Community raises funds for EMT student shot while aiding victim

By EMS1 Staff

BATON ROUGE, La. — After a 17-year-old EMT student put his life on the line to save a shooting victim, his community has begun raising funds to pay for his medical bills.

Daniel Wesley was on his way home from a Sunday shopping trip with his mother when he saw a shooting victim lying on the side of the road. Wesley rushed to the victim, April Peck, and attempted to aid her. 

During the incident, the shooter, Terrell Walker, shot Wesley in the arm and leg, and ran over him twice as he fled from the scene, reported WBRZ. Peck did not survive. Walker was killed later Sunday night in a shootout with East Baton Rouge sheriff's deputies.

Wesley was transported to the hospital, where he underwent surgery on his leg and arm, which "shattered into 18 pieces," his mother, Kathy Wesley, said.

Wesley comes from an EMS family; his father was a longtime paramedic and his mother is also a first responder. 

Wesley's high school has started to sell bracelets to help raise funds for his medical expenses. The school's principal, David Prescott, said, "We're very proud of him. He's always in service to some else. He's come to me before this year with a fundraiser of his own to help someone out."

A GoFundMe page has also been created and it has raised over $6,000.

"Daniel wants to tell all of his friends out there, he's sending a shout out to them, and he's thinking of them as well during this time," Wesley's mother said. 

Heroic, selfless effort by this incredible young man. Strong work Daniel Wesley. https://t.co/SfRMYhYCzY

— MONOC EMS (@MONOCEMS) November 29, 2016

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Endoscopic endonasal pituitary adenomas surgery: the surgical experience of 178 consecutive patients and learning curve of two neurosurgeons

We aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery.

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Functional characterization of two naturally occurring mutations V221G and T449N in the follicle stimulating hormone receptor

Publication date: 15 January 2017
Source:Molecular and Cellular Endocrinology, Volume 440
Author(s): Antara A. Banerjee, Swati K. Achrekar, Shaini Joseph, Bhakti R. Pathak, Smita D. Mahale
Naturally occurring mutations in follicle stimulating hormone receptor (FSHR) affect the receptor function. Here, we characterized two such previously reported mutations, V²²¹G and T⁴⁴⁹N, in the extracellular domain and transmembrane helix 3, of FSHR, respectively. Functional studies with the V²²¹G mutant demonstrated an impairment in FSH binding and signaling. Validation of X-ray crystallography data indicating the contribution of FSHR specific residues in the vicinity of V²²¹ to contribute to FSH-FSHR interaction was carried out. In vitro mutational studies showed that these residues are determinants of both FSH binding and FSH induced signaling. Analysis of the T⁴⁴⁹N mutation revealed that it results in an increase in FSH binding and high cAMP response at lower doses of FSH. A marginal hCG induced and no TSH induced cAMP production was also observed. These findings corroborated with the clinical manifestations of primary amenorrhea (V²²¹G) and spontaneous ovarian hyperstimulation syndrome (T⁴⁴⁹N) in women harbouring these mutations.



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I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties

Publication date: 15 January 2017
Source:Molecular and Cellular Endocrinology, Volume 440
Author(s): Lingman Ma, Lifen Qian, Qidi Ying, Yan Zhang, Changlin Zhou, Guanzhong Wu
Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE^−/− mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4. The data indicated that I4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I4, at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I4 exerts potent inhibitory effects on atherosclerosis onset and development.



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Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3β to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes

Publication date: 15 January 2017
Source:Molecular and Cellular Endocrinology, Volume 440
Author(s): Xiaoguang Li, Na Liu, Yizhu Wang, Jinglong Liu, Haigang Shi, Zhenzhen Qu, Tingting Du, Bin Guo, Bin Gu
Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while β-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3β (GSK-3β) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs. Moreover, over-expression of BMAL1 led to recovered osteogenesis ability and activation of Wnt/β-catenin pathway, which was partially due to inhibition of GSK-3β caused by over-expression of BMAL1. Taken together, our findings provide new insights into the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Over-expressed BMAL1 could recover BMSCs osteogenesis in T2DM partially by decreasing GSK-3β expression to activate Wnt/β-catenin pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic disorders.

Graphical abstract

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Polymorphisms in MIR499A and MIR125A gene are associated with autoimmune thyroid diseases

Publication date: 15 January 2017
Source:Molecular and Cellular Endocrinology, Volume 440
Author(s): TianTian Cai, Jie Li, Xiaofei An, Ni Yan, Danfeng Li, Yanfei Jiang, Wen Wang, Liangfeng Shi, Qiu Qin, Ronghua Song, Guofei Wang, Wenjuan Jiang, Jin-an Zhang
BackgroundSingle nucleotide polymorphisms (SNPs) of the miR-146a, miR-499a and miR-125a have been shown to be associated with the susceptibility to several autoimmune diseases. This study was conducted to identify the association of SNPs rs2910164, rs57095329, rs3746444 and rs12976445 with autoimmune thyroid diseases (AITDs) in a Chinese Han population.MethodsWe enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Four SNPs were selected for genotyping by multiplex polymerase chain reaction and ligase detection reaction.ResultsThe frequencies of rs3746444 genotypes in patients with AITD and GD differed significantly from those in the controls. The frequencies of rs12976445 genotypes in patients with HT differed significantly from those in the controls. The frequencies of allele C in HT groups were significantly higher than those in control group. For the rs3746444 polymorphism, genetic associations between the combinational genotype and AITD/GD risk were observed in the dominant model, recessive model, and overdominant model. For the rs12976445 polymorphism, genetic associations between the combinational genotype and HT risk were also found in the dominant model and overdominant model. Moreover, gene-sex interactions were identified by GMDR and 2 × 2 crossover analysis.ConclusionsOur results suggest rs3746444 (miR-499a) and rs12976445 (miR-125a) associated with AITD susceptibility and potential gene-sex interactions between the four polymorphisms and AITD.



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The human adrenal gland proteome defined by transcriptomics and antibody-based profiling

Endocrinology, Early Release.


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New Imaging Method Can Detect, Monitor and Guide Treatment For, Prostate Cancer

An international group of researchers report success in mice of a method of using positron emission tomography (PET) scans to track, in real time, an antibody targeting a hormone receptor pathway specifically involved in prostate cancer. This androgen receptor pathway drives development and progression of the vast majority of prostate cancers. The technique shows promise, the investigators say, as a novel way to use such an antibody to detect and monitor prostate and other hormone-sensitive cancers, as well as to guide therapy in real time.

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Human Ancestor ‘Lucy’ Was a Tree Climber

Since the discovery of the fossil dubbed Lucy 42 years ago this month, paleontologists have debated whether the 3 million-year-old human ancestor spent all of her time walking on the ground or instead combined walking with frequent tree climbing. Now, analysis of special CT scans by scientists from The Johns Hopkins University and the University of Texas at Austin suggests the female hominin spent enough time in the trees that evidence of this behavior is preserved in the internal structure of her bones. A description of the research study appears November 30 in the journal PLOS ONE.

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New Imaging Method Can Detect, Monitor and Guide Treatment For, Prostate Cancer

An international group of researchers report success in mice of a method of using positron emission tomography (PET) scans to track, in real time, an antibody targeting a hormone receptor pathway specifically involved in prostate cancer. This androgen receptor pathway drives development and progression of the vast majority of prostate cancers. The technique shows promise, the investigators say, as a novel way to use such an antibody to detect and monitor prostate and other hormone-sensitive cancers, as well as to guide therapy in real time.

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Human Ancestor ‘Lucy’ Was a Tree Climber

Since the discovery of the fossil dubbed Lucy 42 years ago this month, paleontologists have debated whether the 3 million-year-old human ancestor spent all of her time walking on the ground or instead combined walking with frequent tree climbing. Now, analysis of special CT scans by scientists from The Johns Hopkins University and the University of Texas at Austin suggests the female hominin spent enough time in the trees that evidence of this behavior is preserved in the internal structure of her bones. A description of the research study appears November 30 in the journal PLOS ONE.

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Vaccination in secondary school students expedites rubella control and prevents congenital rubella syndrome

In order to control the spread of rubella and reduce the risk for congenital rubella syndrome, an additional rubella vaccination program was set up for all secondary school students since 2008 in Zhejiang, China.

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Dysregulation of hepatic microRNA expression profiles with Clonorchis sinensis infection

Clonorchiasis remains an important zoonotic parasitic disease worldwide. The molecular mechanisms of host-parasite interaction are not fully understood. Non-coding microRNAs (miRNAs) are considered to be key r...

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SEOM Clinical Guideline in ovarian cancer (2016)

Abstract

Despite remarkable advances in the knowledge of molecular biology and treatment, ovarian cancer (OC) is the first cause of death due to gynecological cancer and the fifth cause of death for cancer in women in Spain. The aim of this guideline is to summarize the current evidence and to give evidence-based recommendations for clinical practice.

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SEOM Clinical Guideline of localized rectal cancer (2016)

Abstract

Localized rectal adenocarcinoma is a heterogeneous disease and current treatment recommendations are based on a preoperative multidisciplinary evaluation. High-resolution magnetic resonance imaging and endoscopic ultrasound are complementary to do a locoregional accurate staging. Surgery remains the mainstay of treatment and preoperative therapies with chemoradiation (CRT) or short-course radiation (SCRT) must be considered in more locally advanced cases. Novel strategies with induction chemotherapy alone or preceding or after CRT (SCRT) and surgery are in development.

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SEOM Clinical Guideline of management of soft-tissue sarcoma (2016)

Abstract

Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5 cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.

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Factors associated to post-operative nausea and vomiting following oral and maxillofacial surgery: a prospective study

Abstract

Aim

This study aims to address and assess possible factors associated with nausea and vomiting (NV) following oral and maxillofacial surgery.

Material and methods

A prospective study was carried out in the period from December 2013 to January 2016 targeting all attended cases in that period. For statistical analysis, Pearson chi-square and Fisher tests were used to verify association and ANOVA and Student's t tests to test for significant difference, p was defined as ≤0.05. The sample group consisted of 207 patients with an average age of 33.56 years (±13.23), and 70.5% of subjects were male.

Results

Calculations based on the predictive model showed that a female patient with prior history of nausea and vomiting who used opioids and had intra-oral surgical access would have a 96% chance of experiencing a nausea and vomiting episode.

Other factors like age, being overweight, anesthesia, surgery duration, and duration of hospital stay also contribute so that these aspects must be paid careful attention prior to surgery to ensure a suitably orientated treatment that will avoid disturbances caused by post-operative nausea and vomiting.

Conclusion

The occurrence of post-operative nausea and vomiting after oral and maxillofacial surgery was found to be more higher incidence associated to female patients who used opioids, who had a prior history of NV, whose surgery involved intra-oral access, who were in the second or third decades of their lives, who have above average weight, and who have long anesthesia when undergoing surgery, resulting in a long hospital stays.

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A plasma-assisted cataluminescence sensor for ethyne detection

Abstract

The detection of ethyne is crucial not only in environmental monitoring but also in process controlling and mechanism studies in industrial fields. Here, a new sensor based on the plasma-assisted cataluminescence (PA-CTL) has been fabricated for the detection of ethyne. Based on the assistance of low-temperature plasma (LTP) generated by air, which can enhance the catalytic ability of catalysts and the reactivity of the analytes, we observed significant cataluminescence (CTL) emissions on the surface of nanomaterials of Zn/SiO₂. CTL emission has demonstrated to be affected by the type of discharge gases or the metal ions doping on the catalysts of SiO₂. By the optimizations on the working temperature and gas flow rate of the air, a PA-CTL based sensor was constructed for the detection of ethyne. As demonstrated, this sensor exhibited a linearity of 11–1160 ng/mL (10–1000 ppm) with a limit of detection (LOD) of 5 ng/mL (5 ppm), and also showed good selectivity as well as good stability. This sensor is simple, low-cost, and could give stable responses for actual applications, which will expand the applications of CTL and show potentials in industrial substances detections.

Graphical Abstract

A plasma-assisted cataluminescence gas sensor for ethyne detection

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Effect of amino compounds on luminol-H 2 O 2 -gold nanoparticle chemiluminescence system

Abstract

In this work, the effect of amino compounds on the catalytic property of gold nanoparticles (AuNPs) in the luminol-H₂O₂ chemiluminescence (CL) system was systematically investigated. The experimental results showed that the catalytic ability of AuNPs on luminol-H₂O₂ system can be changed after AuNPs interacted with the amino compounds. It was found that two main aspects influence the catalytic property of AuNPs: (1) the electron density in conduction bands of AuNPs and (2) the surface negative charge density of AuNPs. Some amino compounds can decrease the electron density in the conduction bands of AuNPs after they reacted with AuNPs, resulting in a decrease of the catalytic property of AuNPs on luminol-H₂O₂ system. However, some amino compounds can cause AuNPs to aggregate after they reacted with AuNPs. The surface negative charge density of AuNPs would decrease, and zeta potentials were tested to verify the change of the surface negative charge density of AuNPs. As a result, the catalytic property of AuNPs on luminol-H₂O₂ system increased, and an enhanced CL signal can be obtained after the amino compounds reacted with AuNPs. This work will help people understand the catalytic mechanism of AuNPs and establish the CL method for the determination of amino compounds.

Graphical Abstract

Effects of amino compound on luminol-H₂O₂-AuNPs CL system.

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N -Hydroxysuccinimide as an effective chemiluminescence coreactant for highly selective and sensitive detection

Abstract

The development of novel coreactants for chemiluminescence is very important to improve performance and widen its applications without using any other catalyst. N-Hydroxysuccinimide (NHS), a highly popular amine-reactive, activating, or protecting reagent in biochemical applications and organic synthesis, has been explored as an efficient and stable chemiluminescence coreactant for the first time. The chemiluminescence intensity of the newly developed luminol-NHS system is about 22 times higher than that of the traditional luminol-H₂O₂ system. Chemiluminescence of this system is dramatically enhanced by Co²⁺. This new chemiluminescence system is then applied for the highly selective and ultrasensitive detection of Co²⁺ with limit of detection (0.01 nM) better than those of several conventional analytical methods. This system also enables the efficient detection of luminol (LOD = 7 pM) and NHS (LOD = 3.0 μM) with excellent sensitivity. This chemiluminescence method was then also utilized to detect Co²⁺ in tap water and blue silica gel with excellent recoveries in the range 99.20–103.07 %. This novel chemiluminescence system has several advantages, including simple, cost-effective, highly sensitive, selective, and wide linear range. We expect that this chemiluminescence system will be a promising candidate for chemical and biological sensing.

Graphical Abstract

Comparison of CL peak intensities of classical luminol-H₂O₂ CL system and newly developed luminol-NHS CL system.

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MIL-53(Fe) MOF-mediated catalytic chemiluminescence for sensitive detection of glucose

Abstract

Various analytical applications of metal–organic frameworks (MOFs) have been rapidly developed in the past few years. However, the employment of MOFs as catalysts in chemiluminescence (CL) analysis is rare. Here, for the first time, we found that MIL-53(Fe) MOFs could significantly enhance the CL of luminol in the presence of H₂O₂ in an alkaline medium. The CL intensity in the luminol–H₂O₂–MIL-53(Fe) system was about 20 times higher than that in the luminol–H₂O₂ system. Moreover, the XRD pattern of MIL-53(Fe) after CL reaction was almost the same as that of the original MIL-53(Fe), confirming the catalytic role of MIL-53(Fe) in the luminol–H₂O₂–MIL-53(Fe) system. The possible mechanism behind the enhancing phenomenon was discussed based on the results from the CL spectra, FL probe experiments, and active oxygen species measurements. By coupling with the glucose oxidase-based catalytic oxidation reaction, a sensitive and selective CL method was developed for the detection of glucose. There is a linear relationship between the logarithm of CL intensity and the logarithm of glucose concentration in the range from 0.1 to 10 μM, and a detection limit of 0.05 μM (S/N = 3) is obtained. The proposed method has been applied to the determination of glucose in human serum samples with satisfactory results.

Graphical abstract

MIL-53(Fe) MOFs are found to greatly enhance the chemiluminescence emission of the luminol–H₂O₂ system, and this finding resulted in a new chemiluminescence method for biosensing of glucose when coupled with the glucose oxidase.

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Highlights of analytical chemical luminescence and cataluminescence

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Improved sensitivity via layered-double-hydroxide-uniformity-dependent chemiluminescence

Abstract

In the last two decades nanoparticles have been widely applied to enhance chemiluminescence (CL). The morphology of nanoparticles has an important influence on nanoparticle-amplified CL. However, studies of nanoparticle-amplified CL focus mainly on the size and shape effects, and no attempt has been made to explore the influence of uniformity in nanoparticle-amplified CL processes. In this study we have investigated nanoparticle uniformity in the luminol–H₂O₂ CL system using layered double hydroxides (LDHs) as a model material. The results demonstrated that the uniformity of LDHs played a key role in CL amplification. A possible mechanism is that LDHs with high uniformity possess abundant catalytic active sites, which results in high CL intensity. Meanwhile, the sensitivity for H₂O₂ detection was increased by one order of magnitude (1.0 nM). Moreover, the uniform-LDH-amplified luminol CL could be applied to selective detection of glucose in human plasma samples. Furthermore, such a uniformity-dependent CL enhancement effect could adapted to other redox CL systems—for example, the peroxynitrous acid (ONOOH) CL system.

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A primerless molecular diagnostic: phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP)

Abstract

There are various ways that priming can occur in nucleic acid amplification reactions. While most reactions rely on a primer to initiate amplification, a mechanism for DNA amplification has been developed in which hairpin sequences at the 3' terminus of a single-stranded oligonucleotide fold on themselves to initiate priming. Unfortunately, this method is less useful for diagnostic applications because the self-folding efficiency is low and only works over a narrow range of reaction temperatures. In order to adapt this strategy for analytical applications we have developed a variant that we term phosphorothioated-terminal hairpin formation and self-priming extension (PS-THSP). In PS-THSP a phosphorothioate (PS) modification is incorporated into the DNA backbone, leading to a reduction in the thermal stability of dsDNA and increased self-folding of terminal hairpins. By optimizing the number of PS linkages that are included in the initial template, we greatly increased self-folding efficiency and the range of reaction temperatures, ultimately achieving a detection limit of 1 pM. This improved method was readily adapted to the detection of single nucleotide polymorphisms and to the detection of non-nucleic acid analytes, such as alkaline phosphatase, which was quantitatively detected at a limit of 0.05 mU/mL, approximately 10-fold better than commercial assays.

Graphical abstract

Efficient self-folding by phosphorothioate (PS) modification

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Isothermal nucleic acid amplification in bioanalysis

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Fundamental aspects of electromigrative separation techniques

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A cataluminescence sensor with fast response to diethyl ether based on layered double oxide nanoparticles

Abstract

This work proposed a cataluminescence (CTL) sensor for rapid and highly selective detection of diethyl ether using Mg-Al-layered double oxide (Mg-Al LDO). The linear range of the CTL intensity versus the concentration of diethyl ether was 0.1–8.0 mM, with a correlation coefficient (R) of 0.9915. The limit of detection (signal-to-noise ratio (S/N) = 3) was 0.02 mM. The half decay time was ~15 s, indicating a fast CTL process. The CTL sensor showed an excellent selectivity toward diethyl ether and good operational stability. Relative standard deviation (RSD) was less than 3 % in 20 consecutive measurements for diethyl ether. The CTL process was monitored by gas chromatography–mass spectrometry (GC/MS), pH indicator, and CTL spectrum. The results showed that the strong CTL signals were from the specific basic sites of Mg-Al LDO nanoparticle, which was further confirmed by temperature-programmed desorption of carbon dioxide (CO₂-TPD). This work not only provides a facile approach to obtain a CTL sensor based on LDO but also systematically investigates the catalytic mechanism of LDO.

Graphical abstract

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“The Apartment is for You, It’s Not for Anyone Else”: Managing Social Recovery and Risk on the Frontlines of Single-Adult Supportive Housing

Abstract

This multi-method qualitative study examines frontline provider perspectives on consumer social relationships and barriers to social recovery in supportive housing programs for adults with serious mental illness. Thematic analyses show that guest and occupancy policies that enforce the "single" nature of single-adult supportive housing challenge consumer rights to self-determination in the realm of social recovery. Findings also highlight the ways in which providers act to reinforce and subvert these policies while mitigating risk in this service setting. Recommendations for enhancing the recovery orientation of supportive housing and implications for the design of the homeless service system are discussed.

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Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform

We describe the use of a multiplexed high-throughput gene expression platform that quantitates gene expression by barcoding and counting molecules in biological substrates without the need for amplification. We used the platform to quantitate microRNA (miRNA) expression in whole blood in subjects with and without irritable bowel syndrome.

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Deviations from Critical Dynamics in Interictal Epileptiform Activity

The framework of criticality provides a unifying perspective on neuronal dynamics from in vitro cortical cultures to functioning human brains. Recent findings suggest that a healthy cortex displays critical dynamics, giving rise to scale-free spatiotemporal cascades of activity, termed neuronal avalanches. Pharmacological manipulations of the excitation-inhibition balance (EIB) in cortical cultures were previously shown to result in deviations from criticality and from the power law scaling of avalanche size distribution. To examine the sensitivity of neuronal avalanche metrics to altered EIB in humans, we focused on epilepsy, a neurological disorder characterized by hyperexcitable networks. Using magnetoencephalography, we quantitatively assessed deviations from criticality in the brain dynamics of patients with epilepsy during interictal (between-seizures) activity. Compared with healthy control subjects, epilepsy patients tended to exhibit a higher neural gain and larger avalanches, particularly during interictal epileptiform activity. Moreover, deviations from scale-free behavior were exclusively connected to brief intervals at epileptiform discharges, strengthening the association between deviations from criticality and the instantaneous changes in EIB. The avalanches collected during interictal epileptiform activity had not only a stereotypical size range but also involved particular spatial patterns of activations, as expected for periods of epileptic network dominance. Overall, the neuronal avalanche metrics provide a quantitative novel description of interictal brain activity of patients with epilepsy.

SIGNIFICANCE STATEMENT Healthy brain dynamics requires a delicate balance between excitatory and inhibitory processes. Several brain disorders, such as epilepsy, are associated with altered excitation-inhibition balance, but assessing this balance using noninvasive tools is still challenging. In this study, we apply the framework of critical brain dynamics to data from epilepsy patients, which were recorded between seizures. We show that metrics of criticality provide a sensitive tool for noninvasive assessment of changes in the balance. Specifically, brain activity of epilepsy patients deviates from healthy critical brain dynamics, particularly during abnormal epileptiform activity. The study offers a novel quantitative perspective on epilepsy and its relation to healthy brain dynamics.

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Development of Activity in the Mouse Visual Cortex

A comprehensive developmental timeline of activity in the mouse cortex in vivo is lacking. Understanding the activity changes that accompany synapse and circuit formation is important to understand the mechanisms by which activity molds circuits and would help to identify critical checkpoints for normal development. To identify key principles of cortical activity maturation, we systematically tracked spontaneous and sensory-evoked activity with extracellular recordings of primary visual cortex (V1) in nonanesthetized mice. During the first postnatal week (postnatal days P4–P7), V1 was not visually responsive and exhibited long (>10 s) periods of network silence. Activation consisted exclusively of "slow-activity transients," 2–10 s periods of 6–10 Hz "spindle-burst' oscillations; the response to spontaneous retinal waves. By tracking daily changes in this activity, two key components of spontaneous activity maturation were revealed: (1) spindle-burst frequency acceleration (eventually becoming the 20–50 Hz broadband activity caused by the asynchronous state) and (2) "filling-in" of silent periods with low-frequency (2–4 Hz) activity (beginning on P10 and complete by P13). These two changes are sufficient to create the adult-like pattern of continuous activity, alternation between fast-asynchronous and slow-synchronous activity, by eye opening. Visual responses emerged on P8 as evoked spindle-bursts and neuronal firing with a signal-to-noise ratio higher than adult. Both were eliminated by eye opening, leaving only the mature, short-latency response. These results identify the developmental origins of mature cortical activity and implicate the period before eye opening as a critical checkpoint. By providing a systematic description of electrical activity development, we establish the murine visual cortex as a model for the electroencephalographic development of fetal humans.

SIGNIFICANCE STATEMENT Cortical activity is an important indicator of long-term health and survival in preterm infants and molds circuit formation, but gaps remain in our understanding of the origin and normal progression of this activity in the developing cortex. We aimed to rectify this by monitoring daily changes in cortical activity in the nonanesthetized mouse, an important preclinical model of disease and development. At ages approximately equivalent to normal human term birth, mouse cortex exhibits primarily network silence, with spontaneous "spindle bursts" as the only form of activity. In contrast, mature cortex is noisy, alternating between asynchronous/discontinuous and synchronous/continuous states. This work identifies the key processes that produce this maturation and provides a normative reference for murine-based studies of cortical circuit development.

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Parkin Deficiency Reduces Hippocampal Glutamatergic Neurotransmission by Impairing AMPA Receptor Endocytosis

Mutations in the gene encoding Parkin, an E3 ubiquitin ligase, lead to juvenile-onset Parkinson's disease by inducing the selective death of midbrain dopaminergic neurons. Accumulating evidence indicates that Parkin also has an important role in excitatory glutamatergic neurotransmission, although its precise mechanism of action remains unclear. Here, we investigate Parkin's role at glutamatergic synapses of rat hippocampal neurons. We find that Parkin-deficient neurons exhibit significantly reduced AMPA receptor (AMPAR)-mediated currents and cell-surface expression, and that these phenotypes result from decreased postsynaptic expression of the adaptor protein Homer1, which is necessary for coupling AMPAR endocytic zones with the postsynaptic density. Accordingly, Parkin loss of function leads to the reduced density of postsynaptic endocytic zones and to impaired AMPAR internalization. These findings demonstrate a novel and essential role for Parkin in glutamatergic neurotransmission, as a stabilizer of postsynaptic Homer1 and the Homer1-linked endocytic machinery necessary for maintaining normal cell-surface AMPAR levels.

SIGNIFICANCE STATEMENT Mutations in Parkin, a ubiquitinating enzyme, lead to the selective loss of midbrain dopaminergic neurons and juvenile-onset Parkinson's disease (PD). Parkin loss of function has also been shown to alter hippocampal glutamatergic neurotransmission, providing a potential explanation for PD-associated cognitive impairment. However, very little is known about Parkin's specific sites or mechanisms of action at glutamatergic synapses. Here, we show that Parkin deficiency leads to decreased AMPA receptor-mediated activity due to disruption of the postsynaptic endocytic zones required for maintaining proper cell-surface AMPA receptor levels. These findings demonstrate a novel role for Parkin in synaptic AMPA receptor internalization and suggest a Parkin-dependent mechanism for hippocampal dysfunction that may explain cognitive deficits associated with some forms of PD.

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Memory Transformation Enhances Reinforcement Learning in Dynamic Environments

Over the course of systems consolidation, there is a switch from a reliance on detailed episodic memories to generalized schematic memories. This switch is sometimes referred to as "memory transformation." Here we demonstrate a previously unappreciated benefit of memory transformation, namely, its ability to enhance reinforcement learning in a dynamic environment. We developed a neural network that is trained to find rewards in a foraging task where reward locations are continuously changing. The network can use memories for specific locations (episodic memories) and statistical patterns of locations (schematic memories) to guide its search. We find that switching from an episodic to a schematic strategy over time leads to enhanced performance due to the tendency for the reward location to be highly correlated with itself in the short-term, but regress to a stable distribution in the long-term. We also show that the statistics of the environment determine the optimal utilization of both types of memory. Our work recasts the theoretical question of why memory transformation occurs, shifting the focus from the avoidance of memory interference toward the enhancement of reinforcement learning across multiple timescales.

SIGNIFICANCE STATEMENT As time passes, memories transform from a highly detailed state to a more gist-like state, in a process called "memory transformation." Theories of memory transformation speak to its advantages in terms of reducing memory interference, increasing memory robustness, and building models of the environment. However, the role of memory transformation from the perspective of an agent that continuously acts and receives reward in its environment is not well explored. In this work, we demonstrate a view of memory transformation that defines it as a way of optimizing behavior across multiple timescales.

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Network Patterns Associated with Navigation Behaviors Are Altered in Aged Nonhuman Primates

The ability to navigate through space involves complex interactions between multiple brain systems. Although it is clear that spatial navigation is impaired during aging, the networks responsible for these altered behaviors are not well understood. Here, we used a within-subject design and [¹⁸F]FDG-microPET to capture whole-brain activation patterns in four distinct spatial behaviors from young and aged rhesus macaques: constrained space (CAGE), head-restrained passive locomotion (CHAIR), constrained locomotion in space (TREADMILL), and unconstrained locomotion (WALK). The results reveal consistent networks activated by these behavior conditions that were similar across age. For the young animals, however, the coactivity patterns were distinct between conditions, whereas older animals tended to engage the same networks in each condition. The combined observations of less differentiated networks between distinct behaviors and alterations in functional connections between targeted regions in aging suggest changes in network dynamics as one source of age-related deficits in spatial cognition.

SIGNIFICANCE STATEMENT We report how whole-brain networks are involved in spatial navigation behaviors and how normal aging alters these network patterns in nonhuman primates. This is the first study to examine whole-brain network activity in young or old nonhuman primates while they actively or passively traversed an environment. The strength of this study resides in our ability to identify and differentiate whole-brain networks associated with specific navigational behaviors within the same nonhuman primate and to compare how these networks change with age. The use of high-resolution PET (microPET) to capture brain activity of real-world behaviors adds significantly to our understanding of how active circuits critical for navigation are affected by aging.

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Joint Encoding of Object Motion and Motion Direction in the Salamander Retina

The processing of motion in visual scenes is important for detecting and tracking moving objects as well as for monitoring self-motion through the induced optic flow. Specialized neural circuits have been identified in the vertebrate retina for detecting motion direction or for distinguishing between object motion and self-motion, although little is known about how information about these distinct features of visual motion is combined. The salamander retina, which is a widely used model system for analyzing retinal function, contains object-motion-sensitive (OMS) ganglion cells, which strongly respond to local motion signals but are suppressed by global image motion. Yet, direction-selective (DS) ganglion cells have been conspicuously absent from characterizations of the salamander retina, despite their ubiquity in other model systems. We here show that the retina of axolotl salamanders contains at least two distinct classes of DS ganglion cells. For one of these classes, the cells display a strong preference for local over global motion in addition to their direction selectivity (OMS-DS cells) and thereby combine sensitivity to two distinct motion features. The OMS-DS cells are further distinct from standard (non-OMS) DS cells by their smaller receptive fields and different organization of preferred motion directions. Our results suggest that the two classes of DS cells specialize to encode motion direction of local and global motion stimuli, respectively, even for complex composite motion scenes. Furthermore, although the salamander DS cells are OFF-type, there is a strong analogy to the systems of ON and ON-OFF DS cells in the mammalian retina.

SIGNIFICANCE STATEMENT The retina contains specialized cells for motion processing. Among the retinal ganglion cells, which form the output neurons of the retina, some are known to report the direction of a moving stimulus (direction-selective cells), and others distinguish the motion of an object from a moving background. But little is known about how information about local object motion and information about motion direction interact. Here, we report that direction-selective ganglion cells can be identified in the salamander retina, where their existence had been unclear. Furthermore, there are two independent systems of direction-selective cells, and one of these combines direction selectivity with sensitivity to local motion. The output of these cells could assist in tracking moving objects and estimating their future position.

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Context-Dependent Accumulation of Sensory Evidence in the Parietal Cortex Underlies Flexible Task Switching

Switching behavior based on multiple rules is a fundamental ability of flexible behavior. Although interactions among the frontal, parietal, and sensory cortices are necessary for such flexibility, little is known about the neural computations concerning context-dependent information readouts. Here, we provide evidence that neurons in the lateral intraparietal area (LIP) accumulate relevant information preferentially depending on context. We trained monkeys to switch between direction and depth discrimination tasks and analyzed the buildup activity in the LIP depending on task context. In accordance with behavior, the rate of buildup to identical visual stimuli differed between tasks and buildup was prominent only for the stimulus dimension relevant to the task. These results indicate that LIP neurons accumulate relevant information depending on context to decide flexibly where to move the eye, suggesting that flexibility is, at least partly, implemented in the form of temporal integration gain control.

SIGNIFICANCE STATEMENT Flexible behavior depending on context is a hallmark of human cognition. During flexible behavior, the frontal and parietal cortices have complex representations that hinder efforts to conceptualize their underlying computations. We now provide evidence that neurons in the lateral intraparietal area accumulate relevant information preferentially depending on context. We suggest that behavioral flexibility is implemented in the form of temporal integration gain control in the parietal cortex.

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Predicting "When" in Discourse Engages the Human Dorsal Auditory Stream: An fMRI Study Using Naturalistic Stories

The hierarchical organization of human cortical circuits integrates information across different timescales via temporal receptive windows, which increase in length from lower to higher levels of the cortical hierarchy (Hasson et al., 2015). A recent neurobiological model of higher-order language processing (Bornkessel-Schlesewsky et al., 2015) posits that temporal receptive windows in the dorsal auditory stream provide the basis for a hierarchically organized predictive coding architecture (Friston and Kiebel, 2009). In this stream, a nested set of internal models generates time-based ("when") predictions for upcoming input at different linguistic levels (sounds, words, sentences, discourse). Here, we used naturalistic stories to test the hypothesis that multi-sentence, discourse-level predictions are processed in the dorsal auditory stream, yielding attenuated BOLD responses for highly predicted versus less strongly predicted language input. The results were as hypothesized: discourse-related cues, such as passive voice, which effect a higher predictability of remention for a character at a later point within a story, led to attenuated BOLD responses for auditory input of high versus low predictability within the dorsal auditory stream, specifically in the inferior parietal lobule, middle frontal gyrus, and dorsal parts of the inferior frontal gyrus, among other areas. Additionally, we found effects of content-related ("what") predictions in ventral regions. These findings provide novel evidence that hierarchical predictive coding extends to discourse-level processing in natural language. Importantly, they ground language processing on a hierarchically organized predictive network, as a common underlying neurobiological basis shared with other brain functions.

SIGNIFICANCE STATEMENT Language is the most powerful communicative medium available to humans. Nevertheless, we lack an understanding of the neurobiological basis of language processing in natural contexts: it is not clear how the human brain processes linguistic input within the rich contextual environments of our everyday language experience. This fMRI study provides the first demonstration that, in natural stories, predictions concerning the probability of remention of a protagonist at a later point are processed in the dorsal auditory stream. Results are congruent with a hierarchical predictive coding architecture assuming temporal receptive windows of increasing length from auditory to higher-order cortices. Accordingly, language processing in rich contextual settings can be explained via domain-general, neurobiological mechanisms of information processing in the human brain.

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Optimization of an Anti-poly(ethylene glycol) (anti-PEG) Cell-Based Capture System To Quantify PEG and PEGylated Molecules

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b03614

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Using Nanoliposomes To Construct a FRET-Based Ratiometric Fluorescent Probe for Sensing Intracellular pH Values

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b03632

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International Comparison of Enumeration-Based Quantification of DNA Copy-Concentration Using Flow Cytometric Counting and Digital Polymerase Chain Reaction

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b03076

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Unusual Photoconductive Property of Polyiodide and Enhancement by Catenating with 3-Thiophenemethylamine Salt

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC08595D, Communication

Hongtao Yu, Lijia Yan, Yaowu He, Hong Meng, Wei Huang
During our investigation of perovskite solar cell materials, we ser-endipitously discovered an unusual photoconductive property of polyiodide, which can be enhanced greatly through the interaction of in situ-formed polyiodide and...
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Biological and Related Applications of Pillar[n]arenes

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C6CC08967D, Feature Article

Sathiyajith Cuhananthan, Rafik Rajjak Shaikh, Qian Han, Yue Zhang, Kamel Meguellati, Ying-Wei Yang
Pillar[n]arenes are a new class of synthetic supramolecular macrocycles streamlined by their particular pillar-shaped architecture which consists of an electron-rich cavity and two fine-tuneable rims. The ease and diversity of...
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Transcription Factor Response Elements on Tip: A Sensitive Approach for Large-Scale Endogenous Transcription Factor Quantitative Identification

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b03150

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Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b03394

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Development of APTES-Decorated HepG2 Cancer Stem Cell Membrane Chromatography for Screening Active Components from Salvia miltiorrhiza

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b02709

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Neck Pain and Acute Dysphagia

Abstract

The acute tendinitis of the longus colli muscle is an unusual diagnosis in the cases of acute dysphagia with cervical pain. Is a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the prevertebral space and can cause pharyngeal swelling with impaired swallow. It is absolutely critical to make the differential diagnosis with deep cervical infections in order to avoid invasive treatments.

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Associations among oral health-related quality of life, subjective symptoms, clinical status, and self-rated oral health in Japanese university students: a cross-sectional study

Abstract

Background

The present study aimed to elucidate the associations among self-rated oral health, clinical oral health status, oral health behaviors, subjective oral symptoms, and oral health-related quality of life (OHRQoL) in a group of Japanese university students.

Methods

Of 2051 participants, 2027 (98.83%) students received an optional oral examination and answered a questionnaire including items regarding age, sex, self-rated oral health, oral health behaviors, subjective oral symptoms, and OHRQoL [The Oral Health Impact Profile (OHIP)-14]. On oral examination, the decayed, missing, and filled teeth (DMFT) score, Community Periodontal Index (CPI), the percentage of teeth showing bleeding on probing (%BOP), and malocclusion were recorded. Structural equation modelling (SEM) analysis was used to test associations.

Results

The mean score (± SD) of OHIP-14 was 1.92 ± 5.47. In the SEM analysis, the final model showed that self-rated oral health, oral pain, malocclusion, and the DMFT score were directly associated with the OHRQoL, and subjective symptoms of temporomandibular disorders (TMD) and recurrent aphthous stomatitis were both directly and indirectly associated (p < 0.05). CPI, %BOP, and oral health behaviors were excluded from the final model.

Conclusions

OHRQoL was associated with self-related oral health, subjective symptoms of TMD, oral pain and stomatitis, DMFT, and malocclusion in this group of Japanese university students.

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Effectiveness of bovine-derived xenograft versus bioactive glass with periodontally accelerated osteogenic orthodontics in adults: a randomized, controlled clinical trial

Abstract

Background

Periodontally accelerated osteogenic orthodontics (PAOO) combines periodontal therapy with orthodontic therapy, which minimises treatment time. This study compared the effectiveness of a bovine-derived xenograft with that of bioactive glass when combined with PAOO for the treatment of adult patients with moderate crowding of the teeth.

Methods

In this prospective, single-masked clinical trial, 33 orthodontic patients (20 women, 13 men; mean age 21.2 ± 1.43 [18 − 27] years), were randomly allocated to one of three groups. Group 1 underwent a modified corticotomy technique on the labial side only, whereas group 2 was treated with the same technique combined with PAOO using a bovine-derived xenograft and group 3 was treated in the same way but combining PAOO with bioactive glass. The total treatment duration was recorded from the start of active orthodontic treatment, immediately after corticotomy, and at the time of debonding. Probing depth was evaluated clinically and bone density and root length were evaluated radiographically on the day of surgery (baseline, T1), post-treatment at debonding (T2), and 9 months post-treatment (T3).

Results

The duration of orthodontic treatment was markedly reduced to an average of 11.4 ± 0.14 weeks in all groups. All probing depths were < 3 mm, the interdental papillae were well preserved, there was no loss of tooth vitality, and there was no evidence of significant apical root resorption at any time interval. All groups showed a decrease in mean bone density at T2 followed by an increase at T3. The net percentage change that occurred between baseline and 9 months post-treatment was significantly different between the three groups. Groups 2 and 3, where grafts were incorporated, demonstrated a statistically significant greater increase in bone density than group 1 at T3.

Conclusion

Combination of orthodontic treatment and periodontal surgery is an effective treatment for adult patients that decreases the duration of active treatment and reduces the risk of root resorption. Use of a bovine-derived xenograft with modified corticotomy provided superior benefits in terms of increased bone density than did the use of bioactive glass.

Trial registration

The study was retrospectively registered at ClinicalTrials.gov under Clinical Trial Registration Number: NCT02796911.

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Antibiotic prophylaxis in reduction mammaplasty: study protocol for a randomized controlled trial

The role of antibiotics in surgical procedures where the risk of surgical site infection (SSI) is low remains uncertain. There is, to date, no evidence to justify the routine use of antibiotics in postoperativ...

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Advanced Animal Model of Colorectal Metastasis in Liver: Imaging Techniques and Properties of Metastatic Clones

The ability of metastatic clones to colonize distant sites depends on their proliferation capacity and/or their ability to survive in the host microenvironment without significant proliferation. Here, we present an animal model that allows quantitative visualization of both types of liver colonization by metastatic clones.

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Supporting data and code for 2016 Jacob et al Nat Neurosci paper

Jeffery, KJ; (2016) Supporting data and code for 2016 Jacob et al Nat Neurosci paper. [Dataset]. 10.14324/000.ds.1529898 . Green open access

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A Simultaneous Equation Approach to Estimating HIV Prevalence with Non-Ignorable Missing Responses

Marra, G; Radice, R; Barnighausen, T; Wood, SN; McGovern, ME; (2016) A Simultaneous Equation Approach to Estimating HIV Prevalence with Non-Ignorable Missing Responses. Journal of the American Statistical Association 10.1080/01621459.2016.1224713 . (In press).

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Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children

Bienczak, A; Cook, A; Wiesner, L; Mulenga, V; Kityo, C; Kekitiinwa, A; Walker, AS; Bienczak, A; Cook, A; Wiesner, L; Mulenga, V; Kityo, C; Kekitiinwa, A; Walker, AS; Owen, A; Gibb, DM; Burger, D; McIlleron, H; Denti, P; - view fewer (2016) Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children. Journal of Antimicrobial Chemotherapy 10.1093/jac/dkw388 . (In press). Green open access

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Beyond methylammonium lead iodide: prospects for the emergent field of ns(2) containing solar absorbers

Ganose, AM; Savory, CN; Scanlon, DO; (2016) Beyond methylammonium lead iodide: prospects for the emergent field of ns(2) containing solar absorbers. Chemical Communications 10.1039/c6cc06475b . (In press). Green open access

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A simple method for estimating the effective detection distance of camera traps

Hofmeester, T; Rowcliffe, M; Jansen, PAJ; (2016) A simple method for estimating the effective detection distance of camera traps. Remote Sensing in Ecology and Conservation 10.1002/rse2.25 . (In press). Green open access

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On the adoption of privacy-enhancing technologies

Caulfield, T; Ioannidis, C; Pym, D; (2016) On the adoption of privacy-enhancing technologies. In: Zhu, Q and Alpcan, T and Panaousis, E and Tambe, M and Casey, W, (eds.) Decision and Game Theory for Security: Proceedings of the 7th International Conference, GameSec 2016. (pp. pp. 175-194). Springer International Publishing Green open access

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