Head and Neck Diseases by Alexandros G.Sfakianakis: 03/10/17

Παρασκευή 10 Μαρτίου 2017

Application of Ultrasound-guided Pigtail Catheter Drainage for Abscesses in the Head and Neck

Abstract

Abscesses in the head and neck are relatively common diseases with varied symptoms and severities. These abscesses are usually caused by upper respiratory infections, trauma, foreign bodies, postoperative infections, malignancies or dental infections.^1,2 The regions where abscesses can develop in the head and neck, include fascial planes and potential spaces such as submandibular, sublingual, submental, parapharyngeal, retropharyngeal, pretracheal, masticator or infratemporal areas.³

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City Noise Positively Correlates with Hearing Loss

It turns out where you live might determine whether you'll have hearing loss. A study conducted by the German company Mimi Hearing Technologies (http://ift.tt/2lluGPM) and Charité University Hospital in Berlin found hearing loss has a 64 percent positive correlation with noise pollution levels in a city. Researchers used data from 200,000 hearing tests conducted on Mimi's hearing test app in 50 cities worldwide to calculate the average hearing loss of each city, which was then used to assign each city a hearing loss rank and noise pollution rank. The two ranks were then combined to create the combined hearing loss index. Guangzhou, New Delhi, and Cairo topped the list, while Zurich, Oslo, and Vienna were found to be least afflicted by noise pollution.

These findings are preliminary and have yet to be submitted for peer-reviewed publication, according to an article about the study in The Nation. (Mar. 4, 2017; http://bit.ly/2lKWcq8.) But Henrik Matthies, managing director of Mimi Hearing Technologies, said these results are robust. "The fact that noise pollution and hearing loss have such a tight correlation points to an intricate relationship." Matthies told AFP. Mimi published these findings in celebration of this year's World Hearing Day. The complete results and more information about the study's methodology is available here.

Published: 3/10/2017 9:30:00 AM

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Application of Ultrasound-guided Pigtail Catheter Drainage for Abscesses in the Head and Neck

Abstract

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Issue Information - Contents

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Cover Image

The cover image, by Lian Zhou and Wenlong Luo, is based on the Original Article Vascular endothelial growth factor-targeted paclitaxel-loaded liposome microbubbles and inhibition of human epidermoid-2 cell proliferation, DOI: 10.1002/hed.24648.

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Issue Information - Contents

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Cover Image

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Construct validity—Current issues and recommendations for future hand hygiene research

Publication date: Available online 10 March 2017
Source:American Journal of Infection Control
Author(s): Jun Rong Jeffrey Neo
Health care–associated infection is a leading cause of morbidity and mortality. Hand hygiene is widely regarded as an effective prevention strategy. Often, hand hygiene research is designed and conducted by health care practitioners who may lack formal training in research methods, particularly in the area of social science. In a research context, a construct is a concept that can be measured or observed in some way. A construct can be directly or indirectly measured. For example, height can be directly measured by centimeters, whereas depression can be indirectly measured by a scale of 20 items. Every construct needs to be operationalized by measure(s) to make it a variable. Hence, construct validity refers to the degree of fit between the construct of interest and its operational measure. However, issues with construct validity often weaken the translation from construct to measure(s). This article will (1) describe the common threats to construct validity pertaining to hand hygiene research, (2) identify practical limitations in current research design, and (3) provide recommendations to improve construct validity in future hand hygiene research. By understanding how construct validity may affect hand hygiene research design, there is great potential to improve the validity of future hand hygiene research findings.

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Universal versus targeted additional contact precautions for multidrug-resistant organism carriage for patients admitted to an intensive care unit

Publication date: Available online 10 March 2017
Source:American Journal of Infection Control
Author(s): Michel Djibré, Samuel Fedun, Pierre Le Guen, Sophie Vimont, Mehdi Hafiani, Jean-Pierre Fulgencio, Antoine Parrot, Michel Denis, Muriel Fartoukh
BackgroundAlthough additional contact precautions (ACPs) are routinely used to reduce cross-transmission of multidrug-resistant organisms (MDROs), the relevance of isolation precautions remains debated. We hypothesized that the collection of recognized risk factors for MDRO carriage on intensive care unit (ICU) admission might be helpful to target ACPs without increasing MDRO acquisition during ICU stays, compared with universal ACPs.Materials and MethodsThis is a sequential single-center observational study performed in consecutive patients admitted to a French medical and surgical ICU. During the first 6-month period, screening for MDRO carriage and ACPs were performed in all patients. During the second 6-month period, screening was maintained, but ACP use was guided by the presence of at least 1 defined risk factor for MDRO.ResultsDuring both periods, 33 (10%) and 30 (10%) among 327 and 297 admissions were, respectively, associated with a positive admission MDRO carriage. During both periods, a second screening was performed in 147 (45%) and 127 (43%) patients. Altogether, the rate of acquired MDRO (positive screening or clinical specimen) was similar during both periods (10% [n = 15] and 11.8% [n = 15], respectively; P = .66).ConclusionsThe results of our study contribute to support the safety of an isolation-targeted screening policy on ICU admission compared with universal screening and isolation regarding the rate of ICU-acquired MDRO colonization or infection.

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Gestational diabetes mellitus: an updated overview

Abstract

The clinical and public health relevance of gestational diabetes mellitus (GDM) is widely debated due to its increasing incidence, the resulting negative economic impact, and the potential for severe GDM-related pregnancy complications. Also, effective prevention strategies in this area are still lacking, and controversies exist regarding diagnosis and management of this form of diabetes. Different diagnostic criteria are currently adopted worldwide, while recommendations for diet, physical activity, healthy weight, and use of oral hypoglycemic drugs are not always uniform. In the present review, we provide an update of current insights on clinical aspects of GDM, by discussing the more controversial issues.

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Contrast reaction training in US radiology residencies: a (BLINDED) study

Publication date: Available online 10 March 2017
Source:Clinical Imaging
Author(s): Christina A. LeBedis, Andrew B. Rosenkrantz, Hansel J. Otero, Summer J. Decker, Robert J. Ward
ObjectiveTo perform a survey-based assessment of current contrast reaction training in US diagnostic radiology residency programs.MethodsAn electronic survey was distributed to radiology residency program directors from 9/2015–11/2015.Results25.7% of programs responded. 95.7% of those who responded provide contrast reaction management training. 89.4% provide didactic lectures (occurring yearly in 71.4%). 37.8% provide hands-on simulation training (occurring yearly in 82.3%; attended by both faculty and trainees in 52.9%).ConclusionWide variability in contrast reaction education in US diagnostic radiology residency programs reveals an opportunity to develop and implement a national curriculum.

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Response to Tulchinsky and Avram re: “Long-Term Outcomes of Patients with Papillary Thyroid Cancer Undergoing Remnant Ablation with 30 Millicurie Radioiodine”

Thyroid , Vol. 0, No. 0.

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Response to Tulchinsky and Avram re: “Long-Term Outcomes of Patients with Papillary Thyroid Cancer Undergoing Remnant Ablation with 30 Millicurie Radioiodine”

Thyroid , Vol. 0, No. 0.

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Vaccine Development

Viral Immunology , Vol. 0, No. 0.

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Cell membrane integrity and revascularization: The possible functional mechanism of ischemic preconditioning for skeletal muscle protection against ischemic-reperfusion injury

Publication date: Available online 11 March 2017
Source:Acta Histochemica
Author(s): Yang Hong, Bin Zhang, Ling Yu, Shan-Shan Duan
BackgroundThe purpose of this paper was to evaluate whether ischemic preconditioning (IPC) could make protective effects against skeletal muscle injuries induced by ischemic-reperfusion (I/R).MethodsEighteen rats were randomly divided into three groups of 6 subjects each: control group, I/R group, and IPC group. Thigh root ischemia of rats in the I/R group was induced by 3h ischemia and 24h reperfusion. IPC was applied by 3 periods of 15min ischemia/15min reperfusion prior to ischemia. Morphological changes in skeletal muscle cells induced by I/R and IPC were observed by hematoxylin and eosin (HE) staining and electron microscopy. In addition, angiogenesis was evaluated by immunolabeling of CD31.ResultsIPC could prevented morphological alternations induced by ischemia, including myofilament, cell membrane, cell matrix, nucleus, mitochondria, and sarcoplasmic reticulum damage in skeletal muscle cells. The CD31 immunolabeling showed that neovascularization was observed in the IPC group but not in the I/R group. IPC could protect skeletal muscle cells from necrosis, apoptosis, and morphological damages induced by I/R injury.ConclusionRevascularization may play a key role in the mechanism underlying the protective effects of IPC in vivo.

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Skill-related physical fitness versus aerobic fitness as a predictor of executive functioning in children with intellectual disabilities or borderline intellectual functioning

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Esther Hartman, Joanne Smith, Suzanne Houwen, Chris Visscher
Children with intellectual disabilities (ID) or borderline intellectual disabilities (BIF) often demonstrate impairments in executive functioning (EF). Studies in typically developing children show that aerobic fitness (AF) is positively related with EF. Skill-related physical fitness (SF) might, however, be a stronger predictor of EF than AF, as cognitive challenges are inherent in application of these skills. In this study, AF and SF were examined simultaneously in relationship with domains of EF in children with ID or BIF. Seventy-three children (age range 8–11; 51 boys) with ID (IQ range 56–79) or BIF (IQ range 71–79) were measured annually over a period of 4 years on AF (20-m endurance shuttle run test) and SF (plate tapping and 10×5m run). EF was measured with the Stroop Color-Word test (inhibition), Trailmaking and Fluency test (cognitive flexibility), Self-ordered pointing task (working memory) and the Tower of London (planning). Multilevel models showed that SF was significantly associated with inhibition and both measures of cognitive flexibility, but in the same models no significant associations between AF and EF were found. In addition, age was significantly related to working memory and cognitive flexibility, favouring the older children. In children with ID or BIF, SF is of greater importance than AF in relationship with core domains of EF.

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Radical Dissection of Greater Palatine Artery and Dynamic Reconstruction of Cleft Palate

Background: Restoration of proper anatomy and physiology is an integral part of cleft palate repair. The senior author has devised a new technique of radical release of greater palatine vessels, which helps in achieving tension-free closure of palatal cleft. In addition, release and transposition of palatal muscles is performed without the use of operative microscope, resulting in improved palatal function. This technique is applicable to all types of clefts of the palate and can be performed on adult patients as well. Materials and Methods: This is a retrospective case series of cleft palate repairs performed over a period of 3 years. Single-stage repair with modified Bardach's technique for complete cleft palate and von Langenbeck's technique for incomplete cleft palate with radical release of greater palatine vessels and levator complex retropositioning was performed. The outcome measures were closure of palatal defect and speech production. A follow-up of at least 6 months was completed in each patient. Results: A total of 1568 patients were included in the study. Their age ranged from 9 months to 54 years. The overall fistula rate was 6.1%. Improvement of speech was observed even in adult patients. Conclusions: Radical release of greater palatine artery and levator complex transposition can dramatically improve results of cleft palate repair. This technique helps in dynamic reconstruction of cleft palate and can be effectively applied in all age groups.

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Unilateral Pterional Polycraniosynostosis Treated with Craniectomy and Helmet Therapy

Summary: Craniosynostosis is a condition in which one or more of the cranial sutures have fused prematurely, affecting the growth pattern and contours of the infant skull. The pterion is the junction of temporal, frontal, parietal, and sphenoid bones of the skull. We present a case of unilateral pterional craniosynostosis, which was treated with strip craniectomy and helmet therapy.

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Usefulness of self-report questionnaires for psychological assessment of patients with tinnitus and hyperacusis and patients' views of the questionnaires.

Usefulness of self-report questionnaires for psychological assessment of patients with tinnitus and hyperacusis and patients' views of the questionnaires.

Int J Audiol. 2017 Mar 09;:1-10

Authors: Aazh H, Moore BC

Abstract
OBJECTIVE: The objective was to determine the relevance and applicability of psychological questionnaires to patients seeking help for tinnitus and/or hyperacusis.
DESIGN: This was a questionnaire-based survey. The following questionnaires were administered: Generalised Anxiety Disorder (GAD-7), Short Health Anxiety Inventory (SHAI), Mini-Social Phobia Inventory (Mini-SPIN), Obsessive Compulsive Inventory-Revised (OCI-R), Panic Disorder Severity Scale-Self Report (PDSS-SR), Patient Health Questionnaire (PHQ-9) and Penn State Worry Questionnaire-Abbreviated version (PSWQ-A). In addition, a patient feedback questionnaire was completed asking about the extent to which each questionnaire was relevant to them and how strongly they would recommend its use in the assessment of patients with tinnitus and hyperacusis.
STUDY SAMPLE: A total of 150/402 consecutive patients seen in a one-year period completed the questionnaires.
RESULTS: 65% of patients had abnormal scores for one or more of the questionnaires. All questionnaires except the PDSS-SR were rated as relevant and recommended for use.
CONCLUSIONS: The GAD-7, SHAI, Mini-SPIN, OCI-R, PSWQ-A and PHQ-9 are recommended for evaluation of psychological problems for patients seeking help for tinnitus and/or hyperacusis. Abnormal results on these questionnaires may indicate the need for referral for possible treatment of psychological problems.

PMID: 28277857 [PubMed - as supplied by publisher]

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Dynamics of progesterone and estrogen receptor alpha in the ventromedial hypothalamus

Cyclic fluctuations of estradiol and progesterone in females influence neuronal activity in the ventrolateral division of the ventromedial hypothalamic nucleus (VMNvl), through the activation of progesterone (PRs) and estrogen receptors (ERs). The expression of ER and PR in the VMNvl is influenced by their cognate ligands and is a central upstream trigger in the pathway of VMNvl-dependent modulation of endocrine responses. By studying the role played by estradiol and progesterone in PR and ERα expression in the VMNvl along the estrous cycle and how the two receptors interact in the same neuron, we aim at evaluate the synergistic action both ovarian hormones in the regulation of VMNvl activity. It was estimated, along the estrous cycle, the number of VMN neurons expressing PR or ERα, by stereological methods, and it was determined the percentage, and rostro-caudal distribution, of neurons simultaneously expressing both receptors. The highest number of PR- immunoreactive neurons was seen at Proestrus and of ERα-immunoreactive neurons was seen at Proestrus and Metestrus. The ERα/ PR co-localization is increased at caudal levels. About half the neurons expressing PR co-express ERα, a proportion that stays constant along the estrous cycle. The percentage of ERα neurons co-expressing PR changes from 60% at Proestrus to 40% at Metestrus. Fluctuations in circulating ovarian hormone levels promote coordinated changes in PR and ERα expression and co-localization. This may be an important mechanism in the regulation of input relayed by the VMNvl, allowing a precise modulation of endocrine responses.

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Confined polymerization: ARGET ATRP of MMA in the nanopores of modified SBA-15

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Mingsen Chen, Hongwang Zhou, Li Zhou, Faai Zhang
Rod-like mesoporous SBA-15 silica particles were surface modified by different silane coupling agents firstly, then polymethyl methacrylate (PMMA) was prepared in the confined nanopores of the SBA-15 via activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP). The PMMA/SBA-15 nanocomposites and PMMAs inside the nanopores were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption measurements, gel permeation chromatography (GPC), fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), proton magnetic resonance (¹H NMR), and differential scanning calorimetry (DSC), respectively. The results demonstrated that the nanopores of SBA-15 could serve as nanoreactors and had great confinement effects on the MMA polymerization. The morphology of PMMAs obtained in the channels was similar to that of intrinsic structure of SBA-15. The thermal stability, molecular weights, isotacticity of PMMAs inside the pores were all increased significantly compared to the conventional PMMA by ARGET ATRP, while broadened the polydispersity index (PDI) values and reduced the syndiotacticity.

Graphical abstract

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Effect of compositions of acceptor polymers on dark current and photocurrent of all-polymer bulk-heterojunction photodetectors

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Liuyong Hu, Wenqiang Qiao, Xiaokang Zhou, Xiaoqin Zhang, Dongge Ma, Yuning Li, Zhi Yuan Wang
A series of electron-acceptor polymers, copolymers and blends were used in all-polymer BHJ photodetectors and the effect of acceptor compositions on the key device parameters of dark current density and photocurrent was investigated. Compared with acceptor polymers and polymer blends, the devices based on acceptor copolymer showed lowered dark current and higher photocurrent, due to optimal molecular stacking and morphology of the BHJ active layer. The acceptor blends tend to cause a large phase separation and rough surface of the active layer, thus leading to a low detectivity of the device. Among all the acceptor compositions studied in this work, the all-polymer BHJ photodetector based on a donor polymer (PolyD) and an acceptor copolymer (PolyAA′50) exhibited the highest specific detectivity of over 10¹² Jones in the spectral region of 320–980 nm under −0.1 V bias.

Graphical abstract

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Synergistic dielectric and semiconducting properties in fluorescein monopotassium salt random copolymers

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Zhongqiang Zhao, Zhongbo Zhang, Sandra Pejić, Guoqiang Zhang, Yufeng Zhu, Hewen Liu, Morton Litt, Genevieve Sauve, Lei Zhu
The low dielectric constant (εr ∼ 3–4) for semiconducting polymers has been a major cause for their poor performance compared with the inorganic semiconductors, which possess high dielectric constants above 10. This study aimed to increase the electronic/atomic dielectric constant at high frequencies (i.e., εr∞) for semiconducting polymers. A new design strategy was proposed based on the electric field-induced tautomeric structures in conjugated fluorescein. To achieve this goal, fluorescein monopotassium salt-containing random copolymers were synthesized with 50 and 75 mol.% functionality. To reduce the strong electrostatic attraction between the K⁺ cation and the phenolate anion, 18-crown-6 ether was complexed with K⁺ in the fluorescein copolymers. A relatively high εr∞ of ∼5.5 and high electron mobility of 0.153 cm²/(V·s) were achieved for the 75 mol.% fluorescein K⁺/18C6 copolymer. The high electron mobility could be attributed to the relatively high static dielectric constant (εrs ∼ 9 at 1 Hz) of the sample. The fluorescein monopotassium salt copolymers behaved as n-type semiconductors with an optical band gap around 2.26 eV.

Graphical abstract

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Organogelation of self-assembling segmented poly(urethane acylsemicarbazides) and their dye adsorbing properties

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Sravan Baddi, Rati Ranjan Nayak, Aruna Palanisamy
Segmented poly(urethane acylsemicarbazides) carrying aromatic groups in the hard segments were synthesized by two step polymerization technique using commercially available, cost effective raw materials. The resulting polymers with specific ratios of NCO/OH were found to gel organic solvents like dimethylformamide, dimethylacetamide and N-methylpyrrolidone and their corresponding gels were thermoreversible. Tuning of the gelation behaviour and gel properties have been achieved by varying the polyol molecular weight (polypropylene glycol - 1000 and 2000) and NCO/OH ratio. Influence of hard segment content on the gel-sol transition as studied by DSC showed that increasing hard segment content led to stronger gelator-gelator interactions and hence higher Tgel. Broad tanδ peaks of films of xerogels reflected a network kind of structure due to physical crosslinks in the self-assembled state in DMA analysis. The films of xerogels of PPG1000 based gelators exhibited higher tensile strength but lower elongation compared to PPG2000 based gelators. Viscoelastic nature of the supramolecular elastomeric gels was confirmed by dynamic oscillatory studies and stability of the gel was found to increase with increase in hard segment content. H-bonding between the urethane moieties as confirmed by IR spectroscopy and hydrophobic interactions between the PPG units in the soft segments lead to a phase separated structure. Hence phase separation induced gelation mechanism has been proposed and supported by SEM images and XRD data. Both the gelators and xerogels had capability of adsorbing crystal violet from their aqueous solutions and desorbing in organic solvents like acetone and methanol.

Graphical abstract

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Effect of transfer agent, temperature and initial monomer concentration on branching in poly(acrylic acid): A study by 13C NMR spectroscopy and capillary electrophoresis

Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Jean-Baptiste Lena, Alexander K. Goroncy, Joel J. Thevarajah, Alison R. Maniego, Gregory T. Russell, Patrice Castignolles, Marianne Gaborieau
Branching has been investigated in poly(acrylic acid) synthesized by conventional radical polymerization with and without chain transfer agent (CTA) at different temperatures and initial monomer concentrations. The average number of branches per monomer unit (i.e. degree of branching) was quantified by solution-state ¹³C NMR spectroscopy. The heterogeneity of branching (dispersity of the electrophoretic mobility distributions) was measured by capillary electrophoresis in the critical conditions (CE-CC). The degree of branching (DB) increases with the reaction temperature due to a rise in the frequency of reactions leading to branches, while the heterogeneity of branching remains steady. DB is lower in polymer synthesized with CTA. This decrease is due to either the CTA quenching the mid-chain radicals or a reduction of the rate of chain transfer to polymer relative to (chain-end) propagation. No influence of initial monomer concentration on DB and on the heterogeneity of branching was observed.

Graphical abstract

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Corrigendum to “Is meditation always relaxing? Investigating heart rate, heart rate variability, experienced effort and likeability during training of three types of meditation” [Int. J. Psychophysiol. 97/1 (2015) 38–45]

Publication date: Available online 10 March 2017
Source:International Journal of Psychophysiology
Author(s): Anna-Lena Lumma, Bethany E. Kok, Tania Singer

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The relationship of approach/avoidance motivation and asymmetric frontal cortical activity: A review of studies manipulating frontal asymmetry

Publication date: Available online 10 March 2017
Source:International Journal of Psychophysiology
Author(s): Nicholas J. Kelley, Ruud Hortensius, Dennis J.L.G Schutter, Eddie Harmon-Jones
The balance between activity in the left and right frontal cortex, commonly referred to as asymmetric frontal cortical activity, has served as a proxy for an organism's motivational direction (i.e., approach vs. avoidance). Many studies have examined the influence of the manipulation of motivational direction on asymmetrical frontal cortical activity and found results consistent with the idea that greater relative left (right) frontal cortical activity is associated with approach (avoidance) motivation. We critically review literature employing physical (versus psychological) manipulations of frontal asymmetry using a variety of methodologies including neurofeedback training, muscular contractions, and non-invasive brain stimulation. These reviewed methods allow us to make stronger causal inferences regarding the role of asymmetric frontal cortical activity in approach and avoidance motivation.

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The Incidence and Health Care Resource Burden of the Myelodysplastic Syndromes in Patients in Whom First-Line Hypomethylating Agents Fail

Background.

Although hypomethylating agents (HMAs) are effective and approved therapies for patients with myelodysplastic syndromes (MDS), many patients do not benefit from treatment, and nearly all ultimately stop responding to HMAs. The incidence and cost burden of HMA failure are unknown yet needed to appreciate the magnitude and significance of such failure.

Methods.

We analyzed a de-identified dataset of over 5 million individuals with private health insurance in the U.S. to estimate MDS incidence, prevalence, and treatments. Based on MDS provider interviews, a conceptual model of MDS patient management was constructed to create a new, claims-relevant and drug development-relevant definition of HMA treatment failure. This algorithm was used to define resource encumbrance of MDS patients in whom HMA treatment failed.

Results.

We estimated an MDS incidence rate of ~70 cases per 100,000 enrollees per year and a prevalence of 155 cases per 100,000 enrollees. The proportion of MDS patients receiving HMA treatment was low (~3%), and treatment was typically initiated within 1 year of the first MDS claim. Notably, HMA-treated individuals were older and had more comorbidities than the overall MDS cohort. Total health care costs of managing MDS patients after HMA failure were high (~$77,000 during the first 6 months) and were driven primarily by non-pharmacy costs.

Conclusion.

This study quantifies for the first time the burden of significant unmet need in caring for MDS patients following HMA treatment failure. The Oncologist 2017;22:1–7

Implications for Practice: U.S.-based treatment patterns among MDS patients demonstrate the significant clinical, financial, and health care burden associated with HMA failure and call for active therapies for this patient population.

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Clinical Benefit in Response to Palbociclib Treatment in Refractory Uterine Leiomyosarcomas with a Common CDKN2A Alteration

Background.

Uterine leiomyosarcoma (uLMS) responds poorly to conventional chemotherapeutic agents, and personalized therapies have yet to be systematically explored. Comprehensive genomic profiling (CGP) can identify therapeutic targets and provide insight into the biology of this highly aggressive tumor. We report a case of uLMS treated with the CGP-matched therapy palbociclib, a CDK4/6 inhibitor, with sustained clinical benefit in this rare and deadly malignancy.

Materials and Methods.

This study analyzed 279 clinically advanced/recurrent uLMS samples. Median patient age was 54 years (range, 23–83 years). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections, and CGP was performed on hybridization-captured, adaptor ligation-based libraries for up to 405 cancer-related genes plus introns from up to 31 genes frequently rearranged in cancer. Sequencing data were analyzed for base pair substitutions, insertions/deletions, copy number alterations, and rearrangements.

Results.

CGP shows that 97.1% of uLMS harbor at least one alteration, and approximately 57% harbor alterations in one or more therapeutically targetable pathways. CDKN2A mutations that inactivate p16INK4a were identified in 11% of uLMS. We report the first demonstration of clinical benefit in response to palbociclib treatment for a uLMS patient with a CDKN2A mutation, resulting in disease stabilization and significant symptom reduction.

Conclusion.

A patient with uLMS harboring a CDKN2A mutation experienced clinical benefit from treatment with palbociclib, and genomic analysis of 279 uLMS samples revealed that 19% of patients had mutations affecting the cyclin-dependent kinase (CDK) pathway. These observations provide a rationale for a clinical trial investigating treatment with CDK pathway inhibitors for uLMS harboring relevant genomic alterations. The Oncologist 2017;22:1–6

Implications for Practice: Comprehensive genomic profiling (CGP) of individuals with uterine leiomyosarcoma (uLMS) indicates that nearly 20% of patients may harbor a mutation affecting the cyclin-dependent kinase (CDK) pathway. The case presented demonstrates that a CDK inhibitory drug may provide clinical benefit to such individuals. Given the lack of curative therapies for uLMS, CGP could be performed on all cases of advanced uLMS and a CDK inhibitor could be recommended (preferably as part of a clinical trial) for individuals harboring a mutation in the CDK pathway.

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Sucralose Suppresses Food Intake

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Jin Hong Park, Gil B. Carvalho, Keith R. Murphy, Margaux R. Ehrlich, William W. Ja

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Precision Metabolism: Hitting the Mark

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Rosalind Mott, Anne Granger, Taneli Helenius, Nikla Emambokus

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Feeding the Genome: In Silico Optimization of Dietary Amino Acid Composition

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Michael R. MacArthur, James R. Mitchell
Optimizing dietary amino acid ratios to achieve maximal growth and reproduction has historically required tedious empirical studies. In this issue, Piper et al. (2017) present an in silico method of essential amino acid optimization based on the translated portion of an organism's genome, or exome.

Teaser

Optimizing dietary amino acid ratios to achieve maximal growth and reproduction has historically required tedious empirical studies. In this issue, Piper et al. present an in silico method of essential amino acid optimization based on the translated portion of an organism's genome, or exome.

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Integrative Physiology: At the Crossroads of Nutrition, Microbiota, Animal Physiology, and Human Health

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): François Leulier, Lesley T. MacNeil, Won-jae Lee, John F. Rawls, Patrice D. Cani, Martin Schwarzer, Liping Zhao, Stephen J. Simpson
Nutrition is paramount in shaping all aspects of animal biology. In addition, the influence of the intestinal microbiota on physiology is now widely recognized. Given that diet also shapes the intestinal microbiota, this raises the question of how the nutritional environment and microbial assemblages together influence animal physiology. This research field constitutes a new frontier in the field of organismal biology that needs to be addressed. Here we review recent studies using animal models and humans and propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health. Nutritional Geometry sits centrally in the proposed framework and offers means to define diet compositions that are optimal for individuals and populations.

Teaser

How the nutritional environment and microbial assemblages together influence our physiology is a frontier in the field of organismal biology that needs to be addressed. Leulier et al. propose an integrative framework within which to define the study of the diet-physiology-microbiota systems and ultimately link it to human health.

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Beyond Digestion: The Pancreas Shapes Intestinal Microbiota and Immunity

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Herbert Tilg, Timon E. Adolph
Our understanding of the regulatory mechanisms that shape the gut microbiota is rapidly emerging. The intestinal microbial landscape is modulated by a plethora of host-extrinsic and host-intrinsic factors. In this issue of Cell Metabolism, Ahuja and colleagues (2017) demonstrate that mediators secreted by pancreatic acini shape the intestinal microbiota and intestinal immunity.

Teaser

Our understanding of the regulatory mechanisms that shape the gut microbiota is rapidly emerging. The intestinal microbial landscape is modulated by a plethora of host-extrinsic and host-intrinsic factors. In this issue of Cell Metabolism, Ahuja and colleagues demonstrate that mediators secreted by pancreatic acini shape the intestinal microbiota and intestinal immunity.

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Matching Dietary Amino Acid Balance to the In Silico-Translated Exome Optimizes Growth and Reproduction without Cost to Lifespan

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Matthew D.W. Piper, George A. Soultoukis, Eric Blanc, Andrea Mesaros, Samantha L. Herbert, Paula Juricic, Xiaoli He, Ilian Atanassov, Hanna Salmonowicz, Mingyao Yang, Stephen J. Simpson, Carlos Ribeiro, Linda Partridge
Balancing the quantity and quality of dietary protein relative to other nutrients is a key determinant of evolutionary fitness. A theoretical framework for defining a balanced diet would both reduce the enormous workload to optimize diets empirically and represent a breakthrough toward tailoring diets to the needs of consumers. Here, we report a simple and powerful in silico technique that uses the genome information of an organism to define its dietary amino acid requirements. We show for the fruit fly Drosophila melanogaster that such "exome-matched" diets are more satiating, enhance growth, and increase reproduction relative to non-matched diets. Thus, early life fitness traits can be enhanced at low levels of dietary amino acids that do not impose a cost to lifespan. Exome matching also enhanced mouse growth, indicating that it can be applied to other organisms whose genome sequence is known.

Graphical abstract

Teaser

Dietary protein is a critical determinant of health, but the empirical determination of optimal amino acid ratios is challenging. Piper et al. show that a consumer's genome provides a template for optimal dietary amino acid proportions. Low amounts of optimized protein are simultaneously beneficial for appetite, growth, reproduction, and lifespan.

http://ift.tt/2mS5m3R

Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Matthew M. Robinson, Surendra Dasari, Adam R. Konopka, Matthew L. Johnson, S. Manjunatha, Raul Ruiz Esponda, Rickey E. Carter, Ian R. Lanza, K. Sreekumaran Nair
The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.

Graphical abstract

Teaser

Robinson et al. assessed the effects of three different exercise modalities on skeletal muscle adaptations in young and older adults. While all enhanced insulin sensitivity, only HIIT and combined training improved aerobic capacity, associated with enhanced translation of mitochondrial proteins. HIIT effectively improved cardio-metabolic health parameters in aging adults.

http://ift.tt/2mSa8i1

Systems Biology of Metabolism: A Driver for Developing Personalized and Precision Medicine

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Jens Nielsen
Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine for advancing the development of personalized and precision medicine to treat metabolic diseases like insulin resistance, obesity, NAFLD, NASH, and cancer. It will be illustrated how the concept of genome-scale metabolic models can be used for integrative analysis of big data with the objective of identifying novel biomarkers that are foundational for personalized and precision medicine.

Teaser

The advancement of personalized medicine is hindered by a lack of good prognostic biomarkers. Here Nielsen discusses how integrative analysis of big data using genome-scale metabolic models can advance the development of personalized and precision medicine to treat metabolic diseases like insulin resistance, obesity, NAFLD, NASH, and cancer.

http://ift.tt/2maF3kR

Ceramide Is Metabolized to Acylceramide and Stored in Lipid Droplets

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Can E. Senkal, Mohamed F. Salama, Ashley J. Snider, Janet J. Allopenna, Nadia A. Rana, Antonius Koller, Yusuf A. Hannun, Lina M. Obeid
In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets. In summary, this study identifies a metabolic pathway of acylceramide generation and its sequestration in LDs in cells and in livers of mice on a high-fat diet. The study also implicates this pathway in ceramide-mediated apoptosis, and has implications in co-regulation of triglyceride and sphingolipid metabolisms.

Graphical abstract

Teaser

Senkal et al. identify a pathway whereby ceramide is converted to acylceramides by a CerS-ACSL-DGAT complex in lipid droplets for storage. These results raise interesting questions as to the metabolic interplay of TG/DAG and ceramide/acylceramide and the roles of ACSL5 and CerS in regulating these balances.

http://ift.tt/2mS67Kq

Should I Stay or Should I Go: A Clash of α-Cell Identity

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Maria S. Remedi
Understanding mechanisms for maintaining pancreatic islet cell fate and function is important for addressing the urgent challenge of restoring islet β- and α-cell function in T1DM. In this issue of Cell Metabolism, Chakravarthy et al. (2017) identify a genetic mechanism by which mouse β-cells are spontaneously regenerated from adult α-cells.

Teaser

Understanding mechanisms for maintaining pancreatic islet cell fate and function is important for addressing the urgent challenge of restoring islet β- and α-cell function in T1DM. In this issue of Cell Metabolism, Chakravarthy et al. (2017) identify a genetic mechanism by which mouse β-cells are spontaneously regenerated from adult α-cells.

http://ift.tt/2matxGs

Dietary Fat Inflames CD4+ T Cell Memory in Obesity

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Nicole M. Chapman, Hongbo Chi
T cells promote inflammation in obesity, but how metabolic stress associated with obesity alters T cell responses remains unclear. In this issue of Cell Metabolism,Mauro et al. (2017) demonstrate that saturated fatty acids directly increase effector-memory T cell formation by amplifying T cell antigen-receptor-induced PI3K/Akt signaling.

Teaser

T cells promote inflammation in obesity, but how metabolic stress associated with obesity alters T cell responses remains unclear. In this issue of Cell Metabolism, Mauro et al. (2017) demonstrate that saturated fatty acids directly increase effector-memory T cell formation by amplifying T cell antigen-receptor-induced PI3K/Akt signaling.

http://ift.tt/2mScNrU

Insulin Signaling Regulates the FoxM1/PLK1/CENP-A Pathway to Promote Adaptive Pancreatic β Cell Proliferation

Publication date: Available online 9 March 2017
Source:Cell Metabolism
Author(s): Jun Shirakawa, Megan Fernandez, Tomozumi Takatani, Abdelfattah El Ouaamari, Prapaporn Jungtrakoon, Erin R. Okawa, Wei Zhang, Peng Yi, Alessandro Doria, Rohit N. Kulkarni
Investigation of cell-cycle kinetics in mammalian pancreatic β cells has mostly focused on transition from the quiescent (G0) to G1 phase. Here, we report that centromere protein A (CENP-A), which is required for chromosome segregation during the M-phase, is necessary for adaptive β cell proliferation. Receptor-mediated insulin signaling promotes DNA-binding activity of FoxM1 to regulate expression of CENP-A and polo-like kinase-1 (PLK1) by modulating cyclin-dependent kinase-1/2. CENP-A deposition at the centromere is augmented by PLK1 to promote mitosis, while knocking down CENP-A limits β cell proliferation and survival. CENP-A deficiency in β cells leads to impaired adaptive proliferation in response to pregnancy, acute and chronic insulin resistance, and aging in mice. Insulin-stimulated CENP-A/PLK1 protein expression is blunted in islets from patients with type 2 diabetes. These data implicate the insulin-FoxM1/PLK1/CENP-A pathway-regulated mitotic cell-cycle progression as an essential component in the β cell adaptation to delay and/or prevent progression to diabetes.

Graphical abstract

Teaser

Adaptive β cell proliferation contributes to maintenance of functional β cell mass in mouse and man. Shirakawa et al. reveal that growth factor signaling regulates mitotic cell-cycle progression through the FoxM1/PLK1/CENP-A pathway, a critical component in the β cell adaptive response.

http://ift.tt/2matz12

Forecasting Fat Fibrosis

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Brett Shook, Matthew S. Rodeheffer
Excess ECM and fibrosis of white adipose tissue (WAT) is associated with tissue dysfunction and type 2 diabetes. In this issue of Cell Metabolism, Marcelin et al. (2017) elucidate a key mechanism behind WAT fibrosis in which the activation of PDGFRα on adipocyte precursors drives this population toward a fibrotic phenotype.

Teaser

Excess ECM and fibrosis of white adipose tissue (WAT) is associated with tissue dysfunction and type 2 diabetes. In this issue of Cell Metabolism, Marcelin et al. (2017) elucidate a key mechanism behind WAT fibrosis in which the activation of PDGFRα on adipocyte precursors drives this population toward a fibrotic phenotype.

http://ift.tt/2maF745

Lip Sync: Gamma Rhythms Orchestrate Top-Down Control of Feeding Circuits

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Nandakumar S. Narayanan, Ralph J. DiLeone
Feeding involves the coordinated action of networks across many brain regions. New work recently published in Nature indicates that the prefrontal cortex, septum, and lateral hypothalamus circuits synchronize at gamma rhythms (30–90 Hz) to regulate feeding-related behaviors (Carus-Cadavieco et al., 2017).

Teaser

Feeding involves the coordinated action of networks across many brain regions. New work recently published in Nature indicates that the prefrontal cortex, septum, and lateral hypothalamus circuits synchronize at gamma rhythms (30–90 Hz) to regulate feeding-related behaviors (Carus-Cadavieco et al.).

http://ift.tt/2mazYZS

The Role of the Immune System in Metabolic Health and Disease

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Niv Zmora, Stavros Bashiardes, Maayan Levy, Eran Elinav
In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome. Regulators of immune-metabolic interactions include host genetics, nutritional status, and the intestinal microbiome. In this Perspective, we highlight current understanding of immune-metabolism interactions, illustrate differences among individuals and between populations in this respect, and point toward future avenues of research possibly enabling immune harnessing as means of personalized treatment for common metabolic disorders.

Teaser

The immune and metabolic systems intertwine to govern crucial physiological and pathological processes throughout the life of an organism. Zmora et al. delineate the role of individual endogenous and exogenous factors in shaping immune-metabolic interactions in homeostasis and disease settings and suggest that personally tailored immune targeted approaches may tackle metabolic disorders.

http://ift.tt/2mS2hAN

Predicting Polygenic Obesity Using Genetic Information

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Ruth J.F. Loos, A. Cecile J.W. Janssens
Except in rare cases, obesity tends to be a consequence of both an unhealthy lifestyle and a genetic susceptibility to gain weight. With more than 200 common genetic variants identified, there is a growing interest in developing personalized preventive and treatment strategies to predict an individual's obesity risk. We review the literature on the prediction of obesity and show that models based on the established genetic variants have poorer predictive ability than traditional predictors, such as family history of obesity and childhood obesity. Current findings suggest that opportunities for precision medicine in common obesity may be limited.

Teaser

There is a growing interest in using genetic information to predict people's risk of obesity. In this review, Loos and Janssens show that prediction of polygenic obesity based on genetic variants is poor, whereas family history of obesity, childhood obesity, and other traditional risk factors are better predictors.

http://ift.tt/2mS5mkm

Metabolic Inputs into the Epigenome

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Upasna Sharma, Oliver J. Rando
A number of molecular pathways play key roles in transmitting information in addition to the genomic sequence—epigenetic information—from one generation to the next. However, so-called epigenetic marks also impact an enormous variety of physiological processes, even under circumstances that do not result in heritable consequences. Perhaps inevitably, the epigenetic regulatory machinery is highly responsive to metabolic cues, as, for example, central metabolites are the substrates for the enzymes that catalyze the deposition of covalent modifications on histones, DNA, and RNA. Interestingly, in addition to the effects that metabolites exert over biological regulation in somatic cells, over the past decade multiple studies have shown that ancestral nutrition can alter the metabolic phenotype of offspring, raising the question of how metabolism regulates the epigenome of germ cells. Here, we review the widespread links between metabolism and epigenetic modifications, both in somatic cells and in the germline.

Teaser

In this Perspective, Sharma and Rando discuss the wide variety of key roles that metabolites play in regulation of the epigenome, focusing first on mitotic epigenetic inheritance before exploring the less-understood role of epigenetic information in the germline.

http://ift.tt/2mawXJc

Epigenetic Mechanisms of Transmission of Metabolic Disease across Generations

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Vicencia Micheline Sales, Anne C. Ferguson-Smith, Mary-Elizabeth Patti
Both human and animal studies indicate that environmental exposures experienced during early life can robustly influence risk for adult disease. Moreover, environmental exposures experienced by parents during either intrauterine or postnatal life can also influence the health of their offspring, thus initiating a cycle of disease risk across generations. In this Perspective, we focus on epigenetic mechanisms in germ cells, including DNA methylation, histone modification, and non-coding RNAs, which collectively may provide a non-genetic molecular legacy of prior environmental exposures and influence transcriptional regulation, developmental trajectories, and adult disease risk in offspring.

Teaser

Sales et al. provide perspective on how environmental exposures, particularly those experienced during intrauterine life, can influence metabolic disease risk in adulthood. Moreover, both early-life exposures and metabolic disease in adult parents can modulate epigenetic regulation in germ cells, thus providing a non-genetic molecular legacy to influence the health of subsequent generations.

http://ift.tt/2mSfnOB

Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity

Publication date: 7 March 2017
Source:Cell Metabolism, Volume 25, Issue 3
Author(s): Malini Ahuja, Daniella M. Schwartz, Mayank Tandon, Aran Son, Mei Zeng, William Swaim, Michael Eckhaus, Victoria Hoffman, Yiyuan Cui, Bo Xiao, Paul F. Worley, Shmuel Muallem
The gut microbiome participates in numerous physiologic functions and communicates intimately with the host immune system. Antimicrobial peptides are critical components of intestinal innate immunity. We report a prominent role for antimicrobials secreted by pancreatic acini in shaping the gut microbiome that is essential for intestinal innate immunity, barrier function, and survival. Deletion of the Ca²⁺ channel Orai1 in pancreatic acini of adult mice resulted in 60%–70% mortality within 3 weeks. Despite robust activation of the intestinal innate immune response, mice lacking acinar Orai1 exhibited intestinal bacterial outgrowth and dysbiosis, ultimately causing systemic translocation, inflammation, and death. While digestive enzyme supplementation was ineffective, treatments constraining bacterial outgrowth (purified liquid diet, broad-spectrum antibiotics) rescued survival, feeding, and weight gain. Pancreatic levels of cathelicidin-related antimicrobial peptide (CRAMP) were reduced, and supplement of synthetic CRAMP prevented intestinal disease. These findings reveal a critical role for antimicrobial pancreatic secretion in gut innate immunity.

Graphical abstract

Teaser

While gut innate immunity is thought to be primarily maintained by intestinal epithelial cells, Ahuja et al. show that secretion of antimicrobials from pancreatic acinar cells regulates gut microbiota composition and innate immunity. Blocking acinar cell exocytosis in mice leads to gut dysbiosis, inflammation, systemic bacterial translocation, and ultimately death.

http://ift.tt/2mS5lNl

Islet encapsulation with polyphenol coatings decreases pro-inflammatory chemokine synthesis and T cell trafficking

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Dana Pham-Hua, Lindsey E. Padgett, Bing Xue, Brian Anderson, Michael Zeiger, Jessie M. Barra, Maigen Bethea, Chad S. Hunter, Veronika Kozlovskaya, Eugenia Kharlampieva, Hubert M. Tse
Type 1 Diabetes (T1D) is a chronic pro-inflammatory autoimmune disease consisting of islet-infiltrating leukocytes involved in pancreatic β-cell lysis. One promising treatment for T1D is islet transplantation; however, clinical application is constrained due to limited islet availability, adverse effects of immunosuppressants, and declining graft survival. Islet encapsulation may provide an immunoprotective barrier to preserve islet function and prevent immune-mediated rejection after transplantation. We previously demonstrated that a novel cytoprotective nanothin multilayer coating for islet encapsulation consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), was efficacious in dampening in vitro immune responses involved in transplant rejection and preserving in vitro islet function. However, the ability of (PVPON/TA) to maintain islet function in vivo and reverse diabetes has not been tested. Recent evidence has demonstrated that modulation of redox status can affect pro-inflammatory immune responses. Therefore, we hypothesized that transplanted (PVPON/TA)-encapsulated islets can restore euglycemia to diabetic mice and provide an immunoprotective barrier. Our results demonstrate that (PVPON/TA) nanothin coatings can significantly decrease in vitro chemokine synthesis and diabetogenic T cell migration. Importantly, (PVPON/TA)-encapsulated islets restored euglycemia after transplantation into diabetic mice. Our results demonstrate that (PVPON/TA)-encapsulated islets may suppress immune responses and enhance islet allograft acceptance in patients with T1D.

http://ift.tt/2mHapnh

Exploration of the metal coordination region of concanavalin A for its interaction with human norovirus

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Duwoon Kim, Hee-Min Lee, Kyung-Seo Oh, Ah Young Ki, Rachael A. Protzman, Dongkyun Kim, Jong-Soon Choi, Min Ji Kim, Sung Hyun Kim, Bipin Vaidya, Seung Jae Lee, Joseph Kwon
Rapid methods for the detection and clinical treatment of human norovirus (HuNoV) are needed to control foodborne disease outbreaks, but reliable techniques that are fast and sensitive enough to detect small amounts of HuNoV in food and aquatic environments are not yet available. We explore the interactions between HuNoV and concanavalin A (Con A), which could facilitate the development of a sensitive detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange (HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine alanine residues (mCon A^MCR), the affinity for HuNoV (GII.4) diminishes, demonstrating that this Ca²⁺ and Mn²⁺ coordinated region is responsible for the observed virus-protein interaction. The mutated carbohydrate binding region of Con A (mCon A^CBR) does not affect binding affinity significantly, indicating that MCR of Con A is a major region of interaction to HuNoV (GII.4). The results further contribute to the development of a HuNoV concentration tool, Con A-immobilized polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I and II (GI and GII). This method offers many advantages over currently available methods, including a short concentration time. HuNov (GI and GII) can be detected in just 15 min with 90% recovery through Con A-PAB application. In addition, this method can be used over a wide range of pH values (pH 3.0 – 10.0). Overall, this rapid and sensitive detection of HuNoV (GI and GII) will aid in the prevention of virus transmission pathways, and the method developed here may have applicability for other foodborne viral infections.

http://ift.tt/2mRZEiA

A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Yuli Wang, Dulan B. Gunasekara, Mark I. Reed, Matthew DiSalvo, Scott J. Bultman, Christopher E. Sims, Scott T. Magness, Nancy L. Allbritton
The human small intestinal epithelium possesses a distinct crypt-villus architecture and tissue polarity in which proliferative cells reside inside crypts while differentiated cells are localized to the villi. Indirect evidence has shown that the processes of differentiation and migration are driven in part by biochemical gradients of factors that specify the polarity of these cellular compartments; however, direct evidence for gradient-driven patterning of this in vivo architecture has been hampered by limitations of the in vitro systems available. Enteroid cultures are a powerful in vitro system; nevertheless, these spheroidal structures fail to replicate the architecture and lineage compartmentalization found in vivo, and are not easily subjected to gradients of growth factors. In the current work, we report the development of a micropatterned collagen scaffold with suitable extracellular matrix and stiffness to generate an in vitro self-renewing human small intestinal epithelium that replicates key features of the in vivo small intestine: a crypt-villus architecture with appropriate cell-lineage compartmentalization and an open and accessible luminal surface. Chemical gradients applied to the crypt-villus axis promoted the creation of a stem/progenitor-cell zone and supported cell migration along the crypt-villus axis. This new approach combining microengineered scaffolds, biophysical cues and chemical gradients to control the intestinal epithelium ex vivo can serve as a physiologically relevant mimic of the human small intestinal epithelium, and is broadly applicable to model other tissues that rely on gradients for physiological function.

Graphical abstract

http://ift.tt/2mRGLwb

Perivascular medical devices and drug delivery systems: Making the right choices

Publication date: June 2017
Source:Biomaterials, Volume 128
Author(s): Ioanna Mylonaki, Éric Allémann, François Saucy, Jacques-Antoine Haefliger, Florence Delie, Olivier Jordan
Perivascular medical devices and perivascular drug delivery systems are conceived for local application around a blood vessel during open vascular surgery. These systems provide mechanical support and/or pharmacological activity for the prevention of intimal hyperplasia following vessel injury. Despite abundant reports in the literature and numerous clinical trials, no efficient perivascular treatment is available. In this review, the existing perivascular medical devices and perivascular drug delivery systems, such as polymeric gels, meshes, sheaths, wraps, matrices, and metal meshes, are jointly evaluated. The key criteria for the design of an ideal perivascular system are identified. Perivascular treatments should have mechanical specifications that ensure system localization, prolonged retention and adequate vascular constriction. From the data gathered, it appears that a drug is necessary to increase the efficacy of these systems. As such, the release kinetics of pharmacological agents should match the development of the pathology. A successful perivascular system must combine these optimized pharmacological and mechanical properties to be efficient.

Graphical abstract

http://ift.tt/2margLl

Hepatic transcriptomic responses in mice exposed to arsenic and different fat diet

Abstract

Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, effects of HFD on risk assessment of iAs in drinking water are unclear. In this study, we examined how HFD and iAs interact to alter iAs-induced liver injury in C57BL/6 mice. Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Results showed that HFD changed intake and excretion of iAs by mice. Then, HFD increased the amount of iAs-induced hepatic DNA damage and amplified changes in pathways related to cell death and growth, signal transduction, lipid metabolism, and insulin signaling. Compared to gene expression profiles caused by iAs alone or HFD alone, insulin signaling pathway might play important roles in the interactive effects of iAs and HFD. Our data suggest that HFD increases sensitivity of mice to iAs in drinking water, resulting in increased hepatotoxicity. This study highlight that HFD might enhance the risk of iAs hepatotoxicity in iAs-polluted regions. The diet should be considered during risk assessment of iAs in drinking water.

http://ift.tt/2noQ9Ed

Early metal pollution in southwestern Europe: the former littoral lagoon of El Almarjal (Cartagena mining district, S.E. Spain).A sedimentary archive more than 8000 years old

Abstract

A borehole drilling campaign has allowed the study of a former littoral lagoon located next to the harbour city of Cartagena in South-East Spain (close to the Sierra de Cartagena polymetallic ore deposits). This lagoon, which developed during the Holocene, was first a shallow sedimentary marine environment and later evolved into a swampy semi-endorheic basin named "Almarjal" (after the Arab term from the fourteenth century). The lagoon eventually dried out and at present forms part of the substratum of the modern sector of the city urban area. The basin representative sediments are sapropelic black silty facies forming a continuous sedimentary archive, accounting for more than 8000 years of depositional phenomena. The geochemical study of these sediments, together with their absolute calibrated dating by ¹⁴C, allows definition of successive stages of mining and metallurgical activities in the area. In turn, this information provides a more comprehensive perspective regarding metal pollution, particularly lead contamination during different periods of the Recent Prehistory and the Classical Age. The results indicate that the beginning of contamination by lead and other heavy metals occurred as early as 4500 years ago, when the Final Chalcolithic period was taking place in the South-East of the Iberian Peninsula. This finding provides further insights regarding the debate on the origins of lead mining and metallurgy in SE Spain.

http://ift.tt/2noGpKb

How hard they hit? Perception, adaptation and public health implications of heat waves in urban and peri-urban Pakistan

Abstract

Heat waves threaten human health given the fast changing climatic scenarios in the recent past. Adaptation to heat waves would take place when people perceive their impacts based on their knowledge. The present study examines perception level and its determinants resulting in adaptation to heat waves in Pakistan. The study used cross-sectional data from urban and peri-urban respondents of Faisalabad District. The study employs a health belief model to assess risk perception among the respondents. Logistic model is used to determine factors affecting level of knowledge, perception and adaptation to heat waves. Around 30% of peri-urban respondents have a low level of knowledge about the fatal impacts of heat waves. Risk perception of heat waves is very low among urban (57%) and peri-urban (66%) respondents. Households' knowledge on heat waves is significantly related to age, gender, education, wealth and access to health services. Determinants of perception include knowledge of heat waves, age and joint effect of marital status and knowledge while income level, family size, urban/peri-urban background, perceived barriers, perceived benefits and cues to action significantly affect adaptation to heat waves. To reduce deadly health impacts, mass awareness campaigns are needed to build perception and improve adaptation to heat waves.

http://ift.tt/2mvACVb

The key role of biogenic manganese oxides in enhanced removal of highly recalcitrant 1,2,4-triazole from bio-treated chemical industrial wastewater

Abstract

The secondary effluent from biological treatment process in chemical industrial plant often contains refractory organic matter, which deserves to be further treated in order to meet the increasingly stringent environmental regulations. In this study, the key role of biogenic manganese oxides (BioMnOx) in enhanced removal of highly recalcitrant 1,2,4-triazole from bio-treated chemical industrial wastewater was investigated. BioMnOx production by acclimated manganese-oxidizing bacterium (MOB) consortium was confirmed through scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis. Pseudomonas and Bacillus were found to be the most predominant species in acclimated MOB consortium. Mn²⁺ could be oxidized optimally at neutral pH and initial Mn²⁺ concentration below 33 mg L⁻¹. However, 1,2,4-triazole removal by BioMnOx produced occurred optimally at slightly acidic pH. High dosage of both Mn²⁺ and 1,2,4-triazole resulted in decreased 1,2,4-triazole removal. In a biological aerated filter (BAF) coupled with manganese oxidation, 1,2,4-triazole and total organic carbon removal could be significantly enhanced compared to the control system without the participation of manganese oxidation, confirming the key role of BioMnOx in the removal of highly recalcitrant 1,2,4-triazole. This study demonstrated that the biosystem coupled with manganese oxidation had a potential for the removal of various recalcitrant contaminants from bio-treated chemical industrial wastewater.

http://ift.tt/2mvth8d

Comparative study of adsorptive removal of Cr(VI) ion from aqueous solution in fixed bed column by peanut shell and almond shell using empirical models and ANN

Abstract

Cr(VI) is a toxic water pollutant, which causes cancer and mutation in living organisms. Adsorption has become the most preferred method for removal of Cr(VI) due to its high efficiency and low cost. Peanut and almond shells were used as adsorbents in downflow fixed bed continuous column operation for Cr(VI) removal. The experiments were carried out to scrutinise the adsorptive capacity of the peanut shells and almond shells, as well as to find out the effect of various operating parameters such as column bed depth (5–10 cm), influent flow rate (10–22 ml min⁻¹) and influent Cr(VI) concentration (10–20 mg L⁻¹) on the Cr(VI) removal. The fixed bed column operation for Cr(VI) adsorption the equilibrium was illustrated by Langmuir isotherm. Different well-known mathematical models were applied to the experimental data to identify the best-fitted model to explain the bed dynamics. Prediction of the bed dynamics by Yan et al. model was found to be satisfactory. Applicability of artificial neural network (ANN) modelling is also reported. An ANN modelling of multilayer perceptron with gradient descent and Levenberg-Marquardt algorithms have also been tried to predict the percentage removal of Cr(VI). This study indicates that these adsorbents have an excellent potential and are useful for water treatment particularly small- and medium-sized industries of third world countries. Almond shell represents better adsorptive capacity as breakthrough time and exhaustion time are longer in comparison to peanut shell.

http://ift.tt/2mvyQ6L

Determination of toxic metals, trace and essentials, and macronutrients in Sarpa salpa and Chelon labrosus : risk assessment for the consumers

Abstract

Due to increased environmental pollution, monitoring of contaminants in the environment and marine organisms is a fundamental tool for assessing the existence of risk from their consumption to human health. The levels of toxic heavy metals (Cd, Pb, and Al), trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V, and Zn), and macronutrients (Ca, K, Mg, Na) in two species of fish for human consumption were quantified in the present study. Eighty samples of muscle tissue and 80 samples of liver tissue belonging to two species of Osteichthyes fish; Sarpa salpa and Chelon labrosus were analyzed. The studied specimens were caught on the northern coast of Gran Canaria (Canary Islands) with fishing rods. As they caught from the shore, they are suitable samples for assessing the toxic levels of representative species caught by local amateur fishermen. The results show that both species are fit for human consumption since they have toxic levels of heavy metals (Cd, Pb, and Al) which are below the maximum established levels; however, the toxic levels of the liver samples are several orders of magnitude higher than the muscle samples, so we discourage their regular consumption. The risk assessment indicated that the two species of fish are safe for the average consumer; however, if the livers of these species are consumed, there could be risks because they exceed the PTWI for Pb and the TWI for Cd.

http://ift.tt/2mvCLAh

Progress, opportunities, and key fields for groundwater quality research under the impacts of human activities in China with a special focus on western China

Abstract

Groundwater quality research is extremely important for supporting the safety of the water supply and human health in arid and semi-arid areas of China. This review article was constructed to report the latest research progress of groundwater quality in western China where groundwater quality is undergoing fast deterioration because of fast economic development and extensive anthropogenic activities. The opportunities brought by increasing public awareness of groundwater quality protection were also highlighted and discussed. To guide and promote further development of groundwater quality research in China, especially in western China, ten key groundwater quality research fields were proposed. The review shows that the intensification of human activities and the associated impacts on groundwater quality in China, especially in western China, has made groundwater quality research increasingly important, and has caught the attention of local, national, and international agencies and scholars. China has achieved some progress in groundwater quality research in terms of national and regional laws, regulations, and financial supports. The future of groundwater quality research in China, especially in western China, is promising reflected by the opportunities highlighted. The key research fields proposed in this article may also inform groundwater quality protection and management at the national and international level.

http://ift.tt/2noOePO

Organized neurosurgery: Additional facts

K Rajasekharan Nair

Neurology India 2017 65(2):443-445

http://ift.tt/2mvCgpT

The element fluorine and its effects on human health including its neurological manifestations

D Raja Reddy

Neurology India 2017 65(2):238-239

http://ift.tt/2noC4q0

A rare case of giant solitary calvarial plasmacytoma: Can it grow bigger than this?

Dipanker Singh Mankotia, Sachin A Borkar, Kavneet Kaur, Vaishali Suri, Bhawani S Sharma

Neurology India 2017 65(2):420-422

http://ift.tt/2mvEghR

Two founders of Bombay Neurosciences: Professor Gajendra Sinh and Professor Noshir Hormusjee Wadia

Sunil Pandya

Neurology India 2017 65(2):240-244

http://ift.tt/2noZ8oL

A case of infectious intracranial dissecting aneurysm

Xiaoli Zhong, Xiaobo Li, Si Shao, Xiaoping Yang, Xuejun Fan

Neurology India 2017 65(2):405-407

http://ift.tt/2mvyBIG

Hemichorea secondary to non-ketotic hyperglycemia as the presenting manifestation of diabetes mellitus

Lulup Kumar Sahoo, Ashok Kumar Mallick, Geeta Mohanty, Kali Prasanna Swain, Srikanta Kumar Sahoo

Neurology India 2017 65(2):397-398

http://ift.tt/2mvvtwH

Persistent trigeminal artery trunk giant aneurysm and its management

Vivek Gupta, Anuj Prabhakar, Chirag K Ahuja, Ankur Bajaj, Sunil K Gupta, N Khandelwal

Neurology India 2017 65(2):400-402

http://ift.tt/2noGvl0

Deep tendon reflex: The background story of a simple technique

Kalyan B Bhattacharyya

Neurology India 2017 65(2):245-249

Wilhelm Erb and Carl Otto Westphal from Prussia first described the knee jerk in the same issue of the journal Archiv für Psychiatrie und Nervenkrankheiten in January 1875. This article retraces the history of development of 'deep tendon reflex' as an integral clinical sign during every neurological examination. The history of the evolving shapes of the reflex hammer, the iconic trademark and the ultimate signature of a neuroscientist, is also presented.

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The 'reverse' evaluation!

Shashwat Mishra

Neurology India 2017 65(2):433-433

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Description of coma and coma arousal therapy in Caraka Saṁhitā and its corollary in modern medicine

Dhaval Shukla

Neurology India 2017 65(2):250-252

The description of coma and coma arousal therapy in Caraka Saṁhitā is described in sṁtra 24, verses 42–53. It describes the definition of coma, differential diagnosis of coma from other disorders of consciousness, signs of coma, etiology of coma, coma arousal therapy, and emergence from coma. The similarities and differences of these aspects of coma from the perspective of its interpretation in modern medicine are discussed in this article.

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Anaesthesia, chronic pain and brain connectivity

Mary Abraham

Neurology India 2017 65(2):253-254

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Dyke–Davidoff–Masson syndrome

Charan S Jilowa, Parth S Meena, Jitendra Rohilla, Mahendra Jain

Neurology India 2017 65(2):413-414

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Role of functional MRI in identifying network changes in chronic pain syndromes

Uday D Patil

Neurology India 2017 65(2):255-256

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Posterior inferior cerebellar artery susceptibility sign in lateral medullary syndrome

BM Krishna Vadana, R Adhithyan, C Kesavadas, Veerendra Malik

Neurology India 2017 65(2):427-428

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Traumatic brain injury in India: A big problem in need of data

Andrew I R Maas

Neurology India 2017 65(2):257-258

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Hyperdense lenticulostriate sign…or stroke following minor trauma

Mahesh Kamate

Neurology India 2017 65(2):439-439

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The role of systematic collection of epidemiological data from India in reducing the burden of traumatic brain injury

Peter Reilly

Neurology India 2017 65(2):259-260

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The cover page

Neurology India 2017 65(2):237-237

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Quantitative research on traumatic brain injury in India: The travails and the new optimism

Virendra Deo Sinha, Amit Chakrabarty

Neurology India 2017 65(2):261-262

http://ift.tt/2mvA69H

Imaging biomarker correlates with oxidative stress in Parkinson's disease

Rajini M Naduthota, Rose D Bharath, Ketan Jhunjhunwala, Ravi Yadav, Jitender Saini, Rita Christopher, Pramod Kumar Pal

Neurology India 2017 65(2):263-268

Background: While oxidative stress (OS) may be one of the crucial factors determining the initiation and progression of Parkinson's disease (PD), its correlation with gray matter (GM) atrophy is not known. Aims: To determine the GM volume (GMV) changes using voxel-based morphometry (VBM) and correlation with OS marker serum malondialdehyde (MDA) in PD. Materials and Methods: Seventy-two patients with PD were clinically evaluated and underwent magnetic resonance imaging (MRI) on a 3T MRI scanner using a 32-channel head coil. Lipid peroxidation product MDA levels were measured by spectrophotometry. MDA levels and regional GM differences using VBM were compared with 72 healthy controls. Results: The mean age of the patients was 51.3 ± 10.6 years and that of controls was 50.8 ± 10.4 years. The mean age of onset of symptoms in PD was 45.2 ± 11.3 years. In PD, serum MDA level was significantly higher than that in controls (0.592 ± 0.89 μmol/l vs. 0.427 ± 0.055 μmol/l; P < 0.0001). Compared to controls, patients had greater regional GM atrophy in all the brain lobes (P < 0.001, uncorrected). A significant positive correlation was found between GMV and MDA in the caudate nucleus (CN) and posterior cingulate gyrus (PC) in the patient group (P < 0.001, uncorrected). Conclusions: We observed GM atrophy in all major brain lobes of patients when compared to controls. Only in the patient group, a significant positive correlation was observed in CN and PC with MDA. These findings suggest that, even though the whole brain is affected in PD, some of the non-substantia nigra regions of the brain, such as CN, may have some differential compensatory mechanism, which are preserved from oxidative damage.

http://ift.tt/2mvHLVP

Impact of hyperglycemia on the efficacy of chemotherapy—A systematic review of preclinical studies

Publication date: Available online 10 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Maaike C. Gerards, Daphne L. van der Velden, Joke W. Baars, Dees P.M. Brandjes, Joost B.L. Hoekstra, Titia M. Vriesendorp, Victor E.A. Gerdes
BackgroundAntineoplastic agents can provoke hyperglycemia in cancer patients with and without diabetes mellitus. We systematically reviewed the impact of hyperglycemia on the efficacy of chemotherapy.MethodsMEDLINE was searched for preclinical intervention studies which compared chemotherapy response in hyperglycemic and euglycemic conditions.ResultsThirteen preclinical studies, including 23 cell lines and 2 animal experiments were identified. In 14 cell lines and 2 animal studies, chemotherapy response was lower in a hyperglycemic (>15mmol/L) compared to a euglycemic environment (5mmol/L). The response was similar in 4 cell lines. In the remaining 5 cell lines, the hyperglycemic environment potentiated chemotherapy efficacy.ConclusionHyperglycemia attenuated the antiproliferative effect of chemotherapy in preclinical experiments, but the results are inconsistent. Whether hyperglycemia influences efficacy of chemotherapy in patients needs to be explored.

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Refining the indications for scapula tip in mandibular reconstruction

Mandibular reconstruction in osteoradionecrosis or salvage surgery can often be complicated by the lack of suitable recipient vessels in the ipsilateral neck and the associated requirement for significant extraoral skin reconstruction. The scapula tip with its long vascular pedicle and option of a chimeric soft tissue component offers a versatile reconstructive solution in such cases. This article reports four consecutive cases of mandibular reconstruction with poor ipsilateral vascular options and additional soft tissue requirements in which the scapula tip was justified and preferred.

http://ift.tt/2noLp1l

Influence of third molars in mandibular fractures. Part 1: mandibular angle—a meta-analysis

The aim of this systematic review was to investigate the influence of the presence and position of mandibular third molars on angle fractures. An electronic search was conducted in the PubMed, Scopus, Web of Science, Cochrane Library, and VHL databases, through January 2016. The eligibility criteria included observational studies. The search strategy resulted in 704 articles. Following the selection process, 35 studies were included in the systematic review and 28 in the meta-analysis. Twenty studies presented a score of ≤6 stars in the Newcastle–Ottawa scale assessment, indicating a risk of bias in the analysis.

http://ift.tt/2mvCvRN

Erratum to

There were some incorrect values in Tables 11 and 12. The corrected tables are as follows:

http://ift.tt/2mLh8fR

Oesophageal cancer: which treatment is the easiest to swallow? A review of combined modality treatments for resectable carcinomas

Publication date: Available online 9 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Bianca So, Loredana Marcu, Ian Olver, Raghu Gowda, Eva Bezak
Oesophageal cancer is a relatively uncommon malignancy, but with poor prognosis. Despite several treatment options that are available, the 5-year survival rates rarely exceed 40%. This review discusses the main challenges of oesophageal cancer, the available treatment options, and the most effective treatment in terms of overall survival. The outcomes of clinical trials show that neo-adjuvant chemo-radiotherapy using cisplatin and 5-fluorouracil followed by oesophagectomy results in the greatest survival. However, the optimal chemotherapy and radiotherapy schedule remains unclear. There is no satisfactory treatment to date, particularly for patients with co-morbidities or advanced tumours.

http://ift.tt/2mG8Ky6

Usefulness of self-report questionnaires for psychological assessment of patients with tinnitus and hyperacusis and patients' views of the questionnaires.

Usefulness of self-report questionnaires for psychological assessment of patients with tinnitus and hyperacusis and patients' views of the questionnaires.

Int J Audiol. 2017 Mar 09;:1-10

Authors: Aazh H, Moore BC

PMID: 28277857 [PubMed - as supplied by publisher]

http://ift.tt/2lKwNNr

Flexible heartbeat sensor for wearable device

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Yeon Hwa Kwak, Wonhyo Kim, Kwang Bum Park, Kunnyun Kim, Sungkyu Seo
We demonstrate a flexible strain-gauge sensor and its use in a wearable application for heart rate detection. This polymer-based strain-gauge sensor was fabricated using a double-sided fabrication method with polymer and metal, i.e., polyimide and nickel-chrome. The fabrication process for this strain-gauge sensor is compatible with the conventional flexible printed circuit board (FPCB) processes facilitating its commercialization. The fabricated sensor showed a linear relation for an applied normal force of more than 930 kPa, with a minimum detectable force of 6.25Pa. This sensor can also linearly detect a bending radius from 5mm to 100mm. It is a thin, flexible, compact, and inexpensive (for mass production) heart rate detection sensor that is highly sensitive compared to the established optical photoplethysmography (PPG) sensors. It can detect not only the timing of heart pulsation, but also the amplitude or shape of the pulse signal. The proposed strain-gauge sensor can be applicable to various applications for smart devices requiring heartbeat detection.

http://ift.tt/2mcfsJh

Chemical redox modulated fluorescence of nitrogen-doped graphene quantum dots for probing the activity of alkaline phosphatase

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): JingJing Liu, Duosi Tang, Zhitao Chen, Xiaomei Yan, Zhou Zhong, Longtian Kang, Jiannian Yao
Alkaline phosphatase (ALP) as an essential enzyme plays an important role in clinical diagnoses and biomedical researches. Hence, the development of convenient and sensitivity assay for monitoring ALP is extremely important. In this work, on the basis of chemical redox strategy to modulate the fluorescence of nitrogen-doped graphene quantum dots (NGQDs), a novel label-free fluorescent sensing system for the detection of alkaline phosphatase (ALP) activity has been developed. The fluorescence of NGQDs is firstly quenched by ultrathin cobalt oxyhydroxide (CoOOH) nanosheets, and then restored by ascorbic acid (AA), which can reduce CoOOH to Co²⁺, thus the ALP can be monitored based on the enzymatic hydrolysis of L-ascorbic acid-2-phosphate (AAP) by ALP to generate AA. Quantitative evaluation of ALP activity in a range from 0.1 to 5U/L with the detection limit of 0.07U/L can be realized in this sensing system. Endowed with high sensitivity and selectivity, the proposed assay is capable of detecting ALP in biological system with satisfactory results. Meanwhile, this sensing system can be easily extended to the detection of various AA-involved analytes.

http://ift.tt/2mc5Jmq

Simple, sensitive and label–free electrochemical detection of microRNAs based on the in situ formation of silver nanoparticles aggregates for signal amplification

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Leilei Liu, Yong Chang, Ning Xia, Peizhen Peng, Liping Zhang, Mengsha Jiang, Jiebin Zhang, Lin Liu
This work presented a simple, sensitive and label-free electrochemical method for the detection of microRNAs (miRNAs). It is based on the boronate ester covalent interaction between 4-mercaptophenylboronic acid (MPBA) and cis-diol at the 3′-terminal of miRNAs and the MPBA-induced in situ formation of citrate-capped silver nanoparticles (AgNPs) aggregates as labels on the electrode surface. In this design, MPBA acted as the cross-linker of AgNPs assembly. Specifically, the thiolated hairpin-like DNA probe was assembled onto the gold nanoparticles (nano-Au) modified electrode surface through the Ag-S interaction. After hybridization with the target miRNAs, MPBA was anchored onto the 3′-terminal of miRNAs through the formation of a boronate ester bond and then captured AgNP via the Ag-S interaction. Meanwhile, free MPBA molecules in solution induced the in situ assembly of AgNPs on electrode surface through the covalent interactions between α-hydroxycarboxylate of citrate and boronate of MPBA and the formation of Ag-S bonds. The electrochemical signal was therefore amplified due to the formation of AgNPs network architecture. To demonstrate the feasibility and analytical performances of the method, miRNA-21 was determined as a model analyte. The detection limit was found to be 20 aM. The viability of our method for biological sample assays was demonstrated by measuring the miRNA-21 contents in three human serum samples. In contrast to other signal-amplified electrochemical strategies for miRNAs detection, our method requires simple detection principle and easy operation procedure and obviates the specific modification of nanoparticles and capture/detection probes.

http://ift.tt/2mKXr83

Extensible multiplex real-time PCR for rapid bacterial identification with carbon nanotube composite microparticles

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Seungwon Jung, Jungmin Kim, Junsun Kim, Sang Hwa Yang, Sang Kyung Kim
The early diagnosis of pathogenic bacteria is significant for bacterial identification and antibiotic resistance. Implementing rapid, sensitive, and specific detection, molecular diagnosis has been considered complementary to the conventional bacterial culture. Composite microparticles of a primer-immobilized network (cPIN) are developed for multiplex detection of pathogenic bacteria with real-time polymerase chain reaction (qPCR). A pair of specific primers are incorporated and stably conserved in a cPIN particle. One primer is crosslinked to the polymer network, and the other is bound to carbon nanotubes (CNTs) in the particle. At the initiation of qPCR, the latter primer is released from the CNTs and participates in the amplification. The amplification efficiency of this cPIN qPCR is estimated at more than 90% with suppressed non-specific signals from complex samples. In multiplexing, four infective pathogens are successfully discriminated using this cPIN qPCR. Multiplex qPCR conforms with the corresponding singleplex assays, proving independent amplification in each particle. Four bacterial targets from clinical samples are differentially analyzed in 30min of a single qPCR trial with multiple cPIN particles.

http://ift.tt/2mc5ffN

A novel silver nanocluster in situ synthesized as versatile probe for electrochemiluminescence and electrochemical detection of thrombin by multiple signal amplification strategy

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Guifen Jie, Lu Tan, Yang Zhao, Xiaochun Wang
In this work, a novel silver nanoclusters (AgNCs) were in situ synthesized and used as versatile electrochemiluminescence (ECL) and electrochemical (EL) signal probes for thrombin detection by using DNAzyme-assisted target recycling and hybridization chain reaction (HCR) multiple amplification strategy. The presence of target thrombin firstly opened the hairpin DNA, followed by DNAzyme-catalytic recycling cleavage of excess substrates, which could generate large number of substrate fragments (s1). Then these s1 fragments were captured by SH–DNA on the Au nanoparticle-modified electrode, which further triggered the subsequent HCR of the hairpin DNA probes (H1 and H2) to form the long dsDNA. The numerous AgNCs were thus in situ synthesized by incubation the dsDNA template (with cytosine-rich loop)-modified electrode in solution with AgNO3 and sodium borohydride. By integrating the DNAzyme recycling and HCR dual amplification strategy, the amount of AgNCs is dramatically enhanced, leading to substantially amplified ECL and electrochemical signals for sensitive thrombin detection. Importantly, this design introduces the novel AgNCs into versatile ECL and EL bioassays by multiple amplification strategy, thus it is promising to provide a highly sensitive platform for various target biomolecules.

http://ift.tt/2mKT6le

Enhanced photocurrent production by the synergy of hematite nanowire-arrayed photoanode and bioengineered Shewanella oneidensis MR-1

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Gaolong Zhu, Yun Yang, Juan Liu, Feng Liu, Anhuai Lu, Weidong He
Coupling the light-harvesting capabilities of semiconductors with the catalytic power of bacteria is a promising way to increase the efficiency of bioelectrochemical systems. Here, we reported the enhanced photocurrents produced by the synergy of hematite nanowire-arrayed photoanode and the bio-engineered Shewanella oneidensis MR-1 in a solar-assisted microbial photoelectrochemical system (solar MPS) under the visible light. To increase the supply of bioelectrons, the D-lactate transporter, SO1522, was overexpressed in the recombinant S. oneidensis (T-SO1522) that could digest D-lactate 61% faster than the wild-type S. oneidenesis. Without light illumination, the addition of either the wild-type or the recombinant S. oneidensis to the system did not induce any obvious increase in the current output. However, under one-sun illumination, the photocurrent of the abiotic control was 16±2 μA cm⁻² at 0.8V vs. Ag/AgCl, and the addition of the wild-type S. oneidensis and the recombinant S. oneidensis increased the photocurrent to 70±6 and 95±8 μA cm⁻², respectively, at 0.8V vs. Ag/AgCl. Moreover, the solar MPS with T-SO1522 presented quick and repeatable responses to the on/off illumination cycles, and had relatively stable photocurrent generation in the 273-h operation. Scanning electron microscope (SEM) images showed that the cell density on the hematite photoelectrode was similar between the recombinant and the wild-type S. oneidensis. These findings revealed the pronounced influence of metabolic rates on the light-to-electricity conversion in the complex photocatalyst-electricigen hybrid system, which is important to promote the development of the solar MPS for electricity production and wastewater treatment.

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Hybrid detection of target sequence DNA based on phosphorescence resonance energy transfer

Publication date: 15 August 2017
Source:Biosensors and Bioelectronics, Volume 94
Author(s): Yanming Miao, Jinzhi Lv, Guiqin Yan
The severe background fluorescence and scattering light of real biological samples or environmental samples largely reduce the sensitivity and accuracy of fluorescence resonance energy transfer sensors based on fluorescent quantum dots (QDs). To solve this problem, we designed a novel target sequence DNA biosensor based on phosphorescent resonance energy transfer (PRET). This sensor relied on Mn-doped ZnS (Mn-ZnS) room-temperature phosphorescence (RTP) QDs/poly-(diallyldimethylammonium chloride) (PDADMAC) nanocomposite (QDs⁺) as the energy donor and the single-strand DNA-ROX as the energy receptor. Thereby, an RTP biosensor was built and used to quantitatively detect target sequence DNA. This biosensor had a detection limit of 0.16nM and a linear range of 0.5–20nM for target sequence DNA. The dependence on RTP of QDs effectively avoided the interference from background fluorescence and scattering light in biological samples. Moreover, this sensor did not need sample pretreatment. Thus, this sensor compared with FRET is more feasible for quantitative detection of target sequence DNA in biological samples. Interestingly, the QDs⁺ nanocomposite prolonged the phosphorescence lifetime of Mn-ZnS QDs by 2.6 times to 4.94ms, which was 5–6 magnitude-order larger than that of fluorescent QDs. Thus, this sensor largely improves the optical properties of QDs and permits chemical reactions at a long enough time scale.

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Can gene editing and silencing technologies play a role in the treatment of head and neck cancer?

Publication date: May 2017
Source:Oral Oncology, Volume 68
Author(s): Mushfiq H. Shaikh, Daniel T.W. Clarke, Newell W. Johnson, Nigel A.J. McMillan
Conventional treatment strategies have done little to improve the prognosis or disease-free survival in head and neck cancer (HNC) patients. Recent progress in our understanding of molecular aspects of head and neck squamous cell carcinoma (HNSCC) has provided insights into the potential use of molecular targeted therapies in combination with current treatment strategies. Here we review the current understanding of treatment modalities for both HPV-positive and HPV-negative HNSCCs with the potential to use gene editing and silencing technologies therapeutically. The development of sequence-specific RNA interference (RNAi) with its strong gene-specific silencing ability, high target specificity, greater potency and reduced side effects, has shown it to be a promising therapeutic candidate for treating cancers. CRISPR/Cas gene editing is the newest technology with the ability to delete, mutate or replace genes of interest and has great potential for treating HNSCCs. We also discuss the major challenge in using these approaches in HNSCC; that being the choice of target and the ability to deliver the payload. Finally, we highlight the potential combination of RNAi or CRIPSR/Cas with current treatment strategies and outline the possible path to the clinic.

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Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma

Publication date: May 2017
Source:Oral Oncology, Volume 68
Author(s): Andrew C. Birkeland, Susan K. Foltin, Nicole L. Michmerhuizen, Rebecca C. Hoesli, Andrew J. Rosko, Serena Byrd, Megan Yanik, Jacques E. Nor, Carol R. Bradford, Mark E. Prince, Thomas E. Carey, Jonathan B. McHugh, Matthew E. Spector, J. Chad Brenner
ObjectiveMucoepidermoid carcinoma (MEC) is the most common malignant tumor of the salivary glands. Tumor stage and grade have historically been important predictors of survival. An oncogenic CRTC1- or CRTC3-MAML2 gene fusion has been identified in a number of MECs. Historically, these gene fusions have been associated with lower grade tumors and better survival. However, reported gene fusion rates and prognosis varies widely across studies, and have not controlled for tumor grade. We sought to identify gene fusion rates and outcomes in our cohort of MEC patients.Materials and methodsAn IRB-approved retrospective cohort of patients with MEC was identified at the University of Michigan. Clinical, histologic, and outcome data was collected from medical records. RNA was isolated from formalin fixed paraffin-embedded tumor sections, and qRT-PCR was performed to identify CRTC1/3-MAML2 gene fusions. Sanger sequencing of qRT-PCR products was used to confirm gene fusions.ResultsOverall, 90 patient MEC tumors were collected (58 low-grade, 25 intermediate-grade, and 7 high-grade). Gene fusions were identified in 59% (53/90) of tumors. On univariate and bivariate analysis, fusion status did not significantly associate with grade or survival.ConclusionWe have identified a high rate of CRTC1/3-MAML2 gene fusions in a large cohort of MEC. We do not identify any correlation between fusion status with tumor grade or survival. These findings suggest further characterization of MECs is needed before considering the CRTC1/3-MAML2 gene fusion as a prognostic biomarker. Additional genetic drivers may account for survival and grade in MECs.

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Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Παρασκευή 10 Μαρτίου 2017

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Αρχειοθήκη ιστολογίου