, the flakes increased their thickness creating a porous microstructure such that the toasted snacks were crispy having a brittle texture. Popped sorghum and gelatinized starch added doughs exhibited good puffing when toasted at 20–30% moisture content while popped amaranth samples required higher moisture content (30–40%). The grain based gluten-free snacks with improved sensory and nutritional characteristics can be prepared by using different ingredients.

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Forthcoming Issues

Cosmetic and Reconstructive Surgery of Congenital Ear Deformities

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Evidence-Based Medicine in Facial Trauma

This article provides the reader with a comprehensive review of high-level evidence-based medicine in facial trauma and highlights areas devoid of high-level evidence. The article is organized in the order one might approach a clinical problem: starting with the workup, followed by treatment considerations, operative decisions, and postoperative treatments. Individual injuries are discussed within each section, with an overview of the available high-level clinical evidence. This article not only provides a quick reference for the facial traumatologist, but also allows the reader to identify areas that lack high-level evidence, perhaps motivating future endeavors.

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Contributors

J. REGAN THOMAS, MD, FACS

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Advances in the Reconstruction of Orbital Fractures

Orbital reconstruction is one of the most challenging tasks for surgeons who treat craniofacial trauma. Suboptimal outcomes carry a high level of morbidity, with functional, emotional, and aesthetic implications. However, advances in reconstruction techniques, including the use of orbital endoscopy, computer-guided navigation, and mirror image overlay techniques, have been shown to provide significant improvements in outcomes. This article provides practical advice for applying these techniques to orbital reconstruction following trauma.

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Posttraumatic Laser Treatment of Soft Tissue Injury

Laser treatment for posttraumatic injury offers the clinician the unique opportunity for early intervention in mediating early scar formation, or for reducing the appearance of scars after maturation. In this review, the authors focus on the mechanisms by which lasers exert their therapeutic effects, highlighting several popular lasers and dosimetry used, and underscoring the power of combined surgical scar revision in managing posttraumatic facial scars.

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Eyelid and Periorbital Soft Tissue Trauma

Facial trauma often involves injuries to the eyelid and periorbital region. Management of these injuries can be challenging due to the involvement of multiple complex anatomic structures that are in close proximity. Restoration of normal anatomic relationships of the eyelids and periocular structures is essential for optimum functional and aesthetic outcome after trauma. This review provides an overview of the current literature involving soft tissue trauma of the eyelid and periorbital tissue, and highlights key steps in patient evaluation and management with various types of injuries.

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Emergent Soft Tissue Repair in Facial Trauma

Emergency personnel, surgeons, and ancillary health care providers frequently encounter soft tissue injuries in facial trauma. Appropriate evaluation and management is essential to achieve optimal functional and aesthetic outcomes.

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Current Management of Subcondylar Fractures of the Mandible, Including Endoscopic Repair

Treatment of subcondylar fractures has been the subject of debate for many years. Options for treatment include physical therapy, elastic maxillomandibular fixation, and open repair. Proper imaging and clinical evaluation are imperative when deciding on the best management option. In the past, most subcondylar fractures were treated with a closed approach. Recent data support open repair, when feasible. Studies show increased interincisal opening, lateral excursion, and protrusion with less mandibular shortening, jaw deviation, and pain. There are serious side effects that may be associated with open repair. The surgical technique for endoscopic repair is outlined in detail.

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Updates in Management of Craniomaxillofacial Gunshot Wounds and Reconstruction of the Mandible

This article includes updates in the management of mandibular trauma and reconstruction as they relate to maxillomandibular fixation screws, custom hardware, virtual surgical planning, and protocols for use of computer-aided surgery and navigation when managing composite defects from gunshot injuries to the face.

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Management of Zygomaticomaxillary Complex Fractures

Zygomaticomaxillary fractures account for approximately 25% of all facial fractures. They can be grouped into high-velocity and low-velocity injuries. A complete head and neck examination is critical for accurate clinical diagnosis. A thin-cut axial CT scan with sagittal, coronal, and 3-D reconstruction is important for accurate diagnosis and treatment planning. A thorough understanding of bony tetrapod anatomy and fracture mechanics is critical to treatment planning. Treatment options include closed and open reduction with internal fixation. Computer-aided applications can reduce the need for open reduction and improve the accuracy of both closed and open repairs.

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Correction of Nasal Fractures

Nasal fractures are the most frequently fractured facial bone from blunt facial trauma resulting in a significant number of patients seeking treatment. Proper evaluation and treatment in the acute setting can minimize secondary surgeries, lower overall health care costs, and increase patient satisfaction. Nasal fracture management, however, varies widely between surgeons. The open treatment of isolated nasal fractures is a particularly controversial subject. This review seeks to describe the existing literature in isolated nasal fracture management.

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Trauma in Facial Plastic Surgery

The optimal management of frontal sinus fractures remains controversial. Fortunately, the severity of these injuries has diminished with more stringent auto-safety regulations, changing the treatment paradigms used to repair these injuries. Appropriate patient selection and close follow-up may allow for conservative management strategies when dealing with frontal sinus fractures, largely replacing the more morbid and invasive techniques that have been the mainstay for years. Because acute and delayed sequelae can arise after the initial injury, patients should be thoroughly counseled about the importance of follow-up and the need to seek medical care if they develop any concerning signs or symptoms.

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Neurosurgical Considerations in Craniofacial Trauma

Spinal and traumatic brain injuries (TBIs) often accompany craniofacial trauma. Neurosurgical considerations can range from initial emergent surgery to conservative management of closed head injuries in patients with craniofacial injuries. This article discusses the most common disorders managed by neurosurgeons in the setting of craniofacial trauma, and reviews the usual timing and setting for various treatments that patients with TBI encounter throughout the course of treatment. It also highlights the consequences of TBI on the timing and planning of craniofacial repairs and the importance of multidisciplinary cooperation to provide comprehensive care to survivors of trauma.

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Sandwich compression with rubbery tourniquet sheets and cotton balls for auricular pseudocyst

Objectives/Hypothesis

Pseudocyst of the auricle is a benign, noninflammatory cystic disease that is more common in Asians than in Caucasians. When managed conservatively, the results are often unsatisfactory and recurrences are common. We aimed to introduce a novel modified surgical method that involves a deroofing technique followed by a sandwich compression suture using two rubber tourniquet sheets and an iodine-soaked cotton ball for the treatment of auricular pseudocysts and to ascertain its effectiveness.

Study Design

Case series with or without comparison.

Methods

The charts of 100 patients with auricular pseudocysts who were treated with this new method from 2004 to 2016 in a university-affiliated tertiary teaching hospital were retrospectively reviewed and analyzed.

Results

The mean patient age was 37.7 years, and 84% were male. All of the patients had unilateral lesions, with right-side lesions (53.0%) being slightly predominant. The cymba concha (44.1%) was the most common site. Seven patients (7.0%) had trauma to the ear within 3 months before presentation. Previous aspiration or drainage had been performed for the cysts in 35 patients (35.0%), and the recurrences had been treated conservatively. In comparison, 98 of the 100 patients recovered smoothly from surgery without further recurrence or complications after follow-up for at least 1 year.

Conclusions

Based on our experience, not only does this surgical procedure yield reliable results in the treatment of pseudocysts of auricles, but it also has advantages such as using readily available materials, being simple to perform, improving efficacy, and lowering recurrence rates.

Level of Evidence

4 Laryngoscope, 2017

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Adipose-derived mesenchymal stromal cells prevented rat vocal fold scarring

Objectives/Hypothesis

This study aimed to reveal the effects of adipose-derived mesenchymal stromal cells (ASCs) on prevention of vocal fold scarring by investigating how the immediate ASCs transplantation into the injured rat vocal fold affect the levels of gene transcription and translation.

Study Design

Prospective animal experiments with controls.

Methods

ASCs harvested from green fluorescent protein transgenic rat (ASCs group) or saline (sham group) were injected into the thyroarytenoid muscle of Sprague-Dawley rats immediately after stripping the vocal fold. For histological examinations, larynges were extirpated at 3, 14, and 56 days after the injection. Quantitative real-time polymerase chain reaction (PCR) analyses were performed at 3 and 14 days after the injection.

Results

Transplanted ASCs were detected only in larynges at day 3. At days 14 and 56, histological examination showed significantly higher amounts of hyaluronic acid and lower deposition of collagen in the ASCs group compared to the sham group. Real-time PCR revealed that the ASCs group showed low expression of procollagen (Col)1a1, Col1a3, matrix metalloproteinase (Mmp)1 and Mmp8 in each time points. The ASCs group showed high expression of fibroblast growth factor (Fgf)2 and Hepatocyte growth factor (Hgf) compared to the sham group at day 14.

Conclusions

ASCs increased expressions of Fgf2 and Hgf, and suppressed excessive collagen deposition during vocal fold wound healing. Given the fact that ASCs survived no more than 14 days, ASCs were thought to induce upregulations of growth factors' genes in surrounding cells. These results suggested that ASCs have potential to prevent vocal fold scarring.

Level of Evidence

N/A Laryngoscope, 2017

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Association between tumour infiltrating lymphocytes, histotype and clinical outcome in epithelial ovarian cancer

There is evidence that some ovarian tumours evoke an immune response, which can be assessed by tumour infiltrating lymphocytes (TILs). To facilitate adoption of TILs as a clinical biomarker, a standardised met...

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Effect of sodium levothyroxine on histomorphometry, histopathology, histochemistry, and immunohistochemistry of articular cartilage in female mice

Abstract

Sodium levothyroxine is one of the common medicines used for treatment of hypothyroidism. The aim of the present study was to assess the effect of sodium levothyroxine on the middle part of tibia plateau in knee joint and related hormones in individuals affected by hypothyroidism. Fifty female mice were randomized into five groups. The first group was considered as control; the second and third groups were received different doses of levothyroxine; the forth group was undergone hypothyroidism; and the fifth group, the animals with hypothyroidism, was received levothyroxine orally. After 8 weeks, serum samples were taken to determine TSH, T4, FT4, T3, FT3, T3RU, calcium, and phosphorus. The cartilage of tibia plateau was evaluated using hematoxylin–eosin (histomorphometry of tibia plateau), toluidine blue (proteoglycans of matrix), TUNEL (chondrocytes apoptosis), and immunohistochemistry (rate of Collagen-II). The results showed that the number of chondrocytes, cartilage thickness, proteoglycans, and Collagen-II and the rate of T3 in the third group were significantly decreased; whereas, the percentage of apoptotic chondrocytes in the third group was significantly increased compared to those of other experimental groups (P < 0.05). FT3, FT4, TSH, calcium, and phosphorus values in most groups were also significantly different (P < 0.05). Regarding widely consumption of levothyroxine in hypothyroidism and its effects on knee joint cartilage, levothyroxine at high doses should be administered with care.

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Affective priming and cognitive load: Event-related potentials suggest an interplay of implicit affect misattribution and strategic inhibition

Abstract

Prior research suggests that the affective priming effect denoting prime-congruent evaluative judgments about neutral targets preceded by affective primes increases when the primes are processed less deeply. This has been taken as evidence for greater affect misattribution. However, no study so far has combined an experimental manipulation of the depth of prime processing with the benefits of ERPs. Forty-seven participants made like/dislike responses about Korean ideographs following 800-ms affective prime words while 64-channel EEG was recorded. In a randomized within-subject design, three levels of working-memory load were applied specifically during prime processing. Affective priming was significant for all loads and even tended to decrease over loads, although efficiency of the load manipulation was confirmed by reduced amplitudes of posterior attention-sensitive prime ERPs. Moreover, ERPs revealed greater explicit affective discrimination of the prime words as load increased, with strongest valence effects on central/centroparietal N400 and on the parietal/parietooccipital late positive complex under high load. This suggests that (a) participants by default tried to inhibit the processing of the prime's affect, and (b) inhibition more often failed under cognitive load, thus causing emotional breakthrough that resulted in a binding of affect to the prime and, hence, reduced affect misattribution to the target. As a correlate of affective priming in the target ERP, medial-frontal negativity, a well-established marker of (low) stimulus value, increased with increasing negative affect of the prime. Findings support implicit prime-target affect transfer as a major source of affective priming, but also point to the role of strategic top-down processes.

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Presence of periaortic gas in Clostridium septicum-infected aortic aneurysm aids in early diagnosis: a case report and systematic review of the literature

Clostridium septicum-infected aortic aneurysm is a fatal and rare disease. We present a fatal case of C. septicum-infected aortic aneurysm and a pertinent literature review with treatm...

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Spatio-temporal changes in rate of soil loss and erosion vulnerability of selected region in the tropical forests of Borneo during last three decades

Abstract

An attempt has been made to analyze the spatial-temporal characteristics of soil erosion vulnerability and soil loss from the forested region in the north-eastern Borneo, Sarawak, Malaysia during the last three decades (1991–2015) using the revised universal soil loss equation (RUSLE) and geographical information systems (GIS). The components of RUSLE such as rainfall erosivity (R), soil erodibility (K), slope-length and steepness (LS), cover management (C) and conservation practice (P) factors were grouped into two categories by keeping one set as temporally changing and others as static. Among them the R and C factors are calculated for the years 1991, 2001 and 2015 whereas the K and LS factors are considered for the single time frame. Because of the forested nature of the study area, the P factor is kept constant for the whole analysis. The R factor and C factor is shown changes in values and its distribution over the years, which reflected in the final soil loss and erosion vulnerability map as a change in the rate of erosion and spatial domain. The analysis of three time slices has shown that the maximum value of the soil loss per unit area i.e. at erosion hotspots, is relatively similar throughout at around 1636 to 1744 t/ha/y. This is the result of maximum values of R factor and C factor i.e. high rainfall erosivity combined with lack of vegetation cover in those hotspots, which are generally steeply sloping terrain. The reclassification of annual soil loss map into erosion vulnerability zones indicated a major increase in the spatial spread of erosion vulnerability from the year 1991 to 2015 with a significant increase in the high and critical erosion areas from 2.3% (1991) to 31.5% (2015). In 1991, over 84% of the study area was under low erosion vulnerability class but by the year 2015 only 12% was under low erosion vulnerability class. Moreover, a dynamic nature in the erosion pattern was found from the year 1991 to 2015 with more linear areas of land associated with higher rate of soil loss and enhanced erosion vulnerability. The linearity in the spatial pattern is correlated with the development of logging roads and logging activities which has been confirmed by the extraction of exposed areas from satellite images of different years of analysis. The findings of the present study has quantified the changes in vegetation cover from dense, thick tropical forest to open mixed type landscapes which provide less protection against erosion and soil loss during the severe rainfall events which are characteristic of this tropical region.

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Rational and simplified nomenclature for buccinator myomucosal flaps

Abstract

Background

Reconstruction of moderate-sized mucosal defects of the oral cavity or oropharynx represents a surgical challenge. Buccinator myomucosal flaps seem to provide "ideal reconstruction" of oral/oropharyngeal defects because they carry a thin, mobile, well-vascularized, and sensitive tissue, like that excised or lost. Nevertheless, these flaps are not immediately popular because of confusion surrounding the complex terminology used to name them.

Methods

After a retrospective study on our experience and a literature review, the authors propose a new rational and simplified nomenclature for the classification of buccinator myomucosal flaps, which clarifies the source vessel, the composition of the flap, and the type of transfer.

Results

According to this nomenclature, six types of buccinator myomucosal flaps are described.

Conclusions

This proposed nomenclature may bring a consensus on the classification of buccinator myomucosal flaps and can help their spread.

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Rational and simplified nomenclature for buccinator myomucosal flaps

Abstract

Background

Reconstruction of moderate-sized mucosal defects of the oral cavity or oropharynx represents a surgical challenge. Buccinator myomucosal flaps seem to provide "ideal reconstruction" of oral/oropharyngeal defects because they carry a thin, mobile, well-vascularized, and sensitive tissue, like that excised or lost. Nevertheless, these flaps are not immediately popular because of confusion surrounding the complex terminology used to name them.

Methods

After a retrospective study on our experience and a literature review, the authors propose a new rational and simplified nomenclature for the classification of buccinator myomucosal flaps, which clarifies the source vessel, the composition of the flap, and the type of transfer.

Results

According to this nomenclature, six types of buccinator myomucosal flaps are described.

Conclusions

This proposed nomenclature may bring a consensus on the classification of buccinator myomucosal flaps and can help their spread.

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The effects of a rise in cigarette price on cigarette consumption, tobacco taxation revenues, and of smoking-related deaths in 28 EU countries-- applying threshold regression modelling

European Union public healthcare expenditure on treating smoking and attributable diseases is estimated at over €25bn annually. The reduction of tobacco consumption has thus become one of the major social poli...

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Income related inequality and influencing factors: a study for the incidence of catastrophic health expenditure in rural China

Catastrophic health expenditure (CHE) puts a heavy disease burden on patients' families, aggravating income-related inequality. In an attempt to reduce the financial risks of rural families incurring CHE, Chin...

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Evaluation of caregiver-friendly workplace policy (CFWPs) interventions on the health of full-time caregiver employees (CEs): implementation and cost-benefit analysis

Current Canadian evidence illustrating the health benefits and cost-effectiveness of caregiver-friendly workplace policies is needed if Canadian employers are to adopt and integrate caregiver-friendly workplac...

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Early food for future health: a randomized controlled trial evaluating the effect of an eHealth intervention aiming to promote healthy food habits from early childhood

Childhood overweight and obesity is a global public health challenge. Primary prevention initiatives targeting parents have been called for to encourage a positive feeding environment and healthy eating habits...

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Erratum to: understanding how perceptions of tobacco constituents and the FDA relate to effective and credible tobacco risk messaging: a national phone survey of U.S. adults, 2014–2015

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COPD

COPD: Chronic obstructive pulmonary disease. Any disorder that persistently obstructs bronchial airflow. COPD is frequently related to cigarette smoking and mainly involves two related diseases -- chronic bronchitis and emphysema. Both are frequently present and cause chronic obstruction of airflow obstruction of the lungs. The obstruction is generally permanent and progresses (becomes worse) over time.

Asthma is also a pulmonary disease in which there is obstruction to the flow of air out of the lungs, but the obstruction is usually reversible and between attacks of asthma the flow of air through the airways is usually good.

COPD is also called chronic obstructive lung disease (COLD).

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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The Temporal Artery Island Flap: A Good Reconstructive Option for Small to Medium Sized Facial Defects

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Said Algan, Murat Kara, Hakan Cinal, Ensar Zafer Barin, Akin Inaloz, Onder Tan
PurposeThe reconstruction of facial defects is esthetically vital due to unique skin color and texture of the face. The aim of this study is to show the effectiveness of different styles of the temporal artery island flap for the reconstruction of upper and middle facial defects without losing color and texture of the face.Materials and MethodsThis study is retrospective case series conducted between November 2004 and May 2015. Patients over 18 years old, having upper and middle facial defects less than 5 cm were included.ResultsWe used the temporal artery island flapin 34 patients (21 males and 13 females) in our clinic. The etiologies were skin tumor in 17 patients, trauma in 10 patients, and burns in 7 patients. Major defect localization was the temporal area in 12 patients, followed by ear in 9 patients, cheek in 6 patients, eyebrow in 4 patients and nose in 3 patients The flaps' styles composed of antegrade flowed island flap, V-Y flap and reverse flowed island flap in 23, 7 and 4 patients, respectively. All flaps survived completely except of only one partial flap necrosis. Scars in the donor areas were inconspicuous. The median age was 47.5 years (quartiles 40.75-54), 61.8% male and median duration of follow-up was 11 months (ranging from 6 to 18 months).ConclusionsThe temporal artery island flap may be a good option for closure of minor to medium sized defects of the upper and middle face with its advantages including good color and texture match, constant and reliable pedicle, wide pivotal movement, low donor site morbidity, and use in reverse flow pattern.



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A rare, unusual presentation of primary tuberculosis in the temporomandibular joint

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): N.T. Geetha, Amarnath P. Upasi, K.V. Umashakara, Kirthikumar Rai
Tuberculosis (TB) is a very common health problem in developing nations like India. It can present as either its primary form or in secondary forms which are called extrapulmonary tuberculosis. Maxillofacial manifestations of tuberculosis form nearly 10% of all extrapulmonary manifestations of the disease. Extrapulmonary TB involving the maxillofacial region is very rare and it can present in any of the tissues. These infections generally involve the head and neck through haematogenous or lymphatic routes. Very few cases of primary TB of the temporomandibular joint (TMJ) have been reported in the literature. The presentation of TB infection of the TMJ may resemble an arthritis, osteomyelitis, or any other kind of chronic joint disease. It is very important to diagnose this disease at an early stage. If left untreated, it may prove fatal within 5 years in more than half of the cases. So early diagnosis and management of these cases is needed. In this article we describe a case of primary tuberculosis of the TMJ which presented as a preauricular swelling.



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Re: Dr Yang's Meta-Analysis

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Hongpu Wei, Xudong Wang




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Enhance Surgical Outcomes in Patients with Skeletal Class III Facial Asymmetry by 3D Surgical Simulation

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Ellen Wen-Ching Ko, Cheng-Hui Lin, Ying-An Chen, Yu-Ray Chen
PurposeWith the advance of the image fusion techniques, the creation of the 3D virtual head and 3D surgical simulations provided previews of the surgical procedures. The aim of the study was to investigate the surgical outcomes in patients receiving orthognathic surgery (OGS) with the guidance of 3D computer-assisted surgical simulation.MethodsThe study included 34 consecutive patients (15 men and 19 women, 18.1–33.0 years of age) with skeletal Class III facial asymmetry who had bimaxillary OGS. The 1-week postoperative cone-beam computed tomography craniofacial images (Ta) were constructed and superimposed on preoperative simulated virtual images (Ts) at the cranial base and surfaces of the frontal and periorbital regions. The 3D cephalometric landmarks were measured relative to three reference planes. The outcomes among different experience level of surgeons were also compared.ResultsAlthough the means of Ta−Ts were small, statistical differences were observed in center of maxillary and mandibular incisors and B point relative to the midline, and in the maxillary first molar in vertical distances, sagittal dental–skeletal dimensions, and pitch angles. The root mean square deviation (RMSDL) of measurement variables relative to the center landmark accuracy was 1.5 mm and <2 mm at the maxilla and mandible, respectively. RMSDL >2 mm were located at the maxillary first molar in the vertical distance and in the sagittal dimension at points ANS and B point. Variables related to centering the midline structures were highly interrelated. The roll angle deviation was associated with centering the midline landmarks. The yaw angle deviation was not associated with midline correction.ConclusionWith guidance from 3D surgical simulation, surgeons were able to achieve similar outcomes to correct facial asymmetry regardless of their years of practice.



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Reply

Publication date: Available online 19 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Le Yang, Guiqing Liao




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Deviations in conformational rearrangements of thin filaments and myosin caused by the Ala155Thr substitution in hydrophobic core of tropomyosin

Publication date: Available online 20 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Olga E. Karpicheva, Vladimir V. Sirenko, Nikita A. Rysev, Armen O. Simonyan, Danuta Borys, Joanna Moraczewska, Yurii S. Borovikov
Effects of the Ala155Thr substitution in hydrophobic core of tropomyosin Tpm1.1 on conformational rearrangements of the components of the contractile system (Tpm1.1, actin and myosin heads) were studied by polarized fluorimetry technique at different stages of the actomyosin ATPase cycle. The proteins were labelled by fluorescent probes and incorporated into ghost muscle fibres. The substitution violated the blocked and closed states of thin filaments stimulating abnormal displacement of tropomyosin to the inner domains of actin, switching actin on and increasing the relative number of the myosin heads in strong-binding state. Furthermore, the mutant tropomyosin disrupted the major function of troponin to alter the distribution of the different functional states of thin filaments. At low Ca²⁺ troponin did not effectively switch thin filament off and the myosin head lost the ability to drive the spatial arrangement of the mutant tropomyosin. The information about tropomyosin flexibility obtained from the fluorescent probes at Cys190 indicates that this tropomyosin is generally more rigid, that obviously prevents tropomyosin to bend and adopt the appropriate conformation required for proper regulation.



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Masthead

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Table of Contents

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Editorial Board

Publication date: September–October 2017
Source:Brachytherapy, Volume 16, Issue 5





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Sentinel lymph node biopsy in periocular merkel cell carcinoma: a case report

The National Comprehensive Cancer Network guidelines for Merkel cell carcinoma recommend performance of the sentinel lymph node biopsy in all patients with clinically negative nodal disease for staging and tre...

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Magnitude of the Cytomegalovirus infection among pregnant women attending antenatal clinics in the city of Mwanza, Tanzania

Despite, Cytomegalovirus (CMV) infection being associated with a potential risk to the fetus, there is limited data from Tanzania and many other developing countries regarding the epidemiology and the impact o...

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Physical activity and 22-year all-cause and coronary heart disease mortality

Background

This study explores the effects of occupational (OPA) and leisure time physical activity (LTPA) on mortality relative to cardiorespiratory fitness and pre-existing coronary heart disease (CHD).

Methods

Associations between OPA, measured as energy expenditure (kcal/day) and relative aerobic workload (%VO₂max), LTPA, and 22-year mortality among 1891 Finnish men were assessed by Cox regression models stratified by CHD and adjusted for 19 confounders.

Results

In fully adjusted models, each 10% of relative aerobic workload increased all-cause mortality by 13% and CHD mortality 28% (P < 0.01). Compared to healthy subjects, men with CHD experienced lower mortality risks due to OPA and higher risks due to LTPA. While LTPA had no effect among healthy men, in men with CHD each weekly hour of conditioning LTPA increased all-cause mortality risks by 10% and CHD mortality by14%.

Conclusion

OPA was positively associated with both all-cause and CHD mortality. LTPA was not protective. Among men with CHD, LTPA increased mortality risks.

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In-vitro antimicrobial activity and identification of bioactive components using GC–MS of commercially available essential oils in Saudi Arabia

Abstract

This study was designed to evaluate antimicrobial activity and chemical composition of four different plant essential oils i.e. Ginger oil (GiO), Black seed oil (BSO), Oregano oil (OO) and Rose oil (RO) against different bacterial and fungal strains. Anti-microbial activities of selected essential oils were determined by the microbiological technique using Agar well diffusion assay. After in vitro study, most of the essential oils showed antimicrobial activity against all the selected pathogens. Among all the tested oils, GiO showed strong antimicrobial activity. GiO showed highest antimicrobial activity against Shigella (119.79%), Enteococcus hirae (110.61%) and Escherichia coli (106.02%), when compared with the tetracycline (50 µg/mL) activity. However, Antifungal activity of GiO was found to be present against Candida albicans and Aspergilluas flavus, when compared with clotrimazole (50 µg/mL) activity. Among all the selected bacteria, BSO showed maximum antimicrobial activity against the E. coli followed by Citrobacter freundii. Moreover, BSO had highest zone of inhibition against the C. ablicans (33.58%). OO indicated that, Shigella had the highest sensitivity (12.6 ± 0.58, 131.25%), followed by E. hirae (19.1 ± 0.61, 96.46%) and Salmonella typhi (15.2 ± 0.27, 83.06%) when compared with tetracycline activity. OO showed poor sensitivity against all the selected fungal strains. Furthermore, Gas Chromatography analysis revealed that, Gingerol (10.86%) was the chief chemical constituents found in GiO followed by α-Sesquiphellandrene (6.29%), Zingiberene (5.88%). While, BSO, OO and RO had higher percentage of p-Cymene (6.90%), Carvacrol (15.87%) and Citronellol (8.07%) respectively. The results exhibited that the essential oils used for this study was the richest source for antimicrobial activity which indicates the presence of broad spectrum antimicrobial compounds in these essential oils. Hence, essential oils and their components can be recommended for therapeutic purposes as source of an alternative medicine.

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Mechanical property and quality aspects of rice dried in industrial dryers

Abstract

The influence of drying methods on selected mechanical properties and qualities of MR219 rice variety has been investigated. The results showed significant effects of drying methods on bending strength and head rice yields while the average bending strength of paddy were 28.6–31.8 MPa. The effect of drying methods on apparent modulus of elasticity of rice was not significant (204.5–222.4 MPa). The fracture energy of rice varied significantly under control drying but not with industrial drying methods. Higher temperature in drying by IBD contributed in making the grains tougher, where the effect of FBD temperature was positive toward the development of fracture energy inside rice kernel. IBD at temperature above 40 °C resulted in lower bending strength in rice kernels which affected head rice yield. Two stage paddy drying practices with FBD using temperature of 115–125 °C as first stage is still acceptable, and inclined bed dryer either as single stage or as second stage after FBD should be operated at temperature of <40 °C to maintain head rice yield. The whiteness and milling recovery of rice achieved from different drying methods were comparable.

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Improved immunomodulatory and antioxidant properties of unrefined fucoidans from Sargassum angustifolium by hydrolysis

Abstract

The effect of polymer degradation was studied on immunomodulatory and antioxidant properties of fucoidan isolated from S. angustifolium. Partially hydrolyzed fucoidans were prepared using 0.01 N hydrochloric acid after incubation for 10 and 15 min in boiling water. FT-IR analysis showed two major peaks at 850 cm⁻¹ corresponding to bending vibration of C–O–S of sulfate and 1256 cm⁻¹ derived from the stretching vibration of S–O. The native fucoidan consisted mainly of carbohydrate (49.4%), sulfate (22.9%), uronic acid (10.3%) and minor amount of protein (4.1%). The hydrolysis reduced the molecular weight of native fucoidan from 421 × 10³ g/mol to 104.1 × 10³ g/mol after 10 min boiling and 63.9 × 10³ g/mol after 15 min boiling, without a significant change in their chemical compositions. Acid degradation increased the specific volume of gyration from 0.84 to 3.32 cm³/g in hydrolyzed fucoidan polymers. Fucoidan with the lowest molecular weight showed the greatest proliferating effect on RAW264.7 cells and induced the macrophage cells to release more nitric oxide (39.0 μmol) at 50 μg/mL. The DPPH radical scavenging activity, ABTS radical scavenging activity and reducing power remarkably increased after hydrolysis. The current results showed that molecular weight has determinant effect on immunomodulatory and antioxidant activities of unrefined fucoidan and thus acid hydrolysis can be applied on commercial scale to obtain fucoidans with more beneficial effects.

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Extraction of gelatin from salmon ( Salmo salar ) fish skin using trypsin-aided process: optimization by Plackett–Burman and response surface methodological approaches

Abstract

Gelatin from salmon (Salmo salar) skin with high molecular weight protein chains (α-chains) was extracted using trypsin-aided process. Response surface methodology was used to optimise the extraction parameters. Yield, hydroxyproline content and protein electrophoretic profile via sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis of gelatin were used as responses in the optimization study. The optimum conditions were determined as: trypsin concentration at 1.49 U/g; extraction temperature at 45 °C; and extraction time at 6 h 16 min. This response surface optimized model was significant and produced an experimental value (202.04 ± 8.64%) in good agreement with the predicted value (204.19%). Twofold higher yields of gelatin with high molecular weight protein chains were achieved in the optimized process with trypsin treatment when compared to the process without trypsin.

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Carbonated water as a novel washing medium for mackerel ( Auxis thazard ) surimi production

Abstract

Effect of cold carbonated water (CW) washing on the biochemical properties and gel characteristics of mackerel surimi was evaluated. Three washing cycles were performed with different orders of washing medium including T1 (water, water and water), T2 (CW, water and water), T3 (CW, CW and water) and T4 (CW, CW and CW). The results showed that CW washing, especially T4, caused the decrease in pH, Ca²⁺-ATPase activity and surface hydrophobicity and led to the increase in reactive sulfhydryl content. Regardless of washing treatment, haem protein of surimi decreased significantly compared to unwashed mince. However, carbonated water did not improve haem protein removal. The highest lipid reduction was found in T1 and T2. Gels from all CW washing treatments had a comparable whiteness. Breaking force of CW surimi gel increased with increasing washing cycle (T2 < T3 < T4). Deformations of all surimi gels were not much different (~7 mm). Expressible drip increased with increasing CW washing cycle. Numbers of jointed spherical matrices were found in surimi gel microstructures. With increasing CW washing cycle, densely packed aggregates were formed. Therefore, CW washing with appropriate cycle can be used as an alternative means for mackerel surimi production.

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ClearColi BL21(DE3)-based expression of Zika virus antigens illustrates a rapid method of antibody production against emerging pathogens

Publication date: Available online 20 September 2017
Source:Biochimie
Author(s): Wildriss Viranaicken, Brice Nativel, Pascale Krejbich-Trotot, Wissal Harrabi, Sandra Bos, Chaker El Kalamouni, Marjolaine Roche, Gilles Gadea, Philippe Desprès
Available rapid, simple and accurate methods for detection and diagnosis of emerging viral diseases are required. Recently, there was an urgent need for specific antibodies against mosquito-borne Zika virus (ZIKV), which is an emerging zoonotic disease of medical concern in different regions of the world. Here, we showed that overexpression of ZIKV antigens in ClearColi BL21(DE3), a bacteria strain expressing a non-endotoxic form of LPS, is suitable for the production of specific ZIKV antisera. Two major ZIKV antigenic domains, the domain III from envelope E glycoprotein, which brings the virus-specific epitopes, and the N-terminal region of nonstructural NS1 glycoprotein, which is responsible for pathophysiological conditions, were overexpressed in ClearColi BL21(DE3). Immunization of adult rat with insoluble recombinant ZIKV antigens in inclusion bodies resulted in the production of specific antibodies in a few weeks. Anti-E and anti-NS1 antibodies are efficient as biological tools for ZIKV detection by indirect ELISA and immunoblot assay. This method could successfully be applied to any emerging viruses.



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The bacterial meta-cleavage hydrolase LigY belongs to the amidohydrolase superfamily, not to the {alpha}/{beta}-hydrolase superfamily [Microbiology]

Strain SYK-6 of the bacterium Sphingobium sp. catabolizes lignin-derived biphenyl via a meta-cleavage pathway. In this pathway, LigY is proposed to catalyze the hydrolysis of the meta-cleavage product (MCP) 4,11-dicarboxy-8-hydroxy-9-methoxy-2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate. Here, we validated this reaction by identifying 5-carboxyvanillate and 4-carboxy-2-hydroxypenta-2,4-dienoate as the products, and determined the kcat and kcat/Km values of 9.3 ± 0.6 s-1 and 2.5 ± 0.2 × 107 M-1s-1, respectively. Sequence analyses and a 1.9 Å resolution crystal structure established that LigY belongs to the amidohydrolase superfamily, unlike previously characterized MCP hydrolases, which are serine-dependent enzymes of the α/β-hydrolase superfamily. The active-site architecture of LigY resembled that of α-amino-β-carboxymuconic-ϵ-semialdehyde decarboxylase, a class III amidohydrolase, with a single zinc ion coordinated by His-6, His-8, His-179 and Glu-282. Interestingly, we found that LigY lacks the acidic residue proposed to activate water for hydrolysis in other class III amidohydrolases. Moreover, substitution of His-223, a conserved residue proposed to activate water in other amidohydrolases, reduced the kcat to a lesser extent than what has been reported in other amidohydrolases, suggesting that His223 has a different role in LigY. Substitution of Arg-72, Tyr-190, Arg-234 or Glu-282 reduced LigY activity over 100-fold. On the basis of these results, we propose a catalytic mechanism involving substrate tautomerization, substrate-assisted activation of water for hydrolysis, and formation of a gem-diol intermediate. This last step diverges from what occurs in serine-dependent MCP hydrolases. This study provides insight into C-C hydrolyzing enzymes and expands the known range of reactions catalyzed by the amidohydrolase superfamily.

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Direct observation of conformational population shifts in crystalline human hemoglobin [Molecular Biophysics]

Although X-ray crystallography is the most commonly used technique for studying the molecular structure of proteins, it is not generally able to monitor the dynamic changes or global domain motions that often underlie allostery. These motions often prevent crystal growth or reduce crystal order. We have recently discovered a crystal form of human hemoglobin that contains three protein molecules allowed to express a full range of quaternary structures, while maintaining strong X-ray diffraction. Here we use this crystal form to investigate the effects of two allosteric effectors, phosphate and bezafibrate, by tracking the structures and functions of the three hemoglobin molecules following the addition of each effector. The X-ray analysis shows that the addition of either phosphate or bezafibrate not only induces conformational changes in a direction from a relaxed state to a tense state, but also within relaxed state populations. The microspectrophotometric O2 equilibrium measurements on the crystals demonstrate that the binding of each effector energetically stabilizes the lowest affinity conformer more strongly than the intermediate affinity one, thereby reducing the O2 affinity of tense-state populations, and that the addition of bezafibrate causes an approximately 5-fold decrease in the O2 affinity of relaxed-state populations. These results show that the allosteric pathway of hemoglobin involves shifts of populations rather than a unidirectional conversion of one quaternary structure to another, and that minor conformers of hemoglobin may have a disproportionate effect on the overall O2 affinity.

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Asparagine and glutamine ladders promote cross-species prion conversion [Neurobiology]

Prion transmission between species is governed in part by primary sequence similarity between the infectious prion aggregate, PrPSc, and the cellular prion protein of the host, PrPC. A puzzling feature of prion formation is that certain PrPC sequences, such as that of bank vole, can be converted by a remarkably broad array of different mammalian prions, whereas others, such as rabbit, show robust resistance to cross-species prion conversion. To examine the structural determinants that confer susceptibility or resistance to prion conversion, we systematically tested over 40 PrPC variants of susceptible and resistant PrPC sequences in a prion conversion assay. Five key residue positions markedly impacted prion conversion, four of which were in steric zipper segments where side chains from amino acids tightly interdigitate in a dry interface. Strikingly, all 5 residue substitutions modulating prion conversion involved the gain or loss of an asparagine or glutamine residue. For 2 of 4 positions, N and Q residues were not interchangeable, revealing a strict requirement for either an N or Q residue. Bank voles have a high number of N and Q residues and a high N:Q ratio. These findings suggest that a high number of N and Q residues at specific positions may stabilize β-sheets and lower the energy barrier for crossspecies prion transmission, potentially due to hydrogen bond networks from side chain amides forming extended N/Q ladders. These data also suggest that multiple PrPC segments containing N/Q residues may act in concert along a replicative interface to promote prion conversion.

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Structural basis for clonal diversity of the human T cell response to a dominant influenza virus epitope [Protein Structure and Folding]

Influenza A virus (IAV) causes an acute infection in humans that is normally eliminated by CD8+ cytotoxic T lymphocytes. Individuals expressing the major histocompatibility complex (MHC) class I molecule HLA-A2 produce cytotoxic T lymphocytes bearing T cell receptors (TCRs) that recognize the immunodominant IAV epitope GILGFVFTL (GIL). Most GIL-specific TCRs utilize α/β pairs encoded by the TRAV27/TRBV19 gene combination to recognize this relatively featureless peptide epitope (canonical TCRs). However, ~40% of GIL-specific TCRs express a wide variety of other TRAV/TRBV combinations (non-canonical TCRs). To investigate the structural underpinnings of this remarkable diversity, we determined the crystal structure of a non-canonical GIL-specific TCR (F50) expressing the TRAV13-1/TRBV27 gene combination bound to GIL-HLA-A2 to 1.7 Å resolution. Comparison of the F50-GIL-HLA-A2 complex with the previously publishedcomplex formed by a canonical TCR (JM22) revealed that F50 and JM22 engage GIL-HLA-A2 in markedly different orientations. These orientations are distinguished by crossing angles of TCR to peptide-MHC of 29o for F50 versus 69o for JM22, and by a focus by F50 on the C-terminus rather than the center of the MHC α1 helix for JM22. In addition, F50, unlike JM22, uses a tryptophan instead of an arginine to fill a critical notch between GIL and the HLA-A2 α 2 helix. The F50-GIL-HLA-A2 complex shows that there are multiple structurally distinct solutions to recognizing an identical peptide-MHC ligand with sufficient affinity to elicit a broad anti-IAV response that protects against viral escape and T cell clonal loss.

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Improving Blood Pressure Control Using Smart Technology

Telemedicine and e-Health , Vol. 0, No. 0.


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American Telemedicine Association Practice Guidelines for Telemental Health with Children and Adolescents

Telemedicine and e-Health , Vol. 0, No. 0.


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Laryngotracheal reconstruction and swallowing: A review

Significant advances in laryngotracheal reconstruction over the last few decades have revolutionised the management of paediatric patients with complex congenital or acquired airway stenosis. The primary aim of laryngotracheal reconstruction has focused primarily on airway and surgery specific outcomes, often at the expense of voice, as well as swallowing function, which are all intricately related. There is currently a paucity of data on swallowing outcome. The goal of this paper is to review and discuss the existing research on the impact of laryngotracheal on swallowing.

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Clinical variables determining the success of adenotonsillectomy in children with Down syndrome

To evaluate the evolution of polysomnographic parameters of children with Down syndrome and obstructive sleep apnea syndrome submitted to adenotonsillectomy and the interaction of comorbidities on therapeutic outcome.

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Next-generation sequencing identifies three novel missense variants in ILDR1 and MYO6 genes in an Iranian family with hearing loss with review of the literature

Hearing impairment is the most common sensorineural disorder and is genetically heterogeneous. Identification of the pathogenic mutations underlying hearing impairment is difficult, since causative mutations in 127 different genes have so far been reported.

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Readability of online patient education materials for velopharyngeal insufficiency

Evaluate the readability of online and mobile application health information about velopharyngeal insufficiency (VPI).

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Laryngotracheal reconstruction and swallowing: A review

Significant advances in laryngotracheal reconstruction over the last few decades have revolutionised the management of paediatric patients with complex congenital or acquired airway stenosis. The primary aim of laryngotracheal reconstruction has focused primarily on airway and surgery specific outcomes, often at the expense of voice, as well as swallowing function, which are all intricately related. There is currently a paucity of data on swallowing outcome. The goal of this paper is to review and discuss the existing research on the impact of laryngotracheal on swallowing.

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Clinical variables determining the success of adenotonsillectomy in children with Down syndrome

To evaluate the evolution of polysomnographic parameters of children with Down syndrome and obstructive sleep apnea syndrome submitted to adenotonsillectomy and the interaction of comorbidities on therapeutic outcome.

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Next-generation sequencing identifies three novel missense variants in ILDR1 and MYO6 genes in an Iranian family with hearing loss with review of the literature

Hearing impairment is the most common sensorineural disorder and is genetically heterogeneous. Identification of the pathogenic mutations underlying hearing impairment is difficult, since causative mutations in 127 different genes have so far been reported.

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Readability of online patient education materials for velopharyngeal insufficiency

Evaluate the readability of online and mobile application health information about velopharyngeal insufficiency (VPI).

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A phase I study to assess the mass balance, excretion, and pharmacokinetics of [ 14 C]-ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors

Summary

This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics (PK), and safety of ixazomib in patients with advanced solid tumors. In Part A of the study, patients received a single 4.1 mg oral solution dose of [¹⁴C]-ixazomib containing ~500 nCi total radioactivity (TRA), followed by non-radiolabeled ixazomib (4 mg capsule) on days 14 and 21 of the 35-day PK cycle. Patients were confined to the clinic for the first 168 h post dose and returned for 24 h overnight clinic visits on days 14, 21, 28, and 35. Blood, urine, and fecal samples were collected during Part A to assess the mass balance (by accelerator mass spectrometry), excretion, and PK of ixazomib. During Part B of the study, patients received non-radiolabeled ixazomib (4 mg capsules) on days 1, 8, and 15 of 28-day cycles. After oral administration, ixazomib was rapidly absorbed with a median plasma T_max of 0.5 h and represented 70% of total drug-related material in plasma. The mean total recovery of administered TRA was 83.9%; 62.1% in urine and 21.8% in feces. Only 3.23% of the administered dose was recovered in urine as unchanged drug up to 168 h post dose, suggesting that most of the TRA in urine was attributable to metabolites. All patients experienced a treatment-emergent adverse event, which most commonly involved the gastrointestinal system. These findings suggest that ixazomib is extensively metabolized, with urine representing the predominant route of excretion of drug-related material.

Trial ID: ClinicalTrials.gov # NCT01953783.

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Probing Photothermal Effects on Optically Trapped Gold Nanorods by Simultaneous Plasmon Spectroscopy and Brownian Dynamics Analysis

ACS Nano

DOI: 10.1021/acsnano.7b04302

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Increased risk of cancer in children with inflammatory bowel disease

People with inflammatory bowel disease worry about developing cancer.1 These concerns stem in part from drug labels warning of the rare but real increased risk, as well as from websites and peer...

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Development and validation of QMortality risk prediction algorithm to estimate short term risk of death and assess frailty: cohort study

Objectives To derive and validate a risk prediction equation to estimate the short term risk of death, and to develop a classification method for frailty based on risk of death and risk of unplanned...

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Dental emergency sparks major donation by Bob Clarkson and his wife

Bob Clarkson flanked by emergency medical technician Kevin Ralph and paramedic James Spencer as he hands over the keys to a new ambulance yesterday. Photo/John Borren A dental emergency last Christmas sparked Bob Clarkson and his wife to donate a fully kitted out new ambulance to Mount Maunganui St John Ambulance service.

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Are You What You Eat or What Your Mother Ate or Both?

A high-fat high-sugar (HF-HS) diet promotes cancer development and progression. However, does the timing of diet matter? This is an important question with profound public health relevance. By exposing mice to a HF-HS diet either through feeding to a pregnant mother or nursing mother or after weaning and then chemically inducing breast cancer, the authors found the most crucial time for breast cancer risk was after weaning, while a HF-HS in utero diet actually slowed tumor development. Understanding early-life events provides valuable insight for later life events and proves it is never too early to start preventing disease. Cancer Prev Res; 10(10); 1–2. ©2017 AACR.

See related article by Lambertz, p. 553-62.

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The relationship between 2009 pandemic H1N1 influenza during pregnancy and preterm birth: a population-based cohort study.

Background: Previous studies of maternal influenza illness and preterm birth have yielded inconsistent results. Our objective was to assess the association between 2009 pandemic H1N1 (pH1N1) influenza during pregnancy and preterm birth in a large obstetrical population. Methods: We linked a province-wide birth registry with health administrative databases to identify influenza-coded hospitalizations, emergency department visits, or physician visits among pregnant women during the 2009 H1N1 pandemic (our proxy for clinical pH1N1 influenza illness). Using Cox regression, we estimated adjusted hazard ratios (aHR) for preterm birth and spontaneous preterm birth treating influenza as a time-varying exposure. Results: Among 192,082 women with a singleton live birth, 2,925 (1.5%) had an influenza-coded health care encounter during the 2009 H1N1 pandemic. Compared with unexposed pregnancy time, there was no association between exposure to the pandemic, with or without clinical influenza illness, and preterm birth (no pH1N1 diagnosis: aHR=1.0; 95% confidence interval [CI]: 0.98, 1.1; pH1N1 diagnosis: aHR=1.0; 95% CI: 0.88, 1.2). Among women with pre-existing medical conditions, influenza was associated with increased preterm birth (aHR=1.5; 95% CI: 1.1, 2.2) and spontaneous preterm birth (aHR=1.7; 95% CI: 1.1, 2.6), and these associations were strongest in the third trimester and when data were analyzed to allow for a transient acute effect of influenza. Conclusion: In the general obstetrical population, there was no association between pH1N1 influenza illness and preterm birth, but women with pre-existing medical conditions known to increase the risk of influenza-associated morbidity were at elevated risk. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Doppler ultrasonography can be useful to determine the etiology of idiopathic sudden sensorineural hearing loss

This study aims to evaluate clinical features of both carotid and vertebral arteries in the idiopathic sudden sensorineural hearing loss (ISSNHL) patients and healthy individuals to contribute additional knowledge on vascular compromise theory.

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Lamina papyracea position in patients with nasal polypi: A computed tomography analysis

This study aimed to describe the positions of the lamina papyracea (LP) in patients who had nasal polypi, by computed tomography (CT) analysis.

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Altered Expression of MALAT1 lncRNA in Nonalcoholic Steatohepatitis Fibrosis Regulates CXCL5 in Hepatic Stellate Cells

Publication date: Available online 19 September 2017
Source:Translational Research
Author(s): Fatjon Leti, Christophe Legendre, Christopher D. Still, Xin Chu, Anthony Petrick, Glenn S. Gerhard, Johanna K. DiStefano
In the present study, we sought to identify lncRNA expression profiles in NASH patients with histological evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 NAFLD patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively. Functional enrichment analysis revealed lncRNA participation in TGFB1 and TNF signaling, insulin resistance, and extracellular matrix maintenance. Several lncRNAs were highly expressed in fibrosis relative to normal tissue, including nuclear paraspeckle assembly transcript 1 (NEAT1), hepatocellular carcinoma upregulated lncRNA (HULC), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Two potential target mRNAs, syndecan 4 (SDC4) and C-X-C motif chemokine ligand 5 (CXCL5) were identified for HULC and MALAT1, respectively, but only CXCL5 showed differential expression among the different histological classes. Knockdown of MALAT1 expression reduced CXCL5 transcript and protein levels by 50% and 30%, respectively, in HepG2 cells. Expression of MALAT1 and CXCL5 was upregulated in activated hepatic stellate (LX-2) cells compared to cells in the quiescent state, and MALAT1 expression was regulated by hyperglycemia and insulin in HepG2 cells, but only by insulin in LX-2 cells. Dysregulated lncRNA expression is associated with inflammation and fibrosis in NASH. Functionally relevant differences in MALAT1 expression may contribute to the development of fibrosis in NASH through mechanisms involving inflammatory chemokines.



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Doppler ultrasonography can be useful to determine the etiology of idiopathic sudden sensorineural hearing loss

This study aims to evaluate clinical features of both carotid and vertebral arteries in the idiopathic sudden sensorineural hearing loss (ISSNHL) patients and healthy individuals to contribute additional knowledge on vascular compromise theory.

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Lamina papyracea position in patients with nasal polypi: A computed tomography analysis

This study aimed to describe the positions of the lamina papyracea (LP) in patients who had nasal polypi, by computed tomography (CT) analysis.

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Resident Editors of the Journal of Voice Editorial Board

Traditional medical education provides virtually no formal training regarding publication. Not even basic writing techniques are taught, let alone information about the editorial process or skills required to participate effectively on an editorial board. Most nonmedical graduate training programs have similar weaknesses. This problem has been addressed in prior publications.1–5 More than a decade ago, the Ear, Nose and Throat Journal started inviting a small number of residents to participate as student members of the editorial board.

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FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches

Abstract

Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated. The nude severe combined immunodeficiency phenotype is indeed characterized by the clinical hallmarks of athymia with severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. In this review, we summarize recent discoveries in the field and give interesting perspective about new and promising therapeutic approaches for disorders of immune system with athymia.

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Nondysraphic cervicomedullary intramedullary lipoma

Sujeet Kumar Meher, Laxmi Narayan Tripathy, Harsh Jain, Sunandan Basu

Journal of Craniovertebral Junction and Spine 2017 8(3):271-274

Spinal cord lipomas are usually associated with spinal dysraphism and is most common in lumbosacral region. Spinal intradural lipoma is a rare condition accounting for less than 1% of spinal cord tumours and is most prevalent in cervicodorsal region. Intramedullary spinal cord lipoma of cervical spine not associated with spinal dysraphism is one of the rarest lesions. They usually present insidiously with slowly progressive myelopathic deficits. We present a case of nondysraphic intramedullary spinal cord lipoma with exophytic component and intracranial extension. A 30 year male patient presented with wasting of muscles of left shoulder and left forearm with resultant weakness for last two months and myelopathic signs. Magnetic resonance imaging revealed a T1 hyperintense , T2 hypointense lesion on the dorsal aspect of cervical spinal cord with intracranial extension and exophytic component. There was no contrast enhancement, fat suppression image indicated a lipoma. The patient underwent cervical laminectomy with foramen magnum decompression with subtotal resection of intramedullary lipoma. Histopathology examination confirmed the diagnosis of lipoma. Subtotal resection of intramedullary lipoma is a reasonable and acceptable surgical option considering the benign nature of lesion and high probability of neurological deterioration due to dense adhesion between lipoma and neural tissue.

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Short neck, short head, short spine, and short body height – Hallmarks of basilar invagination

Atul Goel

Journal of Craniovertebral Junction and Spine 2017 8(3):165-167



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Vertical spinal instability and cervical spondylosis: Is it focal or multisegmental?

Atul Goel

Journal of Craniovertebral Junction and Spine 2017 8(3):163-164



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Combined anteroposterior fixation using a titanium cage versus solely posterior fixation for traumatic thoracolumbar fractures: A systematic review and meta-analysis

Arjen Johannes Smits, Meaghan Polack, Jaap Deunk, Frank Willem Bloemers

Journal of Craniovertebral Junction and Spine 2017 8(3):168-178

Study Design: Systematic review with meta-analysis. Objective: Additional anterior stabilization might prevent posterior implant failure, but over time, the disadvantageous of bone grafts have become evident. The objective of this systematic review was to compare risks and advantages of additional anterior stabilization with a titanium cage to solely posterior fixation for traumatic thoracolumbar fractures. Methods: An electronic search was performed in the literature from 1980 to March 2016. Studies comparing only posterior with anteroposterior fixation by means of a titanium cage were included in this study. Data extraction and Cochrane risk of bias assessment were done by two independent authors. In addition, the PRISMA statement was followed, and the GRADE approach was used to present results. Results: Of the 1584 studies, two randomized controlled trials (RCTs) and one retrospective cohort study were included in the meta-analysis. The RCTs reported evidence of high quality that anteroposterior stabilization maintained better kyphosis correction than posterior stabilization alone. However, these results were neutralized in the meta-analysis by the cohort study. Implant failure was reported by one study, in the posterior group. No differences in follow-up visual analog scale scores, neurologic improvement, and complications were found. Operation time, blood loss, and hospital stay all increased in the anteroposterior group. Conclusions: Patients with a highly comminuted or unstable fracture could benefit from combined anteroposterior stabilization with a titanium cage, for some evidence suggests this prevents loss of correction. However, large randomized studies still lack. There is a risk of cage subsidence, and increased perioperative risks have to be considered when choosing the optimal treatment.

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Use of C2 vertebroplasty and stereotactic radiosurgery for treatment of lytic metastasis of the odontoid process

Casey Alicen Hribar, Deb A Bhowmick

Journal of Craniovertebral Junction and Spine 2017 8(3):285-287

Improvements in cancer therapy have led to increased patient survival times in spite of metastatic spinal disease in many forms of cancer. Conventional treatment methods often employ radiotherapy with or without surgery depending on the neurological status, mechanical instability, and the extent of tumor. Percutaneous vertebroplasty as well as stereotactic radiosurgery (SRS) have arisen as common modalities of treatment of spinal metastasis in which neurological compromise or spinal instability and deformity is not of significant concern. These treatments, when used in combination, have been shown to provide early pain relief and effective tumor control while avoiding surgical resection, fixation, and lengthy recovery times. We present a case unique in the literature for the use of this combination treatment for tumors of the C2 vertebral body. While limited in application to patients without overt atlantoaxial instability or significant spinal canal compromise, we believe it provides a significant benefit in decreasing morbidity and improving early adherence to systemic therapy.

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Influence of prevertebral soft tissue swelling on dysphagia after anterior cervical discectomy and fusion using a rectangular titanium stand-alone cage

Toru Yamagata, Kentaro Naito, Masaki Yoshimura, Kenji Ohata, Toshihiro Takami

Journal of Craniovertebral Junction and Spine 2017 8(3):179-186

Background: Postoperative oropharyngeal complications such as dysphagia after anterior cervical spine surgery are some of the least discussed surgery-related complications. The purpose of this retrospective study is to investigate the incidence and possible risk factors for 30-day postoperative dysphagia after anterior cervical discectomy and fusion (ACDF). Materials and Methods: This study included 152 consecutive patients who underwent 1- or 2-level ACDF using a rectangular titanium stand-alone cage in our institutes. Surgery-related dysphagia early after surgery was analyzed based on hospital charts. Radiological evaluation of prevertebral soft tissue swelling (PSTS) was performed by comparing plain lateral radiographs of the cervical spine before surgery with those after surgery. The percentage of PSTS (%PSTS) was defined by retropharyngeal soft tissue diameter divided by vertebral diameter. Positive %PSTS was determined when %PSTS exceeded its mean + 2 standard deviations. Results: Twelve patients (7.9%) demonstrated prolonged symptoms of dysphagia within 30-day postoperatively. All patients eventually demonstrated satisfactory or acceptable recovery late after surgery, except one case of hypoglossal nerve palsy. %PSTS was significantly highest early after surgery and returned to presurgical levels within 30 days after surgery. Statistical analysis suggested that the positive %PSTS at C3 or C4 level early after surgery was significantly associated with the occurrence of postoperative dysphagia. Conclusions: Although the possible reasons for postoperative dysphagia may not only be multifactorial but also be highly surgeon-dependent, such a complication is still underestimated and needs to be carefully resolved. %PSTS appeared to be easy and reliable index to judge the possible risk of postoperative dysphagia.

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Surgical planning for cervical deformity based on a 3D model

Juan Barges-Coll, Iulia Peciu-Florianu, Sébastien Martiniere, John Michael Duff

Journal of Craniovertebral Junction and Spine 2017 8(3):263-267

The treatment of fixed cervical deformity is complex, but the principles guiding its correction remain the same as in deformity of other spinal regions, with the goal of deformity correction that results in a solid fusion with adequate decompression of the neural elements. In these challenging cases, osteotomies are necessary to mobilize the rigid spine and to obtain the desired correction, but they can be associated with increased risk of complications. Therefore, careful preoperative planning and a complete understanding of the anatomic variations allow patient-tailored approaches with and case specific techniques for the optimal and safe treatment of a variety of complex cervical deformities. We present a case report with a complex spinal deformity where a 3D model was used for surgical strategy that allowed us to "simulate" the osteotomies and get a better correction of the cervical deformity.

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