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Δευτέρα 28 Μαΐου 2018

Ghrelin-containing neurons in the olfactory bulb send collateralized projections into medial amygdaloid and arcuate hypothalamic nuclei: neuroanatomical study

Abstract

Ghrelin, a gastrointestinal hormone, is a modulator of the sense of smell. The main source of ghrelin in the central nervous system has been mainly observed in specific populations of hypothalamic neurons. An increasing number of studies have reported ghrelin synthesis and its effect on neurons outside the hypothalamus. Ghrelin and its receptors are expressed in the olfactory bulbs and in other centres of the brain, such as the amygdala, for processing olfactory signals, pyramidal neurons of the cerebral cortex and the dorsal vagal complex of the medulla oblongata. It is known that ghrelin is involved in cognitive mechanisms and eating behaviours, in fact, its expression increases in anticipation of food intake. In order to identify the existence of centrifugal direct afferents from the main olfactory bulb to the medial amygdala and the hypothalamus arcuate nucleus, in this work we used two retrograde tracers, Dil and Fluoro Gold, and immunohistochemical procedure to visualize positive ghrelin neurons. Our paper provides neuroanatomic support for the ghrelin modulation of smell. Our results show that ghrelin neuron projections from mitral cells of bulbs can transmit olfactory information via branching connections to the amygdala and the hypothalamus. This pathway could play an important role in regulating feeding behaviour in response to odours.



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Cancers, Vol. 10, Pages 166: Zinc Metallochaperones as Mutant p53 Reactivators: A New Paradigm in Cancer Therapeutics

Cancers, Vol. 10, Pages 166: Zinc Metallochaperones as Mutant p53 Reactivators: A New Paradigm in Cancer Therapeutics

Cancers doi: 10.3390/cancers10060166

Authors: Samuel Kogan Darren R. Carpizo

Restoration of wild-type structure and function to mutant p53 with a small molecule (hereafter referred to as “reactivating” mutant p53) is one of the holy grails in cancer therapeutics. The majority of TP53 mutations are missense which generate a defective protein that is targetable. We are currently developing a new class of mutant p53 reactivators called zinc metallochaperones (ZMCs) and, here, we review our current understanding of them. The p53 protein requires the binding of a single zinc ion, coordinated by four amino acids in the DNA binding domain, for proper structure and function. Loss of the wild-type structure by impairing zinc binding is a common mechanism of inactivating p53. ZMCs reactivate mutant p53 using a novel two-part mechanism that involves restoring the wild-type structure by reestablishing zinc binding and activating p53 through post-translational modifications induced by cellular reactive oxygen species (ROS). The former causes a wild-type conformation change, the later induces a p53-mediated apoptotic program to kill the cancer cell. ZMCs are small molecule metal ion chelators that bind zinc and other divalent metal ions strong enough to remove zinc from serum albumin, but weak enough to donate it to mutant p53. Recently we have extended our understanding of the mechanism of ZMCs to the role of cells’ response to this zinc surge. We found that cellular zinc homeostatic mechanisms, which normally function to maintain free intracellular zinc levels in the picomolar range, are induced by ZMCs. By normalizing zinc levels, they function as an OFF switch to ZMCs because zinc levels are no longer sufficiently high to maintain a wild-type structure. This on/off switch leads to a transient nature to the mechanism of ZMCs in which mutant p53 activity comes on in a few hours and then is turned off. This finding has important implications for the translation of ZMCs to the clinic because it indicates that ZMC concentrations need not be maintained at high levels for their activity. Indeed, we found that short exposures (as little as 15 min) were adequate to observe the mutant p53 reactivating activity. This switch mechanism imparts an advantage over other targeted therapeutics in that efficacy can be accomplished with minimal exposure which minimizes toxicity and maximizes the therapeutic window. This on/off switch mechanism is unique in targeted cancer therapeutics and will impact the design of human clinical trials.



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Social Pursuits Linked With Increased Life Satisfaction

If you want to give a little boost to your life satisfaction a year from now, you may want to try socially-focused strategies over strategies that involve nonsocial pursuits, according to research published in Psychological Science, a journal of the Association for Psychological Science.

"Our research showed that people who came up with 'well-being' strategies that involved other people were more satisfied with their lives one year later — even after taking into account that they were marginally happier to begin with," explains psychological scientist Julia Rohrer of the University of Leipzig, lead author on the study. "In contrast, people who came up with strategies that did not explicitly involve others remained, on average, as satisfied as they were."

Rohrer and coauthors David Richter, Martin Brümmer, Gert G. Wagner, and Stefan C. Schmukle examined data from a subsample of the German Socio-Economic Panel Study, a nationally representative survey of German adults. In 2014, participants in this sample reported how satisfied they were with life, providing a rating from 0 (completely dissatisfied) to 10 (completely satisfied). They also reported how satisfied they thought they would be in 5 years and described the strategies they could take to ensure sustained life satisfaction in the future. One year later, the participants again rated their current level of life satisfaction.

Of the 1178 participants, 596 made a general statement (e.g., "there is not much I could change") or expressed an idea that did not entail individual action (e.g., "different politics would improve life"), whereas 582 reported a specific strategy. These two groups showed no substantive differences in life satisfaction over time.

Rohrer and colleagues further examined the data from the 582 participants who actually described specific strategies. Of these, 184 mentioned approaches centered on some form of social engagement (e.g., "helping others," "spend more time with family," "spend more time with friends"), while 398 described some form of nonsocial strategy (e.g., "stop smoking").

Analyses revealed that individuals who described a social strategy showed increased life satisfaction one year later, whereas those who reported nonsocial strategies showed relatively constant levels.

Data reflecting how much time participants spent on various activities indicated that time spent socializing with family, friends, and neighbors helped to explain the boost in life satisfaction one year later.

Rohrer notes that additional research, including experimental studies and longitudinal studies with multiple follow-up assessments, will help to illuminate why social strategies seem to improve life satisfaction and nonsocial strategies do not.

The results do suggest that spending more time with others may be the more promising avenue toward increased well-being, the researchers conclude.

"Many people are interested in becoming happier, but there is a lack of evidence regarding the long term effects of pursuing happiness through various types of activities. After all, there's no guarantee that trying to become happier doesn't make you more miserable in the end," Rohrer says. "I think our study partly fills that gap in the literature, although more research with a longitudinal perspective is certainly needed."

All data and materials have been made publicly available via the Open Science Framework (OSF). The design and analysis plans for this study were preregistered at the OSF. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Data, Open Materials, and Preregistration.



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Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study, Published online: 29 May 2018; doi:10.1038/s41416-018-0079-9

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study

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Checkpoint blockade in the treatment of breast cancer: current status and future directions

Checkpoint blockade in the treatment of breast cancer: current status and future directions

Checkpoint blockade in the treatment of breast cancer: current status and future directions, Published online: 29 May 2018; doi:10.1038/s41416-018-0126-6

Checkpoint blockade in the treatment of breast cancer: current status and future directions

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High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer

High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer

High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer, Published online: 29 May 2018; doi:10.1038/s41416-018-0136-4

High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer

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Proximity to overhead power lines and childhood leukaemia: an international pooled analysis

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis, Published online: 29 May 2018; doi:10.1038/s41416-018-0097-7

Proximity to overhead power lines and childhood leukaemia: an international pooled analysis

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Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study

Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study

Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study, Published online: 29 May 2018; doi:10.1038/s41416-018-0103-0

Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study

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Hepatic Abscess in a Returning Traveler with Crohn’s Disease: Differentiating Amebic from Pyogenic Liver Abscess

Liver abscess is a rare but serious complication of Crohn's disease. Patients with Crohn's disease are at risk for pyogenic liver abscesses due to immunosuppressive therapy, fistulous disease, and intraabdominal abscesses. Inflammatory bowel disease patients are also known to have a greater prevalence of amebiasis compared to the rest of the population; however, a higher incidence of amebic liver abscess has not been reported. We describe a case of a liver abscess in a patient with Crohn's disease that was initially presumed pyogenic but later determined to be amebic in origin. Epidemiology, clinical presentation, diagnosis, and treatment of amebic and pyogenic liver abscesses are discussed.

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TLR2 regulates allergic airway inflammation through NF-κB and MAPK signaling pathways in asthmatic mice

OBJECTIVE: To investigate the role of toll-like receptor 2 (TLR2) in asthmatic mouse model and its possible signal transduction pathways.

MATERIALS AND METHODS: Mice were divided into three groups: TLR2-/- asthma mouse model group (n=10), C57BL/6 asthma mouse model group (n=10) and control group (n=10). Mice were sensitized and stimulated with ovalbumin (OVA) to establish the asthmatic mouse model. The unilateral bronchoalveolar lavage fluid (BALF) was collected and centrifuged to separate cells, and the cells were classified and counted via smear test under a microscope. Part of the lung tissues on the other side was taken for hematoxylin-eosin (HE) staining to observe the histopathological change in lung tissues. The remaining lung tissues on the other side were taken to detect the messenger ribonucleic acid (mRNA) expression levels of interleukin-4 (IL-4), IL-5 and IL-13 via reverse transcription-polymerase chain reaction (RT-PCR). The levels of nuclear factor-κB (NF-κB) p65, phosphorylated (p)-NF-κB p65, p-IκBα, extracellular signal-regulated kinase (ERK)1/2, p-ERK1/2, Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (MAPK), p-p38 MAPK, IL-4, IL-5 and IL-13 were detected via enzyme-linked immunosorbent assay (ELISA). The protein expressions of NF-κB p65, p-NF-κB p65, p-IκBα, ERK1/2, p-ERK1/2, JNK, p-JNK, p38 MAPK, and p-p38 MAPK were detected using the immunohistochemical method.

RESULTS: HE staining showed that the infiltration degree of inflammatory cells in perivascular tissues in TLR2-/- asthma group was reduced compared with that in C57BL/6 asthma group. Results of electron microscopy showed that the ultrastructural changes in alveolar type I epithelial cells in mice in TLR2-/- asthma group was significantly alleviated. In BALF in TLR2-/- asthma group, the numbers of eosinophils and lymphocytes were significantly decreased, but the number of macrophages was significantly increased compared with those in C57BL/6 asthma group. Results of RT-PCR and ELISA revealed that the mRNA and protein expression levels of IL-4, IL-5, and IL-13 in lung tissues of mice in TLR2-/- asthma group were significantly decreased compared with those in C57BL/6 asthma group. Besides, results of ELISA and immunohistochemistry revealed that the protein expressions of NF-κB p65, p-NF-κB p65, p-IκBα, ERK1/2, JNK, p38 MAPK, p-ERK1/2, p-JNK, and p-p38 MAPK in lung tissues of mice in TLR2-/- asthma group were significantly decreased compared with those in C57BL/6 asthma group.

CONCLUSIONS: TLR2 is involved in the occurrence and development of experimental asthmatic airway inflammation. TLR2 gene knockout in asthmatic mice can alleviate the airway inflammation, whose mechanism may be that the allergic airway inflammation of asthmatic mice is alleviated through inhibiting NF-κB and MAPK signaling pathways.

L'articolo TLR2 regulates allergic airway inflammation through NF-κB and MAPK signaling pathways in asthmatic mice sembra essere il primo su European Review.



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Down-regulation of lncRNA Linc00152 suppressed cell viability, invasion, migration, and epithelial to mesenchymal transition, and reversed chemo-resistance in breast cancer cells

OBJECTIVE: Breast cancer is one of the most common cancer types in women, and long non-coding RNAs (lncRNAs) were found to play important roles in breast cancer progression. The present study examined the effects of Linc00152 on the breast cancer progression and explored the underlying molecular mechanisms.

MATERIALS AND METHODS: The expression levels of relevant genes in tissues and cells were detected by quantitative Real-time PCR (qRT-PCR) assay. Cell viability, growth, invasion, and migration were measured by CCK-8, colony formation, transwell invasion, and migration assays, respectively. Western blot was used to detect the expression levels of proteins.

RESULTS: The results showed that Linc00152 was highly expressed in the breast cancer tissues compared to their adjacent normal tissues, and Linc00152 was also up-regulated in the breast cancer cell lines compared to normal cell lines. Knock-down of Linc00152 by using siRNAs in breast cancer cell lines (MDA-MB-231 and MCF-7) significantly suppressed cell viability, cell growth, cell invasion and migration as measured by the CCK-8, colony formation, transwell invasion, and migration assays. The qRT-PCR and Western blot results showed that knock-down of Linc00152 suppressed epithelial-mesenchymal transition in breast cancer cell lines. In addition, CCK-8 assay showed that knock-down of Linc00152 in MCF-7/ADR cells reversed the chemo-resistance to doxorubicin.

CONCLUSIONS: Our results suggested the oncogenic role of Linc00152 in the breast cancer progression. Understanding the role of Linc00152 in breast cancer progression may provide a novel therapeutic target for the treatment of breast cancer.

L'articolo Down-regulation of lncRNA Linc00152 suppressed cell viability, invasion, migration, and epithelial to mesenchymal transition, and reversed chemo-resistance in breast cancer cells sembra essere il primo su European Review.



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Prevalence, Predictors and Impact of Bacterial Infection in Acute on Chronic Liver Failure Patients

Acute on chronic liver failure (ACLF) is associated with high short term mortality. We aimed to evaluate the prevalence, predictors and impact of bacterial infection in ACLF.

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Significant Infections in Liver Transplant Recipients Undergoing Endoscopic Retrograde Cholangiography are few and Unaffected by Prophylactic Antibiotics

Current practice guidelines recommend prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography (ERCP) in liver transplant recipients (LTR). This study evaluated the risk of clinically significant infections after ERCP in LTR who received antibiotic prophylaxis compared to those who did not.

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Procalcitonin is useful in driving the choice of early antibiotic treatment in patients with bloodstream infections

OBJECTIVE: To evaluate whether PCT levels could be used to distinguish among different bacterial and fungal etiologies in patients with documented bloodstream infection (BSI).

PATIENTS AND METHODS: Monocentric retrospective cohort study on patients admitted to the Fondazione Policlinico Gemelli Hospital between December 2012 and November 2015 with BSI. Those who had undergone PCT determination within 48 hours of when the first positive blood culture was sampled were included in the study.

RESULTS: Four hundred and one patients were included in the study. Both the 24h and 48h PCT values were significantly higher in patients with Gram-negative (GN) BSI than in those with Gram-positive (GP) or candida BSI (p at ANOVA = 0.003). A PCT value of > 1 ng/ml was found in 31.5% of patients with GN BSI. Less than 7% of people with candida BSI had PCT level of > 1 ng/ml. At multivariable regression analysis, GN BSI, septic shock, and plasma creatinine were significantly correlated with PCT values.

CONCLUSIONS: PCT may be of value in distinguishing GN BSI from GP, and fungal BSI and PCT values of > 1 ng/ml could be used to prevent unnecessary antifungal treatment.

L'articolo Procalcitonin is useful in driving the choice of early antibiotic treatment in patients with bloodstream infections sembra essere il primo su European Review.



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Women Deserve Better Health Care

The American College of Physicians position paper on women's health policy in the United States offers 7 recommendations to improve women's health services: 3 pertain to physicians' primary care practice, 2 to public policy issues, 1 to training, and 1 to research needs. The editorialists applaud the recommendations and highlight 3 ways in which integration across recommendations could significantly improve women's health care.

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Women's Health Policy in the United States: An American College of Physicians Position Paper

In this position paper, the American College of Physicians (ACP) examines the challenges women face in the U.S. health care system across their lifespans, including access to care; sex- and gender-specific health issues; variation in health outcomes compared with men; underrepresentation in research studies; and public policies that affect women, their families, and society. ACP puts forward several recommendations focused on policies that will improve the health outcomes of women and ensure a health care system that supports the needs of women and their families over the course of their lifespans.

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Precision Screening for Lung Cancer: Risk-Based but Not Always Preference-Sensitive?

In this issue, Caverly and colleagues present the results of a sophisticated modeling analysis that explores the importance of disutilities in the lung cancer screening decision. The editorialist discusses the unavoidable tensions among the various goals of screening, the role of patient preferences, and how physicians can incorporate Caverly and colleagues' findings into their discussions with patients about lung cancer screening.

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Identifying Patients for Whom Lung Cancer Screening is Preference-Sensitive A Microsimulation Study

Background:
Many health systems are exploring how to implement low-dose computed tomography (LDCT) screening programs that are effective and patient-centered.
Objective:
To examine factors that influence when LDCT screening is preference-sensitive.
Design:
State-transition microsimulation model.
Data Sources:
Two large randomized trials, published decision analyses, and the SEER (Surveillance, Epidemiology, and End Results) cancer registry.
Target Population:
U.S.-representative sample of simulated patients meeting current U.S. Preventive Services Task Force criteria for screening eligibility.
Time Horizon:
Lifetime.
Perspective:
Individual.
Intervention:
LDCT screening annually for 3 years.
Outcome Measures:
Lifetime quality-adjusted life-year gains and reduction in lung cancer mortality. To examine the effect of preferences on net benefit, disutilities (the "degree of dislike") quantifying the burden of screening and follow-up were varied across a likely range. The effect of varying the rate of false-positive screening results and overdiagnosis associated with screening was also examined.
Results of Base-Case Analysis:
Moderate differences in preferences about the downsides of LDCT screening influenced whether screening was appropriate for eligible persons with annual lung cancer risk less than 0.3% or life expectancy less than 10.5 years. For higher-risk eligible persons with longer life expectancy (roughly 50% of the study population), the benefits of LDCT screening overcame even highly negative views about screening and its downsides.
Results of Sensitivity Analysis:
Rates of false-positive findings and overdiagnosed lung cancer were not highly influential.
Limitation:
The quantitative thresholds that were identified may vary depending on the structure of the microsimulation model.
Conclusion:
Identifying circumstances in which LDCT screening is more versus less preference-sensitive may help clinicians personalize their screening discussions, tailoring to both preferences and clinical benefit.
Primary Funding Source:
None.

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Starving the Hungry Tapeworm: How Businessmen May Reform Health Care Cost

News that the CEOs of Amazon, Berkshire Hathaway, and JPMorgan Chase are coming together to combat high health care costs has been met with anticipation and skepticism. This commentary speculates on how these business giants might apply a Six Sigma approach to achieve the cost containment that has so far eluded the U.S. health care system.

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Severe Hyponatremia After Drinking Horsetail Juice



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Clonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and Cancer: A Newly Recognized Link Between Two Major Killers

The presence of a somatic mutation associated with hematologic cancer in the peripheral blood at a variant allele frequency of at least 2% in the absence of hematologic cancer defines clonal hematopoiesis of indeterminate potential (CHIP). CHIP is common, confers a risk for hematologic cancer of about 5% over 10 years, and is associated with a dramatic increase in cardiovascular risk independent of traditional risk factors. This commentary discusses CHIP's potential in cardiovascular risk assessment and as a biomarker for response to interventions to reduce cardiovascular risk.

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Is It Ethical to Use Genealogy Data to Solve Crimes?

Information from online geneology services might be used in manners not anticipated by consumers, including as forensic evidence in crime solving. The authors discuss the informed consent, privacy, and justice issues involved in such use.

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Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study



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High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer



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Proximity to overhead power lines and childhood leukaemia: an international pooled analysis



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Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study



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Checkpoint blockade in the treatment of breast cancer: current status and future directions



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Petroleum degradation by Pseudomonas sp. ZS1 is impeded in the presence of antagonist Alcaligenes sp. CT10

Enhanced bioremediation is a favorable approach for petroleum pollutant cleanup, which depends on the growth of oil-eating microorganisms. In this study, we show that, by using the modified T-RFLP (mT-RFLP) me...

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Antifungal activity of lactobacilli isolated from Armenian dairy products: an effective strain and its probable nature

Different strains of lactobacilli isolated from Armenian dairy products (matsoun, sour cream and different types of cheeses), were studied for antifungal activity. Lactobacillus rhamnosus MDC 9661 strain was show...

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Estimation of voluntary elicited motor neuron discharge using a peripheral nerve collision technique at different contraction strengths

Motor evoked potentials (MEP) are facilitated when the cortical stimulus is given during an ongoing voluntary contraction of the target muscle (Arányi et al., 1998; Hess et al., 1987). During voluntary contractions, a greater pool of spinal motor neurons (MN) are closer to their firing threshold, and are therefore brought to discharge by the cortical magnetic stimulus. The pool of MN just below firing threshold has been termed "subliminal fringe" (Denny-Brown and Sherrington, 1928). A motor evoked potential obtained during a voluntary contraction is therefore composed of those motor units discharging by voluntary activation plus those near-threshold "fringe" motor units that were additionally recruited by the brain stimulus.

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Tox & Hound – Pour Some Octreotide on Me

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by Kavita Babu       In 1999, a toddler encountered glipizide during an exploratory ingestion. When he wouldn't wake up from a nap, the family called the EMTs, who found a fingerstick blood sugar of 13 mg/dL. He received several D25 boluses – each time his sugar would respond appropriately, then fall. His care […]

EMCrit Project by Tox & Hound.



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A case report of multiple cervical artery dissection after peripheral type facial palsy and use of steroids

Cervical artery dissection is one of the most important causes of ischemic stroke in young age patients. However, multiple cervical artery dissection simultaneously involving the anterior and posterior circula...

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Inhibitory effects of fluoxetine, an antidepressant drug, on masseter muscle nociception at the trigeminal subnucleus caudalis and upper cervical spinal cord regions in a rat model of psychophysical stress

Abstract

This study aimed to determine whether psychophysical stress conditionings had facilitatory effects on masseter muscle nociception in the central nervous system via serotonergic mechanisms in rats. Two experiments were conducted to assess: (1) whether repeated forced swim stress for 3 days increased the number of Fos-positive neurons evoked by masseter muscle injury due to formalin injection; and (2) whether serotonin-reuptake inhibitor, fluoxetine, administered daily after each stress conditioning, had modulatory roles on Fos expression. The number of Fos-positive cells was quantified in several areas within the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord regions (Vc areas), including the ventrolateral area of the trigeminal subnucleus interpolaris/Vc transition, and the middle or caudal portion of the Vc regions, since nociceptive neural activity in the Vc region could play critical roles in deep craniofacial nociception. We found that forced swim stress conditionings increased depression-like behaviors, which was prevented by fluoxetine. Repeated forced swim stress significantly increased Fos expression in all Vc areas compared with those of non-stressed rats, while systemic administration of fluoxetine significantly decreased Fos expression in all areas, but mainly in the caudal Vc region, in stressed rats. Fluoxetine had no effect on Fos expression in non-stressed rats. These results indicate that repeated forced swim stress conditionings increase Fos expression in the Vc areas, and the contribution of serotonergic mechanisms to masseter muscle nociception could be greater in stressed rats than in sham rats. These results support the hypothesis that changes in brain function, including serotonergic mechanisms, in the Vc areas play critical roles in enhanced masseter muscle nociceptive responses under psychophysical stress conditions.



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mRNA transcript distribution bias between Borrelia burgdorferi bacteria and their outer membrane vesicles

Abstract
Borrelia burgdorferi, a bacterium in the spirochete phylum, is the causative agent of Lyme disease. B. burgdorferi has a linear chromosome with a number of circular and linear plasmids. Bacteria, including B. burgdorferi, release spherical outer membrane vesicles (OMVs) that are known to carry secretory products including metabolites, nucleic acids and proteins. Herein, we provide the first comparative transcriptomic analysis of the vesicles released from B. burgdorferi. We identified a total of ∼1200 unique transcripts with at least one mapped read from the bacterial cell and its OMVs. We compared the spectrum of transcripts between bacterial cell and its OMVs, and found a biased distribution based on the source of transcripts, i.e. plasmid-encoded transcripts are more likely to be enriched in the OMVs. We validated the distribution for some of the transcripts by qPCR. This analysis provides the first evidence that some of the B. burgdorferi transcripts are preferentially packaged in OMV which further suggest that the bacteria might use its OMVs for bacteria-bacteria or bacteria-host communications. This report also suggests a possible involvement of Borrelia-derived OMVs in the development of Lyme disease in both early and post disease syndromes.

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Ciprofloxacin binding to GyrA causes global changes in the proteome of Pseudomonas aeruginosa

Abstract
Ciprofloxacin is one of the most widely-used antibiotics, and has proven especially effective at controlling infections associated with the opportunistic human pathogen, Pseudomonas aeruginosa. In this work, we show that sub-inhibitory concentrations of ciprofloxacin induce discrete changes in the intracellular proteome. Central metabolism and cell envelope-associated functions are particularly affected. In spite of the low magnitude of the intracellular proteomic changes, we found that sub-lethal concentrations of ciprofloxacin had substantial effects on motility and exoprotein secretion. Crucially, the proteomic and phenotypic modulations that we observed were absolutely dependent upon the presence of wild-type GyrA; an isogenic strain of P. aeruginosa carrying a ciprofloxacin-insensitive form of GyrA (a T83→I mutant) did not display ciprofloxacin-dependent changes unless complemented with wild-type gyrA in trans. These results show that the diverse effects of sub-inhibitory ciprofloxacin on the cell are routed through its primary target in the cell, DNA gyrase.

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Applying GRADE Criteria to Clinical Inputs to Cost-Effectiveness Modeling Studies

Abstract

Background

Concerns have been raised about the use of clinical data in cost-effectiveness models. The aim of this analysis was to evaluate the appropriate use of data on clinical effectiveness in cost-effectiveness modeling studies that were published between 2001 and 2015.

Methods

Assessors rated 72 modeling studies obtained from three therapeutic areas by applying criteria defined by the Grading of Recommendations Assessment, Development and Evaluation group for assessing the quality of clinical evidence: selection of clinical data (publication bias), imprecision, indirectness, inconsistency (i.e., heterogeneity), and study limitations (risk of bias). For all parameters included in the analyses, potential changes over time were assessed.

Results

Although three out of four modeling studies relied on randomized controlled trials, more than 60% of the modeling studies were based on clinical data with a high or unclear risk of bias, in more than 80%, a risk of publication bias was found, and in about 30%, evidence was based on indirect clinical evidence, having significantly increased over the years. Study limitations were inadequately described in more than one third of the studies. However, less than 10% of clinical studies showed inconsistency or imprecision in study results.

Conclusion

Despite the fact that the majority of economic evaluations are based on precise and consistent randomized controlled trials, their results are often affected by limitations arising from methodological shortcomings in the underlying data on clinical efficacy. Modelers and assessors should be more aware of aspects surrounding the quality of clinical evidence as considered by the Grading of Recommendations Assessment, Development and Evaluation group.



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EMCrit Podcast 225 – Tox(&Hound)idromes with Howard & Dan

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The real scoop on toxidromes

EMCrit Project by Scott Weingart.



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Management of Resistance to First-Line Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor Therapy

Opinion statement

A decade after the discovery of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (EML4-ALK) rearrangements in non-small cell lung cancer (NSCLC), several inhibitors have gained regulatory approval, and their sequential use has deferred platinum-based chemotherapy to later lines of therapy. Nevertheless, although most ALK-driven tumors dramatically respond to ALK TKIs , all patients ultimately develop drug-resistant disease. Analysis of post-progression biopsy samples has provided invaluable insight into the mechanisms of resistance, now informing on subsequent therapeutic strategies. In particular, the identification of secondary ALK mutations, which are a common mechanism of resistance to both first-generation and to an even larger extent to second-generation ALK TKIs, may shape a personalized optimal treatment strategy beyond the current first-line choice. Alectinib has now become a preferred treatment option in the first line of therapy, and extrapolation of data obtained from post-progression samples after second-line next-generation ALK TKIs suggests that acquired resistance is likely to be mediated in more than half of patients by ALK resistance mutations. Nevertheless, clinical and preclinical evidence suggests that multiple resistance mechanisms may co-exist at different levels in the same TKI-resistant patient. Newer ALK tyrosine kinase inhibitors (TKIs) overcome some resistance mutations through higher exposure and potency, and generally present greater CNS activity, but are unlikely to overcome resistance mediated through separate oncogenic pathway activations, or epithelial to mesenchymal transition (EMT) and small cell lung cancer (SCLC) transformation. Furthermore, while resistance mutations can be detected through commonly available sequencing methods, the identification of other mechanisms of resistance is much less straightforward in the clinic. We hypothesize that the ALK resistance mutation status will likely be crucially important in the choice of second-line therapy after a second-generation TKI. Emerging clinical data also refines the optimal placing of PD-1- and PD-L1-directed immunotherapy in the treatment sequence.



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Overview of Current and Future Adjuvant Therapy for Muscle-Invasive Urothelial Carcinoma

Opinion statement

Muscle-invasive bladder cancer (MIBC) has high metastatic potential at diagnosis but is still often curable with aggressive management, which may give patients the best odds for a favorable clinical outcome. The standard-of-care management of MIBC includes a radical cystectomy and pelvic lymph node dissection. If the patient is cisplatin-eligible, neoadjuvant cisplatin-based combination chemotherapy should also be given. Post-surgery adjuvant treatments include observation, chemotherapy, radiation, or enrollment in a clinical trial. Several adjuvant immunotherapy trials with checkpoint inhibitors, which block the interaction between PD-1 and PD-L1, as monotherapy or in combinations with chemotherapy, radiation, or other immunotherapy agents are currently ongoing. Given the lack of level 1 evidence for the survival benefit of adjuvant therapies post-cystectomy, the standard of care remains observation with radiologic and clinical surveillance. However, in patients who did not receive neoadjuvant cisplatin-based combination chemotherapy and are cisplatin-eligible, adjuvant cisplatin-based chemotherapy should be considered and discussed. Genomic alterations and gene expression profiles may eventually help to identify patient subgroups for more effective adjuvant therapy. Genetic abnormalities in the DNA repair genes and basal intrinsic tumor subtype appear to predict response to neoadjuvant cisplatin-based chemotherapy in MIBC. In the coming years, validating these genetic markers will be key to individualizing perioperative chemotherapy.



https://ift.tt/2siXfhu

A Biosemiotic Encyclopedia: an Encyclopedic Model for Evolution

Abstract

New discoveries in the life sciences have affirmed that the virtual script as well as its context-dependent reading and interpretation determine the final living creature (cell, protein or animal). An extended understanding of Darwinian Theory is crucial for understanding life as semiosis in terms of Peirce and Eco's semiotic models. The semiosis of living systems is potentially unlimited. Genes are not static and unchangeable scripts, but can always be reinterpreted by new interpretants that illuminate them from different points of view, depending on which properties are relevant in a particular context. The encyclopedia is a term, in Umberto Eco's semiotics, which represents the multidimensional space of semiosis that is governed by a self-sustaining production of interpretants. The paper will present the idea of understanding the Extended Synthesis in terms of a biosemiotic enyclopedia.



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Alpine soil microbial ecology in a changing world

Abstract
Climate change has a disproportionally large impact on alpine soil ecosystems, leading to pronounced changes in soil microbial diversity and function associated with effects on biogeochemical processes at the local and supraregional scales. However, due to restricted accessibility, high-altitude soils remain largely understudied and a considerable heterogeneity hampers the comparability of different alpine studies. Here, we highlight differences and similarities between alpine and arctic ecosystems, and we discuss the impact of climatic variables and associated vegetation and soil properties on microbial ecology. We consider how microbial alpha-diversity, community structures and function change along altitudinal gradients and with other topographic features such as slope aspect. In addition, we focus on alpine permafrost soils, harboring a surprisingly large unknown microbial diversity and on microbial succession along glacier forefield chronosequences constituting the most thoroughly studied alpine habitat. Finally, highlighting experimental approaches, we present climate change studies showing shifts in microbial community structures and function in response to warming and altered moisture, interestingly with some contradiction. Collectively, despite harsh environmental conditions, many specially adapted microorganisms are able to thrive in alpine environments. Their community structures strongly correlate with climatic, vegetation and soil properties and thus closely mirror the complexity and small-scale heterogeneity of alpine soils.

https://ift.tt/2J8muO5

Prokaryotic assemblages in suspended and subglacial sediments within a glacierized catchment on Qeqertarsuaq (Disko Island), west Greenland

Abstract
Microbes transported by glacial meltwater streams are thought to be a product of passive dispersal from both supra- and subglacial sources, though studies investigating the origins of these assemblages are scarce. Here, we conducted a survey within a large catchment containing multiple glaciers on Qeqertarsuaq (Disko Island), west Greenland, to investigate whether meltwater-exported microbial assemblages in suspended sediments differ between glacial meltwater streams, and if they reflect corresponding bulk subglacial and extraglacial sediment communities. Using 16S rRNA gene amplicon sequencing, we found proglacial stream assemblages substantially differ from one another, despite their close spatial proximity. Furthermore, proglacial stream assemblages were composed of greater proportions of Cyanobacteria compared to bulk subglacial sediment communities, dominated by Betaproteobacteria, demonstrating large contributions of meltwater and microbial cells from supraglacial habitats. Corresponding physico-chemical characteristics of meltwater suggest that streams draining smaller glaciers had more equal contributions of both supra- and subglacial inputs compared with the main catchment outlet, aligning with observed changes in assemblage structure, such as the decreased proportion of Cyanobacteria. These results suggest that glacier size and hydrological drainage systems may influence the structure of exported microbial assemblages, and collectively provide insights into their formation and fate in this current age of deglaciation.

https://ift.tt/2sinV1Z

Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity

Abstract

The recent success of checkpoint inhibitors in the treatment of Merkel cell carcinoma (MCC) confirms that MCC tumors can be immunogenic. However, no treatment directly targeting the tumor is available for use in combination with these checkpoint inhibitors to enhance their efficacity. This study was carried out to characterize MCC line sensitivity to cellular lysis and to identify cell surface antigens that could be used for direct targeting of this tumor. For five representative MCC lines, the absence or low expression of MICA, MICB, HLA-I, and ICAM-1 was associated with low level of recognition by NK cells and T lymphocytes. However, expression of HLA-I and ICAM-1 and sensitivity to cellular lysis could be restored or increased after exposure to INFγ. We tested 41 antibodies specific for 41 different antigens using a novel antibody-dependent cellular cytotoxicity (ADCC) screening system for target antigens. Anti-CD326 (EpCAM) was the only antibody capable of inducing ADCC on the five MCC lines tested. Because MCC tumors are often directly accessible, local pharmacologic manipulation to restore HLA class-I and ICAM-1 cell surface expression (and thus sensitivity to cell lysis) can potentially benefit immune therapeutic intervention. In line with this, our observation that ADCC against EpCAM can induce lysis of MCC lines and suggests that therapeutic targeting of this antigen deserves to be explored further.



https://ift.tt/2LCOIi5

Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers

Abstract

GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing. We found 10 frameshift mutations in the repeat, nine for CRCs and one for GC. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (10/113) and MSS (0/90). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the mutations exhibited regional ITH in three of the CRCs (18.8%). Our data indicate GLI1 harbored not only frameshift mutation but also its mutational ITH, which together could be a feature of GC and CRC with MSI-H.



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Erratum to: Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population



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Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population

Abstract

Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4–4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6–9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6–5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0–91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7–101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).



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Erratum to: TERT Promoter Mutation and Telomere Length in Salivary Gland Tumors



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TERT Promoter Mutation and Telomere Length in Salivary Gland Tumors



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Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population

Abstract

Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific – PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.



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Pitfalls of Combining Novel Agents in Lymphoma

Opinion statement

As our knowledge of lymphoma and its intricate signaling pathways has grown, so has the development of novel agents. While their mechanisms of action vary considerably, these therapies supplement and in some cases offer alternatives to standard chemotherapy. Initial studies have highlighted tolerable side effects though in the majority of instances limited efficacy when used as monotherapy. Research has focused on combining these novel agents to improve outcomes and perhaps offer refined treatment options. Novel combinations represent new territory, inherently dissimilar to combination chemotherapy with new pitfalls and challenges given their unique mechanisms of action. Though promising, it is crucial to consider the complex interplay that can occur. While there is potential for improved outcomes, there is also the possibility of unexpected toxicities. For this reason, it is critical that novel combinations be carefully considered and tested in clinical trials before widespread use. Thus far, research has shown that combination therapies are successful when not only avoiding overlapping toxicity but also capitalizing on synergy. We believe that more specific targets and an improved understanding of their off-/on-target effects will further successful novel combinations.



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Letter to the Editor



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2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary

Abstract

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2–9% of all cancer patients, mostly 60–75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.



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Antiangiogenic Herbal Composition Ob-X Reduces Abdominal Visceral Fat in Humans: A Randomized, Double-Blind, Placebo-Controlled Study

Adipose tissue growth is angiogenesis-dependent, and angiogenesis inhibitors can regulate adipose tissue mass by cutting off the blood supply. We examined whether antiangiogenic herbal composition Ob-X can reduce fast-growing abdominal fat, especially visceral fat in humans by inhibiting angiogenesis. Eighty abdominally obese subjects (body mass index: 25-29.9 kg/m2, waist circumference: exceeding 90 cm for males and 85 cm for females) participated in a 12-week randomized, double-blind, placebo-controlled human study to evaluate the efficacy and safety of Ob-X. 690 mg of Ob-X was administered orally twice a day. The Ob-X group showed a noticeable reduction in visceral fat of 20.5% after the 12-week treatment as compared to baseline measured by computed tomography. The change in visceral fat in the Ob-X group was statistically significant as compared to the placebo group (p = 0.0495) and 1.9 times higher than in the placebo group. Therefore, angiogenesis inhibitor Ob-X has the potential to improve obesity-related metabolic syndrome by reducing dangerous visceral fat.

https://ift.tt/2skYFbl

The activity and role of autophagy in the pathogenesis of diabetic nephropathy

OBJECTIVE: Evidence suggested that deficiency of autophagy is involved in the pathogenesis of diabetic nephropathy (DN). However, some recent studies have also shown that autophagy is activated in renal cells under diabetic conditions. In this review, we discuss whether autophagy is inactivated in renal cells in DN as well as the therapeutic potential of autophagy for treating DN, in order to aid future investigation in this field.

MATERIALS AND METHODS: Relevant information, original research articles and reviews, were gathered primarily through a search in PubMed and Cochrane database. The activity and role of autophagy, as well as the relevant signaling pathways, were analyzed in different intrinsic renal cells, including podocyte, renal tubular epithelial cell, glomerular mesangial and endothelial cells.

RESULTS: The upstream of autophagic pathway, but not whole pathway, was predominately studied in these intrinsic renal cells, such as the induction of autophagy, an amount of autophagic vacuoles and so on. In most cases, autophagic inactivation occurred, which is an important mechanism underlying DN progression. Targeting the autophagic pathway to activate autophagy activity might have renoprotective effect. However, autophagic activation was also found in a few studies, in which there was a debate on the role of activated autophagy: mounting an adaptive response or leading to autophagic apoptosis.

CONCLUSIONS: The downstream of autophagic pathway, including the degradation of autophagic vacuoles, and lysosomal function, should be well studied to clarify the activity and role of autophagy in the progression of DN. Autophagy activation is likely a potential therapy for combatting DN.

L'articolo The activity and role of autophagy in the pathogenesis of diabetic nephropathy sembra essere il primo su European Review.



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Visual outcome and complications of cataract extraction after pars plana vitrectomy

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Diabetic corneal neuropathy: clinical perspectives

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Postoperative outcomes following trabeculectomy and nonpenetrating surgical procedures: a 5-year longitudinal study

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https://ift.tt/2IU9snK

Study on the correlation of changes of IGF-1, GH, and NGB levels and NBNA score in neonates with hypoxic ischemic encephalopathy

OBJECTIVE: The aim of this work was to investigate the correlation between dynamic changes of serum insulin-like growth factor 1 (IGF-1), growth hormone (GH), neuroglobin (NGB), and neonatal behavioral neurological assessment (NBNA) scores in different periods in neonates with hypoxic ischemic encephalopathy (HIE).

PATIENTS AND METHODS: Sixty HIE patients in the Neonatal Department of our hospital were selected. They were divided into the mild group (35 cases), moderate group (19 cases), and severe group (six cases) according to the diagnostic criteria. During the same period, 18 neonatal patients born at term in our hospital were chosen as the control group. Data were analyzed by SPSS19.0 statistical software (SPSS Inc., Chicago, IL, USA). The dynamic changes of IGF-1, GH, and NGB in different periods, as well as NBNA scores in HIE patients and in the control group, were analyzed. Furthermore, we analyzed the degree of correlation of IGF-1, GH, and NGB in different periods as well as NBNA scores in HIE patients and in the control group.

RESULTS: 1- IGF-1 levels between the three groups of HIE patients and control group had significant differences (p<0.05); 2- Comparing GH levels between the HIE experimental groups and control group, there was no statistical significance; 3-Comparing serum NGB levels between the three HIE experimental groups and control group, there were significant differences (p<0.05); 4- Comparing NBNA scores of the three groups of HIE patients and control group, there was a significant difference between the mild group and control group; 5- Serum IGF-1 and NBNA scores were positively correlated in the acute and recovery phase, while NGB level and NBNA scores were negatively correlated in the acute and recovery phase (p<0.05), which had statistical significance.

CONCLUSIONS: In neonatal HIE, serum IGF-1, GH, and NGB levels change. IGF-1 and NGB levels correlate with the prognosis of HIE.

L'articolo Study on the correlation of changes of IGF-1, GH, and NGB levels and NBNA score in neonates with hypoxic ischemic encephalopathy sembra essere il primo su European Review.



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Neuronal nitric oxide synthase inhibition reduces brain damage by promoting collateral recruitment in a cerebral hypoxia-ischemia mice model

OBJECTIVE: The collateral circulation development is considered as a compensatory inherent mechanism to restore damaged blood perfusion after ischemia. We aimed to detect the collateral flow and the mean blood-flow velocities (mBFVs) level in the basilar trunk during or after cerebral hypoxia-ischemia in the mice brain and explore the effect of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow.

MATERIALS AND METHODS: C57BL/6J mice and the nNOS knockout (KO) mice were randomly divided into a sham-operated group (control) and the hypoxia-ischemia (HI) groups that were treated with the phosphate buffered solution (PBS) control or 7-nitroindazole (7-NI). Cortexes were harvested after the HI treatment for analysis of nNOS expression using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Ultrasound imaging experiments were performed to detect the collateral flow and the mBFVs level in the basilar trunk.

RESULTS: After cerebral HI, the cortical nNOS mRNA and protein levels increased markedly compared with the sham-operated control mice. Besides, 7-NI treatment had no effect on the blood flow in the sham-operated control mice. What's more, either the 7-NI pretreatment or the nNOS gene knockdown before the HI procedure could attenuate the brain injury by the increased collateral flow and the decreased mBFVs level in the basilar trunk.

CONCLUSIONS: nNOS inhibition protected hypoxic-ischemic-induced mice brain damage by the increased collateral flow and the decreased mBFVs level in the basilar trunk. Therefore, the 7-NI administration may have potential utility for the treatment of HI injury in human beings.

L'articolo Neuronal nitric oxide synthase inhibition reduces brain damage by promoting collateral recruitment in a cerebral hypoxia-ischemia mice model sembra essere il primo su European Review.



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Screening Circulating Tumor Cells as a Noninvasive Cancer Test in 3388 Individuals from High-Risk Groups (ICELLATE2)

Cancer is known to spread up to 12 years before clinical symptoms occur, but few screening tests exist. Early detection would give the opportunity for early treatment, potentially improving prognosis. To this end, 3388 subjectively healthy individuals of age 45 to 80 who had been exposed to cancer risk factors were screened for the occurrence of circulating tumor cells in their blood. Presence of circulating tumor cells is a suspicious finding indicative of spreading cancer, since cancer metastasizes by way of the blood and offers the opportunities to (a) follow up the individual clinically based on established guidelines for early detection of cancer and (b) evaluate the cells further analytically. 107 individuals showed one or more circulating tumor cells in a 7.5 ml blood sample, which constitutes a positive circulating tumor cell test, based on the iCellate IsoPic™ laboratory test. That number compares favorably with the cancer incidence per 100,000 people/year that is 157.1 in Peru, given that a high-risk group of individuals was screened and that the screening results would be expected to correspond to an accumulated incidence of up to 12 years. The present findings therefore identify screening for circulating tumor cells as a promising new test.

https://ift.tt/2ITFfWh

Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study

Abstract

Anti-PD-1 and anti-CTLA-4 antibodies cause immune-related side effects such as autoimmune type 1 diabetes (T1D). It has also been suggested that by increasing TNF-α, IL-2 and IFN-γ production, anti-PD-1 and/or anti-CTLA-4 treatment could affect pancreatic beta cell function and insulin sensitivity. This study was based on a retrospective observational analysis from 2 July 2014 to 27 June 2016, which evaluated the occurrence of T1D and changes in glycemia and C-reactive protein (CRP) plasma concentrations in patients undergoing anti-PD-1 and/or anti-CTLA-4 treatment for melanoma at the Saint Louis Hospital. All cases of T1D that developed during immunotherapy registered in the French Pharmacovigilance Database (FPVD) were also considered. Among the 132 patients included, 3 cases of T1D occurred. For the remaining subjects, blood glucose was not significantly affected by anti-PD-1 treatment, but CRP levels (mg/l) significantly increased during anti-PD-1 treatment (p = 0.017). However, 1 case of type 2 diabetes (T2D) occurred (associated with a longer therapy duration). Moreover, glycemia of patients pretreated (n = 44) or concomitantly treated (n = 8) with anti-CTLA-4 tended to increase during anti-PD-1 therapy (p = 0.068). From the FPVD, we obtained 14 cases of T1D that occurred during immunotherapy and were primarily characterized by the rapidity and severity of onset. In conclusion, in addition to inducing this rare immune-related diabetes condition, anti-PD-1 treatment appears to increase CRP levels, a potential inflammatory trigger of insulin resistance, but without any short-term impact on blood glucose level.



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Update on Idiopathic Intracranial Hypertension

Abstract

Purpose of review

This review presents a critical appraisal of current therapeutic strategies for patients with idiopathic intracranial hypertension (IIH). We present the reader with the most recent evidence to support medical and surgical interventions in patients with IIH and provide recommendations about treatment initiation and escalation. We also indicate areas where knowledge gaps exist regarding therapeutic efficacy and superiority of one intervention over another.

Recent findings

A double-masked, randomized prospective study of medical management of patients with mild IIH (Idiopathic Intracranial Hypertension Treatment Trial—IIHTT) has established that acetazolamide therapy has additional efficacy when compared to weight loss alone. Furthermore, management of IIH-related headache, even in patients with papilledema, may require treatment other than ICP lowering for patients to experience symptomatic relief. Finally, a number of uncontrolled interventional studies have shown transverse sinus stenting to be a potentially effective treatment for medically refractory IIH.

Summary

Medical therapy with acetazolamide should be considered in addition to structured weight loss in patients with mild IIH. Surgical treatment for patients with vision-threatening disease IIH can be performed by either optic nerve sheath fenestration or cerebrospinal fluid diversion, with venous sinus stenting emerging as an alternate therapy. Headache relief from ICP lowering therapy is variable and often not sustained.



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Current Treatment Options for Peripheral Nerve Hyperexcitability Syndromes

Abstract

Purpose of review

Peripheral nerve hyperexcitability (PNH) syndromes are divided into primary and secondary groups based on the presence or absence of demonstrable peripheral nerve disease. In this review, we systematically evaluate the evidence for current therapies and supportive managements based on autoimmune, paraneoplastic, and genetic components in pathophysiology reported in the literature.

Recent findings

Current therapy options are based on symptomatic management as well as focusing the underlying immune/genetic/paraneoplastic pathology by immunosuppressants, chemotherapy, and surgery.

Summary

Further research is desired to provide treatment options geared specifically towards addressing PNH. Supportive care can also be an area for future research.



https://ift.tt/2LDDXMv

Surgical Treatment of Adult Moyamoya Disease

Abstract

Purpose of review

Moyamoya disease (MMD) is being increasingly diagnosed with the development of radiological surveillance technology and increased accessibility to medical care. Accordingly, there have been several recent reports on treatment outcomes in MMD. In this review, we summarize recent advances in surgical treatment and outcomes of adult MMD, while addressing related controversies.

Recent findings

Recent studies suggest that revascularization surgery leads to significantly more favorable outcomes for stroke prevention, angiographic and hemodynamic changes, and clinical outcomes than does conservative treatment for adult patients with ischemic MMD. Moreover, direct revascularization methods should be considered as the first-line treatment over indirect methods, although the latter may be considered if a direct method is not possible. In cases of hemorrhagic MMD, several studies have demonstrated that surgical treatment is more effective than conservative treatment in preventing further hemorrhage. In addition to revascularization surgery, endovascular treatment is emerging as a breakthrough therapy for hemorrhagic MMD.

Summary

Accumulating evidence regarding the surgical treatment of adult MMD suggests the benefit of revascularization over conservative management for both ischemic and hemorrhagic patients. However, the benefit of revascularization in asymptomatic adult MMD remains unclear.



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Completion pneumonectomy: a valuable option for lung cancer recurrence or new primaries

Abstract

Background

The preoperative selection of patients with lung cancer recurrence remains a major clinical challenge. Several aspects of this kind of surgery are still insufficiently evidence-based, with only a few series with more than 50 patients.

Methods

A retrospective study on 29 patients who underwent a completion pneumonectomy for postoperative lung cancer recurrence or new primary was done in the period between October 2004 and December 2015. Inclusion criteria include complete (R0) first and second resections, histologically proven recurrent or new malignancy, complete pathohistological report after both operations, and exact data about the treatment outcome at the time of the last contact with patients or their families.

Results

There were 25 (86.2%) males and 4 (13.8%) females (M:F 6.2:1). In 13/29 patients, the interval between the first and second operations was less than 2 years, while in the remaining 16 patients, it was longer than 2 years. Concerning the operative stage distribution, stage I was more frequent after the first operation (44.8 vs. 22%), while stage III was dominant after the second operation (40.7 vs. 10.3%). The same tumor histology after the first and second operations existed in 24 (82.8%) patients. Adjuvant treatment was given to 53.6% of patients after the first and to 45.5% of patients after the second operation. The overall 5-year survival was 30%, median survival being 35 ± 16.9 months (1.896, 68.104 95% CI). A median survival of patients in post-surgery stage I after re-do surgery was better in comparison with that in higher stages (35 ± 22.6 vs.17.2 ± 15.1 vs. 21 ± 6.7 months, p > 0.05). Patients with the same tumor type at both operations lived significantly longer (median survival 48 ± 21.5 vs. 7.7 ± 1.9 months) than patients with different tumor histology after the second operation. Patients under 60 years (42.9%) lived longer than patients older than 60 years (median survival 69 ± 4.5 vs. 17.2 ± 14.3 months). The Cox regression analysis revealed only the disease stage at first operation and the same/different tumor histology as significant prognostic factors. One patient died from cardiac insufficiency caused by bronchopleural fistula (3.4% operative mortality). Operative morbidity was 34.4%.

Conclusion

Completion pneumonectomy may be a reasonable option for postoperative lung cancer recurrence or new primaries only in carefully selected patients, in whom the potential oncological benefits overweigh the surgical risk.



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Lactobacillus plantarum with Functional Properties: An Approach to Increase Safety and Shelf-Life of Fermented Foods

Lactobacillus plantarum (widespread member of the genus Lactobacillus) is one of the most studied species extensively used in food industry as probiotic microorganism and/or microbial starter. The exploitation of Lb. plantarum strains with their long history in food fermentation forms an emerging field and design of added-value foods. Lb. plantarum strains were also used to produce new functional (traditional/novel) foods and beverages with improved nutritional and technological features. Lb. plantarum strains were identified from many traditional foods and characterized for their systematics and molecular taxonomy, enzyme systems (α-amylase, esterase, lipase, α-glucosidase, β-glucosidase, enolase, phosphoketolase, lactase dehydrogenase, etc.), and bioactive compounds (bacteriocin, dipeptides, and other preservative compounds). This review emphasizes that the Lb. plantarum strains with their probiotic properties can have great effects against harmful microflora (foodborne pathogens) to increase safety and shelf-life of fermented foods.

https://ift.tt/2J9kepI

The Role of Combination Maintenance with Pemetrexed and Bevacizumab for Advanced Stage Nonsquamous Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Purpose. To evaluate the effect of combination maintenance therapy of pemetrexed plus bevacizumab for patients with advanced non-small cell lung cancer. Methods. We identified relevant studies by electronic search (Embase, PubMed, Cochrane, and Web of Science from 1 January 1960 to 29 October 2016) and manual search. The primary outcome of interest was progression-free survival (PFS) and secondary end point included overall survival (OS) and toxicities. The data was pooled for quantitative analysis and the final effect size was reported as hazard ratio (HR) for survival outcomes and relative risk (RR) for safety outcomes, both with a random-effects model. Results. Three randomized controlled trials enrolling 1302 patients with advanced non-small cell lung cancer were included in this meta-analysis. An evident PFS improvement (HR = 0.73, 95% CI = 0.63–0.83,

https://ift.tt/2GUinzL

Impact of Coordinated-Bilateral Physical Activities on Attention and Concentration in School-Aged Children

Purpose. This study examined the effects of 4-week, daily 6-minute coordinated-bilateral physical activity (CBPA) breaks in classroom on attention and concentration in school-aged children. Methods. Participants (n=116) in fifth grade from two elementary schools were assigned to three groups: two intervention groups (n= 60) and one control group (n = 56). All three groups were pre- and post-tested with the d2 Test of Attention (d2 test). One intervention group (n = 31) took part in six minutes of daily classroom-based coordinated-bilateral physical activity (CBPA) break for four weeks. Another intervention group (n = 29), the Fitbit Only (Fitbit-O), wore Fitbits per day during a school, five days per week for four weeks without CBPA breaks. A 2 × 3 ANOVA was conducted, followed by the post hoc comparisons. Results. The CBPA showed significant increases in processing speed ( = 6.876, p = .010), focused attention ( = 10.688, p = .002), concentration performance ( = 26.46, p = .000), and attention span ( = 14.090, p = .000) over the control, but not in accuracy (Error %). The CBPA showed significant improvement in concentration performance ( = 24.162, p = .000) and attention span ( = 6.891, p = .011), compared to the Fitbit-O. No significant changes in all five attention parameters were found between the Fitbit-O and the control. Conclusion. It was concluded that daily brief coordinated-bilateral activities can improve attention and concentration in fifth-grade students over the course of four weeks.

https://ift.tt/2IQuAeD

Evolution of Therapeutic Antibodies, Influenza Virus Biology, Influenza, and Influenza Immunotherapy

This narrative review article summarizes past and current technologies for generating antibodies for passive immunization/immunotherapy. Contemporary DNA and protein technologies have facilitated the development of engineered therapeutic monoclonal antibodies in a variety of formats according to the required effector functions. Chimeric, humanized, and human monoclonal antibodies to antigenic/epitopic myriads with less immunogenicity than animal-derived antibodies in human recipients can be produced in vitro. Immunotherapy with ready-to-use antibodies has gained wide acceptance as a powerful treatment against both infectious and noninfectious diseases. Influenza, a highly contagious disease, precipitates annual epidemics and occasional pandemics, resulting in high health and economic burden worldwide. Currently available drugs are becoming less and less effective against this rapidly mutating virus. Alternative treatment strategies are needed, particularly for individuals at high risk for severe morbidity. In a setting where vaccines are not yet protective or available, human antibodies that are broadly effective against various influenza subtypes could be highly efficacious in lowering morbidity and mortality and controlling unprecedented epidemic/pandemic. Prototypes of human single-chain antibodies to several conserved proteins of influenza virus with no Fc portion (hence, no ADE effect in recipients) are available. These antibodies have high potential as a novel, safe, and effective anti-influenza agent.

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Comparison of Aggressive Surgical Treatment and Palliative Treatment in Elderly Patients with Poor-Grade Intracranial Aneurysmal Subarachnoid Hemorrhage

Objective. To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after aggressive surgical treatment. Method. This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. Results. At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3–5, and palliative treatment were independent predictors of poor prognoses. Conclusion. Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.

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The Female Athlete’s Heart: Comparison of Cardiac Changes Induced by Different Types of Exercise Training Using 3D Echocardiography

We aimed to characterize female athlete's heart in elite competitors in the International Federation of Bodybuilding and Fitness (IFBB) Bikini Fitness category and compare them to athletes of a more dynamic sport discipline and healthy, sedentary volunteers using 3D echocardiography. Fifteen elite female fitness athletes were recruited and compared to 15 elite, age-matched female water polo athletes and 15 age-matched healthy, nontrained controls. Using 3D echocardiography, left ventricular (LV) and right ventricular (RV) end-diastolic volume index (EDVi) and LV mass index (LVMi) were measured. Fitness athletes presented similar LV and RV EDVi compared to healthy, sedentary volunteers. Water polo athletes, however, had higher LV and also RV EDVi (fitness versus water polo versus control; LVEDVi: versus versus  ml/m2, ANOVA ; RVEDVi: versus versus  ml/m2, ). LVMi was significantly higher in the athlete groups; the hypertrophy, however, was even more prominent in water polo athletes ( versus versus  g/m2, ). To the best of our knowledge, this is the first study to characterize female athlete's heart of IFBB Bikini Fitness competitors. The predominantly static exercise regime induced a mild, concentric-type LV hypertrophy, while in water polo athletes higher ventricular volumes and eccentric LV hypertrophy developed.

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Clinical and Biological Signature of Osteochondritis Dissecans in a Cross-Sectional Study

The healing potential of knee osteochondritis dissecans (OCD) focal lesions is not well defined. We performed a cross-sectional study correlating local and systemic biological characteristics with the patients' characteristics. We evaluated both local tissue markers (CD34, CD146, CD166, and tartrate-resistant acid phosphatase (TRAP)) and systemic serum biomarkers (fragments or propeptide of type II collagen: C2C, CTX-II, CPII, and TRAP5b) on histologically scored osteochondral fragments or serum from OCD patients. These biological features were associated with the patients' characteristics (IKDC subjective score, age, and body mass index (BMI)). Histological cartilage tissue score correlated with patients' IKDC and C2C and CPII biomarkers. CPII correlated also with histological bone tissue score. The percentage of CD146 positive cells in cartilage and CD34 positive cells in bone highly correlated with the patient's age and BMI, respectively. The percentage of TRAP in bone was directly correlated with both IKDC and age. Multivariate statistical analysis evidenced that only four parameters significantly predicted IKDC. In conclusion, a complete picture of OCD knee characteristics, defined by local and systemic markers of cartilage and bone remodeling, together with the patients' characteristics, might help to better understand the healing potential of each patient and to target and improve current OCD treatments.

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Potential of the Novel PTA Score to Identify Patients with Peritonsillar Inflammation Profiting from Medical Treatment

Peritonsillar inflammation is a common characteristic of both peritonsillar abscess (PTA) and peritonsillitis (PC). The aim of the present study was to apply the PTA score as an objective criterion to identify patients with peritonsillar inflammation (PI) who might profit from medical treatment. Hence, the recently developed PTA score was applied retrospectively on patients suffering from acute tonsillitis, peritonsillitis, and peritonsillar abscess. Analysis of the clinical data, the follow-up, and the initial PTA score was performed. Patients with peritonsillar inflammation show significant higher PTA score values compared to patients with acute tonsillitis without peritonsillar inflammation and healthy controls. Patients with a PTA score ≤ 2 profited from medical treatment consisting of antibiotics in 92.3% of the cases. In 89.2% of the patients with a PTA score > 2, pus was detected during abscess relief. Patients with peritonsillar inflammation who profited from medical treatment had significantly reduced PTA score values and a reduced duration of hospitalization compared to the patients with abscess relief. Thus, the PTA score has the potential as an objective criterion to identify patients with peritonsillar inflammation profiting from medical treatment. Hence, application of the PTA score helps to determine an optimal, individualized treatment approach and might reduce utilization of medical resources.

https://ift.tt/2IRDWqL

Irisin Maternal Plasma and Cord Blood Levels in Mothers with Spontaneous Preterm and Term Delivery

Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB) by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661). Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (). On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.

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Current issues with luminal subtype classification in terms of prediction of benefit from endocrine therapy in early breast cancer

Histopathology, EarlyView.


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Standardized Kaempferia parviflora Wall. ex Baker (Zingiberaceae) Extract Inhibits Fat Accumulation and Muscle Atrophy in ob/ob Mice

Obesity, a metabolic disorder caused by an imbalance between energy intake and energy expenditure, is accompanied with fat accumulation and skeletal muscle atrophy. Kaempferia parviflora Wall. ex Baker, also called black ginger, is known to increase physical fitness performance and improve energy metabolism. In this study, we investigated whether Kaempferia parviflora extract (KPE) alleviates both obesity and muscle atrophy using ob/ob mice. Wild-type C57BL/6J and ob/ob mice were provided with a normal diet ad libitum, and ob/ob mice were orally given KPE at a dose of 100 mg/kg/day or 200 mg/kg/day for eight weeks. KPE significantly decreased body weight, fat volume, and fat weight without affecting appetite. It inhibited the expression of adipogenic transcription factors and lipogenic enzymes by upregulating AMP-activated protein kinase (AMPK) in epididymal fat. In contrast, it markedly increased the muscle fiber size, muscle volume, and muscle mass, resulting in the enhancement of muscle function, such as exercise endurance and grip strength. On the molecular level, it activated the phosphatidylinositol 3 kinase (PI3K)/Akt pathway, a key regulator in protein synthesis in skeletal muscle. KPE could be a promising material to alleviate obesity by inhibiting adipogenesis, lipogenesis, and muscle atrophy.

https://ift.tt/2L0YDgt

Protein Hydrolyzates from Changbai Mountain Walnut (Juglans mandshurica Maxim.) Boost Mouse Immune System and Exhibit Immunoregulatory Activities

The Changbai Mountain walnut (Juglans mandshurica Maxim.) is a rich source of essential amino acids. Walnut dregs are byproducts of edible oil production and primarily used as fodder and fertilizers. We systematically examined the effect of three types of walnut protein hydrolyzates—albumin, glutelin, and globin—on the immune system of mice and aimed to provide the theoretical basis for developing and utilizing J. mandshurica Maxim. protein resources. In comparison with the normal control mice, those treated with different doses of walnut proteins showed improved immune indices, including organ index, spleen lymphocyte proliferation, macrophage activity, number of CD4+ and CD8+ T cells, immunoglobulin A (IgA) and secretory IgA content, and mRNA and protein expression levels of cytokine factors. Our results indicated that these walnut proteins may have positive effects on the immune system and perform their immunomodulatory functions by inducing splenic enlargement. These findings support the use of walnut proteins as nutritional sources to boost the immune system.

https://ift.tt/2JblOar

Custom-Made Direct Metal Laser Sintering Titanium Subperiosteal Implants: A Retrospective Clinical Study on 70 Patients

Purpose. To present a digital technique for the fabrication of custom-made subperiosteal implants and to report on the survival and complication rates encountered when using these fixtures. Methods. The data used for this retrospective clinical study were derived from the medical records of five different private dental practices. Inclusion criteria were patients over the age of 60, treated with custom-made direct metal laser sintering (DMLS) titanium subperiosteal implants (Eagle-Grid®, BTK, Dueville, Vicenza) during a two-year period (2014-2015) and restored with fixed restorations; all enrolled patients needed to have complete pre- and postoperative clinical and radiographic documentation, with at least 2 years of follow-up. Exclusion criteria were smoking and bruxism. The main outcomes looked at were implant survival and complications. Results. Seventy patients (39 males and 31 females, aged 62-79 years) who had been treated with custom-made DMLS titanium subperiosteal implants were enrolled in this study. After 2 years of follow-up, three implants were lost due to recurrent, untreatable infections; the survival rate was therefore 95.8% (67/70 implants). Four patients reported pain/discomfort/swelling after implant placement; the incidence of immediate postoperative complications was therefore 5.7% (4/70 implants). During the follow-up period, one patient suffered from recurrent infections classified as a biologic complication; the incidence of biologic complications was therefore 1.4% (1/67 surviving implants). Finally, four patients experienced prosthetic problems with their implant-supported restorations during the provisional phase (fracture of the acrylic restoration) and two patients had ceramic chipping of the definitive restoration; the incidence of prosthetic complications was therefore 8.9% (6/67 surviving implants). Conclusions. Within the limits of the present study (limited follow-up time and low number of patients treated, retrospective design), the application of custom-made DMLS titanium subperiosteal implants showed satisfactory implant survival (95.8%) and low complication rates. Further studies are needed to confirm the positive outcomes found in this research.

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Stable isotope probing of hypoxic toluene degradation at the Siklós aquifer reveals prominent role of Rhodocyclaceae

Abstract
The availability of oxygen is often a limiting factor for the degradation of aromatic hydrocarbons in subsurface environments. However, while both aerobic and anaerobic degraders have been intensively studied, degradation betwixt, under micro- or hypoxic conditions has rarely been addressed. It is speculated that in environments with limited, but sustained oxygen supply, such as in the vicinity of groundwater monitoring wells, hypoxic degradation may take place. A large diversity of subfamily I.2.C extradiol dioxygenase genes has been previously detected in a BTEX-contaminated aquifer in Hungary. Older literature suggests that such catabolic potentials could be associated to hypoxic degradation. Bacterial communities dominated by members of the Rhodocyclaceae were found, but the majority of the detected C23O genotypes could not be affiliated to any known bacterial degrader lineages. To address this, a stable isotope probing (SIP) incubation of site sediments with 13C7-toluene was performed under microoxic conditions. A combination of 16S rRNA gene amplicon sequencing and T-RFLP fingerprinting of C23O genes from SIP gradient fractions revealed the central role of degraders within the Rhodocyclaceae in hypoxic toluene degradation. The main assimilators of 13C were identified as members of the genera Quatrionicoccus and Zoogloea, and a yet uncultured group of the Rhodocyclaceae.

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Prokaryotic community successions and interactions in marine biofilms: the key role of Flavobacteriia

Abstract
Despite clear advances in characterizing marine biofilms, details on their formation and species succession remain scarce particularly during the early stage of development. We investigated the microbial community composition and succession in coastal marine biofilms on plastic. Samples were collected over 75 days of immersion with strengthened samplings during the early stages of biofilm establishment. Biofilm composition was estimated using Illumina Miseq and microbial community interactions were assessed through microbial association network analysis. In silico analyses showed that primers used in most of previous studies considerably underestimated marine biofilm diversity. Unintentionally ignored so far, we showed that Flavobacteriia might be key actors in the functioning of marine biofilms. Gamma-proteobacteria from the genus Oleibacter strongly dominated microbial communities during the first hours of biofilm formation. These pioneer communities were quickly replaced by alpha-proteobacteria and Flavobacteriia. Bacterial communities exhibited fast temporal structure dynamics with taxa displaying rapid increases and declines. A total of 90% of operational taxonomic units (OTUs) were intermittent or ephemeral reinforcing the conclusion that marine biofilms are highly dynamics. With 2/3 of positive significant connections between bacterial OTUs, microbial biofilm communities appear to be more inclined to develop inter-specific cooperation rather than competition and might thus form sets of functional guilds with mutual metabolic exchanges.

https://ift.tt/2LA8tal

Redox-gradient driven electron transport in a mixed community anodic biofilm

Abstract
Here, we describe the long-distance (multi-cell-length) extracellular electron transport (LD-EET) that occurs in an anode-grown mixed community biofilm (MCB) enriched from river sediment that contains 3%–45% Geobacter spp. High signal-to-noise temperature-dependent electrochemical gating measurements (EGM) using interdigitated microelectrode arrays reveal a peak-shaped electrical conductivity vs. potential dependency, indicating MCB acts as a redox conductor, similar to pure culture anode-grown Geobacter sulfurreducens biofilms (GSB). EGM also reveal that the maximum sustained rate of LD-EET in MCB is comparable to GSB, and the same whether under acetate-oxidizing or acetate-free conditions. Voltammetry indicated that MCB possesses 3- to 5-fold less electrode-accessible redox cofactors than GSB, suggesting that MCB may be more efficiently organized than GSB for LD-EET or that a small portion of electrode accessible redox cofactors of GSB are involved in LD-EET. The activation energy for LD-EET (0.11 ± 0.01 eV) was comparable to GSB, consistent with the possible role of c-type cytochromes as LD-EET cofactors, detected in abundance by confocal resonance Raman microscopy. Taken together, the results demonstrate LD-EET for a mixed community anode-grown microbial biofilm that is remarkably similar to GSB even though it contains many different types of microorganisms and appears to utilize far fewer EET redox cofactors.

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Deciphering the genome and secondary metabolome of the plant pathogen Fusarium culmorum

ABSTRACT
Fusarium culmorum is one of the most important fungal plant pathogens that causes diseases on a wide diversity of cereal and non-cereal crops. We report herein for the first time the genome sequence of F. culmorum strain PV and its associated secondary metabolome that plays a role in the interaction with other microorganisms and contributes to its pathogenicity on plants. The genome revealed the presence of two terpene synthases, trichodiene and longiborneol synthase, which generate an array of volatile terpenes. Furthermore, we identified two gene clusters, deoxynivalenol and zearalenone, which encode for the production of mycotoxins. Linking the production of mycotoxins with in vitro bioassays, we found high virulence of F. culmorum PV on maize, barley and wheat. By using ultra-performance liquid chromatography–mass spectrometry, we confirmed several compounds important for the behaviour and lifestyle of F. culmorum. This research sets the basis for future studies in microbe–plant interactions.

https://ift.tt/2LCUdgU