Managing the oral side effects of medications used to treat multiple sclerosis

Abstract

Background

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms.

Methods

The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side Effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS.

Results

Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection related side-effects.

Conclusions

Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists.

This article is protected by copyright. All rights reserved.

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Decontamination tips

http://medicine-greece.blogspot.com/2017/03/decontamination-tips.html

VAPOR-BASED DECONTAMINATION EQUIPMENT

The AeroClave ADS is a decontamination system that can be directly integrated into a new or existing ambulance. The ADS utilizes an EPA-approved hospital disinfectant to decontaminate surfaces in the patient care compartment and equipment after every patient transport.

The ADS is a convenient, hands-off solution for decontaminating an ambulance's patient care compartment. A nozzle, installed inside the patient care compartment, disperses a mist of disinfectant solution that is designed to meet OSHA and NFPA specifications.

Zimek's Z-vac Micro-Particle Evacuator uses disinfectant misting technology to decontaminate an ambulance's interior and the equipment carried aboard the ambulance. When connected to the vehicle and activated using a window overlay, an installed port or window insert, the system automatically disperses a disinfectant vapor throughout the vehicle's interior. Upon completion of a decontamination cycle, any remaining mist is removed using the company's Z-vac Vehicle Adapter.

The Bioquell BQ-EMS uses hydrogen peroxide vapor to eradicate pathogens from exposed surfaces in the ambulance, including patient care equipment, controls for on-board electronics and the stretcher. A decontamination cycle can be done within a sealed vehicle by placing the hydrogen peroxide vapor generator and the aerators in the patient care compartment of the ambulance.

A wireless control panel is used to start and stop the process. The vehicle's contents need to be prepared before system activation to ensure decontamination of exposed surfaces.

The Ambustat atomizes Actril Cold Sterilant, a disinfectant with peracetic acid and hydrogen peroxide, into small droplets — fog, mist or spray— by shearing them in a highly turbulent section of the nozzle. A blower in the power head supplies air to create the turbulence, and the flow rate can be adjusted for desired droplet size.

COMBINATION APPROACH

The Klenitise ambulance cleaning and disinfection system uses a three-step process that employs both manual disinfection and vapor disinfection technologies. The first step in the process is to scan surfaces in the ambulance using a handheld UV light to highlight areas that have been in contact with patients and where surface residues are present. Visually identifying contaminated surfaces allows the EMS provider to manually decontaminate those surfaces with a disinfectant spray and towels. The ambulance can then be completely decontaminated using a fogger system.

ULTRAVIOLET GERMICIDAL IRRADIATION

Ultraviolet germicidal irradiation for disinfection has been used primarily in medical sanitation and sterile work facilities. In recent years UVGI has found renewed application in air and surface sanitization in medical care settings such as hospitals, clinics and laboratories.

"Ultraviolet germicidal irradiation (UVGI) is an established means of disinfection and can be used to prevent the spread of certain infectious diseases. Low-pressure mercury (Hg) discharge lamps are commonly used in UVGI applications and emit shortwave ultraviolet-C (UV-C, 100–280 nanometer [nm]) radiation, primarily at 254 nm. UV-C radiation kills or inactivates microbes by damaging their deoxyribonucleic acid (DNA)."

The History of Ultraviolet Germicidal Irradiation for Air Disinfection

MRSA-UV has produced several products that use UVGI for safer, more effective and more efficient decontamination of ambulances and equipment. The Turbo-UV is a compact unit (22 x 8 x 8 inches) that can be placed in the closed patient compartment of an ambulance for as little as 15 minutes. The Turbo-UV is compact enough that it can also be used for decontaminating EMS station sleeping rooms, EMS equipment and personal protective gear that may have been exposed to infectious pathogens.

The EMS-UV air sanitizer employs UVGI to circulate and clean the interior air of an ambulance to reduce airborne viruses, bacteria, mold, allergens and odors. The EMS-UV can be mounted on a wall in the patient care compartment and allowed to run continuously. The UV-C bulb inside the unit requires minimal electricity and annual replacement.

The Rapid Razor-UV is a handheld, rechargeable UVGI device designed for decontamination of surfaces inside the ambulance. The user simply passes the device closely over the contaminated surface area, allowing the energy from the high-output UVC Emitter to rapidly decontaminate surfaces. The unit includes an internal pacer that sets the scan speed to ensure a complete and accurate scan. A recessed safety shield prevents direct exposure to UVC energy while also adding reflectance that increases its effectiveness.

Ambulance decontamination is necessary to protect EMS personnel and patients. Consider the practices and products listed above to fully eliminate dangerous pathogens from the ambulances in your fleet.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Design, synthesis and biological evaluation of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as BRD4 inhibitors

Publication date: Available online 7 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Leilei Zhao, Yifei Yang, Yahui Guo, Lingyun Yang, Jian Zhang, Jinpei Zhou, Huibin Zhang
BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76 nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18 μM respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment.

Graphical abstract

http://ift.tt/2n1GhnC

Design and Synthesis of Pyrazolo[3,4-d]Pyrimidines: Nitric Oxide Releasing Compounds Targeting Hepatocellular Carcinoma

Publication date: Available online 7 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yaseen A.M.M. Elshaier, Mohamed A. Shaaban, Mohammed K. Abd El Hamid, Mostafa H. Abdelrahman, Mahrous A. Abou-Salim, Sara M. Elgazwi, Fathi Halaweish
A new series of pyrazolo[3,4-d]pyrimidines tethered with nitric oxide (NO) producing functionality was designed and synthesized. Sulforhodamine B (SRB) protein assay revealed that NO releasing moiety in the synthesized compounds significantly decreased the cell growth more than the des-NO analogues. Compounds 7C and 7G possessing N-para-substituted phenyl group, released the highest NO concentration of 4.6% and 4.7% respectively. Anti-proliferative activity of synthesized compounds on HepG2 cell line identified compounds 7h, 7p, 14a and 14b as the most cytotoxic compounds in the series of IC50 = 3, 5, 3 and 5 µM, respectively, compared to erlotinib as a reference drug (IC50 = 25 µM). Flow cytometry studies revealed that 7h arrested the cells in G0/G1 phase of cell cycle while 7p arrested the cells in S phase. Moreover, docking study of the synthesized compounds on EGFR (PDB code: 1M17) and cytotoxicity study indicated that N-1 phenyl para substitution, pyrazole C-3 alkyl substitution and tethering the nitrate moiety through butyl group had a significant impact on the activity.

Graphical abstract

http://ift.tt/2n1y3vQ

Nodular colloid milium mimicking keloid

Summary

Colloid milium is a rare cutaneous deposit disease that usually presents clinically by the development of yellowish translucent or flesh-colored papules or plaques on sun-exposed skin. Histologically, it is characterized by the presence of colloid in the dermal papillae. In this case report, we present a 52-year-old man who presented with a nodule on his upper lip that mistakenly was diagnosed and treated as keloid.

http://ift.tt/2mIIkfR

Microsurgery approaches for local drug delivery to the inner ear : Bullostomy Versus Transtympanic Injection

http://orlhealth.blogspot.com/2017/03/microsurgery-approaches-for-local-drug.html

Bullostomy

NOTE: Bullostomy is a unilateral procedure. Operate one ear of the mouse and use the contralateral ear as the control.

Place the mouse in a decubitus supine position. Prepare the surgical area at the ventral surface of the neck using clippers to remove the fur. Clean the skin with povidone iodine based antiseptic solution, and cover it with sterile drapes.

Using a scalpel, make a 2 cm longitudinal incision from the mandible to the clavicle.

Under magnification with a surgical microscope, identify the submandibular glands and separate both with forceps. Retract the submandibular glands and localize the origin of the digastric muscle and the facial nerve.

Make an incision in the origin of the digastric muscle with a scissors, and retract it ventrally, exposing the underlying inferior-medial aspect of the tympanic bulla.

Make an opening in the bulla by drilling into it with a 27 G needle (Figure 2A). Localize the stapedial artery and the RW membrane caudal to it (Figure 2B). Clean the blood from the drilled area with an absorbable gelatin sponge.

Using a 34 G catheter and a glass micro syringe, slowly inject 3-5 µL of vehicle solution (CGP-hydrogel or RL) through the bullostomy directly onto the RW niche, filling it (Figure 2C). Seal the bullostomy with 1-2 drops of tissue adhesive.

Return the submandibular glands to their initial position and close the skin incisions with 5-0 silk surgical suture. Apply a chlorhexidine-based antiseptic around the incision to avoid wound infection. NOTE: Absorbable and non-absorbable sutures could be used. Non-absorbable sutures must be removed  in 2 weeks. Silk is not recommended for skin closure since its use is associated with incision infection and local tissue reactions.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Comparison of two-dimensional synthesized mammogram (2DSM) and conventional full-field digital mammogram (FFDM) for evaluation of breast cancer

Publication date: Available online 8 March 2017
Source:Clinical Imaging
Author(s): Gayoung Choi, Ok Hee Woo, Hye Seon Shin, Seonah Jang, Kyu Ran Cho, Bo Kyoung Seo
PurposeTo compare the diagnostic efficacy of 2DSM and FFDM for evaluation of breast cancer.Materials and methodsA retrospective observer performance study was done by 3 breast radiologists. The diagnostic accuracy, image quality, and detailed lesion characterization of each 2DSM and FFDM were evaluated blindly to determine superior modality.ResultsThe diagnostic accuracy was not significantly different between two modalities. The image quality was superior in 2DSM (p-value 0.0362).Conclusions2DSM showed equivalent diagnostic accuracy and superior image quality to FFDM. Overall characterization of the lesion was better in 2DSM, and 2DSM showed superiority in evaluation of spiculated margins.



http://ift.tt/2mIHsYt

MR imaging of intestinal angioedema related to angiotensin-converting enzyme inhibitors: Report of three cases and review of literature

Publication date: Available online 8 March 2017
Source:Clinical Imaging
Author(s): Michael R. Savino, Pardeep K. Mittal, Frank H. Miller
Angioedema is a condition in which an increase in vascular permeability leads to the swelling of body tissues. There are both hereditary and acquired forms of the disease, with the latter often associated with the administration of angiotensin-converting enzyme inhibitor medication. Involvement of the intestinal tract is a rare manifestation of angioedema, and can present with abdominal pain, nausea, and vomiting. It is critical for radiologists to be aware of this entity, as they may have the only opportunity to make the diagnosis. We present three cases of intestinal angioedema diagnosed on MRI with discussion of the imaging findings.



http://ift.tt/2mlB8n6

Postnatal MRI for CDH: A pictorial review of late-presenting and recurrent diaphragmatic defects

Publication date: Available online 8 March 2017
Source:Clinical Imaging
Author(s): Wendy Kim, Jesse Courtier, Cara Morin, Narendra Shet, Eric Strauch, Jane S. Kim
Late-presenting or recurrent diaphragmatic defects can pose a diagnostic challenge due to varying clinical presentations. Current diagnostic approaches include plain film radiograph for initial assessment, with other imaging modalities such as fluoroscopy, ultrasound, CT and MRI mainly utilized for troubleshooting. As a radiation-free modality, MRI can provide a more definitive diagnosis in particular cases due to its ability to visualize discontinuity of the diaphragm, distinguishing it from eventration. MRI can also accurately characterize hernia contents, defect location and size. We present our MRI technique and review cases of different hernia types with relevant discussion of the imaging findings and correlation with intraoperative findings. MRI can be a useful diagnostic tool in the assessment of late presenting or recurrent diaphragmatic hernias.



http://ift.tt/2mIVvx8

Architectural Overlap between Benign Endocervix and Pattern-A Endocervical Adenocarcinoma: Are All Pattern-A Tumors Invasive?

Publication date: Available online 8 March 2017
Source:Pathology - Research and Practice
Author(s): Gregory Douglas, Brooke E. Howitt, John K. Schoolmeester, Lauren Schwartz, Zuzana Kos, Shahidul Islam, Bojana Djordjevic, Carlos Parra-Herran
Studies on the pattern-based classification for invasive endocervical adenocarcinoma showed that tumors with nondestructive invasion (pattern-A) have a 0% rate of nodal metastases. Our understanding of pattern-A tumors and their distinction from in-situ adenocarcinoma requires further study. Thirteen sections diagnosed independently as pattern-A adenocarcinoma by three gynecologic pathologists, and 14 sections of benign endocervix were selected. Three additional pathologists (reviewers) evaluated a digital image from each section and classified it as pattern-A or benign based on architecture only. To blind the interpretation to cytologic features, nuclei and cytoplasm were obscured using morphometric software (Zen 2011, Carl Zeiss Microscopy, Germany). 13/27 cases (48%; 8 pattern-A, 5 benign) were correctly classified by all reviewers; 19/27 (70%; 10 pattern-A, 9 benign) were correctly classified by ≥2 reviewers. 3/13 pattern-A cases (23%) were interpreted as benign by ≥2 reviewers. Conversely, 5/14 benign cervices (36%) were misinterpreted as pattern-A by ≥2 reviewers. The number of glands per 20x field was higher in pattern-A cases with high reviewer agreement (p=0.004). An abnormal architecture is seen in many pattern-A adenocarcinomas in support of their invasive nature; some, however, have architecture that overlaps with that of benign endocervix thus may actually represent in-situ lesions. Likewise, normal cervix can be architecturally complex and mirror patterns that pathologists would classify as pattern-A if malignant cytologic features were present. Based on this overlap and the nil risk of nodal spread, an emphasis on the non-destructive, rather than the invasive, nature of pattern-A adenocarcinoma is recommended.



http://ift.tt/2lG3N9r

Edmondson-Steiner grade: a crucial predictor of recurrence and survival in hepatocellular carcinoma without microvascular invasio

Publication date: Available online 8 March 2017
Source:Pathology - Research and Practice
Author(s): Li Zhou, Jing-An Rui, Wei-Xun Zhou, Shao-Bin Wang, Shu-Guang Chen, Qiang Qu
BackgroundMicrovascular invasion (MVI), an important pathologic parameter, has been proven to be a powerful predictor of long-term prognosis in hepatocellular carcinoma (HCC). However, prognostic factors in HCC without MVI remain unknown. The present study aimed to identify the risk factors of recurrence and poor post-resectional survival in this type of HCC.Methods and methodsA total of 109 patients with MVI-absent HCC underwent radical hepatectomy were enrolled. The influence of clinicopathologic variables on recurrence and patient survival was assessed using univariate and multivariate analyses.ResultsChi-square test found that Edmondson-Steiner grade and satellite nodule were significantly associated with recurrence, while the former was the single marker for early recurrence. Stepwise logistic regression analysis demonstrated the independent predictive role of Edmondson-Steiner grade for recurrence. On the other hand, Edmondson-Steiner grade, serum AFP level and satellite nodule were significant for overall and disease-free survival in univariate analysis, whereas tumor size was linked to disease-free survival. Of the variables, Edmondson-Steiner grade, serum AFP level and satellite nodule were independent indicators.ConclusionsEdmondson-Steiner grade, a histological classification, carries robust prognostic implications for all the endpoints for prognosis, thus being potential to be a crucial prognosticator in HCC without MVI.



http://ift.tt/2m53hxM

Roles of microRNAs in cancer associated fibroblasts of gastric cancer

Publication date: Available online 8 March 2017
Source:Pathology - Research and Practice
Author(s): Yu Yan, Ruifen Wang, Wenbin Guan, Meng Qiao, Lifeng Wang
Cancer associated fibroblasts (CAFs) are a key component of the tumor microenvironment (TME). They play critical roles in the occurrence and development of gastric cancer (GC) through controlling various cytokines secretion and direct cell-to-cell interaction. However, the underlying mechanism of CAFs in tumor progression has not been entirely elucidated. MicroRNAs (miRNAs) as important factors have a central role in the interplay between tumor cell and TME. Recent studies also highlight that the aberrant expression of miRNAs in CAFs is involved in multiple functions in tumorigenesis and malignant process of GC. In this article, we shortly introduce the miRNAs biogenesis and provide an overview of the mechanisms and emerging roles of CAFs-related miRNAs. Focusing on these miRNAs as potential therapeutic targets may bring better treatment effect on GC and other diseases.



http://ift.tt/2m5391n

Microbe Hunting Hits Home

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Ivaylo I. Ivanov
Ten years ago, we discovered that microbiota composition controls intestinal T cell homeostasis and alters T cell responses of mice in different animal facilities. Here I discuss how these discoveries, reported in Cell Host & Microbe in 2008, came to be and contributed to our understanding of microbiota immune effects.

Teaser

Ten years ago, we discovered that microbiota composition controls intestinal T cell homeostasis and alters T cell responses of mice in different animal facilities. Here I discuss how these discoveries, reported in Cell Host & Microbe in 2008, came to be and contributed to our understanding of microbiota immune effects.


http://ift.tt/2mDL6T2

Exercising Restraint

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Stuart J.D. Neil
Ten years ago, while in Paul Bieniasz's group, I determined that an interferon-induced antiviral activity inhibited the release of enveloped viruses by tethering them to the plasma membrane of infected cells. This commentary examines the lead up to this study and how our observations led to the identification of tetherin.

Teaser

Ten years ago, while in Paul Bieniasz's group, I determined that an interferon-induced antiviral activity inhibited the release of enveloped viruses by tethering them to the plasma membrane of infected cells. This commentary examines the lead up to this study and how our observations led to the identification of tetherin.


http://ift.tt/2mDSGNF

MAP Kinase Signaling Pathways: A Hub of Plant-Microbe Interactions

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Guozhi Bi, Jian-Min Zhou
In 2007, we reported that a phytopathogen effector directly inhibits a MAP kinase cascade. In the decade since, many more effectors have been found to inhibit MAP kinase cascades, providing not only a mechanistic understanding of pathogenesis and immunity in plants, but also the identification of previously unknown enzymes.

Teaser

In 2007, we reported that a phytopathogen effector directly inhibits a MAP kinase cascade. In the decade since, many more effectors have been found to inhibit MAP kinase cascades, providing not only a mechanistic understanding of pathogenesis and immunity in plants, but also the identification of previously unknown enzymes.


http://ift.tt/2m1BH3V

Microbes and Diet-Induced Obesity: Fast, Cheap, and Out of Control

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Peter J. Turnbaugh
Here I revisit our early experiments published in Cell Host & Microbe (Turnbaugh et al., 2008) showing that a diet rich in fat and simple sugars alters the gut microbiome in a manner that contributes to host adiposity, and reflect upon the remarkable advances and remaining challenges in this field.

Teaser

Here I revisit our early experiments published in Cell Host & Microbe (Turnbaugh et al., 2008) showing that a diet rich in fat and simple sugars alters the gut microbiome in a manner that contributes to host adiposity, and reflect upon the remarkable advances and remaining challenges in this field.


http://ift.tt/2m1kQOB

Generation of a Live Attenuated Influenza Vaccine that Elicits Broad Protection in Mice and Ferrets

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Lulan Wang, Su-Yang Liu, Hsiang-Wen Chen, Juan Xu, Maxime Chapon, Tao Zhang, Fan Zhou, Yao E. Wang, Natalie Quanquin, Guiqin Wang, Xiaoli Tian, Zhanlong He, Longding Liu, Wenhai Yu, David Jesse Sanchez, Yuying Liang, Taijiao Jiang, Robert Modlin, Barry R. Bloom, Qihan Li, Jane C. Deng, Paul Zhou, F. Xiao-Feng Qin, Genhong Cheng
New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones.

Graphical abstract

Teaser

Wang et al. use in vivo screening of a mutant influenza virus library to identify W7-791, an attenuated mutant strain. A single administration of W7-791 provided heterologous protection against lethal virus challenge in mice and ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection to naive animals.


http://ift.tt/2mE7pIb

Malaria Parasite Invasion: Achieving Superb Resolution

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Jake Baum, Dave Richard, David T. Riglar
It is only in the last decade that sub-cellular resolution of red cell invasion by the malaria parasite Plasmodium falciparum has been possible. Here we look back on the development of methodologies that led to this possibility and the subsequent advancements made in understanding this key event in malaria disease.

Teaser

It is only in the last decade that sub-cellular resolution of red cell invasion by the malaria parasite Plasmodium falciparum has been possible. Here we look back on the development of methodologies that led to this possibility and the subsequent advancements made in understanding this key event in malaria disease.


http://ift.tt/2mDPrFR

DAI Another Way: Necroptotic Control of Viral Infection

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Jason W. Upton, William J. Kaiser
Interrogation of murine cytomegalovirus (MCMV)-encoded cell-death suppressors revealed that necroptosis functions as a trap door to eliminate virally infected cells. This crucial host defense pathway is orchestrated by the sensing of infection by DAI/ZBP-1, engagement of the kinase RIPK3, and subsequent membrane permeablization by the pseudokinase MLKL.

Teaser

Interrogation of murine cytomegalovirus (MCMV)-encoded cell-death suppressors revealed that necroptosis functions as a trap door to eliminate virally infected cells. This crucial host defense pathway is orchestrated by the sensing of infection by DAI/ZBP-1, engagement of the kinase RIPK3, and subsequent membrane permeablization by the pseudokinase MLKL.


http://ift.tt/2m1BEVN

A Microbiome Foundation for the Study of Crohn’s Disease

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Dirk Gevers, Subra Kugathasan, Dan Knights, Aleksandar D. Kostic, Rob Knight, Ramnik J. Xavier
Our 2014 study published in Cell Host & Microbe, "The Treatment-Naive Microbiome in New-Onset Crohn's Disease," was designed to improve our understanding of the microbiome's role in Crohn's disease by studying a unique, well-suited cohort and sample set. This commentary provides a hindsight perspective of this original study as well as future outlook.

Teaser

Our 2014 study published in Cell Host & Microbe, "The Treatment-Naive Microbiome in New-Onset Crohn's Disease," was designed to improve our understanding of the microbiome's role in Crohn's disease by studying a unique, well-suited cohort and sample set. This commentary provides a hindsight perspective of this original study as well as future outlook.


http://ift.tt/2mE7pYH

A Sour Relationship between BabA and Lewis b

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Masanori Hatakeyama
Helicobacter pylori survives in the hostile acidic environment of the stomach through extensive adaptation. In this issue of Cell Host & Microbe, Bugaytsova et al. (2017) report an acid-responsive, reversible adherence of H. pylori BabA to the gastric mucosa, the strength of which is tuned by dynamic BabA adaptation.

Teaser

Helicobacter pylori survives in the hostile acidic environment of the stomach through extensive adaptation. In this issue of Cell Host & Microbe, Bugaytsova et al. (2017) report an acid-responsive, reversible adherence of H. pylori BabA to the gastric mucosa, the strength of which is tuned by dynamic BabA adaptation.


http://ift.tt/2m1xT2s

A Feast of Malaria Parasite Genomes

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Jane M. Carlton, Steven A. Sullivan
The Plasmodium genus has evolved over time and across hosts, complexifying our understanding of malaria. In a recent Nature paper, Rutledge et al. (2017) describe the genome sequences of three major human malaria parasite species, providing insight into Plasmodium evolution and raising the question of how many species there are.

Teaser

The Plasmodium genus has evolved over time and across hosts, compounding our understanding of malaria. In a recent Nature paper, Rutledge and colleagues (2017) describe the genome sequences of three major human malaria parasite species, providing insight into Plasmodium evolution and raising the question of how many species there are.


http://ift.tt/2m1pBrk

From Striking Out to Striking Gold: Discovering that Type VI Secretion Targets Bacteria

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Rachel D. Hood, S. Brook Peterson, Joseph D. Mougous
Specialized secretion systems are infamous for their contribution to host-pathogen interactions. Our discovery that the type VI secretion system delivers toxins between bacterial cells has broadened our understanding of how both pathogens and non-pathogens interact with one another, whether within or outside of the host.

Teaser

Specialized secretion systems are infamous for their contribution to host-pathogen interactions. Our discovery that the type VI secretion system delivers toxins between bacterial cells has broadened our understanding of how both pathogens and non-pathogens interact with one another, whether within or outside of the host.


http://ift.tt/2m1t2hN

Marking a Decade with Storytelling

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Lakshmi Goyal




http://ift.tt/2mDRcTr

Trained Immunity: An Ancient Way of Remembering

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Mihai G. Netea, Jos W.M. van der Meer
The innate arm of the immune system has generally been regarded as primitive and non-specific and, in contrast to adaptive immunity, not to possess memory. Here we review the growing body of evidence that innate immunity has an important capacity to adapt, a de facto innate immune memory (also termed trained immunity), and this provides broad protection against infections.

Teaser

The innate arm of the immune system has generally been regarded as primitive and non-specific and, in contrast to adaptive immunity, not to possess memory. Here we review the growing body of evidence that innate immunity has an important capacity to adapt, a de facto innate immune memory (also termed trained immunity), and this provides broad protection against infections.


http://ift.tt/2m1kOWZ

What to Expect When You’re Expecting Zika

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Helen M. Lazear
The 2015 emergence of Zika virus (ZIKV) in the Americas brought new attention to this previously obscure virus. Experimental model systems have been instrumental in rapidly advancing our understanding of ZIKV pathogenesis. Here, Lazear looks back on the events leading to the development of the ZIKV mouse model reported in Cell Host & Microbe.

Teaser

The 2015 emergence of Zika virus (ZIKV) in the Americas brought new attention to this previously obscure virus. Experimental model systems have been instrumental in rapidly advancing our understanding of ZIKV pathogenesis. Here, Lazear looks back on the events leading to the development of the ZIKV mouse model reported in Cell Host & Microbe.


http://ift.tt/2m1tsEY

Life-Saving Degeneracy in the Human Immune System

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Petter Brodin
Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.

Teaser

Different human immune system components coordinate to ensure effective control of pathogens. Israel et al. (2017) examine the immune system of a patient with an inborn genetic error, presenting as impaired TLR signaling and staphylococcal disease, and uncover a beautiful example of degeneracy between innate and adaptive branches of immunity.


http://ift.tt/2mDRbz2

Unsweetened IgG Is Bad for Dengue Patients

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Shee-Mei Lok
Dengue hemorrhagic fever is shown to correlate with secondary infection with a virus serotype different from the previous infection. However, only a small fraction of secondary infections leads to hemorrhagic fever. A recent Science paper suggests that the fucosylation state and isotype of IgGs elicited in patients may enhance disease severity.

Teaser

Dengue hemorrhagic fever is shown to correlate with secondary infection with a virus serotype different from the previous infection. However, only a small fraction of secondary infections leads to hemorrhagic fever. A recent Science paper suggests that the fucosylation state and isotype of IgGs elicited in patients may enhance disease severity.


http://ift.tt/2mDWTkp

Attenuated Vaccines for Augmented Immunity

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Stylianos Bournazos, Jeffrey V. Ravetch
Live attenuated vaccines are more immunogenic and have the capacity to elicit long-lasting immune responses. In two recent studies, Wang et al. (2017) and Si et al. (2016) describe strategies for the generation of live attenuated influenza viruses, which elicited robust humoral, mucosal, and cellular immunity against diverse virus strains.

Teaser

Live attenuated vaccines are more immunogenic and have the capacity to elicit long-lasting immune responses. In two recent studies, Wang et al. (2017) and Si et al. (2016) describe strategies for the generation of live attenuated influenza viruses, which elicited robust humoral, mucosal, and cellular immunity against diverse virus strains.


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West African Ebola Virus Strains: Unstable and Ready to Invade?

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Christopher F. Basler
Recent studies demonstrate that the Ebola virus glycoprotein (GP) acquired an A82V change during the West Africa epidemic and that this change altered the capacity of GP to be activated by host factors, enhancing infection of human cells. How this may alter the outcome of disease remains to be determined.

Teaser

Recent studies demonstrate that the Ebola virus glycoprotein (GP) acquired an A82V change during the West Africa epidemic and that this change altered the capacity of GP to be activated by host factors, enhancing infection of human cells. How this may alter the outcome of disease remains to be determined.


http://ift.tt/2mDPqSl

Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Géraldine Engels, Alexandra Maximiliane Hierweger, Julia Hoffmann, René Thieme, Swantje Thiele, Stephanie Bertram, Carola Dreier, Patricia Resa-Infante, Henning Jacobsen, Kristin Thiele, Malik Alawi, Daniela Indenbirken, Adam Grundhoff, Svenja Siebels, Nicole Fischer, Violeta Stojanovska, Damián Muzzio, Federico Jensen, Khalil Karimi, Hans-Willi Mittrücker, Petra Clara Arck, Gülsah Gabriel
Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8⁺ T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues.

Graphical abstract

Teaser

Pregnant women are at highest risk during influenza pandemics. Engels and colleagues present influenza infection models in mice and show that the immune response, which is tailored to accommodate the semiallogenic fetus, restricts the anti-viral immune response during gestation. Under these conditions, highly pathogenic virus variants can emerge.


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Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity

Publication date: 8 March 2017
Source:Cell Host & Microbe, Volume 21, Issue 3
Author(s): Mark J.G. Bakkers, Yifei Lang, Louris J. Feitsma, Ruben J.G. Hulswit, Stefanie A.H. de Poot, Arno L.W. van Vliet, Irina Margine, Jolanda D.F. de Groot-Mijnes, Frank J.M. van Kuppeveld, Martijn A. Langereis, Eric G. Huizinga, Raoul J. de Groot
Human beta1-coronavirus (β1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like related animal β1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. β1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43's introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation of mutations in the HE lectin domain. Consequently, virion-associated receptor-destroying activity toward multivalent glycoconjugates was reduced and altered such that some clustered receptor populations are no longer cleaved. Loss of HE lectin function was also observed for another respiratory human coronavirus, HKU1. This thus appears to be an adaptation to the sialoglycome of the human respiratory tract and for replication in human airways. The findings suggest that the dynamics of virion-glycan interactions contribute to host tropism. Our observations are relevant also to other human respiratory viruses of zoonotic origin, particularly influenza A virus.

Graphical abstract

Teaser

Coronavirus OC43 entered the human population relatively recently. Bakkers et al. report that as an adaptation to replication in human airways, the OC43 hemagglutinin-esterase lost its receptor-binding function. Consequently, virion-associated receptor-destroying activity toward clustered sialoglycan-based receptor determinants was reduced. Suggestive of convergent evolution, human respiratory coronavirus HKU1 underwent similar changes.


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Effect of Androgen Supplementation on 24-Hour Activity-Rest Patterns of Aged Male Rhesus Macaques

Publication date: Available online 8 March 2017
Source:Neurobiology of Aging
Author(s): Henryk F. Urbanski
Like elderly men, old male rhesus macaques show attenuated circulating levels of testosterone and dehydroepiandrosterone sulfate (DHEAS), and many of them also show reduced levels of daytime activity. It is unclear, however, if this age-associated behavioral change is causally related to the underlying decrease in circulating androgen levels. To test this possibility, old male rhesus macaques were given daily supplements of testosterone and DHEA for 6 months, designed to mimic the mean 24-hour circulating hormone patterns of young adults. Compared to the young adults, the old controls showed attenuated daytime activity levels. However, there was no difference between the androgen supplemented old animals and the aged-matched controls, even after 6 months of treatment. The data suggest that age-associated decreases in circulating androgen levels are unlikely to be a primary reason for altered activity-rest patterns in elderly men, and that androgen supplementation paradigms might not provide any obvious therapeutic benefit.



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Current Techniques for Postoperative Monitoring of Microvascular Free Flaps.

Author: Khatri, Nasir; Zhang, Shuhao; Kale, Santosh S.

Page: 148-152

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Context for Practice: Leakage From the Ostomy Pouch, Constipation in Patients With Colostomies.

Author: Gray, Mikel

Page: 108-109

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Pressure Injury Prevalence and the Rate of Hospital-Acquired Pressure Injury Among Pediatric Patients in Acute Care.

Author: Razmus, Ivy; Bergquist-Beringer, Sandra

Page: 110-117

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Validation of a Model for Predicting Pressure Injury Risk in Patients With Vascular Diseases.

Author: Moyse, Tonya; Bates, Jacqueline; Karafa, Matthew; Whitman, Angela; Albert, Nancy M.

Page: 118-122

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Attitudes of Nursing Students About Pressure Injury Prevention.

Author: Garrigues, Layla J.; Cartwright, Juliana C.; Bliss, Donna Z.

Page: 123-128

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Development of a Survey to Explore Factors Influencing the Adoption of Best Practices for Diabetic Foot Ulcer Offloading.

Author: Bleau Lavigne, Maude; Reeves, Isabelle; Sasseville, Marie-Josee; Loignon, Christine

Page: 129-137

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Prevention of Medical Device-Related Pressure Injuries Associated With Respiratory Equipment Use in a Critical Care Unit: A Quality Improvement Project.

Author: Padula, Cynthia A.; Paradis, Heidi; Goodwin, Robert; Lynch, Judith; Hegerich-Bartula, Deborah

Page: 138-141

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Pressure Mapping in Elderly Care: A Tool to Increase Pressure Injury Knowledge and Awareness Among Staff.

Author: Hultin, Lisa; Olsson, Estrid; Carli, Cheryl; Gunningberg, Lena

Page: 142-147

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View From Here: Formal and Informal Leadership Translating Evidence-Based Practices for Pressure Injury Prevention in the Hospital Setting.

Author: Padula, William; Makic, Mary Beth F.

Page: 153-154

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Psychological and Physical Environmental Factors in the Development of Incontinence in Adults and Children: A Comprehensive Review.

Author: von Gontard, Alexander; de Jong, Tom P. V. M.; Badawi, Jasmin Katrin; O'Connell, Kathleen A.; Hanna-Mitchell, Ann T.; Nieuwhof-Leppink, Anka; Cardozo, Linda

Page: 181-187

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Differences in Ostomy Pouch Seal Leakage Occurrences Between North American and European Residents.

Author: Fellows, Jane; Forest Lalande, Louise; Martins, Lina; Steen, Anne; Storling, Zenia M.

Page: 155-159

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Conservative Measures for Managing Constipation in Patients Living With a Colostomy.

Author: Kuczynska, Barbara; Bobkiewicz, Adam; Studniarek, Adam; Szmyt, Krzsztof; Krokowicz, Lukasz; Matysiak, Konrad; Szmeja, Jacek; Walkowiak, Jaroslaw; Drews, Michal; Banasiewicz, Tomasz

Page: 160-164

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Incidence and Predictors of Incontinence-Associated Skin Damage in Nursing Home Residents With New-Onset Incontinence.

Author: Bliss, Donna Z.; Mathiason, Michelle A.; Gurvich, Olga; Savik, Kay; Eberly, Lynn E.; Fisher, Jessica; Wiltzen, Kjerstie R.; Akermark, Haley; Hildebrandt, Amanda; Jacobson, Megan; Funk, Taylor; Beckman, Amanda; Larson, Reed

Page: 165-171

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Clinical Evaluation of a Skin Protectant for the Management of Incontinence-Associated Dermatitis: An Open-Label, Nonrandomized, Prospective Study.

Author: Brennan, Mary R.; Milne, Catherine T.; Agrell-Kann, Marie; Ekholm, Bruce P.

Page: 172-180

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Psychological and Physical Environmental Factors in the Development of Incontinence in Adults and Children: A Comprehensive Review.

Author:

Page: E1

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Medical Adhesive-Related Skin Injury Following Emergent Appendectomy: A Case Study of MARSI and Missed Opportunities in Nursing Care.

Author: Britt, Sylvia E.; Coles, Karen M.; Polson, Shannon S.

Page: 188-192

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WOCN(R)-Accredited Professional Education Programs.

Author:

Page: 193-194

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Wound Versus Foot Care: Is There a Difference?.

Author: Ellefson, Laurie; Wilson, Francis; Hoffman, Kathleen; Wells, Belinda

Page: E2-E4

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Metabolomics through the lens of precision cardiovascular medicine

Publication date: Available online 8 March 2017
Source:Journal of Genetics and Genomics
Author(s): Sin Man Lam, Yuan Wang, Bowen Li, Jie Du, Guanghou Shui
Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development. Major issues concerning the statistical handling of big data generated by metabolomics, as well as its interpretation, will be briefly addressed. Finally, the need for integration of various omics branches and adopting a multi-omics approach to precision medicine will be discussed.



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G protein-coupled calcium-sensing receptor is a crucial mediator of MTA-induced biological activities

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Jin Man Kim, Seulki Choi, Kyu Hwan Kwack, Sun-Young Kim, Hyeon-Woo Lee, Kyungpyo Park
Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs). We found that MTA activates diverse CaSR downstream pathways; notably, CaSR activation essentially requires dual modulation of extracellular Ca²⁺ and pH via MTA. Among the CaSR downstream pathways, Ca²⁺ mobilization from intracellular stores by the phospholipase C pathway plays an important role in osteogenic differentiation of hDPCs by regulating transcriptional activity. Our findings shed light on the signal transduction mechanism of MTA, thus providing a crucial molecular basis for the use of MTA in regenerative dental therapy.



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Surface engineering of semiconducting polymer nanoparticles for amplified photoacoustic imaging

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Xu Zhen, Xiaohua Feng, Chen Xie, Yuanjin Zheng, Kanyi Pu
Despite the deeper tissue penetration of photoacoustic (PA) imaging, its sensitivity is generally lower than optical imaging. This fact partially restricts the applications of PA imaging and greatly stimulates the development of sensitive PA imaging agents. We herein report that the surface coating of semiconducting polymer nanoparticles (SPNs) with the silica layer can simultaneously amplify fluorescence and PA brightness while maintaining their photothermal conversion efficiency nearly unchanged. As compared with the bare SPNs, the silica-coated SPNs (SPNs-SiO2) have higher photothermal heating rate in the initial stage of laser irradiation due to the higher interfacial thermal conductance between the silica layer and water relative to that between the SP and water. Such an interfacial effect consequently results in sharp temperature increase and in turn amplified PA brightness for SPNs-SiO2. By conjugating poly(ethylene glycol) (PEG) and cyclic-RGD onto SPNs-SiO2, targeted PA imaging of tumor in living mice is demonstrated after systemic administration, showing a high signal to background ratio. Our study provides a surface engineering approach to amplify the PA signals of organic nanoparticles for molecular imaging.

Graphical abstract

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Ultra-strong metals created in a smash

Publication date: Available online 8 March 2017
Source:Nano Today





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Investigation on the association between thyroid tumorigeneses and herpesviruses

Abstract

Herpesviruses have been associated with various human malignancies and with thyroid autoimmunity. Aiming to investigate the presence of these viruses in thyroid nodules, we analyzed serum and thyroid tissue from 183 patients (83 benign and 100 malignant thyroid nodules). We also obtained 104 normal thyroid tissues extracted from the contralateral lobe of these patients. We used ELISA to screen the serology of all patients and a real-time quantitative PCR to analyze thyroid tissue viral load in antibody-positive patients. In addition, the presence of herpesviruses was tested by histological analysis in 20 EBV-positive tissues using the expression of LMP-1 by immunohistochemistry (IHC) and EBER by in situ hybridization (ISH). There was no evidence of HSV-2 or CMV DNA, but we found EBV DNA sequences in 29 (16%) thyroid tissue samples. We also found 7 positive EBV cases out of 104 normal tissues. Viral load was higher in tumors than in their respective normal tissues (p = 0.0002). ISH analysis revealed EBER expression in 11 out of 20 (52%) EBV-positive tissues, mostly in malignant cases (8/11, 73%). The presence of high EBV copy numbers in thyroid tumors and the expression of EBER only in malignant cases suggest an association between EBV and thyroid malignancies. However, we did not find any association between the presence of EBV and/or its viral load and any clinical or pathological tumor feature. Further studies aiming to clarify the mechanisms of EBV infection in thyroid cells are necessary to support a possible role in the development of thyroid cancer.

http://ift.tt/2m4FbmJ

Intra-clutch and inter-colony variability in element concentrations in eggshells of the black-headed gull, Chroicocephalus ridibundus , in northern Poland

Abstract

Eggshells are good bioindicators of environmental contamination, and therefore, the concentrations of 17 trace elements in 87 eggshells of black-headed gulls, Chroicocephalus ridibundus, were determined in five breeding colonies in an area dominated by farmland in northern Poland. The intra-clutch variability in the eggshell concentrations of heavy metals and other elements was also investigated, and the concentrations of the elements showed the following pattern: Ca > Mg > Sr > Fe > Zn > Al > Cr > Se > Mn > Cu > Pb > As > Ni > Mo = V > Sc > Cd. The concentrations of Fe, Al, and Mn decreased with the order in which the eggs were laid, but Sr concentrations increased. In contrast, the concentration of Cu significantly increased with the laying date. The concentrations of all elements significantly differed among the studied colonies; the highest concentration of eight elements was found in the eggshells from the Kusowo colony, which may have resulted from the intensive use of fertilizers, manure, and slurry in the surrounding agricultural region. The concentrations of Mg, Sr, and Zn in the eggshells from Skoki Duże were higher than those of the other studied colonies, which may have occurred because the gulls were nesting in a functioning gravel pit; soil and the parent rock are natural reservoirs of these elements. The observed element levels indicate that the environment where the black-headed gull eggs were formed, i.e., primarily near the breeding colonies, remains in a relatively unpolluted state, which was reflected by the low levels of Cd, Ni, and Pb and the lack of measurable levels of Hg.

http://ift.tt/2mIGQSD

Effect of molar mass on the α′/α-transition in poly (l-lactic acid)

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): René Androsch, Maria Laura Di Lorenzo
The effect of molar mass on the reorganization behavior of α′-crystals of poly (l-lactic acid) (PLLA) has been investigated by fast scanning chip calorimetry. The α′-crystals of PLLA were formed by isothermal crystallization of the relaxed melt at 90 °C or lower temperatures, and were then heated at different rates between 2 and 200 K s⁻¹. Slow heating permits for all PLLA samples of different molar mass between 2 and 576 kDa reorganization of α′- into α-crystals. It was found that the α′/α-transition is suppressed if heating occurs faster than 10 K s⁻¹ in case of the sample with a molar mass of 576 kDa, while the critical heating rate to suppress the formation of α-crystals is increased to 30 and 100 K/s in PLLA with molar masses of around 100 kDa and 2 kDa, respectively. The faster kinetics of the α′/α-transition in case of shorter macromolecules may be explained by faster melting of smaller α′-crystals, faster growth of α-crystals from the non-isotropic melt containing remnants/self-seed from molten α′-crystals, and/or a higher number of such α′-crystal remnants/self-seed.

Graphical abstract

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The effects of branching and deuterium labeling on blend miscibility

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Jeffrey DeFelice, Julia S. Higgins, Jane E.G. Lipson
The individual and combined effects of 4-arm star branching and deuterium labeling on polystyrene (PS) influence its compatibility in upper critical solution temperature (UCST) and lower critical solution temperature (LCST) mixtures. In this article, we use our Locally Correlated Lattice (LCL) model to characterize a set of PS samples in their pure states in order to predict miscibility trends for blends of PS with poly(vinyl methyl ether) (PVME) (LCST-type mixtures) and isotopic variants of PS (UCST-type mixtures). We find that 4-arm star branching and/or deuterium labeling can shift the pure component properties of PS, such as its percent free volume or cohesive energy density, which affects how the properties of PS 'match' those of the other mixture component. In another section of this article, we turn to modeling the blends, themselves, and provide fundamental thermodynamic insight about the PS/PVME mixtures by calculating the relative enthalpic and entropic contributions to the free energies of mixing. We observe trends in the values of the entropies and enthalpies of mixing for the PS/PVME blends that qualitatively match our pure component properties analysis of the pure PS samples.

Graphical abstract

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Gene expression of miRNA-138 and cyclin D1 in oral lichen planus

Abstract

Objectives

This study aimed to evaluate microRNA-138 (miR-138) gene expression and its target cyclin D1 (CCND1) gene and protein expression in oral lichen planus (OLP) mucosa in an attempt to investigate their possible roles in OLP immunopathogenesis.

Methods

Sixty oral biopsy specimens were harvested from 30 healthy subjects and 30 OLP patients, subdivided into reticular, atrophic, and erosive groups (n = 10 each). Samples were subjected to quantitative real-time polymerase chain reaction analysis for quantification of miR-138 and CCND1 relative gene expression and immunohistochemical analysis to determine CCND1 protein expression.

Results

Samples from OLP patients had a significant underexpression of miR-138 gene and overexpression of CCND1 at both gene and protein levels compared to normal mucosa samples. The lowest levels of miR-138 expression were observed in atrophic and erosive OLP compared to reticular OLP, and the highest levels of CCND1 gene and protein expression were in atrophic OLP. An inverse correlation was demonstrated between the miR-138 expression and both CCND1 gene and protein expression in OLP patients. A significant positive correlation between CCND1 gene and protein expression was also observed.

Conclusion

Downregulation of miR-138 increases the gene and protein expression of its potential target CCND1 in OLP mucosa which might have a pivotal role in the disease pathogenesis.

Clinical relevance

This research implied that miR-138 may have a role in identification of symptomatic OLP lesions. MiR-138 might be considered as a potential tool in future OLP molecular therapy.

http://ift.tt/2n0WUjd

The benefits (and misfortunes) of SDS in top-down proteomics

Publication date: Available online 8 March 2017
Source:Journal of Proteomics
Author(s): Carolyn Kachuk, Alan A. Doucette
Top-down proteomics (TDP) has great potential for high throughput proteoform characterization. With significant advances in mass spectrometry (MS) instrumentation permitting tandem MS of large intact proteins, a limitation to the widespread adoption of TDP still resides on front-end sample preparation protocols (e.g. fractionation, purification) that are amenable to MS analysis of intact proteins. Chromatographic strategies are improving but pose higher risk of sample loss. Gel-based separations (e.g. GELFrEE) may alleviate this concern but at the expense of requiring sodium dodecyl sulfate (SDS). While this surfactant maintains protein solubility during fractionation, the advantage is short-lived, as the detergent must ultimately be depleted to avoid MS signal suppression. To do so requires overcoming strong interactions between SDS and protein. Adding to the challenge, one must now consider upholding the solubility of purified protein(s) in the absence of SDS. This review explores uses of SDS in TDP workflows, addressing front-end strategies that reduce matrix interferences while maximizing recovery of intact proteins in MS-compatible formats.SignificanceThe benefits of employing SDS in a TPD workflow can easily outweigh the disadvantages. Several SDS depletion strategies are available, though not all are equally amenable to TDP. This review provides a comprehensive and critical accounting of SDS in TDP, demonstrating methods that are suited to MS analysis of intact proteins.

Graphical abstract

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iTRAQ-based quantitative proteomic analysis reveals potential virulence factors of Erysipelothrix rhusiopathiae

Publication date: Available online 8 March 2017
Source:Journal of Proteomics
Author(s): Ya Wang, Jingtao Li, Anding Zhang, Weifeng Zhu, Qiang Zhang, Zhongmin Xu, Shuxian Yan, Xiaomei Sun, Huanchun Chen, Meilin Jin
Erysipelothrix rhusiopathiae is a ubiquitous pathogen that has caused considerable economic losses to pig farmers. However, the mechanisms of E. rhusiopathiae pathogenesis remain unclear. To identify new virulence-associated factors, the differentially abundant cell wall-associated proteins (CWPs) between high- and low-virulence strains were investigated through isobaric Tags for Relative and Absolute Quantitation (iTRAQ) combined with liquid chromatography-quadrupole mass spectrometry (LC-MS/MS). In total, 100 CWPs showed significant differences in abundance. Selected differences were verified by western blotting to support the iTRAQ data. Among the differential proteins, the proteins with higher abundance in the high-virulence strain were mostly ABC transporter proteins and adhesion proteins, and the proteins with lower abundance in the high-virulence strain were mainly stress-response proteins. The more abundant proteins in the high-virulence strain may be related to bacterial virulence. The iTRAQ results showed that the abundance of the sugar ABC transporter substrate-binding protein Sbp (No. 5) was higher by 1.73-fold. We further constructed an sbp-deletion mutant. Experiments in animal models showed that the sbp-deletion mutant caused decreased mortality. Together, our data indicated that transporter proteins and adhesion proteins may play important roles in E. rhusiopathiae virulence and confirmed that sbp contributed to the virulence of E. rhusiopathiae.Biological significanceTo our knowledge, this is the first proteomic analysis comparing differentially abundant CWPs between high- and low-virulence E. rhusiopathiae strains by iTRAQ. We generated comprehensive and accurate lists of E. rhusiopathiae CWPs proteomes and identified many differences at the protein level. Among the differential proteins with higher abundance in the high-virulence strain, sbp was verified to contribute to the virulence of E. rhusiopathiae through the construction of an sbp-deletion mutant. The differential proteins with higher abundance in the high-virulence strain identified in the present study should provide a foundation for future evaluation of virulence factors.

Graphical abstract

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A single seizure attack induced rhabdomyolysis

Jiajia Zhou, Benyan Luo, Guoping Peng

Neurology India 2017 65(7):93-94



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The cover page

Neurology India 2017 65(7):1-1



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Epilepsy management-beyond prescription

HV Srinivas

Neurology India 2017 65(7):2-3



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Detection and management of intraoperative seizure with bispectral index monitoring in a paralyzed patient

Keta Thakkar, Ramamani Mariappan, Bijesh R Nair

Neurology India 2017 65(7):100-101



http://ift.tt/2m13xNm

Phenytoin-induced fatal drug reactions in two patients with brain tumors: Need to re-think our routine anticonvulsant usage

Izhar Faisal, Pragati Ganjoo, Deepali Garg, Upma B Batra, Arvind K Srivastava, Hukum Singh

Neurology India 2017 65(7):95-97



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From resection to ablation: A review of resective surgical options for temporal lobe epilepsy and rationale for an ablation-based approach

Anne Coyle, Jonathan Riley, Chengyuan Wu, Ashwini Sharan

Neurology India 2017 65(7):71-77

Surgical intervention is of proven benefit in an appropriately selected subset of patients with medically refractory temporal lobe epilepsy. In these patients, a surgical cure both provides the quality of life improvement that comes from seizure freedom as well as a survival benefit. However, patients who undergo open surgical intervention may have a worsening in neurobehavioral outcomes. Laser interstitial thermal therapy (LITT) represents a minimally invasive surgical intervention that has shown promise in improving post-operative neurobehavioral outcomes. Further, the minimally invasive nature of this procedure holds the possibility to shift the significant under-penetration of surgical intervention that exists for eligible medically refractory patients. Herein, we review open surgical resection-based techniques and the clinical data to date for LITT.

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Addressing the burden of epilepsy in India…

Malla Bhaskara Rao

Neurology India 2017 65(7):4-5



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New-onset focal epilepsy in adults: Antiepileptic drug treatment

J M K Murthy

Neurology India 2017 65(7):78-82

Focal epilepsy, non-syndromic, is by far the most prevalent epilepsy in adults. Antiepileptic drug (AED) prescription in patients with new-onset focal epilepsy is often challenging. The factors that determine AED of choice depends both on the patient-specific and AED-specific variables. Monotherapy should the initial strategy. Failure to monotherapy can be due to lack of efficacy, severe adverse events, or a hypersensitivity reaction. In such patients, the next strategy should be alternate monotherapy trials. In patients who fail up to three monotherapy trials, duotherapy with drugs having different primary mechanisms of action should be the next step. Multiple duotherapy should be tried before considering adding polytherapy. In spite of such pragmatic strategies, about 25% of patients may never become seizure free for any complete year throughout follow-up. Patients in this group should be evaluated for non-pharmacological treatment options, particularly epilepsy surgery.

http://ift.tt/2m14SnI

Evidence-based guidelines for the management of epilepsy

Sanjay P Singh, Ram Sankaraneni, Arun R Antony

Neurology India 2017 65(7):6-11

Approximately 50 million people live with epilepsy worldwide. The aim of this review is to present an overview of the current evidence and management recommendations for evaluation and treatment of patients with epilepsy. Systematic literature reviews were undertaken. A review of contemporary published evidence-based guidelines (American Academy of Neurology, American Epilepsy Society, and the Indian Epilepsy Society) and published peer reviewed scientific publications was done. The guideline is addressed to all clinicians who manage epilepsy patients. Evidence-based recommendations are provided for the evaluation and treatment of the first seizure, use of antiepileptic medications, treatment of status epilepticus, use of epilepsy surgery, and the management of epilepsy in specific populations as well as in unique clinical situations such as neurocysticercosis infestation, brain tumor and human immunodeficiency virus infection. It also addresses the special considerations in women with epilepsy.

http://ift.tt/2n1086i

Status epilepticus: Refractory and super-refractory

Deepanshu Dubey, Jayantee Kalita, Usha K Misra

Neurology India 2017 65(7):12-17

Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%–48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2–20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

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Transient lesion in the splenium of corpus callosum due to abrupt phenytoin withdrawal

Dhananjay Duberkar, Rajesh Jawale

Neurology India 2017 65(7):104-104



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Comorbidities of epilepsy

HV Srinivas, Urvashi Shah

Neurology India 2017 65(7):18-24

In epilepsy management, control of seizures is the prime objective. However, the quality of life is affected by comorbid conditions that include the neurological, neuropsychiatric, and neurobehavioural disorders. These are not only reactive processes to a chronic condition but also have a bidirectional relationship, sharing common underlying pathogenesis. This article besides addressing these issues also explores the therapeutic management. A systematic search of PubMed from Jan 2006 to August 2016 was undertaken using the terms "comorbidities" and "epilepsy." In addition, articles specifically from India and other original papers were selected based on relevance. In this review, the neuropsychiatric, neurobehavioral (mood disorders, behaviour issues, attention deficits, psychosis), and neurologic [cognitive impairment, migraine, SUDEP-Sudden unexpected death in epilepsy (SUDEP)] comorbidities are covered in relation to epilepsy and its treatment. The incidental disorders such as hypertension, diabetes, and cancer that are mentioned in some reports have not been addressed here. Comorbidities in epilepsy are common but poorly understood and often remain unaddressed. The prevalence of comorbid conditions is considerably higher in epilepsy than seen in the general population and other chronic conditions. There is a wide spectrum of secondary disorders that have a marked impact and significantly increase the burden of the primary epilepsy condition. There is a need to acknowledge, screen, and intervene early in newly diagnosed cases for the optimal management of epilepsy.

http://ift.tt/2n14RFe

Use of resting-state fMRI in planning epilepsy surgery

Sharon Chiang, Zulfi Haneef, John M Stern, Jerome Engel

Neurology India 2017 65(7):25-33

Epileptic seizures result from abnormal neuronal excitability and synchronization, affecting 0.5–1% of the population worldwide. Although anti-seizure drugs are often effective, a significant number of patients with epilepsy continue to experience refractory seizures and are candidates for surgical resection. Whereas standard presurgical evaluation has relied on intracranial electroencephalography (icEEG) and direct cortical stimulation to identify epileptogenic tissue and areas of cortex for which resection would produce clinical deficits, the invasive nature and limited spatial extent of icEEG has led to the investigation of less invasive imaging modalities as adjunctive tools in the presurgical workup. In the past few decades, functional connectivity MRI has emerged as a promising approach for presurgical mapping, leading to a surge in the number of proposed methods and biomarkers for identifying epileptogenic tissue. This review focuses on recent advances in the use of functional connectivity MRI toward its application for presurgical planning, including epilepsy localization and eloquent cortex mapping.

http://ift.tt/2n0SOYj

Recent advances in Epilepsy Research in India

Aparna B Dixit, Jyotirmoy Banerjee, P Sarat Chandra, Manjari Tripathi

Neurology India 2017 65(7):83-92

There are more than 10 million persons with epilepsy (PWE) in India. Despite availability of antiepileptic drugs (AEDs), there is a large treatment gap varying from 50 to 70% among PWE. For treatable epilepsy, this gap can be attributed to poor education, poverty, cultural beliefs, stigma, and poor healthcare infrastructure; whereas for chronic epilepsy, this gap can be attributed to lack of proper diagnosis and treatment. To prevent, treat, and cure epilepsy, researchers worldwide have made exciting advances across all areas of epilepsy research. Studies carried out in India have also shown substantial progress; however, most of them are focused on the epidemiological aspects of epilepsy, genetic associations, identification, and validation of new AEDs in animal models of epilepsy.Very few studies are reported on understanding the process of epileptogenesis, a dynamic process by which neurons begin to display abnormal firing patterns that cause epileptic seizures. Animal epilepsy models can be used for in depth studies; however, studies conducted on resected brain tissues from epilepsy patients are clinically relevant. Finally, more funding support from government and collaborations among basic research institutes, medical institutes, as well as industries is required to raise the standards of epilepsy research in India.This review focuses on the evaluation of the current status of epilepsy research in India and the need to identify potential anti-epileptogenic interventions.

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Role of magnetoencephalography and stereo-electroencephalography in the presurgical evaluation in patients with drug-resistant epilepsy

V Jayabal, Ashok Pillai, S Sinha, N Mariyappa, P Satishchandra, S Gopinath, Kurupath Radhakrishnan

Neurology India 2017 65(7):34-44

In selected patients with drug-resistant focal epilepsies (DRFE), who otherwise are likely to be excluded from epilepsy surgery (ES) because of the absence of a magnetic resonance imaging (MRI)-demonstrable lesion or discordant anatomo-electro-clinical (AEC) data, magnetoencephalography (MEG) may help to generate an AEC hypothesis and stereo-electroencephalography (SEEG) may help to verify the hypothesis and proceed with ES. The sensitivity of MEG is much better in localizing the spiking zone in relation to lateral temporal and extratemporal cortical regions compared to the mesial temporal structures. MEG has a dominant role in the presurgical evaluation of patients with MRI-negative DRFEs, insular epilepsies, and recurrent seizures after failed epilepsy surgeries, and in guiding placement of invasive electrodes. Moreover, postoperative seizure freedom is better if MEG spike source localized cortical region is included in the resection. When compared to subdural grid electrode recording, SEEG is less invasive and safer. Those who are otherwise destined to suffer from uncontrolled seizures and their consequences, SEEG guided ES is a worthwhile and a cost-effective option. Depending on the substrate pathology, there is > 80-90% chance of undergoing ES and 60-80% chance of becoming seizure-free following SEEG. Recent noninvasive techniques aimed at better structural imaging, delineating brain connectivity and recording specific intracerebral EEG patterns such as high frequency oscillations might decrease the need for SEEG; but more importantly, make SEEG exploration more goal-directed and hypothesis-driven.

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Pyridoxine responsive seizures secondary to isoniazid prophylaxis in an infant

Amitabh Singh, Smita Nair, Rahul Jain

Neurology India 2017 65(7):94-95



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The evolution of epilepsy surgery

CE Polkey

Neurology India 2017 65(7):45-51

This review traces the evolution of epilepsy surgery from its early beginnings in the 20th century with the development of neurophysiology, and later the identification of pathology in surgical specimens, to the tremendous boost given by direct brain imaging in the late 20th century. This resulted in the sophisticated methods of presurgical investigation, surgical techniques, and postsurgery care available from the millennium. In parallel, functional surgery, which modifies the nervous system's behaviour, available throughout, has attained a greater place by the use of stimulation.

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Sandhoff disease in two siblings of a Malaysian family: Description of novel beta hexosaminidase mutations, magnetic resonance imaging, and spectroscopic findings

Chermaine D Antony, Meow-Keong Thong, Kartini Rahmat, Roziah Muridan

Neurology India 2017 65(7):98-100



http://ift.tt/2m0UlbY

Epidemiology of epilepsy surgery in India

Chaturbhuj Rathore, Kurupath Radhakrishnan

Neurology India 2017 65(7):52-59

Epilepsy surgery in India has seen remarkable advances over the last twenty years. Presently 39 centers are undertaking epilepsy surgeries in India on a regular basis. Out of these, 18 centers have become operational in the last five years. Many of them are well equipped with high end technologies and have expertise to undertake all kinds of epilepsy surgeries. Till July 31st, 2016, approximately 7143 epilepsy surgeries have been performed in India. Presently, 734 epilepsy surgeries are carried out in India every year representing an increase of approximately 58% over the last three and a half years as compared to the previous years. The reported postoperative outcomes from all these centers are comparable to those reported from the well-established centers in high income countries. Still, only 2 in 1000 eligible patients In India undergo epilepsy surgery, because of which, the enormous surgical treatment gap continues to persist. To tackle this, by the year 2020, India should have at least 60 state-level epilepsy surgery centers (with each undertaking at least 50 surgeries per year) and 6 national centers of excellence. Here, we discuss the current prevalence and practice of epilepsy surgery in India and suggest pragmatic steps and solutions to make epilepsy surgery affordable and widely available. The steps also include a framework for the development of a national epilepsy surgery program.

http://ift.tt/2n160wr

Visualization of a musical videoclip as a manifestation of simple focal epilepsy in neurocysticercosis

Marian-Magaña Ricardo, Roque-Villavicencio Yuridia, Parada-Garza Juan, Villaseñor-Cabrera Teresita, Ruiz_sandoval Jose

Neurology India 2017 65(7):101-103



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Short Takes

Publication date: Available online 7 March 2017
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis




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Editorial Board and Masthead

Publication date: March 2017
Source:Pediatric Neurology, Volume 68





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Table of Contents

Publication date: March 2017
Source:Pediatric Neurology, Volume 68





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Novel presentation of Rosai-Dorfman histiocytosis with a prolonged course of cranial and peripheral neuropathies

Publication date: Available online 8 March 2017
Source:Pediatric Neurology
Author(s): Richa Tripathi, Fatema Serajee, H. Jiang, A.H.M.M. Huq
IntroductionRosai-Dorfman disease is a form of histiocytosis affecting the systemic lymph nodes. Intracranial Rosai-Dorfman disease is very rare and presents with extra or intraparenchymal proliferative mass lesions. Cranial neuropathy except mass effect by surrounding lesion has not been reported in Rosai-Dorfman disease.MethodsWe describe a case of Rosai-Dorfman Disease presenting with peripheral as well as multiple cranial neuropathies. Detailed clinical, immunological, neurophysiology, imaging and genetic studies were performed.ResultThe patient had a prolonged course but recovered fully after immune therapies. She had elevated titers of striated muscle and smooth muscle antibodies. Imaging studies revealed contrast enhancement of cranial nerves and striated muscles. Demyelination was evident in the nerve twigs from muscle biopsy. Exome sequencing did not reveal any genetic mutations.ConclusionMost patients with Rosai-Dorfman disease have a benign course. But severe neurological complication with bulbar involvement and cranial and peripheral neuropathy may occur. Treatment with Immunoglobulin and steroids may be of benefit.



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Meetings of Interest

Publication date: March 2017
Source:Pediatric Neurology, Volume 68





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Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers

Publication date: May 2017
Source:Biomaterials, Volume 127
Author(s): Yilong Cheng, Drew L. Sellers, James-Kevin Y. Tan, David J. Peeler, Philip J. Horner, Suzie H. Pun
Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)–b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery.



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Editorial board

Publication date: May 2017
Source:Biomaterials, Volume 126





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Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy

Publication date: May 2017
Source:Biomaterials, Volume 126
Author(s): Nan Lu, Peng Huang, Wenpei Fan, Zhantong Wang, Yijing Liu, Sheng Wang, Guofeng Zhang, Junkai Hu, Wenfei Liu, Gang Niu, Richard D. Leapman, Guangming Lu, Xiaoyuan Chen
The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.



http://ift.tt/2ncuP4G

Tracing sialoglycans on cell membrane via surface-enhanced Raman scattering spectroscopy with a phenylboronic acid-based nanosensor in molecular recognition

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Lijia Liang, Huixin Qu, Biying Zhang, Jing Zhang, Rong Deng, Yanting Shen, Shuping Xu, Chongyang Liang, Weiqing Xu
Sialoglycan expression is critical for assessing various diseases progression. Especially, its abnormal levels are commonly believed to be associated with tumor and metastatic cancer types. While, complicated structures, multiple types and dynamic distributions make it challenging for in situ investigating sialoglycans at the physiological status. Herein, we developed a 4-mercaptophenylboronic acid (MPBA)-based surface-enhanced Raman scattering (SERS) nanosensor to in situ study sialoglycan levels and dynamic expression processes of different cell types based on molecular recognition between phenylboronic acid and sialoglycans at physiological condition. This nanosensor is designed by the MPBA decorated silver nanoparticle (AgNP), which is unique and multifunctional because of its three-in-one role involving the Raman signal enhancer (AgNP), the sensing reporter of MPBA and the target receptor based on the recognition of phenylboronic acid and sialoglycans. When this nanosensor binds to sialoglycans, the molecular vibrational modes of MPBA will change, which can be traced by ultrasensitive SERS technique. The superiority of this study is that we built the relation between the spectral changes of MPBA (relative intensities) in molecular recognition with the sialoglycan dynamic expression of cells. We believe that our SERS strategy could be further extended to explore crucial physiological processes and significant biological system that glycans are involved in.



http://ift.tt/2n0MwrL

Hierarchical templating in deposition of semi-covalently imprinted inverse opal polythiophene film for femtomolar determination of human serum albumin

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Marcin Dabrowski, Maciej Cieplak, Piyush Sindhu Sharma, Pawel Borowicz, Krzysztof Noworyta, Wojciech Lisowski, Francis D'Souza, Alexander Kuhn, Wlodzimierz Kutner
Nanostructured artificial receptor materials with unprecedented hierarchical structure for determination of human serum albumin (HSA) are designed and fabricated. For that purpose a new hierarchical template is prepared. This template allowed for simultaneous structural control of the deposited molecularly imprinted polymer (MIP) film on three length scales. A colloidal crystal templating with optimized electrochemical polymerization of 2,3′-bithiophene enables deposition of an MIP film in the form of an inverse opal. Thickness of the deposited polymer film is precisely controlled with the number of current oscillations during potentiostatic deposition of the imprinted poly(2,3′-bithiophene) film. Prior immobilization of HSA on the colloidal crystal allows formation of molecularly imprinted cavities exclusively on the internal surface of the pores. Furthermore, all binding sites are located on the surface of the imprinted cavities at locations corresponding to positions of functional groups present on the surface of HSA molecules due to prior derivatization of HSA molecules with appropriate functional monomers. This synergistic strategy results in a material with superior recognition performance. Integration of the MIP film as a recognition unit with a sensitive extended-gate field-effect transistor (EG-FET) transducer leads to highly selective HSA determination in the femtomolar concentration range.

Graphical abstract

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A fluorogenic probe for imaging protein S-nitrosylation in live cells

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Shiyi Shao, Bo Chen, Juan Cheng, Chengkun Wang, Yanli Zhang, Lingxiao Shao, Yongzhou Hu, Yifeng Han, Feng Han, Xin Li
S-nitrosylation is a posttranslational modification of protein cysteine residues leading to the formation of S-nitrosothiols and its detection is crucial to understanding of redox regulation and NO-based signaling. Prototypical detection methods for S-nitrosylation are always carried out ex situ. However, the reversible nature and the tendency of transnitrosylation highlight the necessity of its probing in intact live biological contexts. Herein we provide a fluorogenic chemical probe for the detection of S-nitrosylation in live endothelial cells. The probe is weakly emissive alone and becomes highly fluorescent only after undergoing a reaction with S-nitrosothiols in live cellular environments. This probe features high degrees of specificity and desirable sensitivity. Furthermore, it has been successfully applied to image the dynamic change of protein S-nitrosylation in live endothelial cells. The applicability of the probe in complex biological systems has been additionally verified by imaging a known target of S-nitrosylation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in live cells. Due to the versatility exemplified, this probe holds great promise for exploring the role of protein S-nitrosylation in the pathophysiological process of a variety of vascular diseases.

Graphical abstract

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Vulvar cancer in Tunisia: Epidemiological and clinicopathological features multicentric study

Publication date: Available online 8 March 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Mehdi Kehila, Souad Harabi, Raoudha Mhiri, Omar Touhami, Hassine Saber Abouda, Abdeljalil Khlifi, Mohamed Hsairi, Dalenda Chelli, Mohamed Derbel, Sahbi Kebaili, Nadia Boujelbane, Kais Chaabene, Mohamed Badis Chanoufi
ObjectiveTo describe for the first time the epidemiologic and clinico-pathologic characteristics of vulvar cancer in Tunisia.DesignTwo parts are distinguished in this study:Part1: Multicentric retrospective study about the characteristics of all cancer cases diagnosed during a 17-years period (January 1998–December 2014) in three departments of Gynecology and Obstetrics: one in south Tunisia and two in the capital.Part 2: To determine the Incidence trend of invasive vulvar cancer in North Tunisia 1994–2009, on the basis of North Cancer Registry of Tunisia.ResultsA total of 76 cases of vulvar cancer were recorded. The median age at diagnosis was 65.4years and 86.9% of patients were more than 55years old. The symptomatology was dominated by vulvar pruritus in 48.7%. The average size of the tumor was 3.96cm. Stage III was the most frequent (53.7%) followed by stage II (28.3%). Only 10.4% of tumors were at stage I. The most common histologic type of vulvar malignancy was squamous cell carcinoma (SCC) (94.7%).Standardized incidence varied from 1.2/100 000 (1994) to 0.5/100 000 (2009). There was significant decrease of Standardized incidence (APC of −8.8% per year, 95% CI: −5.5%, −9.0%–p<0.001).ConclusionVulvar cancer in Tunisia is a rare disease, occurs mostly in elderly women, and is diagnosed at advanced stages. Our findings emphasize that a greater effort should be made to facilitate early diagnosis, as treatment in earlier stages is less extensive and potentially curative.



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Ionotropic AMPA-type glutamate and metabotropic GABAB receptors: determining cellular physiology by proteomes

Publication date: August 2017
Source:Current Opinion in Neurobiology, Volume 45
Author(s): Bernhard Bettler, Bernd Fakler
Ionotropic AMPA-type glutamate receptors and G-protein-coupled metabotropic GABAB receptors are key elements of neurotransmission whose cellular functions are determined by their protein constituents. Over the past couple of years unbiased proteomic approaches identified comprehensive sets of protein building blocks of these two types of neurotransmitter receptors in the brain (termed receptor proteomes). This provided the opportunity to match receptor proteomes with receptor physiology and to study the structural organization, regulation and function of native receptor complexes in an unprecedented manner. In this review we discuss the principles of receptor architecture and regulation emerging from the functional characterization of the proteomes of AMPA and GABAB receptors. We also highlight progress in unraveling the role of unexpected protein components for receptor physiology.



http://ift.tt/2m0kA2i

Sculpting memory during sleep: concurrent consolidation and forgetting

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Gordon B Feld, Jan Born
There is compelling evidence that sleep actively supports the formation of long-lasting memory representations. Experimental cuing of memories proved that neural replay of representations during sleep plays a causal role for this consolidation, which has also been shown to promote neocortical synaptic plasticity and spine formation. Concurrently, sleep has been proposed to facilitate forgetting through processes of synaptic renormalisation. This view received indirect support by findings in humans of sleep enhancing TMS-evoked plasticity and capabilities for encoding new information. First direct behavioural evidence of sleep inducing forgetting has only recently emerged after encoding large amounts of stimuli in adults. We propose forgetting complements sleep-dependent consolidation and facilitates gist abstraction especially at high memory loads, when reactivation-based consolidation reaches capacity limits.

Graphical abstract

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Astrocytes and the modulation of sleep

Publication date: June 2017
Source:Current Opinion in Neurobiology, Volume 44
Author(s): Philip G Haydon
Astrocytes are being identified as having multiple roles in sleep. Initially they were shown to modulate the process of sleep homeostasis through the release of adenosine which acts on adenosine A1 receptors (A1R) to promote sleep drive. More recent studies indicate that the astrocyte also plays pivotal, sleep-dependent roles in 'cleaning the brain' during sleep. This work indicates that a glymphatic pathway that critically relies on astrocytic aquaporin 4, is able to flush solutes from the brain and that deficits in this pathway may contribute to Alzheimer's disease. Finally, astrocytes are known to play important metabolic roles and provide energy on demand to neurons through an astrocyte-neuron shuttle. Given that the time course of astrocytic function is orders of magnitude slower than that of the neuron, this non-neuronal cell is perfectly tuned to modulating slow, state-dependent changes in the brain.



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