Αρχειοθήκη ιστολογίου

Σάββατο 29 Ιουλίου 2017

Surgical shunts compared with endoscopic sclerotherapy for the treatment of variceal bleeding in adults with portal hypertension: a systematic review and meta-analysis

Aim

Portal hypertension is a common complication of chronic liver disease and can cause variceal bleeding which is associated with high mortality. Choices for the treatment of variceal bleeding include surgical shunts and endoscopic sclerotherapy. The aim of this study was to compare the efficacy of surgical shunts and endoscopic sclerotherapy in treating variceal bleeding due to portal hypertension.

Design

Systematic review and meta-analysis.

Setting

Medline, PubMed, Cochrane and Google Scholar databases were searched until 12 February 2015, for relevant randomised control trials. Twenty studies with a total of 1540 participants were included.

Patients

Patients with variceal bleeding due to portal hypertension.

Interventions

Surgical shunts compared to endoscopic sclerotherapy.

Main outcome measures

Rates of rebleeding, survival and hepatoencephalopathy, and length of hospital stay.

Results

Pooled data for 17 studies showed that the rate of rebleeding was significantly more frequent with sclerotherapy compared with surgical shunt therapy (OR 3.99, 95% CI 2.98 to 5.33, p<0.001). The sclerotherapy patient group compared with the shunt group was less likely to develop hepatoencephalopathy (15 studies: pooled OR 0.53, 95% CI 0.31 to 0.91, p=0.021) and had shorter hospital stays (pooled mean difference –4.32, 95% CI –7.97 to –0.66, p=0.021). No significant difference in the survival rate was observed between the two groups (seven studies: OR 1.01, 95% CI 0.63 to 1.62, p=0.964).

Conclusion

This analysis indicated that the two types of treatment have similar mortality rates but differed with respect to rebleeding rate, incidence of hepatoencephalopathy and length of hospital stay.



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The recognition and management of sepsis and septic shock: a guide for non-intensivists

Sepsis is common, often fatal and requires rapid interventions to improve outcomes. While the optimal management of sepsis in the intensive care setting is the focus of extensive research interest, the mainstay of the recognition and initial management of sepsis will occur outside the intensive care setting. Therefore, it is key that institutions and clinicians remain well informed of the current updates in sepsis management and continue to use them to deliver appropriate and timely interventions to enhance patient survival. This review discusses the latest updates in sepsis care including the new consensus definition of sepsis, the outcome of the proCESS, ProMISe and ARISE trials of early goal directed therapy (EGDT), and the most recent guidelines from the Surviving Sepsis Campaign.



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Transcriptomic analysis reveals the molecular mechanism of apoptosis induced by Muscovy duck reovirus

Abstract

This study was to investigate the molecular mechanism underlying the apoptosis induced by Muscovy duck reovirus (MDRV) through a transcriptomic analysis. Muscovy ducklings were infected with MDRV strain YB and the apoptotic cells in their livers were examined with terminal-deoxynucleotidyl-transferase-mediated nick end labeling and flow cytometry. Genes differentially expressed in the livers of the MDRV-infected ducklings were screened by comparing them with those of uninfected ducklings and were analyzed with a transcriptomic method to illuminate the mechanism of MDRV infection. The results showed that MDRV infection strongly induced apoptotic cells in liver. Significant pathway enrichment determined by a Kyoto Encyclopedia of Genes and Genomes analysis showed that MDRV activated the death receptor family signaling pathway (Fas, TNFR1), the interleukin receptor signaling pathway (IL1, IL3), the phosphatidylinositol 3-kinase signaling pathway, NF-ҝB signaling pathway and calcium ions signaling pathway to induce apoptosis. This was verified by SYBR-Green-based fluorescence quantitative PCR. In conclusion, MDRV induce apoptosis by activation multi signaling pathways.



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Nolvadex alternative bodybuilding - Tamoxifen cancer drug - Island Eye News

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Norcantharidin induces mitochondrial-dependent apoptosis through Mcl-1 inhibition in human prostate cancer cells

Publication date: Available online 29 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Chu-Liang Lin, Chien-Min Chen, Chia-Liang Lin, Chun-Wen Cheng, Chien-Hsing Lee, Yi-Hsien Hsieh
Norcantharidin (NCTD) is the demethylated form of cantharidin that exhibits anticancer potential in many cancer cell types. Recent reports suggest that NCTD targeting ROS/AMPK and DNA replication signaling pathway could be an effective strategy for the treatment of PCa cells. However, supportive evidence is limited to the effect of NCTD that induction of apoptosis through suppression of the Mcl-1. Here, we show that NCTD induced PCa cell apoptosis and triggered caspase activation, which was associated with mitochondria dysfunction. Mechanistic investigations suggested that NCTD modulated the Akt signaling via increased nuclear translocation and interaction with the myeloid cell leukemia-1 (Mcl-1) promoter by FOXO4, resulting in an apoptotic effect. Moreover, miR-320d, which targets Mcl-1, was significantly upregulated after NCTD treatment. Overexpression of miR-320d by NCTD induced mitochondria dysfunction and apoptosis, which was notably attenuated with a miR-320d inhibitor. In vivo xenograft analysis revealed that NCTD significantly reduced tumor growth in mice with PC3 tumor xenografts. Taken together, our results provide new insights into the critical role of NCTD in suppressing Mcl-1 via epigenetic upregulation of miR-320d, resulting in PCa cell apoptosis.

Graphical abstract

image


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The E3 ubiquitin ligase MID1/TRIM18 promotes atypical ubiquitination of the BRCA2-associated factor 35, BRAF35

Publication date: Available online 29 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Melania E. Zanchetta, Luisa M.R. Napolitano, Danilo Maddalo, Germana Meroni
MID1/TRIM18 is a member of the TRIM family of ubiquitin E3 ligases characterized by the presence of a conserved RING-containing N-terminal tripartite motif. Mutations in the MID1 gene have been associated with the X-linked form of Opitz Syndrome, a developmental disorder characterized by midline defects and intellectual disability. The effect of MID1 E3 ligase activity within the cell and the role in the pathogenesis of the disease is still not completely unraveled. Here, we report BRAF35, a non-canonical HMG nuclear factor, as a novel MID1 substrate. MID1 is implicated in BRAF35 ubiquitination promoting atypical poly-ubiquitination via K6-, K27- and K29-linkages. We observed a partial co-localization of the two proteins within cytoplasmic bodies. We found that MID1 depletion alters BRAF35 localization in these structures and increases BRAF35 stability affecting its cytoplasmic abundance. Our data reveal a novel role for MID1 and for atypical ubiquitination in balancing BRAF35 presence, and likely its activity, within nuclear and cytoplasmic compartments.



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The peroxisomal import receptor PEX5 functions as a stress sensor, retaining catalase in the cytosol in times of oxidative stress

Publication date: Available online 29 July 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Paul A. Walton, Chantal Brees, Celien Lismont, Oksana Apanasets, Marc Fransen
Accumulating evidence indicates that peroxisome functioning, catalase localization, and cellular oxidative balance are intimately interconnected. Nevertheless, it remains largely unclear why modest increases in the cellular redox state especially interfere with the subcellular localization of catalase, the most abundant peroxisomal antioxidant enzyme. This study aimed at gaining more insight into this phenomenon. Therefore, we first established a simple and powerful approach to study peroxisomal protein import and protein-protein interactions in living cells in response to changes in redox state. By employing this approach, we confirm and extend previous observations that Cys-11 of human PEX5, the shuttling import receptor for peroxisomal matrix proteins containing a C-terminal peroxisomal targeting signal (PTS1), functions as a redox switch that modulates the protein's activity in response to intracellular oxidative stress. In addition, we show that oxidative stress affects the import of catalase, a non-canonical PTS1-containing protein, more than the import of a reporter protein containing a canonical PTS1. Furthermore, we demonstrate that changes in the local redox state do not affect PEX5-substrate binding and that human PEX5 does not oligomerize in cellulo, not even when the cells are exposed to oxidative stress. Finally, we present evidence that catalase retained in the cytosol can protect against H2O2-mediated redox changes in a manner that peroxisomally targeted catalase does not. Together, these findings lend credit to the idea that inefficient catalase import, when coupled with the role of PEX5 as a redox-regulated import receptor, constitutes a cellular defense mechanism to combat oxidative insults of extra-peroxisomal origin.

Graphical abstract

image


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Tumori, gli avevano dato 6 settimane: vivo dopo 5 anni nonostante ... - Meteo Web

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Gli avevano dato 6 settimane di vita al massimo, ma Leland Fay, 46 anni,papa' di due bimbi, dopo 5 anni e' ancora in vita.

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Ricostruita laringe usando i muscoli del collo, primo caso in Italia - Impronta Unika

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I tumori maligni della laringe sono i più frequenti tumori del distretto testa- collo; rappresentano circa il 2,5% di tutte le neoplasie maligne nell'uomo e lo 0,5% nella donna. In Italia attualmente vengono diagnosticati circa 5.000 nuovi casi di ...



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Air Force to spend $30 million this year on Pease cleanup - CT Post

Air Force to spend $30 million this year on Pease cleanup
CT Post
The Environmental Protection Agency says exposure has been linked in animal studies to low birth weight, accelerated puberty, cancer and thyroid problems, among other maladies. The Air Force said this week it already spent $25 million addressing the ...



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Blocking the back-door that cancer cells use to escape death by radiotherapy - Science Daily

Blocking the back-door that cancer cells use to escape death by radiotherapy
Science Daily
According to Brindley, the strategy also holds great promise for the treatment of other types of cancer such as thyroid cancer and glioblastoma. The team believes the same strategy can be used to improve the efficacy of chemotherapy. They hope to soon ...



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Blood and Nasal Epigenetics Correlate to Allergic Rhinitis Symptom Development in the Environmental Exposure Unit

Abstract

Background

Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the Environmental Exposure Unit (EEU).

Methods

38 AR-sufferers and 8 non-allergic controls were exposed to grass pollen for 3h on two consecutive days. We interrogated DNA methylation at baseline and 3h in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg), and verified hits using bisulfite PCR-pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen.

Results

In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12) and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (p<0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (p<0.05). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman r = 0.314, p = 0.034), and MUC4 gene expression was significantly increased (p<0.0001).

Conclusion

This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, identified baseline epigenetic status as a predictor of symptom severity.

This article is protected by copyright. All rights reserved.



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Raising Awareness of Graves’ Orbitopathy with Early Warning Cards

Abstract

Background

Clinically significant Graves' orbitopathy (GO) develops in about 25% of those with Graves' disease (GD); most cases of GD in the UK are managed by endocrinologists. Despite this, patients report significant delays before a diagnosis of GO is made. Measures to increase awareness of the early signs of GO and establishing a fast-track referral pathway to specialist care should overcome these delays and potentially improve outcomes.

Aims

We aimed to determine whether issuing a "GO early warning card" to all GD patients raises awareness of GO and facilitates early diagnosis, what percentage of cards result in a telephone contact, the number of "false reports" from card carriers and patient perceptions of the cards.

Methods

We designed cards, detailing common GO symptoms and a telephone number for patients developing symptoms. Cards were distributed to 160 GD patients, without known GO, attending four endocrine clinics in the UK (December 2015 - March 2016). We recorded telephone contacts over twelve months from when the last card was distributed and gathered patient feedback.

Results

The early warning cards were well received by patients in general. Over twelve months, ten telephone contacts from nine patients, all related to ocular symptoms, were received (6% of cards issued). Nine calls resulted in an additional clinic review (for eight patients) and four diagnoses of GO were made.

Conclusions

This pilot study demonstrates that it is feasible to distribute GO early warning cards in clinic and that they can be used to facilitate an early diagnosis of GO.

This article is protected by copyright. All rights reserved.



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A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma

Summary

Background

Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis as well as cell status like metabolism changes in distant metastatic tumors have not been clearly elucidated.

Objective

To identify serum metabolic signature of distant metastatic PTC.

Design, patients and measurementsIn

this study, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the serum from 77 patients diagnosed with PTC (37 in distant metastasis group and 40 in ablation group). Principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA)scores plots were used to analyze the data.

Results

PCA and OPLS-DA analyses demonstrated an evident trend of separation between 40 serum samples from the ablation group and 37 samples from distant metastasis group. A total of 31 metabolites were identified which are related to amino acid, lipid, glucose, vitamin metabolism and diet/gut microbiota interaction. Pathway analysis showed 'alanine, aspartate and glutamate metabolism' and 'inositol phosphate metabolism' were the most relevant pathways.

Conclusion

Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biologic behaviors of tumor cells including proliferation, invasion/migration, and immune escape. Diet/gut microbiota produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding to the distant metastasis of PTC as well as potential adjuvant therapy targets.

This article is protected by copyright. All rights reserved.



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A synthetic peptide hijacks the catalytic subunit of class I PI3K to suppress the growth of cancer cells

Publication date: 1 October 2017
Source:Cancer Letters, Volume 405
Author(s): Weiwei Guo, Xue You, Xiao Wang, Lin Wang, Yan Chen
Activation of class I Phosphoinositide 3-kinases (PI3Ks) by mutation or overexpression closely correlates with the development of various human cancers. Class I PI3Ks are heterodimers composed of p110 catalytic subunits and regulatory subunits represented by p85. PAQR3 has been found to inhibit p110α activity by blocking its interaction with p85. In this study, we identified the N-terminal 6–55 amino acid residues of PAQR3 being sufficient for its interaction with p110α. A synthetic peptide, P6-55, that contains the N-terminus of PAQR3 could disrupt the interactions of p110α with both PAQR3 and p85. The activity of PI3K was also inhibited by P6-55, accompanied by significant inhibition of cancer cell proliferation. In a xenograft mouse model, P6-55 was able to reduce tumor growth in vivo. Furthermore, P6-55 was capable of inhibiting the elevated basal PI3K activity of H1047R, a hotspot mutation found in many types of human cancers. The cell proliferation and migration of cancer cells bearing H1047R mutation were also reduced by P6-55. In conclusion, our study provides a proof of concept that blocking the interaction of p110α with p85 by a peptide can serve as a new strategy to inhibit the oncogenic activity of PI3K in cancer therapy.



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Sensitivity towards the GRP78 inhibitor KP1339/IT-139 is characterized by apoptosis induction via caspase 8 upon disruption of ER homeostasis

Publication date: 28 September 2017
Source:Cancer Letters, Volume 404
Author(s): Beatrix Schoenhacker-Alte, Thomas Mohr, Christine Pirker, Kushtrim Kryeziu, Paul-Steffen Kuhn, Alicia Buck, Thilo Hofmann, Christopher Gerner, Gerrit Hermann, Gunda Koellensperger, Bernhard K. Keppler, Walter Berger, Petra Heffeter
The ruthenium drug and GRP78 inhibitor KP1339/IT-139 has already demonstrated promising anticancer activity in a phase I clinical trial. This study aimed to identify mechanisms underlying increased sensitivity to KP1339 treatment. Based on a screen utilizing 23 cell lines, a small panel was selected to compare KP1339-sensitive and low-responsive models. KP1339 sensitivity was neither based on differences in ruthenium accumulation, nor sensitivity to oxidative stress or constituents of KP1339 (ruthenium chloride and indazole). Subsequently, the biochemical response to KP1339 was analyzed using whole genome expression arrays indicating that, while sensitive cell lines were characterized by "response to chemical stimuli" and "regulation of cell death", low-responsive cells preferentially activated pathways controlling cell cycle, DNA repair, and metabolism. Cell culture experiments confirmed that, while low-responsive cells executed cell cycle arrest in G2 phase, pronounced apoptosis induction via activation of caspase 8 was found in sensitive cells. Cell death induction is based on a unique disruption of the ER homeostasis by depletion of key cellular chaperones including GRP78 in combination with enhanced KP1339-mediated protein damage.



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Sialidase NEU3 defines invasive potential of human glioblastoma cells by regulating calpain-mediated proteolysis of focal adhesion proteins

Publication date: Available online 29 July 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Kohta Takahashi, Sergei Proshin, Kazunori Yamaguchi, Yoji Yamashita, Ryuichi Katakura, Koji Yamamoto, Hiroshi Shima, Masahiro Hosono, Taeko Miyagi
BackgroundGlioblastoma multiforme is one of the most malignant tumors of the human central nervous system characterized by high degree of invasiveness. Focusing on this invasive nature, we investigated whether ganglioside-specific sialidase NEU3 might be involved, because gangliosides are major components of brain tissues, and cell surface sialic acids, as target residues of sialidase catalysis, are thought to be closely related to cell invasion.MethodsNEU3 mRNA levels of human glioblastoma specimens were evaluated by quantitative RT-PCR. Human glioblastoma cell lines, U251, A172, and T98G were used for cell invasion and migration by transwell and cell scratching assay. The molecules involved in the signaling cascade were investigated by western blot and immunofluorescent microscopy.ResultsNEU3 expression was down-regulated in human glioblastoma specimens. In the human glioblastoma cell lines, NEU3 overexpression reduced invasion and migration by promoting the assembly of focal adhesions through reduced calpain-dependent proteolysis, but NEU3 silencing resulted in accelerating cell invasion via disassembly of focal adhesions. In NEU3-silenced cells, elevation of calpain activity and GM3 accumulation were observed, as results of reduced sialidase hydrolysis, localization of calpain and GM3 at the cell lamellipodium being demonstrated by immunofluorescence microscopy.ConclusionSialidase NEU3 was found to exert a great influence on cell invasion in regulation of calpain activity and focal adhesion disassembly and consequent invasive potential of glioblastoma cells.General significanceThis first demonstration of sialidase involvement in invasive potential of gliolastoma cells may point to NEU3 as an attractive treatment target of human gliomas.



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Genetic variation in IRF4 expression modulates growth characteristics, tyrosinase expression and interferon-gamma response in melanocytic cells

Summary

A SNP within intron4 of the Interferon Regulatory Factor4 (IRF4) gene, rs12203592*C/T has been independently associated with pigmentation and age-specific effects on nevus count in European-derived populations. We have characterised the cis-regulatory activity of this intronic region and using human foreskin-derived melanoblast strains we have explored the correlation between IRF4 rs12203592 homozygous C/C and T/T genotypes with TYR enzyme activity, supporting its association with pigmentation traits. Further, higher IRF4 protein levels directed by the rs12203592*C allele were associated with increased basal proliferation but decreased cell viability following UVR, an etiological factor in melanoma development. Since UVR, and accompanying IFNγ-mediated inflammatory response is associated with melanomagenesis we evaluated its effects in the context of IRF4 status. Manipulation of IRF4 levels followed by IFNγ treatment revealed a subset of chemokines and immuno-evasive molecules that are sensitive to IRF4 expression level and genotype including CTLA4 and PD-L1.

This article is protected by copyright. All rights reserved.



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Stab injury to the preauricular region with laceration of the external carotid artery without involvement of the facial nerve: a case report

Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external...

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John Kelso, longtime Austin humor columnist, dead at 73 - KRIS Corpus Christi News

John Kelso, longtime Austin humor columnist, dead at 73
KRIS Corpus Christi News
AUSTIN, Texas (AP) - John Kelso, longtime humor columnist for the Austin American-Statesman, has died in Austin at the age of 73. Kelso, who since 2015 had been battling a cancer that cost him his larynx, died Friday of complications from a recent fall ...

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Contents

Publication date: August 2017
Source:Health Policy, Volume 121, Issue 8





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Editorial Board

Publication date: August 2017
Source:Health Policy, Volume 121, Issue 8





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For An Almost Daily Eclipse, Go To Mars

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Earth may get great solar eclipses, but they don't happen all the time

-- Read more on ScientificAmerican.com
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Archaeobotany in central Argentina: macro- and microscopic remains at several archaeological sites from early Late Holocene to early colonial times (3,000–250 bp )

Abstract

Recent archaeobotanical research on 16 archaeological sites in the Sierras de Córdoba, central Argentina, provides new insights into the livelihoods and subsistence practices of the peoples who inhabited this mountainous region from c. 3,000–250 bp. Significantly, the plant macro- and microbotanical remains, identified as primarily fruit from wild trees, crops and weeds, provide evidence for a continuation in the consumption and manipulation of plant resources. During the late pre-Hispanic period (1,500–350 bp) people used domesticated plants such as maize, as well as new types of plant processing techniques that permitted the consumption of otherwise inedible wild seeds such as chenopods. The introduction of cultivated plants through contact with agricultural societies at around 1,000 bp was slow and did not substantially change the existing foraging way of life. Instead, crop plants were added to the existing, highly diversified subsistence systems in use in the Sierras de Córdoba, rather than replacing wild plant gathering.



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The roots of pollen analysis: the road to Lennart von Post

Abstract

In 2016 the 100th birthday of palynology was celebrated: Lennart von Post introduced the scientific discipline in 1916 at lectures in Oslo and Stockholm. However, von Post was not the first to study pollen, and research dates back to the works of Nehemiah Grew and Marcello Malpighi in the late 17th century. Afterwards studies focussed mainly on the role of pollen for plant reproduction, and on pollen morphology. The first scientist who observed fossil pollen was Heinrich Göppert in 1836. However, it was not until the 1890s and 1900s that the study of pollen became a regular component in the reconstruction of past vegetation. Lennart von Post subsequently developed theoretical and practical concepts and methods of pollen analysis, and raised palynology from its infancy into the mature scientific discipline that flourished greatly during the century that followed.



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Intricatinol synergistically enhances the anticancerous activity of cisplatin in human A549 cells via p38 MAPK/p53 signalling

Abstract

Platinum containing drugs are widely used to treat advanced lung carcinomas. However, their clinical success is still limited due to severe side effects, and drug resistance. Alternative approaches are warranted to augment efficacy of platinum based chemotherapeutic drugs with minimal side effects. Intricatinol (INT), a homoisoflavonoid, has been shown to possess anti-tubercular, antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer activity largely remains unknown. In the present study, we have evaluated anticancer potential of INT alone or in combination with cisplatin (CIS) in non-small cell lung carcinoma (A549) cells. Treatment with INT alone reduced the viability of A549 cells in a dose-dependent manner. Interestingly, the combination of low doses of INT and CIS exerted a synergistic effect and induced apoptosis as evident by DNA fragmentation and Annexin V positive cells. Enhanced Bax:Bcl-2 ratio, loss of Δψm, cytochrome c release, cleavage of caspase 3 and PARP1 strongly corroborated our findings. Further, increased expression of p53, p38 MAPK and their phosphorylated counterparts, loss of clonogenicity and reduced migration potential were also recorded with INT + CIS treatment. Most interestingly, INT could not induce any significant cell death in primary mouse embryonic fibroblasts (MEFs). Moreover, no additive or synergistic effect was noted with INT + CIS in MEFs under similar treatment conditions. In conclusion, INT has a selective anticancer potential and could synergize cytotoxicity of CIS. Therefore, the combination of INT and CIS may serve as an effective anticancer strategy for the treatment of non-small cell lung carcinoma.



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Experimental and computational analysis of micromotions of an uncemented femoral knee implant using elastic and plastic bone material models

Publication date: Available online 29 July 2017
Source:Journal of Biomechanics
Author(s): Sanaz Berahmani, Dennis Janssen, Nico Verdonschot
It is essential to calculate micromotions at the bone-implant interface of an uncemented femoral total knee replacement (TKR) using a reliable computational model. In the current study, experimental measurements of micromotions were compared with predicted micromotions by Finite Element Analysis (FEA) using two bone material models: linear elastic and post-yield material behavior, while an actual range of interference fit was simulated. The primary aim was to investigate whether a plasticity model is essential in order to calculate realistic micromotions. Additionally, experimental bone damage at the interface was compared with the FEA simulated range.TKR surgical cuts were applied to five cadaveric femora and micro- and clinical CT- scans of these un-implanted specimens were made to extract geometrical and material properties, respectively. Micromotions at the interface were measured using digital image correlation. Cadaver-specific FEA models were created based on the experimental set-up. The average experimental micromotion of all specimens was 53.1± 42.3 µm (mean± standard deviation (SD)), which was significantly higher than the micromotions predicted by both models, using either the plastic or elastic material model (26.5± 23.9 µm and 10.1± 10.1 µm, respectively; p-value< 0.001 for both material models). The difference between the two material models was also significant (p-value< 0.001). The predicted damage had a magnitude and distribution which was comparable to the experimental bone damage. We conclude that, although the plastic model could not fully predict the micro motions, it is more suitable for pre-clinical assessment of a press-fit TKR implant than using an elastic bone model.



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Comparative transcriptome analysis of tube feet of different colors in the sea urchin Strongylocentrotus intermedius

Abstract

The Strongylocentrotus intermedius is an important commercially cultivated marine animal in China. In recent years, some individuals with diaphanous tube feet, rather than the normal red tube feet, have been observed among animals under cultivation; the basis of this phenotypic change is uncertain. In order to better understand the differences between two color tube feet of S. intermedius at the molecular level, we constructed four cDNA libraries from tube feet and coelomocytes of S. intermedius individuals with red or diaphanous tube feet. A total of 216,729,214 clean reads were assembled into 87,510 transcripts with an average size of 1677 bp. A BlastX search showed that 72,690 transcripts had significant matches in at least one target database. Expression profile analysis was performed on the four libraries and many differentially expressed genes were identified. Using gene enrichment analysis, several biological processes related to immune responses as well as immune-related candidate genes were identified. A total of 1694 genes were immune-related, and the genes expression of red tube feet were higher than that of diaphanous tube feet. In addition, 50,427 simple sequence repeats were obtained from the S. intermedius transcriptomes, while 32,650 and 42,264 single nucleotide polymorphisms were found in S. intermedius with diaphanous tube feet and red tube feet, respectively. These results provide valuable information for the future studies involving marker-assisted breeding and the studies of population genetics and genomics on S. intermedius.



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Cortical morphology of the pars opercularis and its relationship to motor-inhibitory performance in a longitudinal, developing cohort

Abstract

This study investigates the relationship between variability in cortical surface area and thickness of the pars opercularis of the inferior frontal gyrus and motor-inhibitory performance on a stop-signal task in a longitudinal, typically developing cohort of children and adolescents. Linear mixed-effects models were used to investigate the hypotheses that (1) cortical thinning and (2) a relatively larger cortical surface area of the bilateral pars opercularis of the inferior frontal gyrus would predict better performance on the stop-signal task in a cohort of 110 children and adolescents 4–13 years of age, with one to four observations (totaling 232 observations). Cortical thickness of the bilateral opercular region was not related to inhibitory performance. However, independent of age, gender, and total cortical surface area, relatively larger cortical surface area of the bilateral opercular region of the inferior frontal gyrus was associated with better motor-inhibitory performance. Follow-up analyses showed a significant effect of surface area of the right pars opercularis, but no evidence for an effect of area of left pars opercularis, on motor-inhibitory performance. These findings are consistent with the previous work in adults showing that cortical morphology of the pars opercularis is related to inhibitory functioning. It also expands upon this literature by showing that, in contrast to earlier work highlighting the importance of cortical thickness of this region in adults, relative cortical surface area of the pars opercularis may be related to developing motor-inhibitory functions during childhood and adolescence. Relationships between cortical phenotypes and individual differences in behavioral measures may vary across the lifespan.



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Laterality of anterior temporal lobe repetitive transcranial magnetic stimulation determines the degree of disruption in picture naming

Abstract

The bilateral anterior temporal lobes play a key role in semantic representation. This is clearly demonstrated by the performance of patients with semantic dementia, a disorder characterised by a progressive and selective decline in semantic memory over all modalities as a result of anterior temporal atrophy. Although all patients exhibit a progressive decline in both single-word production and comprehension, those with greater atrophy to the left anterior temporal lobe show a stronger decline in word production than comprehension. This asymmetry has been attributed to the greater connectivity of the left anterior temporal lobe with left-lateralised speech production mechanisms. Virtual lesioning of the left ATL using offline repetitive transcranial magnetic stimulation (rTMS) has been shown to disrupt picture naming, but, the impact of right ATL rTMS is yet to be explored. We tested the prediction that disruption of picture naming in normal participants by rTMS should be greater for the left than the right ATL. We found a significant increase in picture naming latencies specifically for stimulation of the left ATL only. Neither left nor right ATL TMS slowed performance in a number naming control task. These results support the hypothesis that although both temporal lobes are part of a widespread semantic network in the human brain, the left anterior temporal lobe possesses a stronger connection to left-lateralised speech production areas than the right temporal lobe.



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Development of Pyriform Sinus Suctioning Programs for Aspiration Pneumonia Prevention During the Acute Stroke

Abstract

Aspiration due to dysphagia is a factor associated with pneumonia during acute stroke. In such cases, it is likely that secretions in the pyriform sinuses enter the laryngeal inlet. The present study was based on the idea that it is possible to reduce aspiration pneumonia by periodically suctioning and removing such secretions (pyriform sinus suctioning), a study was conducted in a single facility. The incidence of pneumonia as a dependent variable was compared between before (control) and after (intervention group) intervention with pyriform sinus suctioning as an independent variable. With a view of unifying the quality and frequency of intervention, two programs to: initially confirm the safety of such suctioning; subsequently enhance/evaluate knowledge and skills related to the procedure (educational); and specify conditions for the implementation and criteria for determining its appropriateness (practical), were developed. The study involved 33 (mean age: 74.6 ± 12.4) and 30 (80.0 ± 8.8) control and intervention group members, respectively, 25 (83.3%) of the latter were treated with pyriform sinus suctioning for 5 days after a stroke. Pneumonia developed in 7 (21.2%) and 2 (6.7%) of the former and latter, respectively. As individuals with a Japan Coma Scale (JCS) score of III or a midline shift on head CT tend to develop pharyngeal dysphagia, the patients were also divided into 2 groups to compare the incidence of pneumonia based on the risk level: low: Japan Coma Scale scores of I-II without a midline shift on head CT; and high: scores of II-III with it. In the latter, the incidence after intervention was markedly lower (p = 0.06, φ = 0.326), while the former did not show changes (p = 0.574, φ = 0.066), supporting the effectiveness of pyriform sinus suctioning to prevent aspiration pneumonia among patients with a low risk level.



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IJMS, Vol. 18, Pages 1653: Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer

IJMS, Vol. 18, Pages 1653: Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer

International Journal of Molecular Sciences doi: 10.3390/ijms18081653

Authors: Xiaoying Sun Weijing Zhang Han Li Chunhao Niu Yulan Ou Libing Song Yanna Zhang

Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.



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Levitra 10mg vs viagra 50mg - Levitra bayer 20 mg preis - Island Eye News


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Nanog suppresses the expression of vasa by directly regulating nlk1 in the early zebrafish embryo

Publication date: Available online 29 July 2017
Source:Biochimie
Author(s): Yanhua Liu, Weiwei Xue, Lin Zhu, Ding Ye, Xiaoqin Zhu, Huannan Wang, Yonghua Sun, Fengjiao Deng
Nanog is a homeodomain transcription factor that is essential for maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). In the present study, we demonstrate that zebrafish Nanog (zNanog) directly binds to the promoter region of zebrafish nlk1 (znlk1) by ChIP-Seq analysis and that it up-regulates the expression of znlk1 in fibroblast-like embryonic cells of Danio rerio (ZEM-2S cells) and in zebrafish embryos at 30% epiboly both at the mRNA and protein levels. In addition, compared with control (MO-C) embryos at 30% epiboly, the mRNA and protein expression of vasa and the numbers of vasa-positive cells were increased in embryos injected with zNanog morpholino (MO-zNanog). Further, injection of znlk1 mRNA into zNanog-depleted embryos restored the expression of vasa and the number of vasa-positive cells. These data indicated that zNanog up-regulates the expression of znlk1 through directly binding to the znlk1 promoter, thereby suppressing the expression of vasa. Vasa is a marker gene for PGCs. Our results suggest that zNanog plays a role in restraint of PGC cell number through regulating the expression of znlk1 in the early embryonic development. The current results provide fundamental information to support further investigation regarding the regulatory mechanism of zNanog during the development of PGCs.



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Editorial Board

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Information for readers

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Caught but released

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Laurance Jerrold




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Common errors observed at the American Board of Orthodontics clinical examination

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Chun-Hsi Chung, Larry P. Tadlock, Nicholas Barone, Valmy Pangrazio-Kulbersh, David G. Sabott, Patrick F. Foley, Timothy S. Trulove, Jae Hyun Park, Steven A. Dugoni
The American Board of Orthodontics has developed tools to help examinees select patients to be used for the Board examination. The Case Management Form can be used to evaluate aspects of a patient's treatment that cannot be measured by other tools. The Case Management Form is a structured treatment-neutral assessment of orthodontic objectives and outcomes associated with a patient's treatment. Despite the availability of this form, examiners continue to see problems, including lack of attention to finishing details, inappropriate treatment objectives, excessive proclination of mandibular incisors due to treatment mechanics, excessive expansion of mandibular intercanine width, closing skeletal open bite with extrusion of anterior teeth leading to excessive gingival display, and failure to recognize the importance of controlling the eruption or extrusion of molars during treatment. In addition, some examinees exhibit a lack of understanding of proper cephalometric tracing and superimposition techniques, which lead to improper interpretation of cephalometric data and treatment outcomes.



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Comparison of survival time and comfort between 2 clear overlay retainers with different thicknesses

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Santosh Kumar Goje, Rashmi Bhavasar




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Authors' response

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Yafen Zhu, Jianchang Lin, Hu Long, Niansong Ye, Renhuan Huang, Xin Yang, Fan Jian, Wenli Lai




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Table of Contents

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Transport distraction osteogenesis combined with orthodontic treatment

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Sanjeev Verma, Sombir Singh, S.P. Singh




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August 2017:152(2)

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Allen H. Moffitt




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Authors' response

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Seo Yeon Jung, Hyoung Seon Baik




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Bisphenol A in orthodontic adhesives

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): S. Divya, Arun S. Urala




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Authors' response

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Mírian A.N. Matsumoto, Paulo Nelson-Filho, Marília R. Moreira




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CBCT imaging vs conventional radiography

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Katja Kritzler




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Residents' journal review

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Dan Grauer




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Courtesy counts

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Peter M. Greco




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Orthodontic-surgical retreatment of facial asymmetry with occlusal cant and severe root resorption: A 3-year follow-up

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Cinthia de Oliveira Lisboa, Marlon Sampaio Borges, Paulo José D'Albuquerque Medeiros, Alexandre Trindade Motta, José Nelson Mucha
Our objective was to report the orthodontic and surgical retreatment of a patient who had undergone a prolonged orthodontic treatment with extractions, but who had unsatisfactory results and persistent side effects. The man, aged 25 years 3 months, sought treatment with major complaints of facial and smile asymmetries. The clinical examination showed a mandibular deviation to the right and a maxillary occlusal cant. A Class II Division 1 subdivision right was observed. Radiographic examination showed extensive root resorptions in the maxillary second premolars and absence of the 4 first premolars. The maxillary midline was deflected 2 mm to the left, and the mandibular midline was shifted 5 mm to the right. Aligning and leveling were performed with orthodontic fixed appliances, with a standard edgewise system (0.022 × 0.028 in), followed by LeFort I maxillary impaction and bilateral sagittal split osteotomy with asymmetrical advancement. Retreatment showed outstanding results that remained stable after 3 years of follow-up. Root resorption in the second premolars did not seem to increase. Orthodontic-surgical intervention is the main choice for correcting esthetic and functional problems in facial asymmetry, particularly in cases of retreatment.



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Randomized controlled trial of a patient decision-making aid for orthodontics

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Kate Parker, Susan J. Cunningham, Aviva Petrie, Fiona S. Ryan
IntroductionPatient decision-making aids (PDAs) are instruments that facilitate shared decision making and enable patients to reach informed, individual decisions regarding health care. The objective of this study was to assess the efficacy of a PDA compared with traditional information provision for adolescent patients considering fixed appliance orthodontic treatment.MethodsBefore treatment, orthodontic patients were randomly allocated into 2 groups: the intervention group received the PDA and standard information regarding fixed appliances, and the control group received the standard information only. Decisional conflict was measured using the Decisional Conflict Scale, and the levels of decisional conflict were compared between the 2 groups.ResultsSeventy-two patients were recruited and randomized in a ratio of 1:1 to the PDA and control groups. Seventy-one patients completed the trial (control group, 36; PDA group, 35); this satisfied the sample size calculation. The median total Decisional Conflict Scale score in the PDA group was lower than in the control group (15.63 and 19.53, respectively). However, this difference was not statistically significant (difference between groups, 3.90; 95% confidence interval of the difference, −4.30 to 12.11). Sex, ethnicity, age, and the time point at which patients were recruited did not have significant effects on Decisional Conflict Scale scores. No harm was observed or reported for any participant in the study.ConclusionsThe results of this study showed that the provision of a PDA to adolescents before they consented for fixed appliances did not significantly reduce decisional conflict. There may be a benefit in providing a PDA for some patients, but it is not yet possible to say how these patients could be identified.RegistrationThis trial was registered with the Harrow National Research Ethics Committee (reference 12/LO/0279).ProtocolThe protocol was not published before trial commencement.



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Poisson regression

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Despina Koletsi, Nikolaos Pandis




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Individualized intervention to reduce anxiety in adult orthodontic patients based on Q methodology

Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2
Author(s): Feiou Lin, Yan He, Zhenyu Ni, Richard Olive, Manman Ren, Linjie Yao, Qingsong Ye
IntroductionIn this study, we used Q methodology to assess the concerns of adults seeking orthodontic treatment and to determine individualized interventions to reduce their anxiety.MethodsStatements of concern were derived by in-depth interviews with 70 adult patients. Q sorting methodology was then used to identify the main factors associated with anxiety in a cohort of 40 adults who had not been involved in the first part of the study. The final stage involved a randomized study in which 160 new adult patients were recruited and randomized into intervention and control groups. Participants in the intervention group sorted the statements, after which individualized interventions were implemented. Participants in the control group received routine treatment. The State-Trait Anxiety Inventory was used to measure changes in participants' anxiety levels before and during treatment.ResultsIn total, 41 statements were identified, and participants were classified according to 5 factors. Factor 1 participants were concerned about the lack of treatment information; factor 2 represented concerns about cost and other people's opinions; factor 3 represented concerns about impact on work related to wearing braces; factor 4 encompassed concerns about treatment effects, pain, and dental fears; and factor 5 reflected concerns about side effects and finding a partner. The mean state anxiety inventory scores for both the intervention and control groups were highest 24 hours after bonding (intervention group, 44.63 ± 4.49; control group, 49.43 ± 5.42). The intragroup state anxiety inventory scores differed significantly across the 6 time points (P <0.01), with the state anxiety inventory scores of the intervention group significantly lower than those of the control group (P <0.01) at all time points except baseline. No significant intergroup or intragroup differences were found in relation to trait anxiety.ConclusionsAdult orthodontic patients expressed diverse concerns. Individualized interventions based on Q methodology may reduce anxiety in this patient population.



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Directory: AAO Officers and Organizations

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Publication date: August 2017
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 152, Issue 2





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Informal care networks’ views of palliative care services: Help or hindrance?

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Factorial structure of the persistent complex bereavement inventory: Testing a hierarchical factor model

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Longtime Humor Columnist John Kelso Dead At 73 - Patch.com

Patch.com
Longtime Humor Columnist John Kelso Dead At 73
Patch.com
He died from complications stemming after a recent fall, after his immune system had been weakened from a second bout with cancer that had already claimed his larynx, robbing him of a "raucous staccato laugh," the newspaper reported. Despite his muting ...



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A Randomized, Open-Label, Two-Way Crossover, Single-Dose Bioequivalence Study of Temozolomide 200 mg/m 2 (Dralitem ® vs. Temodal ® Capsules) in Patients with Primary Tumors of the Central Nervous System Under Fasting Conditions

Abstract

Background

Temozolomide is an antineoplastic agent of proven efficacy against high-grade gliomas.

Purpose

The objective of this crossover, single-dose, bioequivalence study was to compare the rate and extent of absorption of oral temozolomide after administration of the study product (Dralitem®, Monte Verde Sociedad Anónima) and the reference product (Temodal®, originator product manufactured by Schering Plough Laboratories) in patients with primary central nervous system (CNS) tumors under fasting conditions.

Methods

Sixteen male and female subjects with primary CNS tumors (excluding CNS lymphoma) were recruited, and were administered temozolomide 200 mg/m2 (Dralitem®) on days 1, 2 and 5 of a 5-day treatment. On days 3 and 4, subjects received the same dose of the test product (Dralitem®), or the reference product (Temodal®) on alternate days. The single dose of 200 mg/m2 was reached with three different temozolomide capsule strengths: 20, 100 and 250 mg. On days 3 and 4, blood samples were obtained for pharmacokinetic (PK) evaluation after drug administration.

Results

Bioequivalence assessment was made for the 90% confidence interval (CI) for the ratio of log-transformed means (μT/μR) of the area under the concentration–time curve (AUC from time zero to the final quantifiable sample [AUCt] and AUC from time zero to infinity [AUC]) and maximum concentration (C max) of both the test (Dralitem®) and reference (Temodal®) products. The point estimate and 90% CI of the ratios of C max, AUCt and AUC values were 94.37 (82.69–107.69), 100.99 (97.81–104.28) and 101.53 (98.60–104.54), respectively. The ratio met the predefined bioequivalence criteria (i.e. 90% CI between 80.00 and 125.00) for C max and AUC. The most commonly reported adverse events (AE) on this study were vomiting, abdominal pain, asthenia and weakness. One subject experienced expressive aphasia, possibly unrelated to the study drug and with no significant sequelae upon recovery. No serious AEs or unexpected AEs were reported.

Conclusions

Temozolomide Dralitem® capsules, 20, 100 and 250 mg, were bioequivalent to Temodal® capsules under fasting conditions in patients with CNS primary tumors, supporting that they are therapeutic equivalents.

ClinicalTrials.gov Identifier: NCT02343081.



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Effects of Central Nervous System Drugs on Recovery After Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background and Objective

Pilot trials have suggested that pharmacotherapy may aid stroke recovery. The aim of this study was to systematically review the effects of antidepressants, anti-Alzheimer drugs, anti-Parkinson drugs, central nervous system (CNS) stimulants and piracetam on gross motor function, cognition, disability, dependency and quality of life (QOL) after stroke.

Methods

PubMed, EMBASE and the Cochrane Central Register of Controlled Trials databases were searched, and 44 randomized controlled trials that compared outcomes of interest between drug treatment and placebo or no treatment were included. For each study, standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) were calculated. Meta-analyses were conducted to pool results using either the fixed-effects or random-effects model.

Results

Selective serotonin reuptake inhibitors (SSRIs) improved gross motor function (SMD 0.54, 95% CI 0.22–0.85; three studies), disability (SMD 0.49, 95% CI 0.32–0.66; 14 studies) and QOL (MD 6.46, 95% CI 4.71–8.22; two studies), but there was insufficient evidence for their use in enhancing global cognition (SMD 0.23, 95% CI −0.01 to 0.46; five studies) and dependency (risk ratio 0.81, 95% CI 0.68–0.97; one fluoxetine study). In particular, gross motor function was improved by fluoxetine (SMD 0.64, 95% CI 0.31–0.98; two studies), while disability was improved by paroxetine (SMD 1.05, 95% CI 0.63–1.46; two studies), citalopram (SMD 0.51, 95% CI 0.08–0.93; two studies) and fluoxetine (SMD 0.41, 95% CI 0.22–0.60; nine studies). There is insufficient evidence for the use of anti-Alzheimer drugs, anti-Parkinson drugs, CNS stimulants and piracetam to promote stroke recovery.

Conclusions

Administration of SSRIs may improve gross motor function, reduce disability and enhance QOL for patients recovering from stroke.



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IJMS, Vol. 18, Pages 1655: Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

IJMS, Vol. 18, Pages 1655: Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition

International Journal of Molecular Sciences doi: 10.3390/ijms18081655

Authors: Laura Mercatali Federico La Manna Giacomo Miserocchi Chiara Liverani Alessandro De Vita Chiara Spadazzi Alberto Bongiovanni Federica Recine Dino Amadori Martina Ghetti Toni Ibrahim

Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts. We evaluated the osteoclastogenesis modulation of human peripheral blood monocytes (PBMC) indirectly induced by the conditioned medium (CM) of the human BC cell line SCP2, cultured singly or with MSC. Osteoclastogenesis was evaluated by TRAP analysis. The effect of the EGFR blockade was assessed by treating the cells with gefitinib, and analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western Blot (WB). We observed that SCP2 co-cultured with MSC increased the differentiation of PBMC. This effect was underpinned upon pre-treatment of the co-culture with gefitinib. Co-culture of SCP2 with MSC increased the expression of both the bone-related marker Receptor Activator of Nuclear Factor κB (RANK) and EGFR in BC cells. These upregulations were not affected by the EGFR blockade. The effects of the CM obtained by the cells treated with gefitinib in combination with the treatment of the preosteoclasts with the bone-targeted agents and everolimus enhanced the inhibition of the osteoclastogenesis. Finally, we developed a fully human co-culture system of BC cells and bone progenitor cells. We observed that the interaction of MSC with cancer cells induced in the latter molecular changes and a higher power of inducing osteoclastogenesis. We found that blocking EGFR signaling could be an efficacious strategy for breaking the interactions between cancer and bone cells in order to inhibit bone metastasis.



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IJMS, Vol. 18, Pages 1654: A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

IJMS, Vol. 18, Pages 1654: A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

International Journal of Molecular Sciences doi: 10.3390/ijms18081654

Authors: Giovanni Bacci Alessio Mengoni Ersilia Fiscarelli Nicola Segata Giovanni Taccetti Daniela Dolce Patrizia Paganin Patrizia Morelli Vanessa Tuccio Alessandra De Alessandri Vincenzina Lucidi Annamaria Bevivino

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease.



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Learning to be fair: Lessons from the deep past

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While Thomas Piketty's bestseller fuelled a major rethink on economics and inequality, creating change is tough – and may depend on reimagining hunter-gatherer societies

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Learning to be fair: Lessons from the deep past

While Thomas Piketty's bestseller fuelled a major rethink on economics and inequality, creating change is tough – and may depend on reimagining hunter-gatherer societies

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IJERPH, Vol. 14, Pages 854: Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

IJERPH, Vol. 14, Pages 854: Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14080854

Authors: Hae-Miru Lee Soo-Min Kim Kyung-Chul Choi

Cigarette smoke (CS) causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In this study, the effects of formaldehyde (FA) and benzene (Bz), the main components of CS, on cell proliferation and epithelial mesenchymal transition (EMT) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS components and placenta carcinoma. Upon MTT assay, FA (10−8 M to 10−5 M) and Bz (10−11 M to 10−8 M) increased JEG-3 cell proliferation. Western blot assay revealed that the protein expression of cyclin D1 and E1 increased, while the levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10−8 M and 10−5 M) and Bz (10−11 M and 10−8 M) increased migration of JEG-3 cells at 24 h and 48 h compared with that at 0 h. In addition, the expression of the epithelial marker, E-cadherin, was significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by FA (10−8 M and 10−5 M) and Bz (10−11 M and 10−8 M). snail and slug transcriptional factors were associated with EMT, which were also up-regulated by FA and Bz, indicating that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma cells. We further evaluated reactive oxygen species (ROS) and activation of antioxidant effect using dichlorofluorescin diacetate (DCFH-DA) and Western blot assay. FA and Bz increased the ROS production and an antioxidant related marker, Nrf2, in JEG-3 cells. However, eIF2α levels were reduced by FA and Bz via activation of the antioxidant reaction. Taken together, these results indicated that FA and Bz induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and EMT and activation of ROS and antioxidant related markers.



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IJERPH, Vol. 14, Pages 853: Heat Exposure and Maternal Health in the Face of Climate Change

IJERPH, Vol. 14, Pages 853: Heat Exposure and Maternal Health in the Face of Climate Change

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14080853

Authors: Leeann Kuehn Sabrina McCormick

Climate change will increasingly affect the health of vulnerable populations, including maternal and fetal health. This systematic review aims to identify recent literature that investigates increasing heat and extreme temperatures on pregnancy outcomes globally. We identify common research findings in order to create a comprehensive understanding of how immediate effects will be sustained in the next generation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide, we systematically reviewed articles from PubMed and Cochrane Reviews. We included articles that identify climate change-related exposures and adverse health effects for pregnant women. There is evidence that temperature extremes adversely impact birth outcomes, including, but not limited to: changes in length of gestation, birth weight, stillbirth, and neonatal stress in unusually hot temperature exposures. The studies included in this review indicate that not only is there a need for further research on the ways that climate change, and heat in particular, may affect maternal health and neonatal outcomes, but that uniform standards for assessing the effects of heat on maternal fetal health also need to be established.



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Metagenomic Sequencing of an Echovirus 30 Genome From Cerebrospinal Fluid of a Patient With Aseptic Meningitis and Orchitis

Abstract
Enteroviruses cause a wide spectrum of clinical disease. In this study, we describe the case of a young man with orchitis and aseptic meningitis who was diagnosed with enterovirus infection. Using unbiased "metagenomic" massively parallel sequencing, we assembled a near-complete viral genome, the first use of this method for full-genome viral sequencing from cerebrospinal fluid. We found that the genome belonged to the subgroup echovirus 30, which is a common cause of aseptic meningitis but has not been previously reported to cause orchitis.

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Biphasic Zika Illness With Rash and Joint Pain

Abstract
During the current Zika virus (ZIKV) outbreak, acute symptomatic ZIKV infection in adults appears to be a mild-to-moderate, self-limited illness. We present a case of ZIKV rash illness that improved and then relapsed without repeat exposure to ZIKV. Clinicians should be alert for relapses in patients with ZIKV infection.

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Evaluation of Viral Surrogate Markers for Study of Pathogen Dissemination During Simulations of Patient Care

Abstract
During patient care simulations, cauliflower mosaic virus DNA and bacteriophage MS2 performed similarly as surrogate markers of pathogen dissemination. These markers disseminated to the environment in a manner similar to Clostridium difficile spores but were more frequently detected on skin and clothing of personnel after personal protective equipment removal.

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Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus–Associated Cryptococcal Meningitis

Abstract
Background
Cryptococcus is the most common etiology of adult meningitis in Africa. Amphotericin B deoxycholate remains paramount to treatment, despite toxicities, including acute kidney injury (AKI). We assessed the ability of the following urine markers to predict AKI in patients who received amphotericin B: urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein.
Methods
One hundred and thirty human immunodeficiency virus (HIV)–infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models.
Results
Participants were 48% female with a median age of 35 years, a median CD4 count of 21 cells/μL, and 44% died within 12 months. Incident AKI occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] = 2.8; P < .001). Development of AKI was associated with female sex (P = .04) and with higher CD4 count (49 vs 14 cells/μL; P < .01). Urine protein level in the highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04; aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile independently predicted AKI (aHR = 1.65; P = .04).
Conclusions
Acute kidney injury occurred in 42% of patients, and AKI was associated with mortality. Urine biomarkers, specifically urine protein, may be useful for antecedent prediction of amphotericin-associated AKI but need further evaluation.

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Efficacy and Safety of Intravenous Peramivir Compared With Oseltamivir in High-Risk Patients Infected With Influenza A and B Viruses: A Multicenter Randomized Controlled Study

Abstract
Background
Clinical studies comparing the different neuraminidase inhibitors for treatment of at-risk patients with influenza have not been performed. To optimize such treatments, we assessed the efficacy and safety of intravenous peramivir compared with oral oseltamivir in treating seasonal influenza A or B virus infection.
Methods
A multicenter, randomized, controlled clinical trial was conducted from December 2012 to May 2014 in high-risk patients infected with seasonal influenza. A total of 92 adult inpatients and outpatients with high risk factors (HRFs) were treated by either a single intravenous infusion of peramivir (600 mg) or oral administration of oseltamivir (75 mg, twice per day for 5 days).
Results
The median times to clinical stability (time to reach <37°C) were 40.0 hours (95% confidence interval [CI] = 23.3–64.5) and 37.8 hours (95% CI = 26.3–45.3) in the peramivir and oseltamivir groups, respectively; these values did not reveal a significant difference. The virus titer and change of mean total symptom scores decreased similarly with both treatments. Results of step-wise regression suggested that virus type was a significantly effective prognostic factor with respect to illness resolution. Adverse events (AEs) with peramivir and oseltamivir occurred in 2.2% (n = 1/46) and 13.0% (n = 6/46) of patients, respectively. The severity of AEs was mild in all cases except 2 patients who showed pneumonia or COPD aggravation; both were in the oseltamivir group.
Conclusions
Intravenous peramivir was effective based on the result of direct comparison with oral oseltamivir. Thus our data show that peramivir is a useful option for the treatment of influenza-infected patients with HRFs.

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Pleural Effusion Caused by Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer

Abstract
Intravesical bacillus Calmette Guérin (BCG) instillation has been used as immunotherapy for early stage bladder cancer for >40 years. Complications from this therapy are rare but may result in a spectrum of infectious sequelae. Here we describe the case of an elderly man who presented with a pleural effusion and subcutaneous nodule several years after treatment with BCG.

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Implementation of a Large System-Wide Hepatitis C Virus Screening and Linkage to Care Program for Baby Boomers

Abstract
Background
We implemented and evaluated a large health system-wide hepatitis C virus (HCV) screening and linkage to care program for persons born between 1945 and 1965 ("baby boomers").
Methods
An electronic health record (EHR) clinical decision support (CDS) tool for HCV screening for baby boomers was introduced in August 2015 for patients seen in the outpatient University of California, Los Angeles healthcare system setting. An HCV care coordinator was introduced in January 2016 to facilitate linkage to HCV care. We compared HCV testing in the year prior (August 2014–July 2015) to the year after (August 2015–July 2016) implementation of the CDS tool. Among patients with reactive HCV antibody testing, we compared outcomes related to the care cascade including HCV ribonucleic acid (RNA) testing, HCV RNA positivity, and linkage to HCV specialty care.
Results
During the study period, 19606 participants were screened for HCV antibody. Hepatitis C virus antibody screening increased 145% (from 5676 patients tested to 13930 tested) after introduction of the CDS intervention. Screening increased across all demographic groups including age, sex, and race/ethnicity, with the greatest increases among those in the older age groups. The addition of an HCV care coordinator increased follow-up HCV RNA testing for HCV antibody positive patients from 83% to 95%. Ninety-four percent of HCV RNA positive patients were linked to care postimplementation.
Conclusions
Introduction of an EHR CDS tool and care coordination markedly increased the number of baby boomers screened for HCV, rates of follow-up HCV RNA testing, and linkage to specialty HCV care for patients with chronic HCV infection.

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The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

Abstract
Background
Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting.
Methods
We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016.
Results
Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009).
Conclusions
Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

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quality of care; +853 new citations

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quality of care

These pubmed results were generated on 2017/07/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids

Cancers doi: 10.3390/cancers9080098

Authors: Elvira Forte Isotta Chimenti Paolo Rosa Francesco Angelini Francesca Pagano Antonella Calogero Alessandro Giacomello Elisa Messina

The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target.



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The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment.

http:--linkinghub.elsevier.com-ihub-imag Related Articles

The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment.

Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):868-883

Authors: Maggiore R, Zumsteg ZS, BrintzenhofeSzoc K, Trevino KM, Gajra A, Korc-Grodzicki B, Epstein JB, Bond SM, Parker I, Kish JA, Murphy BA, VanderWalde NA, CARG-HNC Study Group

Abstract
Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC-particularly those undergoing concurrent chemoradiation therapy-and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population.

PMID: 28602414 [PubMed - indexed for MEDLINE]



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Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

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Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

BJU Int. 2017 Aug;120(2):286-292

Authors: Katz L, Tripp DA, Carr LK, Mayer R, Moldwin RM, Nickel JC

Abstract
OBJECTIVES: To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS.
PATIENTS AND METHODS: The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires.
RESULTS: An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation.
CONCLUSIONS: The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability.

PMID: 28386966 [PubMed - indexed for MEDLINE]



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Αναζήτηση αυτού του ιστολογίου

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