Neuroinvasive microbes are capable of applying their influences on the autonomic nervous system (ANS) of the host followed by the involvement of central nervous system (CNS) by releasing extracellular metabolites that may cause alterations in the biochemical and neurophysiological environment. Consequently synaptic, neuroendocrine, peripheral immune, neuro-immune, and behavioural responses of the host facilitate the progression of infection. The present study was designed to extrapolate the effects of crude and purified extracellular peptides of neuropathogenic bacteria on behavioural responses and neurotransmission of Sprague Dawley (SD) models. Listeria monocytogenes (Lm) and Neisseria meningitides (Nm) were isolated from the 92 cerebrospinal fluid (CSF) samples collected from mentally compromised patients. Bacillus cereus (Bc) and Clostridium tetani (Ct) were also included in the study. All bacterial strains were identified by the standard biochemical procedures. Filter sterilized cell free cultural broths (SCFBs) were prepared of different culture media. Behavioural study and neurotransmitter analysis were performed by giving an intraperitoneal (i.p.) injection of each bacterial SCFB to four groups (Test; n = 7) of SD rats, whereas two groups each (Control; n = 7) received a nutrient broth (NB) control and sterile physiological saline control, respectively. Extracellular bioactive peptides of these bacteria were screened and purified. All experiments were repeated using purified bacterial peptides on SD rat cohorts. Our study indicated promising behavioural changes, including fever, swelling, and hind paw paralysis, in SD rat cohorts. Purified bacterial peptides of all bacteria used in the present study elicited marked changes in behaviour through the involvement of the autonomic nervous system. Furthermore, these peptides of meningitis bacteria were found to potently affect the dopaminergic neurotransmission in CNS.
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Σάββατο 1 Ιουλίου 2017
Pathogens, Vol. 6, Pages 27: Implications of Neuroinvasive Bacterial Peptides on Rodents Behaviour and Neurotransmission
IJMS, Vol. 18, Pages 1415: Theranostic Liposome–Nanoparticle Hybrids for Drug Delivery and Bioimaging
Advanced theranostic nanomedicine is a multifunctional approach which combines the diagnosis and effective therapy of diseased tissues. Here, we investigated the preparation, characterization and in vitro evaluation of theranostic liposomes. As is known, liposome–quantum dot (L–QD) hybrid vesicles are promising nanoconstructs for cell imaging and liposomal-topotecan (L-TPT) enhances the efficiency of TPT by providing protection against systemic clearance and allowing extended time for it to accumulate in tumors. In the present study, hydrophobic CdSe/ZnS QD and TPT were located in the bilayer membrane and inner core of liposomes, respectively. Dynamic light scattering (DLS), zeta potential (ζ) measurements and fluorescence/absorption spectroscopy were performed to determine the vesicle size, charge and spectroscopic properties of the liposomes. Moreover, drug release was studied under neutral and acidic pH conditions. Fluorescence microscopy and flow cytometry analysis were used to examine the cellular uptake and intracellular distribution of the TPT-loaded L–QD formulation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to investigate the in vitro cytotoxicity of the formulations on HeLa cells. According to the results, the TPT-loaded L–QD hybrid has adequate physicochemical properties and is a promising multifunctional delivery vehicle which is capable of a simultaneous co-delivery of therapeutic and diagnostic agents.
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Breast cancer rate reflects lifestyle - Independent Online
Independent Online | Breast cancer rate reflects lifestyle Independent Online Many cancers are linked to these lifestyle factors, including those of the mouth and larynx, lung, stomach, pancreas, liver, bowel, breast, prostate and kidney. Professor Martin Wiseman, medical and scientific adviser for the WCRF, said: "We know that ... |
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Abuse Potential for Narcolepsy Drugs? The FDA Wants to Know
For many drugs on the path to Food and Drug Administration (FDA) approval, the road to the prescription pad runs through "abuse potential assessment." Few people in the world know more about the topic than Jack E. Henningfield, PhD, professor adjunct of Behavioral Biology in the Department of Behavioral Sciences at the Johns Hopkins University school of Medicine.
Henningfield was an advisor on a study on the abuse potential of JZP-110, and a co-author on a poster describing their findings which was on display at the recent American Professional Sleep Societies (APSS) meeting in Denver. The poster was entitled, A Randomized, Double-Blind, Placebo-Controlled, Crossover Study for Evaluation of Human Abuse Liability of JZP-110.
"What the FDA promotes is for developers to find drugs that work as well or better than amphetamines, but have a lower risk of abuse profile," explains Henningfield. Up until a decade ago, drugs for helping people stay alert and awake were mostly "schedule II" stimulant drugs.
"Amphetamines work for that [staying alert], but they are highly abusable drugs," he says. "What's really exciting about JZP-110 is that it looks like it has a substantially lower risk of abuse. For the FDA to be assured that a new drug really is of lower abuse potential, it requires a lot of questions to be answered by scientific studies.
"For example, FDA wants to know where it works in the brain and what it does," continues Henningfield. "Does it look like amphetamine? We want to know if it looks like an abusable drug in animals. Does it look less abusable by the many tests we rely upon?"
There are many studies and at this point, Henningfield says, "the signals suggest a new medicine with significantly less abuse potential than amphetamine."
Although all lines of evidence are important, the most important single study to evaluate the relative abuse potential of new drugs is the human abuse potential study. Thus, this human abuse liability study "is a big deal" in assessing JZP-110.
Troublesome findings can halt a drug's approval, and it's certainly a phenomenon that Henningfield has seen during his abuse liability work that started in the 1970s. High profile celebrity deaths have fueled a renewed focus on abuse potential by the public, but it's nothing new for the FDA that has been evaluating drugs for abuse potential for decades, or for scientist such as Henningfield, who has studied countless pharmaceuticals and non-prescribed substances. "I live and breathe abuse potential assessment," he says.
The American Sleep & Breathing Academy (ASBA) sat down with Henningfield to learn more about his specific work with JZP-110, as well as the overall topic of abuse potential assessment.
ASBA: What is the rationale behind abuse potential assessment?
Jack E. Henningfield, PhD, professor adjunct of Behavioral Biology in the Department of Behavioral Sciences at the Johns Hopkins University school of Medicine: Any time you are dealing with and developing a drug that is a new drug—a new molecular or chemical entity— that affects the central nervous system [CNS] you have to do what is called an abuse potential assessment for the FDA. In the same way that you have to look at the safety from the perspective of cardiovascular risk and liver disease and everything else, you have to thoroughly investigate its abuse potential risk.
ASBA: What is your definition of abuse potential?
Henningfield: Abuse potential is the risk that a drug will be used by people for inappropriate reasons like getting high, and that it might pose a risk for patients, and/or might be a target for people who are not patients. When the FDA knows that, they have to look at the data and base a recommendation as to how to restrict the drug, under what is called the Controlled Substance Act laws and regulations.
ASBA: What are some examples of schedule I drugs?
Henningfield: Drugs that have no medical use but carry a significant risk of addiction or abuse like heroin are placed in schedule I. Drugs that are highly addictive but have medical use and are approved are placed in schedule II—that would be like oxycodone or morphine or amphetamine.
ASBA: What types of wakefulness drugs have there been?
Henningfield: For helping people stay alert and awake, until a decades or so ago, the main drugs were the schedule II stimulus. An amphetamine works for that, but it's a highly abusable drug, and so what FDA promotes is for developers to find drugs that work as well or better than amphetamines, but have a lower risk of abuse profile. What's really exciting about JZP-110 is that it looks like it has a substantially lower risk of abuse.
ASBA: What types of conclusions were researchers developing decades ago?
Henningfield: What they found decades ago was that if you take people from the general population who do not abuse drugs and give them drugs of abuse, some people like them and others don't. But if you take people who have histories of drug abuse, they are kind of like the wine connoisseurs who know the good wine and can even tell you what type of wine it is by tasting it. In studies like this, you look for people who have histories of abusing the category of drug of interest because are expert in evaluating such drugs. That way, you have people who are sensitive. They know what they are looking for when they are looking for an abusable drug. They also represent a population of great concern for abuse of that category of drug.
ASBA: And what were the particulars of the JZP-110 study?
Henningfield: So in this case, there were 43 adults that ended up in the study. Thirty-seven completed all of the conditions, and they all had histories of recreational stimulant abuse. For abuse potential studies this is a large and adequately powered size to provide reliable findings. The volunteers must bepeople who were healthy; they weren't currently so heavily using that they could not safely and ethically participate, but they were all people who knew a good stimulant for abuse when they felt it. In other words, they've tried stimulants like cocaine and amphetamine and they like to use them.
Then, in a very careful laboratory environmentthat is designed to be safe and ethical, and provide valid results, they participate as in patients, on an in-patient research unit. And that way you can make sure that they are safe, not getting any other drugs and that you can get reliable and valid data. You give them what is called the positive control, and the positive control will be something that you know produced an affect—and you also are using it to compare the new drug.
ASBA: What comparisons can be made to other medications?
Henningfield: Abuse potential is always relative. In this case, the comparator drug was a weak stimulant called Phentermine. It is a stimulant that's placed in schedule IV of the controlled substances act. Remember I said amphetamine was schedule II, so Phentermine is down the road quite a ways. If caffeine is a stimulant, but it's not scheduled because it has been used for millennia in a generally safe manner and its use and even dependent use by some is accepted by society.
ASBA: If caffeine were introduced today, what would be its classification?
Henningfield: If caffeine was a new drug, I think the FDA might say, you know what, we're going to think about placing it in III, IV, or V. I'm not sure where they would put it, but from an abuse potential perspective it would seem to be well within the range of many Schedule IV drugs with respect to risk for compulsive use, physical dependence, and reinforcing effects.
In other words, Phentermine is closer to caffeine than it is to amphetamine, but it does have a documented abuse potential—and some people do abuse it, so that is the comparator. You look at how quickly does its effects onset, and what effects does it produce and how strong the effects are. The single most powerful measure is how much you like it right now. It seems so simple, but this measure of abuse potential does go back a half a century—liking at the moment.
ASBA: How did you account for dosage variations in the JZP-110 study?
Henningfield: Another characteristic of a valid study, is you push the dose…for the purpose of the study, it was assumed that it was around 300 milligrams. What's important is that on the street, people take higher doses than what are approved. What you do for a valid study is you push the dose, basically as high as you think you safely can, and in this case it went up to 1,200 milligrams. And that was considered, based on all of the preliminary data, an extremely high dose. A dose where, quite frankly, you start getting at least some side effects that people don't like. That is an important factor that makes this a powerful study. Depending on how you look at it, it went up to 3 or 4 times what is likely to be the highest clinical dose.
ASBA: What did you find when you did that?
Henningfield: What we found is that every dose of JZP-110, the liking score was lower than the high dose Phentermine. That doesn't necessarily mean that it is going to be scheduled less restrictively, but it fits with the other data that we are seeing, that conservatively, it looks no more abusable than Phentermine—and if anything, on the lower side. So for someone like me who is on the search for medicine with lower risk of abuse, lower risk of diversion, lower risk of addiction—to help people with medical needs, this is what we are looking for.
ASBA: What happens now? What will they do with these results?
Henningfield: The company will ultimately develop a new drug application to the FDA, and I don't know what their timeline is. At this point, on many aspects of the research program, FDA has input on the studies, like this abuse potential study. The NDA will have a section called the Integrated Safety Summary. That will look at all of the safety profile, from all the data that they have. It will look at how well it works – its efficacy. Everything that is related to safety, benefits, labeling will be carefully considered by FDA. One part of that package will be called the abuse potential assessment.
ASBA: What will the abuse potential document look like?
Henningfield: The abuse potential assessment will be a major document that will bring together everything that is potentially relevant to the abuse potential; where does it work, how does it act? What did the animal data look like? In animals, by the way JZP-110 it looks less abusable than amphetamine. The human abuse potential study, among all of the lines of evidence will be one of the single most important studies that FDA will consider, and that the company will consider in their recommendation. It's premature for me to say what the recommendation would be, because all lines of evidence, including the pivotal phase 3 efficacy and safety data need to be carefully assess in the abuse potential section that has yet to be developed.
ASBA: What is the profile of medicine at this point?
Henningfield: At this point, what we see from this study, is the profile of a medicine that looks more in the range of the schedule IV drugs than the schedule II drugs. I'm being very careful here, because there will be a single sentence at the end of the abuse potential assessment, it will be probably 100 or 200 pages with 1,000 or so pages of supplements, and there will be one sentence at the end recommending the schedule placement, a single number.
Whatever the number will be is to be determined, but now it's exciting because it looks like it's heading in the direction of something that will have a lower risk for abuse than strong stimulants like amphetamine. By law of the Controlled Substances Act, FDA develops its own recommendation, and they will look at what they call eight factors, and they will come up with their own scheduling placement number. Generally, when the companies are working with experts in this area, they try to come up with what they believe represents all of the scientific data and will be credible to the FDA.
We will all work together to make sure that we make a recommendation that will be credible and hopefully accepted by the FDA. By law, the National Institute on Drug Abuse (NIDA) will also have input and the input of FDA and NIDA will be the basis for the Assistant Secretary of the Department of Health and Human Services's recommendation to the US Department of Justice (DOJ). The DOJ's Drug Enforcement Administration, will take the DHHS's recommendation into consideration as it develops its proposed rule for scheduling.
This scheduling recommendation will be published in the Federal Register, allowing typically 60 days for public comment. After the comment period, DOJ/DEA will publish the final rule – the official schedule for the drug. Then the drug labeling can be completed and the drug can be marketed. In practice, FDA's recommendation is rarely deviated from by NIDA and DOJ/DEA.
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Tunga penetrans
Tunga penetrans: a type of burrowing flea that has also been referred to as the chigger flea, sand flea, chigoe, jigger, nigua, pigue, or le bicho de pe. It causes an infestation of humans known as tungiasis. Tunga penetrans is found in tropical and subtropical regions of the world, including Mexico to South America, the West Indies and Africa. The fleas live in sandy climates, including beaches, stables and farms. Humans are infected when pregnant females burrow into the skin. This stage is usually painless. Later, itching and irritation develop as the females develop fully. The inflammation may be severe and lead to ulcer formation. When the lesions occur in the feet, the affected person may have difficulty walking. Secondary bacterial infections are a known complication of tungiasis.
MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
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IJMS, Vol. 18, Pages 1384: Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches
Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term "metabolic epilepsy" can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Some of these disorders are amenable to specific treatment interventions; hence timely and appropriate diagnosis is critical to improve outcomes. In this review, we discuss those disorders in which epilepsy is a dominant feature and present an approach to the clinical recognition, diagnosis, and management of these disorders, with a greater focus on primarily treatable conditions. Finally, we propose a tiered approach that will permit a clinician to systematically investigate, identify, and treat these rare disorders.
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Waste Derived Bioeconomy in India: A Perspective
Publication date: Available online 1 July 2017
Source:New Biotechnology
Author(s): Venkata Mohan S., Chiranjeevi P., Shikha Dahiya, Naresh Kumar A.
Environmental and climatic change issues, population explosion, rapid urbanization, depletion of fossil reserves, need for energy security, huge waste generation, etc. are some of the inherent issues associated with the fossil based linear economy which need sustainable attention. In this realm, the world is gradually transforming from fossil-based economy to a sustainable circular economy. The biogenic waste which is generated in enormous quantity in India can be considered as potential feedstock for structuring the bio-based economy. This communication makes a comprehensive attempt to depict the need for waste based bioeconomy in the Indian perspective. Waste is now being perceived as a resource with value and believed to supplement petroleum feedstock to a great extent if properly utilized. The necessity to induce waste as the core element for the future economic model which allows sustainable development was discussed. The review establishes drivers for the bioeconomy and structures the waste based bioeconomy in a sustainable format to address the futuristic need, scope and opportunity envisaged in the business and economic realm. The enabling technologies/processes that can be applied for biogenic wastes valorisation were elaborated. Circularizing the economy in a waste biorefinery model for the production of biobased products including bioenergy is illustrated.
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EU ambition to build the world’s leading bioeconomy—uncertain times demand innovative and sustainable solutions
Publication date: Available online 1 July 2017
Source:New Biotechnology
Author(s): John Bell, Lino Paula, Thomas Dodd, Szilvia Németh, Christina Nanou, Voula Mega, Paula Campos
This article outlines the current context and the development of the European Bioeconomy Strategy. It analyses the current situation, challenges and needs for EU action and concludes with the next steps that the European Commission will undertake to review and update the Bioeconomy Strategy. Bioeconomy offers great opportunities to realising a competitive, circular and sustainable economy with a sound industrial base that is less dependent on fossil carbon. A sustainable bioeconomy also contributes to climate change mitigation, with oceans, forests and soils being major carbon sinks and fostering negative CO2 emissions. The EU has invested significantly in research and innovation in this field and the European Commission is committed to lead on European bioeconomy strategy.
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Tony Gwynn's Family Sues Tobacco Industry, Seeking Recourse Over Fatal Habit - New York Times
Washington Post | Tony Gwynn's Family Sues Tobacco Industry, Seeking Recourse Over Fatal Habit New York Times The family of Tony Gwynn, a baseball Hall of Famer who died of salivary gland cancer in 2014, filed a wrongful-death lawsuit Monday against the tobacco industry, charging that Gwynn had been manipulated into the addiction to smokeless tobacco that ... The family of a baseball legend is suing 'Big Tobacco' over his death from cancerBusiness Insider Tony Gwynn's family suing tobacco industry over his death from cancerWashington Post Tony Gwynn's children put blame on tobacco industryLos Angeles Times Deadspin all 121 news articles » |
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Serum cytokine profile in pediatric Sweet’s syndrome: a case report
Sweet's syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an a...
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Genome-wide identification and characterization of the SPL gene family in Ziziphus jujuba
Source:Gene, Volume 627
Author(s): Fenjuan Shao, Qiang Lu, Iain W. Wilson, Deyou Qiu
SQUAMOSA Promoter-Binding Protein-Likes (SPLs) are plant specific transcription factors playing important roles in plant growth and development. The SPL gene family has been studied in various plant species; however, there is no report about SPLs in Zizyphus jujuba. In this study, we identified 18 putative ZjSPL genes in Z. jujuba using a genome-wide analysis. Sequence features, gene structures, conserved domains and motifs were analyzed. The phylogenetic relationships of SPLs in Z. jujuba and A. thaliana were revealed. A total of 5 pairs of ZjSPLs were identified, suggesting the importance of gene duplication in SPL gene expansion in Z. jujuba. In addition, 11 of the 18 ZjSPLs, belonging to G1, G2 and G5 subgroups, were found to be targets of miR156, suggesting the conservation of miR156-mediated posttranscriptional regulation in plants. Expression analysis revealed that eight ZjSPL genes were responsive to the infection of witches'-broom phytoplasma. Our results provide a basis for the further elucidation of the biological function of ZjSPLs and their regulation in witches'-broom disease.
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IL-6 and IL-18 cytokine gene variants of pulmonary tuberculosis patients with co-morbid diabetes mellitus and their household contacts in Hyderabad
Source:Gene, Volume 627
Author(s): Meenakshi Ponnana, Ramya Sivangala, Lavanya Joshi, Vijayalakshmi Valluri, Sumanlatha Gaddam
PurposeAssociation of cytokine genes reflects their susceptibility towards infection and disease in household contacts (HHC) of pulmonary tuberculosis (PTB) patients. Hyperglycemia, a common factor in diabetics might influence their risk towards mycobacterium tuberculosis infection and disease development. This study determines the association of IL-6 and IL-18 cytokine gene variants of TB patients with diabetes mellitus (TBDM) and their HHC in Hyderabad.MethodsSingle nucleotide polymorphisms of IL-6 (-174 G>C and -572 G>C) and IL-18 (-137 G>C and -607 C>A) cytokine genes were genotyped by Amplification Refractory Mutation System and Restriction Fragment Length polymerase chain reaction in total of 705 subjects comprising of TBDM, their HHC, PTB, DM and Healthy controls (HC).ResultsAt IL-6 -174G>C variant, GG genotype, G allele in TBDM and TBDM HHC, at -572G>C variant, C allele in TBDM and GG haplotype in TBDM HHC were showing positive association, however DM have not shown any association at IL-6 polymorphic sites. With respect to the IL-18 gene polymorphisms, at -137 G>C variant, GG genotype was positively associated in PTB while at -607 C>A variant positive association was shown with AC genotype in TBDM, their HHC and DM; GACC diplotype in TBDM and GCGC in PTB.ConclusionOur findings suggest that susceptible combination of IL-6 and IL-18 cytokine genes associated with disease in the HHCs highlight their risk of inclination towards the disease.
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Mesenchymal stem cells can induce regulatory T cells via modulating miR-126a but not miR-10a
Source:Gene, Volume 627
Author(s): Maryam Khosravi, Mohammad Hossein Karimi, Mahdokht Hossein Aghdaie, Mehdi Kalani, Sina Naserian, Ali Bidmeshkipour
Among the different immunosuppressive properties attributed to mesenchymal stem cells (MSCs), one relies on their ability to induce regulatory T cells (iTregs) from conventional T cells under particular inflammatory context. Stable Foxp3 expression plays a major role in the phenotypic and functional stability of iTregs. However, the mechanism behind Foxp3 induction in iTregs by MSCs remains unknown. Here, we assessed the possible effect of MSCs on miR-126a and miR-10a expression in iTregs and, consequently on Foxp3 stability, a regulatory pathway that has not yet been explored. We first demonstrated that in vitro MSC-iTreg generation was directly associated with strong modifications of miR-126a. We next infused high doses of MSCs in a murine model of allogeneic skin transplantation (C57BL/6 into Balb/c). This treatment significantly prolonged skin allograft survival compared to PBS treated mice. When splenocytes from grafted mice were collected, we observed that the expression of Foxp3 gene was elevated at day 5 and 10 post-graft merely in MSCs treated mice. Moreover, Foxp3 expression was not associated with modified miR-10a expression comparable to in vitro experiments. Thus, our data identify a solid mechanism where MSCs induce conversion of conventional T cells to iTregs through strong modifications of miR-126a. Although miR-10a expression level remains unchanged in vitro and in vivo, we observed expression of this miR in MSC-DC condition.
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Mitochondrial genome of Helice tientsinensis (Brachyura: Grapsoidea: Varunidae): Gene rearrangements and higher-level phylogeny of the Brachyura
Source:Gene, Volume 627
Author(s): Zhao-Zhe Xin, Yu-Liu, Dai-Zhen Zhang, Zheng-Fei Wang, Hua-Bin Zhang, Bo-Ping Tang, Chun-Lin Zhou, Xin-Yue Chai, Qiu-Ning Liu
The mitochondrial genome (mt genome) provides important information for understanding molecular evolution and phylogeny. The further understand the molecular evolution and phylogeny of Helice tientsinensis, the complete mt genome was determined. It is 16,212bp long and includes 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes and a control region. The genome composition of H. tientsinensis was highly A+T biased 69.0% and showed negative AT skew (−0.017) and GC skew (−0.289). One PCG, all rRNAs and 12 of the tRNAs appeared to be rearranged with respect to the pancrustacean ground pattern gene order. Tandem duplication, followed by random deletion, is widely considered to explain translocation of mitochondrial genes. Consecutive recombinations events could explain inversions of genes. The phylogenetic analyses showed that H. tientsinensis has close relationships with Eriocheir japonica sinensis, E. j. hepuensis and E. j. japonica; this indicated that H. tientsinensis belongs in the Grapsoidea, part of the Varunidae family. This study provides evidence for a better understanding of gene rearrangements, as well as the evolutionary status of H. tientsinensis and related species.
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Identification of potential crucial genes associated with steroid-induced necrosis of femoral head based on gene expression profile
Source:Gene, Volume 627
Author(s): Zhe Lin, Yongsheng Lin
The aim of this study was to explore potential crucial genes associated with the steroid-induced necrosis of femoral head (SINFH) and to provide valid biological information for further investigation of SINFH. Gene expression profile of GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using LIMMA package. After functional enrichment analyses of DEGs, protein–protein interaction (PPI) network and sub-PPI network analyses were conducted based on the STRING database and cytoscape. In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up-regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and Il7R), and the downregulated DEGs were mainly enriched in muscle system process (e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and 300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based on both subgraph centrality and degree centrality evaluation. These three genes interacted with each other in the network. Furthermore, the significant network module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These genes were mainly enriched in functions like muscle system process. The DEGs related to the regulation of immune system process (e.g. Fcer1A and Il7R), and DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be closely associated with the progress of SINFH, which is still needed to be confirmed by experiments.
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Editorial Board
Source:American Journal of Otolaryngology, Volume 38, Issue 4
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Table of Contents
Source:American Journal of Otolaryngology, Volume 38, Issue 4
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Guidelines for Contributing Authors
Source:American Journal of Otolaryngology, Volume 38, Issue 4
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miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma
miRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including c...
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Sharing hope, joy - McGlasson uses music in ministry - Miami News Record
Miami News Record | Sharing hope, joy - McGlasson uses music in ministry Miami News Record Doctors discovered she had developed thyroid cancer. At the same time, she received a call many dream about. Officials with Redemption World Records heard a recording of her music. They had an opening to develop a new artist. "I thought 'is this a ... |
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Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08)
Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of th...
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Inhibition of HDAC6 activity through interaction with RanBPM and its associated CTLH complex
Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase that promotes many cellular processes that lead to cell transformation and tumour development. We previously documented an interaction betw...
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Precision oncology using a limited number of cells: optimization of whole genome amplification products for sequencing applications
Sequencing analysis of circulating tumor cells (CTCs) enables "liquid biopsy" to guide precision oncology strategies. However, this requires low-template whole genome amplification (WGA) that is prone to error...
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The expression of transglutaminase 2 (TG-2) in oral squamous cell carcinoma and its clinical significance
Glutamine has a very important role in the human body, including pH balance in an acidic environment, as well as supporting the TCA cycle in cancer cell growth. However, the expression of transglutaminase-2 (TG-2) in oral cancer growth related to renal function is unknown. Here we examined TG-2 and its expression as a prognostic tool.
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Metformin reduces intrahepatic fibrosis and intrapulmonary shunts in biliary cirrhotic rats
Liver fibrosis causes portal hypertension which dilates collateral vasculature and enhances extra-hepatic angiogenesis including intrapulmonary shunts, which subsequently complicates with hepatopulmonary syndrome. Metformin is an anti-diabetic agent which possesses anti-inflammation and anti-angiogenesis properties. This study evaluated the effect of metformin treatment on liver and lung in a non-diabetic rat model with biliary cirrhosis induced via common bile duct ligation (CBDL).
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A modified tongue depressor facilitates the insertion of ProSeal laryngeal mask airway: Comparison with digital and introducer techniques
The larger and softer cuff of the ProSeal laryngeal mask airway (LMA) may cause difficulty in insertion. We introduced a novel technique using a modified tongue depressor to aid the ProSeal LMA insertion.
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Urolithiasis secondary to primary obstructive megaureter in an adult: a case report
Primary obstructive megaureter is relatively uncommon in adults. This condition usually regresses spontaneously or is treated during infancy. It can remain asymptomatic for decades until adulthood when symptom...
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Suppressive effects of thermal-treated oyster shells on cadmium and copper translocation in maize plants
Abstract
The effect of varied concentrations of thermal-treated oyster shells (TOS) on the suppression of cadmium (Cd) and copper (Cu) uptake and translocation into the shoots of maize plants was examined. Maize plants were grown in Cd- and Cu-contaminated Andosol for 70 days. The concentration of mobile Cd (extracted with 1 M NH4NO3) decreased with increasing TOS applications, whereas an increase in the concentration of mobile Cu in soil resulted from cumulative TOS additions. The addition of 2% TOS had no prohibitive effects on Cd uptake in maize shoots, but the 4 and 8% TOS treatments decreased Cd accumulation in shoots by 41 and 59%, respectively. The possible mechanisms underlying Cd suppression in maize shoots were the enhanced Cd adsorption caused by pH-induced increases in the negative charge of the soil and the antagonistic effects of Ca resulting from competition for exchange sites at the root surface. Cu accumulation in maize shoots increased by 34, 51, and 53% with the addition of 2, 4, and 8% TOS, respectively, but this increase was not observed for Cd accumulation. These results suggested that, in multi-metal-contaminated soils, attention should be paid to the potential mobility of target metals and the pH of the contaminated soil. From a plant physiological perspective, contaminated soils slightly reduced photosynthetic performance. However, the addition of TOS to the soil at levels higher than 4% substantially decreased photosynthetic performance, indicating that CaO-based suppressants at critical loads might damage the net photosynthetic rates of sensitive maize plants.
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Simultaneous effect of dissolved organic carbon, surfactant, and organic acid on the desorption of pesticides investigated by response surface methodology
Abstract
Desorption of pesticides (fenobucarb, endosulfan, and dichlorodiphenyltrichloroethane (DDT)) from soil to aqueous solution with the simultaneous presence of dissolved organic carbon (DOC), sodium dodecyl sulfate (SDS), and sodium oxalate (Oxa) was investigated in batch test by applying a full factorial design and the Box–Behnken response surface methodology (RSM). Five concentration levels of DOC (8 to 92 mg L−1), SDS (0 to 6.4 critical micelle concentration (CMC)), and Oxa (0 to 0.15 M) were used for the experiments with a rice field topsoil. The results of RSM analysis and analysis of variance (ANOVA) have shown that the experimental data could be well described by quadratic regression equations with determination coefficients (R 2) of 0.990, 0.976, and 0.984 for desorption of fenobucarb, endosulfan, and DDT, respectively. The individual effects and interaction of DOC, SDS, and Oxa were evaluated through quadratic regression equations. When the aqueous solution includes 50 mg L−1 DOC, 3.75 CMC SDS, and 0.1 M Oxa, the maximum desorption concentrations of fenobucarb, endosulfan, and DDT were 96, 80, and 75 μg L−1, respectively. The lowest concentration of SDS, DOC, and Oxa caused the minimum desorption. This point at conditions of concern for flooding water is high content of organic compounds causing potentially high contamination by desorption, and the remarkably lower desorption at organic matter-free conditions. The suspended organic matter is one of the common characteristics of flooding and irrigation water in rice fields, and surfactants from pollution increase the problem with desorption of legacy pesticides in the rice fields.
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Cancer survivor doctors bounce back to practice - Times of India
Times of India | Cancer survivor doctors bounce back to practice Times of India Dr Takhatsinh Chauhan (56), a Silvassa-based paediatrician who has been practising for 20 years, survived tongue cancer. "I was operated on January 2 and my food-pipe was removed. I was discharged from hospital on January 17 and started attending to ... |
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Apparent diffusion coefficient as it relates to histopathology findings in post-chemotherapy nephroblastoma: a feasibility study
Abstract
Background
Nephroblastomas represent a group of heterogeneous tumours with variable proportions of distinct histopathological components.
Objective
The purpose of this study was to investigate whether direct comparison of apparent diffusion coefficient (ADC) measurements with post-resection histopathology subtypes is feasible and whether ADC metrics are related to histopathological components.
Materials and methods
Twenty-three children were eligible for inclusion in this retrospective study. All children had MRI including diffusion-weighted imaging (DWI) after preoperative chemotherapy, just before tumour resection. A pathologist and radiologist identified corresponding slices at MRI and postoperative specimens using tumour morphology, the upper/lower calyx and hilar vessels as reference points. An experienced reader performed ADC measurements, excluding non-enhancing areas. A pathologist reviewed the corresponding postoperative slides according to the international standard guidelines. We tested potential associations with the Spearman rank test.
Results
Side-by-side comparison of MRI–DWI with corresponding histopathology slides was feasible in 15 transverse slices in 9 lesions in 8 patients. Most exclusions were related to extensive areas of necrosis/haemorrhage. In one lesion correlation was not possible because of the different orientation of sectioning of the specimen and MRI slices. The 25% ADC showed a strong relationship with percentage of blastema (Spearman rho=−0.71, P=0.003), whereas median ADC was strongly related to the percentage stroma (Spearman rho=0.74, P=0.002) at histopathology.
Conclusion
Side-by-side comparison of MRI–DWI and histopathology is feasible in the majority of patients who do not have massive necrosis and hemorrhage. Blastemal and stromal components have a strong linear relationship with ADC markers.
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CSPG4: a prototype oncoantigen for translational immunotherapy studies
Thanks to striking progress in both the understanding of anti-tumor immune response and the characterization of several tumor associated antigens (TAA), a more rational design and more sophisticated strategies...
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Near-infrared light-triggered drug release from a multiple lipid carrier complex using an all-in-one strategy
Publication date: 10 September 2017
Source:Journal of Controlled Release, Volume 261
Author(s): Huipeng Li, Xue Yang, Zhanwei Zhou, Kaikai Wang, Chenzi Li, Hongzhi Qiao, David Oupicky, Minjie Sun
The present study reports a drug delivery system comprising nanostructured lipid carrier (NLCs) within liposomes (Lip-NLCs). This multiple lipid carrier complex features laser-triggered responsive drug release. Both hydrophobic and hydrophilic drugs can be loaded into the same formulation by applying an all-in-one strategy. We hypothesized that if we loaded the hydrophobic near-infrared (NIR) dye IR780 into the liposome phospholipid bilayer, the bilayer would be disrupted by laser irradiation so that drug release would be triggered remotely at the tumor site. We used in vitro and in vivo methods to verify that laser irradiation facilitated controlled release of both hydrophobic and hydrophilic drugs. The degree of drug release triggered by NIR laser light could be adjusted by varying the laser intensity and irradiation time. Following laser treatment, hydrophilic AMD3100 was released from the aqueous liposome chamber and then bound with CXCR4 receptors on the tumor cell surface to inhibit metastasis. NLCs carrying lipophilic IR780 were also released from the aqueous chamber of liposomes and taken up into tumor cells to enhance the photothermal therapeutic effect of IR780. More importantly, Lip-NLCs loaded with IR780 and AMD3100 (IR780-AMD-Lip-NLCs) exhibited enhanced anti-tumor and anti-metastasis effects. These results suggest that Lip-NLCs are a safe and simply prepared all-in-one platform for delivery of drugs with different solubilities. This system facilitates easily controlled release of cargoes to achieve multi-functional combined therapy.
Graphical abstract
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Liposomal temozolomide drug delivery using convection enhanced delivery
Publication date: 10 September 2017
Source:Journal of Controlled Release, Volume 261
Author(s): Mirjam M. Nordling-David, Roni Yaffe, David Guez, Hadar Meirow, David Last, Etty Grad, Sharona Salomon, Shirley Sharabi, Yael Levi-Kalisman, Gershon Golomb, Yael Mardor
Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity. We hereby describe a novel approach for treating GBM by CED of liposomes containing the known chemotherapeutic agent, temozolomide (TMZ). A new technique for encapsulating TMZ in hydrophilic (PEGylated) liposomes, characterized by nano-size (121nm), low polydispersity index (<0.13) and with near-neutral charge (−ʒ,0.2mV), has been developed. Co-infusion of PEGylated Gd-DTPA liposomes and TMZ-liposomes by CED in GBM bearing rats, resulted in enhanced tumor detection with longer residence time than free Gd-DTPA. Treatment of GBM-bearing rats with either TMZ solution or TMZ-liposomes resulted in greater tumor inhibition and significantly higher survival. However, the longer survival and smaller tumor volumes exhibited by TMZ liposomal treatment in comparison to TMZ in solution were insignificant (p<0.053); and only significantly lower edema volumes were observed. Thus, there are no clear-cut advantages to use a liposomal delivery system of TMZ via CED over a drug solution.
Graphical abstract
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Effects of residual hearing on cochlear implant outcomes in children: A systematic-review
to investigate if preoperative residual hearing in prelingually deafened children can interfere on cochlear implant indication and outcomes. Methods: a systematic-review was conducted in five international databases up to November-2016, to locate articles that evaluated cochlear implantation in children with some degree of preoperative residual hearing. Outcomes were auditory, language and cognition performances after cochlear implant. The quality of the studies was assessed and classified according to the Oxford Levels of Evidence table - 2011.
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Hearing loss in children with growth hormone deficiency
Although insulin-like growth factor 1 (IGF-1) has been shown to be important for inner-ear development in animal models, little is known about the otologic and audiologic findings of children with growth hormone deficiency (GHD). The goal of this study is to evaluate the prevalence, type, and severity of hearing impairment in children with GHD.
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Intracranial complications of CSOM in pediatric patients: A persisting problem in developing countries
Intracranial complications (ICC) of chronic suppurative otitis media (CSOM) occur even in the antibiotic area. These complications are commonly seen in pediatric patients due to poor hygiene and low immunity. They are more prevalent in developing countries due to illiteracy, low socioeconomic status and lack of access to health care facilities.
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Resolution of bilateral sensorineural hearing loss following ventriculoperitoneal shunt and literature review
The purpose of this study is to highlight the relationship between obstructive hydrocephalus, changes in intracranial pressure, and sensorineural hearing loss.
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Exploring reasons for late identification of children with early-onset hearing loss
Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children.
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Exploring reasons for late identification of children with early-onset hearing loss
Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children.
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Resolution of bilateral sensorineural hearing loss following ventriculoperitoneal shunt and literature review
The purpose of this study is to highlight the relationship between obstructive hydrocephalus, changes in intracranial pressure, and sensorineural hearing loss.
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Hearing loss in children with growth hormone deficiency
Although insulin-like growth factor 1 (IGF-1) has been shown to be important for inner-ear development in animal models, little is known about the otologic and audiologic findings of children with growth hormone deficiency (GHD). The goal of this study is to evaluate the prevalence, type, and severity of hearing impairment in children with GHD.
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Intracranial complications of CSOM in pediatric patients: A persisting problem in developing countries
Intracranial complications (ICC) of chronic suppurative otitis media (CSOM) occur even in the antibiotic area. These complications are commonly seen in pediatric patients due to poor hygiene and low immunity. They are more prevalent in developing countries due to illiteracy, low socioeconomic status and lack of access to health care facilities.
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Effects of residual hearing on cochlear implant outcomes in children: A systematic-review
to investigate if preoperative residual hearing in prelingually deafened children can interfere on cochlear implant indication and outcomes. Methods: a systematic-review was conducted in five international databases up to November-2016, to locate articles that evaluated cochlear implantation in children with some degree of preoperative residual hearing. Outcomes were auditory, language and cognition performances after cochlear implant. The quality of the studies was assessed and classified according to the Oxford Levels of Evidence table - 2011.
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A patient with monoclonal gammopathy-related nephrotic syndrome revealed no electrophoretic “nephrotic pattern” or skewed free light chain ratio
Publication date: Available online 1 July 2017
Source:Clinical Biochemistry
Author(s): Dorothy Truong, Ivan M. Blasutig, Vathany Kulasingam, Pak Cheung Chan
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Informal caregivers experience of supplemental oxygen in pulmonary fibrosis
Patients prescribed supplemental oxygen (O2) therapy face challenges as they adjust to being constantly "tethered" to an oxygen delivery device. Informal caregivers (ICs) of patients with pulmonary fibrosis (PF) ...
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Driving the Beat road - SFGate - SFGate
SFGate | Driving the Beat road - SFGate SFGate SAN FRANCISCO - If they're starving, the best minds of this generation can order $19.50 lobster rolls at the former site of the Six Gallery in San Francisco. [. and more » |
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What wildfires are doing to your family's health - Deseret News
Deseret News | What wildfires are doing to your family's health Deseret News Amid growing concern that wildfires are occurring more frequently, the Environmental Protection Agency assures Americans that, unless we're firefighters exposed to smoke every day, we're probably not going to get cancer from occasionally breathing air ... and more » |
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Health, Disease and Naturalism: Hausman on the Public Value of Health
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Introduction to Symposium on Daniel Hausman’s Valuing Health: Well-Being, Freedom and Suffering
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Responses to My Critics
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Global Health Inequality: Comparing Inequality-Adjusted Life Expectancy over Time
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Value Choices in Summary Measures of Population Health
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Public Value, Maximization and Health Policy: An Examination of Hausman’s Restricted Consequentialism
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Global Health Solidarity
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Is Well-being Measurable After All?
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Distinguishing between Experienced Utility and Remembered Utility
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Public Values for Health States Versus Societal Valuations of Health Improvements: A Critique of Dan Hausman’s ‘Valuing Health’
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Why One Should Count Only Claims with which One Can Sympathize
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“Forgotten” Chapters in the History of Transcervical Sterilization: Carl Clauberg and Hans-Joachim Lindemann
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“His Native, Hot Country” 1 : Racial Science and Environment in Antebellum American Medical Thought
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“Enquire into All the Circumstances of the Patient Narrowly”: John Rutherford’s Clinical Lectures in Edinburgh, 1749–53
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“One Simply Doesn’t Arbitrate Authorship of Thoughts”: Socialized Medicine, Medical McCarthyism, and the Publishing of Rural Health and Medical Care (1948)
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Richard H. Nollan. Blood Picture: L. W. Digg’s Sickle Cell Anemia, and the South’s First Blood Bank
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Catherine L. Thompson. Patient Expectations: How Economics, Religion, and Malpractice Shaped Therapeutics in Early America
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Susanne M. Klausen. Abortion Under Apartheid: Nationalism, Sexuality, and Women’s Reproductive Rights in South Africa
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Luis A. Campos. Radium and the Secret of Life
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Courtney Q. Shah. Sex Ed, Segregated: The Quest for Sexual Knowledge in Progressive-Era America
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Detection of circulating tumor cells from cryopreserved human sarcoma peripheral blood mononuclear cells
Publication date: 10 September 2017
Source:Cancer Letters, Volume 403
Author(s): Heming Li, Qing H. Meng, Hyangsoon Noh, Izhar Singh Batth, Neeta Somaiah, Keila E. Torres, Xueqing Xia, Ruoyu Wang, Shulin Li
Circulating tumor cells (CTCs) enter the vasculature or lymphatic system after shedding from the primary tumor. CTCs may serve as "seed" cells for tumor metastasis. The utility of CTCs in clinical applications for sarcoma is not fully investigated, partly owing to the necessity for fresh blood samples and the lack of a CTC-specific antibody. To overcome these drawbacks, we developed a technique for sarcoma CTCs capture and detection using cryopreserved peripheral blood mononuclear cells (PBMCs) and our proprietary cell-surface vimentin (CSV) antibody 84-1, which is specific to tumor cells. This technique was validated by sarcoma cell spiking assay, matched CTCs comparison between fresh and cryopreserved PBMCs, and independent tumor markers in multiple types of sarcoma patient blood samples. The reproducibility was maximized when cryopreserved PBMCs were prepared from fresh blood samples within 2 h of the blood draw. In summary, as far as we are aware, ours is the first report to capture and detect CTCs from cryopreserved PBMCs. Further validation in other types of tumor may help boost the feasibility and utility of CTC-based diagnosis in a centralized laboratory.
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Effects of Bu Shen Yi sui capsule on NogoA/NgR and its signaling pathways RhoA/ROCK in mice with experimental autoimmune encephalomyelitis
Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule ...
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Ecotoxicity of 1,3-dichloropropene, metam sodium, and dazomet on the earthworm Eisenia fetida with modified artificial soil test and natural soil test
Abstract
1,3-Dichloropropene (1,3-D), metam sodium (MS), and dazomet (DZ) are widely used as preplant soil fumigants to solve soilborne problems. To provide a more scientific and accurate evaluation of 1,3-D, MS, and DZ toxicity to the earthworm Eisenia fetida, modified artificial soil test and natural soil test were studied. The suitable soil moisture to maintain over 90% survival of the earthworms after 4 weeks of treatment in an enclosed system for modified artificial soil test and natural soil test were 26.9 to 86.4% of water-holding capacity (WHC) and 66.2 to 84.3% of WHC, respectively. The optimal soil moisture levels for modified artificial soil test and natural soil test (75 and 55% of WHC, respectively) were finally used to evaluate the toxicity of 1,3-D, MS, and DZ on earthworms. Each desiccator with 10 earthworms and natural or artificial soil was stored at 20 ± 1 °C under constant light of 400 to 800 lx for 2 weeks. The modified artificial soil test showed LC50 values for 1,3-D, MS, and DZ of 3.60, 1.69, and 5.41 mg a.i. kg−1 soil, respectively. The modified natural soil test of the fumigants showed similar LC50 values of 2.77 and 0.65 mg a.i. kg−1 soil, except for DZ at 0.98 mg a.i. kg−1 soil. The present study confirms that both modified artificial soil test and modified natural soil test offer standard methods for acute toxicity test of 1,3-D, MS, and DZ on the earthworms and scientific evidences for assessing the effects of soil fumigants on non-target organisms in the soils.
Graphical Abstract
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Trichomonas vaginalis infection and risk of prostate cancer: associations by disease aggressiveness and race/ethnicity in the PLCO Trial
Abstract
Purpose
Results from previous sero-epidemiologic studies of Trichomonas vaginalis infection and prostate cancer (PCa) support a positive association between this sexually transmitted infection and aggressive PCa. However, findings from previous studies are not entirely consistent, and only one has investigated the possible relation between T. vaginalis seropositivity and PCa in African-American men who are at highest risk of both infection and PCa. Therefore, we examined this possible relation in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, including separate analyses for aggressive PCa and African-American men.
Methods
We included a sample of participants from a previous nested case–control study of PCa, as well as all additional Caucasian, aggressive, and African-American cases diagnosed since the previous study (total n = 438 Gleason 7 Caucasian cases, 487 more advanced Caucasian cases (≥Gleason 8 or stage III/IV), 201 African-American cases, and 1216 controls). We tested baseline sera for T. vaginalis antibodies.
Results
No associations were observed for risk of Gleason 7 (odds ratio (OR) = 0.87, 95% confidence interval (CI) 0.55–1.37) or more advanced (OR = 0.90, 95% CI 0.58–1.38) PCa in Caucasian men, or for risk of any PCa (OR = 1.06, 95% CI 0.67–1.68) in African-American men.
Conclusions
Our findings do not support an association between T. vaginalis infection and PCa.
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Preimplantation genetic diagnosis for mitochondrial DNA mutations: analysis of one blastomere suffices
Background
Preimplantation genetic diagnosis (PGD) is a reproductive strategy for mitochondrial DNA (mtDNA) mutation carriers, strongly reducing their risk of affected offspring. Embryos either without the mutation or with mutation load below the phenotypic threshold are transferred to the uterus. Because of incidental heteroplasmy deviations in single blastomere and the relatively limited data available, we so far preferred relying on two blastomeres rather than one. Considering the negative effect of a two-blastomere biopsy protocol compared with a single-blastomere biopsy protocol on live birth delivery rate, we re-evaluated the error rate in our current dataset.
MethodsFor the m.3243A>G mutation, sufficient embryos/blastomeres were available for a powerful analysis. The diagnostic error rate, defined as a potential false-negative result, based on a threshold of 15%, was determined in 294 single blastomeres analysed in 73 embryos of 9 female m.3243A>G mutation carriers.
ResultsOnly one out of 294 single blastomeres (0.34%) would have resulted in a false-negative diagnosis. False-positive diagnoses were not detected.
ConclusionOur findings support a single-blastomere biopsy PGD protocol for the m.3243A>G mutation as the diagnostic error rate is very low. As in the early preimplantation embryo no mtDNA replication seems to occur and the mtDNA is divided randomly among the daughter cells, we conclude this result to be independent of the specific mutation and therefore applicable to all mtDNA mutations.
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Influence of environmental factors on absorption characteristics of suspended particulate matter and CDOM in Liaohe River watershed, northeast China
Abstract
Absorption characteristics of optically active substances, including non-algal particles, phytoplankton, and chromophoric dissolved organic matter (CDOM), were measured in conjunction with environmental factors in five rivers within the Liaohe River watershed. Spectral absorption of non-algal particles [a NAP(λ)] was similar to that of total particles for most samples, suggesting that the absorption of the total particles [a p(λ)] was dominated by a NAP(λ). The CDOM absorption spectra [a CDOM(λ)] of West Liaohe and Taizihe rivers were easily distinguished from those of Hunhe, Liaohe, and East Liaohe rivers. Redundancy analysis indicated that absorption by optically active substances and anthropogenic nutrient disturbances probably resulted in the diversity of water quality parameters. The environmental variables including dissolved organic carbon, total alkalinity (TAlk), and total nitrogen (TN) had a significant correlation with CDOM absorption at 440 nm [a CDOM(440)]. There was almost no correlation between a p(λ) and chlorophyll a, TN, total phosphorus, and TAlk. Moreover, total copper ion concentration and mercury ion concentration had a strong correlation with a p(440), a p(675), a NAP(440), and a NAP(675). The concentration of total aluminum ions exhibited a positive correlation with a p(675) and a NAP(675) (p < 0.05), and a significant correlation was observed between total arsenic concentration and a CDOM(440). Furthermore, the interaction between metal ions and optically active substances provided an insight into particulates and CDOM properties linked to water quality characteristics for rivers in semiarid areas.
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GNAO1-related movement disorder with life-threatening exacerbations: movement phenomenology and response to DBS
Background
GNAO1 (OMIM 139311) encodes a Gα0CNS protein responsible for regulation of GABA-B and α2-receptors, and neurotransmitter release. Mutations of GNAO1 are reported in patients with epileptic encephalopathy (EE) at times with a movement disorder (MD); some display severe hyperkinetic movements without EE, three underwent Deep Brain Stimulation (DBS) with reduction in exacerbations.1–4 (see online , supporting information (SI)).
MethodsWe describe the MD phenomenology and course in three patients identified from neurology services in Brisbane and Glasgow with GNAO1-related MD, highlighting effectiveness of DBS in exacerbations.
Informed consent was obtained. Four MD specialists reviewed videos (baseline, exacerbations, post-DBS) using a Proforma (SI) and reached a consensus on movement phenomenology.
ResultsAll patients had global delay, central hypotonia and MD noted in early life (see online , patient synopsis, SI). Patient 3 initially showed bradykinesia, rigidity and dystonia; patient 1 resting tremor. All had been diagnosed with dyskinetic Cerebral...
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Towards an early clinical diagnosis of sporadic CJD VV2 (ataxic type)
Introduction
Sporadic Creutzfeldt-Jakob disease (sCJD) includes a broad spectrum of clinical–pathological subtypes, which complicates the clinical differential diagnosis with other rapidly progressive neurological syndromes.
AimTo provide a better characterisation of clinical features and results of diagnostic investigations, especially at an early disease stage, in patients with sCJDVV2, the second most common sCJD subtype.
MethodsWe evaluated neurological symptoms/signs, and results of brain diffusion-weighted resonance imaging (DW-MRI), electroencephalographic recordings (EEG) and cerebrospinal fluid (CSF) biomarker studies in 120 patients with a definite (n=93) or probable (n=27) diagnosis of sCJDVV2.
ResultsAll patients presented with prominent cerebellar signs, which were often associated with memory loss and/or oculomotor, visual or peripheral/spinal cord signs. In contrast, dementia was invariably a late finding. All CSF samples were positive for the 14-3-3 protein assay and had total-tau protein levels above 1250 pg/mL. Brain DW-MRI showed hyperintensity of basal ganglia, thalamus and cerebral cortex, respectively in 91.5%, 57.4% and 19.1% of cases. EEG revealed periodic sharp-wave complexes in only 17.8% of cases.
ConclusionssCJDVV2 should be considered in any patient presenting with a rapidly progressive ataxia, especially when associated with oculomotor, visual or peripheral/spinal cord signs, even in the absence of dementia or myoclonus. CSF assays and brain DW-MRI represent sensitive diagnostic tests, even at an early stage. These data strongly suggest that sCJDVV2 can be clinically diagnosed early and accurately based on clinical data, DW-MRI, CSF assays and codon 129 genotyping and provide the basis for improved and subtype-specific diagnostic criteria of sCJD.
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Radiation-Associated Sarcomas
Patient with history of radiation therapy for head and neck cancer. Radiation field extended into the supraclavicular nodal stations. CT shows an osteoid producing soft tissue mass to the right of midline. Bone scan and PET show uptake in the lesion, as well as contralateral lymph nodes. PET shows an FDG-avid lung nodule. T1-WI post-contrast MRI with FS shows a peripherally enhancing soft tissue mass.
The incidence of radiation-associated sarcomas of bone and soft tissue is about 0.1%. They are more commonly seen in patients with breast cancer, lymphoma, head and neck malignancies, and gynecologic cancers. The distribution of primary cancers is likely related to the larger numbers of patients with these cancers and the high survival rates for these tumors.
The majority of radiation-associated tumors are soft tissue sarcomas, with bone sarcomas making up about 20-30% of cases. The majority are high grade and aggressive. The most common soft tissue sarcomas are unclassified pleomorphic sarcoma (UPS, formerly MFH), followed by angiosarcoma (particularly in breast cancer), fibrosarcoma and leiomyosarcoma (particularly in retinoblastoma). The most common bone sarcomas are osteosarcomas.
The latency between radiation and sarcoma ranges from as little as a few months to 54 years. The average is 7 to 16 years. In breast cancer, the average is 10 to 11 years (4-8 years for angiosarcomas). In childhood cancers, the average latency is between 12 to 13 years.
Risk factors include, dose (Rarely seen with low doses: Li-Fraumeni syndrome).
References
Maki, R. et al. Radiation-Associated Sarcomas. UpToDatefrom # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2syOiyG
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Improving gentamicin B and gentamicin C1a production by engineering the glycosyltransferases that transfer primary metabolites into secondary metabolites biosynthesis
Source:Microbiological Research
Author(s): Zheng Wu, Wenli Gao, Shaotong Zhou, Zhaolin Wen, Xianpu Ni, Huanzhang Xia
Gentamicin B and gentamicin C1a are the direct precursor for Isepamicin and Etimicin synthesis, respectively. Although producing strains have been improved for many years, both gentamicin B titer and gentamicin C1a titer in the fermentation are still low. Because all gentamicin components are biosynthesized using UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) and UDP-xylose as precursors, we tried to explore strategies for development of strains capable of directing greater fluxes of these precursors into production of gentamicins. The glycosyltransferases KanM1 and GenM2, which are responsible for UDP-GlcNAc and UDP-xylose transfer, respectively, were overexpressed in gentamicin B producing strain Micromonospora echinospora JK4. It was found that gentamicin B could be improved by up to 54% with improvement of KanM1 and GenM2 expression during appropriately glucose feeding. To prove this strategy is widely usable, the KanM1 and GenM2 were also overexpressed in gentamicin C1a producing strain, titers of gentamicin C1a improved by 45% when compared with titers of the starting strain. These results demonstrated overexpression the glycosyltransferases that transfer primary metabolites into secondary metabolites is workable for improvement of gentamicins production.
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Validation of ApneaLink™ Plus for the diagnosis of sleep apnea
Abstract
Purpose
The aim of this study is to evaluate the validation of ApneaLink™ Plus (ALP) based on a large number of subjects in a prospective design.
Method
We recommended enrolling of 200 consecutive patients who had been referred because of habitual snoring or witnessed apnea during sleep. If consent was obtained, patients underwent standard polysomnography (PSG) and ALP evaluation simultaneously at the hospital (ALPlab), and repeated ALP at home (ALPhome) within 1 month. The parameters of ALP were scored based on three different systems, Manual, Auto AASM, and Auto scoring systems.
Result
Among the 200 patients who were recommended for enrollment, 149 completed the study. Sensitivity was good for all three scoring systems, while specificity was poor for the Auto scoring system. The area under curve was highest for the manual scoring system and lowest for the auto scoring system, and increased as the apnea-hypopnea index (AHI) cutoff value increased from 5 to 30. Regarding agreement with PSG, the manual scoring system was most superior, followed by the Auto AASM, and Auto scoring systems. The degree of agreement between PSG and ALP was affected by sleep efficiency and the arousal index. Moderate agreement between PSG and ALP based on central apnea index was observed.
Conclusion
ALP is an accurate and reliable device for the diagnosis of OSA. Manual scoring is recommended; however, Auto AASM is also acceptable. ALP detects central sleep apnea to a certain degree. Both sleep efficiency and the arousal index affect the results of ALP.
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