Syndecan-1 in mechanosensing of nanotopological cues in engineered materials

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B. Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment. Nanotopological cues have become recognized as major regulators of cell growth, migration and phenotype. We hypothesized that syndecan-1 could serve as a mechanosensor for nanotopological cues and can mediate the responsiveness of vascular smooth muscle cells to nanoengineered materials. We created engineered substrates made of polyurethane acrylate with nanogrooves using ultraviolet-assisted capillary force lithography. We cultured vascular smooth muscle cells with knockout of syndecan-1 on engineered substrates with varying compliance and nanotopology. We found that knockout of syndecan-1 reduced alignment of vascular smooth muscle cells to the nanogrooves under inflammatory treatments. In addition, we found that loss of syndecan-1 increased nuclear localization of Yap/Taz and phospho-Smad2/3 in response to nanogrooves. Syndecan-1 knockout vascular smooth muscle cells also had elevated levels of Rho-associated protein kinase-1 (Rock1), leading to increased cell stiffness and an enhanced contractile state in the cells. Together, our findings support that syndecan-1 knockout leads to alterations in mechanosensing of nanotopographical cues through alterations of in rho-associated signaling pathways, cell mechanics and mediators of the Hippo and TGF-β signaling pathways.



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Tracking and protection of transplanted stem cells using a ferrocenecarboxylic acid-conjugated peptide that mimics hTERT

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Hyun-Hee Park, Kyu-Yong Lee, Dong Woo Park, Na-Young Choi, Young Joo Lee, Jeong-Woo Son, Sangjae Kim, Chanil Moon, Hyun-Wook Kim, Im Joo Rhyu, Seong-Ho Koh
In vivo tracking of transplanted stem cells has been a central aim of stem cell therapy. Although many tracking systems have been introduced, no method has yet been validated for clinical applications. We developed a novel sophisticated peptide (GV1001) that mimics hTERT (human telomerase reverse transcriptase) and analysed its ability to track and protect stem cells after transplantation. Ferrocenecarboxylic acid-conjugated GV1001 (Fe-GV1001) efficiently penetrated stem cells with no adverse effects. Moreover, Fe-GV1001 improved the viability, proliferation, and migration of stem cells under hypoxia. After Fe-GV1001-labelled stem cells were transplanted into the brains of rats after stroke, the labelled cells were easily tracked by MRI. Our findings indicate that Fe-GV1001 can be used for the in vivo tracking of stem cells after transplantation into the brain and can improve the efficacy of stem cell therapy by sustaining and enhancing stem cell characteristics under disease conditions.



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Nanoscaled red blood cells facilitate breast cancer treatment by combining photothermal/photodynamic therapy and chemotherapy

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Guoyun Wan, Bowei Chen, Ling Li, Dan Wang, Shurui Shi, Tao Zhang, Yue Wang, Lianyun Zhang, Yinsong Wang
Red blood cells (RBCs)-based vesicles have been widely used for drug delivery due to their unique advantages. Intact RBCs contain a large amount of oxyhemoglobin (oxyHb), which can assist with photodynamic therapy (PDT). Indocyanine green (ICG), a photosensitizer both for photothermal therapy (PTT) and PDT, shows potent anticancer efficacy when combined with chemotherapeutic drug doxorubicin (DOX). In this study, we prepared nanoscaled RBCs (RAs) containing oxyHb and gas-generating agent ammonium bicarbonate (ABC) for co-loading and controlled release of ICG and DOX, thus hoping to achieve synergistic effects of PTT/PDT and chemotherapy against breast cancer. Compared to free ICG, ICG and DOX co-loaded RAs (DIRAs) exhibited nearly identical PTT efficiency both in vitro and in vivo, but meanwhile their PDT efficiency was enhanced significantly. In mouse breast cancer cells, DIRAs significantly inhibited cell growth and induced cell apoptosis after laser irradiation. In breast tumor-bearing mice, intratumoral injection of DIRAs and followed by local laser irradiation almost completely ablated breast tumor and further suppressed tumor recurrence and metastasis. In conclusion, this biomimetic multifunctional nanosystem can facilitate breast cancer treatment by combining PTT/PDT and chemotherapy.



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Heteromultivalent targeting of integrin αvβ3 and neuropilin 1 promotes cell survival via the activation of the IGF-1/insulin receptors

Publication date: February 2018
Source:Biomaterials, Volume 155
Author(s): Tao Jia, Jungyoon Choi, Jéremy Ciccione, Maxime Henry, Ahmad Mehdi, Jean Martinez, Béatrice Eymin, Gilles Subra, Jean-Luc Coll
Angiogenesis strongly depends on the activation of integrins, especially integrin αvβ3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted molecules that simultaneously block both of them are expected have increased anti-angiogenic and antitumor activity. Toward this goal, we generated bifunctional 40 nm-sized silica nanoparticles (NPs) coated with controlled amounts of cRGD and ATWLPPR peptides and studied their affinity, selectivity and biological activity in HUVECs. Sub-nanomolar concentrations of NPs grafted either with ATWLPPR alone or in combination with cRGD exhibit potent and specific antagonist activity against VEGFR2/AKT signaling. However, a 1 nM concentration of the cRGD/ATWLPPR-heteromultivalent particles (RGD/ATW-NPs) also blocks the phosphorylation of VEGFR2 while co-inducing an unexpected long-lasting activation of AKT via IGF-1R/IR-AKT/GSK3β/eNOS signaling that stimulates cell survival and abrogates the intrinsic toxicity of silica-NPs to serum-starved HUVECs. We also showed that their repeated intravenous administration was associated with the proliferation of human U87MG tumor cells engrafted in nude mice and a dilatation of the tumor blood vessels.We present biochemical evidence for the complex cross-talk generated by the binding of the heteromultivalent NPs with αvβ3-integrin and with NRP1. In particular, we show for the first time that such heteromultivalent NPs can trans-activate IGF-1/insulin receptors and exert dose-dependent pro-survival activity. This study demonstrates the difficulties in designing targeted silica-based NPs for antiangiogenic therapies and the possible risks posed by undesirable side effects.

Graphical abstract

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Spontaneous hair follicle germ (HFG) formation in vitro, enabling the large-scale production of HFGs for regenerative medicine

Publication date: February 2018
Source:Biomaterials, Volume 154
Author(s): Tatsuto Kageyama, Chisa Yoshimura, Dina Myasnikova, Ken Kataoka, Tadashi Nittami, Shoji Maruo, Junji Fukuda
Hair follicle morphogenesis is triggered by reciprocal interactions between hair follicle germ (HFG) epithelial and mesenchymal layers. Here, we developed a method for large-scale preparation of HFGs in vitro via self-organization of cells. We mixed mouse epidermal and mouse/human mesenchymal cells in suspension and seeded them in microwells of a custom-designed array plate. Over a 3-day culture period, cells initially formed a randomly distributed single cell aggregate and then spatially separated from each other, exhibiting typical HFG morphological features. These self-sorted hair follicle germs (ssHFGs) were shown to be capable of efficient hair-follicle and shaft generation upon intracutaneous transplantation into the backs of nude mice. This finding facilitated the large-scale preparation of approximately 5000 ssHFGs in a microwell-array chip made of oxygen-permeable silicone. We demonstrated that the integrity of the oxygen supply through the bottom of the silicone chip was crucial to enabling both ssHFG formation and subsequent hair shaft generation. Finally, spatially aligned ssHFGs on the chip were encapsulated into a hydrogel and simultaneously transplanted into the back skin of nude mice to preserve their intervening spaces, resulting in spatially aligned hair follicle generation. This simple ssHFG preparation approach is a promising strategy for improving current hair-regenerative medicine techniques.



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Association of oxidative stress and dynamic thiol-disulphide homeostasis with atopic dermatitis severity and chronicity in children: a prospective study

Summary

Background

Oxidative stress (OS) has an important effect on the pathogenesis of atopic dermatitis (AD). Thiols are antioxidants that regulate intracellular redox metabolism and protect keratinocytes against OS damage in the stratum corneum.

Aim

To investigate dynamic thiol-disulphide homeostasis (dTDH) as a novel OS parameter in children with AD, and its relationship with disease severity and chronicity.

Methods

Severity of AD was determined by using the instruments SCORing Atopic Dermatitis (SCORAD) and Eczema Area And Severity Index (EASI) upon enrolment in the study (SCORAD₁ and EASI₁) and after 1 year (SCORAD₂ and EASI₂). Native thiol, total thiol and disulphide levels were measured as novel OS parameters, and the ratios of disulphide/native thiol, disulphide/total thiol and native/total thiol were calculated as dTDH.

Results

In the AD group, the serum disulphide level and the ratios of disulphide/native thiol and disulphide/total thiol were significantly lower than in healthy controls (P = 0.01, P < 0.01 and P < 0.01, respectively). There was no significant association between OS parameters and disease severity (P > 0.05). SCORAD₂ and EASI₂ were positively correlated with disulphide/native thiol ratio (r = 0.29, P < 0.03 and r = 0.35, P < 0.01, respectively), whereas they were negatively correlated with the native/total thiol ratio (r = −0.30, P = 0.02 for both).

Conclusions

Both OS and impaired dTDH were found to be related to childhood AD. None of the OS parameters was associated with AD severity. dTDH is a possible diagnostic tool to predict AD chronicity.

http://ift.tt/2hRIBwr

Association of oxidative stress and dynamic thiol-disulphide homeostasis with atopic dermatitis severity and chronicity in children: a prospective study

Summary

Background

Oxidative stress (OS) has an important effect on the pathogenesis of atopic dermatitis (AD). Thiols are antioxidants that regulate intracellular redox metabolism and protect keratinocytes against OS damage in the stratum corneum.

Aim

To investigate dynamic thiol-disulphide homeostasis (dTDH) as a novel OS parameter in children with AD, and its relationship with disease severity and chronicity.

Methods

Severity of AD was determined by using the instruments SCORing Atopic Dermatitis (SCORAD) and Eczema Area And Severity Index (EASI) upon enrolment in the study (SCORAD₁ and EASI₁) and after 1 year (SCORAD₂ and EASI₂). Native thiol, total thiol and disulphide levels were measured as novel OS parameters, and the ratios of disulphide/native thiol, disulphide/total thiol and native/total thiol were calculated as dTDH.

Results

In the AD group, the serum disulphide level and the ratios of disulphide/native thiol and disulphide/total thiol were significantly lower than in healthy controls (P = 0.01, P < 0.01 and P < 0.01, respectively). There was no significant association between OS parameters and disease severity (P > 0.05). SCORAD₂ and EASI₂ were positively correlated with disulphide/native thiol ratio (r = 0.29, P < 0.03 and r = 0.35, P < 0.01, respectively), whereas they were negatively correlated with the native/total thiol ratio (r = −0.30, P = 0.02 for both).

Conclusions

Both OS and impaired dTDH were found to be related to childhood AD. None of the OS parameters was associated with AD severity. dTDH is a possible diagnostic tool to predict AD chronicity.

http://ift.tt/2hRIBwr

Ischaemic pituitary tumour apoplexy and concurrent meningitis: a diagnostic dilemma

Pituitary tumour apoplexy is a rare but potentially life threatening clinical syndrome that mostly results from haemorrhage in the pre-existent tumour. Pure ischaemic subtype of apoplexy is even rarer. The presentation can be hard to differentiate clinically from bacterial meningitis. Moreover, the presence of one does not necessarily exclude the other and early diagnosis of both conditions is imperative for timely management. We report a case of ischaemic pituitary tumour apoplexy that may have precipitated in the setting of bacterial meningitis.

http://ift.tt/2A5b6eZ

Hyperacute leucopenia associated with furosemide

A 72-year-old man presented to the hospital with exacerbation of congestive heart failure. He was given furosemide 40 mg intravenously twice at 4 hours apart. At 4 hours after the second dose of furosemide, his white blood cells (WBC) dropped acutely from 9.8 to 2.4x10⁹/L (reference range 4.1 to 9.3x10⁹/L). With the discontinuation of furosemide, the WBC trended up to 7.1x10⁹/L about 13 hours after the second dose of intravenous furosemide and remained in normal range for the next 3 days. However, when the oral furosemide was started on hospital day 4, there was a mild drop in WBC count, which returned to and maintained at baseline since the next day. The dynamic changes in the patient's WBC were coincident with the use of furosemide. The possible mechanisms of furosemide-associated transient hyperacute leucopenia were discussed.

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Giant insulinoma: an unusual cause of hypoglycaemia

Description 

A 70-year-old non-diabetic man presented to the accident and emergency department with convulsions and symptoms of hunger, anxiety and blurred vision. A non-tender epigastric mass was identified, and he was found to be hypoglycaemic, with plasma glucose levels of 1.5 mmol/L (4.4–6.1 mmol/L). C-peptide and insulin levels were both inappropriately elevated.

After stabilisation with glucose, the patient was investigated with CT, which revealed a 154 mm mass in the pancreas that displaced the stomach and encased the coeliac trunk, the superior mesenteric vein and the splenic vein (figure 1). Collaterals were found at the level of the hepatic hilum, the gastro-oesophageal junction and adjacent to the mass itself. Calcifications typical of insulinomas were evident (figure 2). No metastases were seen. Fine-needle aspiration was then performed, confirming the diagnosis (figure 3).

Figure 1

Multiplanar reconstruction identifying the 154 mm insulinoma.

...

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Severe panniculitis and polyarthritis caused by acinar cell carcinoma arising from an ectopic pancreas

The pancreatitis, panniculitis and polyarthritis (PPP) syndrome is a rare condition caused by pancreatic diseases, such as acute or chronic pancreatitis or pancreatic carcinoma. We report the first case of PPP syndrome caused by metastatic acinar cell carcinoma from an ectopic pancreas. The symptoms were successfully managed by the treatment of the metastatic carcinoma. Pancreatic cytosteatonecrosis should be always considered in a patient who is showing symptoms of panniculitis and polyarthritis.

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Retrobulbar heavy liquid discovered 5 years postvitrectomy

Description

This report of a mass in the upper eyelid resulting from long-term complications of heavy liquid tamponade therapy of retinal detachment is a good example of learning from rare cases.

Retinal detachments may be repaired by scleral buckling, vitrectomy surgery or by a combination of both techniques. Retinal detachments repaired by vitrectomy are typically tamponaded by either gas or silicone oil. In certain complex cases, heavy liquid (perfluorohexyloctane/polydimethylsiloxane) is used as a short-term tamponading agent that is subsequently replaced with gas or silicone oil.1 2

A 16-year-old woman presented with bilateral retinal detachments secondary to giant tears. The patient had no relevant ocular history and denied trauma. The left eye had a macula-sparing detachment and the right eye had a macula-off retinal detachment. Both retinas were reattached sequentially with a combination of scleral buckling and vitrectomy with heavy liquid tamponade. The heavy...

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Sino-Nasal outcome test-22 outcomes after sinus surgery: A systematic review and meta-analysis

Objectives/Hypothesis

The goal of the study was to perform a systematic review with meta-analysis to determine the mean change in the 22-item Sino-Nasal Outcome Test (SNOT-22) across patients who have had endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) in the literature.

Methods

A literature search was performed to identify studies that assessed SNOT-22 scores before and after ESS in adult patients with CRS. A random effects model with inverse variance weighting was used to generate the mean change after surgery, along with the forest plot and 95% confidence interval (CI). The impact of patient-specific factors across studies was assessed using a mixed-effects meta-regression.

Results

The final study list included 40 unique patient cohorts published from 2008 to 2016. All studies showed a statistically significant change in mean SNOT-22 scores between baseline and postoperative time points (P < .001), ranging from 12.7 to 44.8, at an average follow-up of 10.6 months. The summary change in mean SNOT-22 across all studies was 24.4 (95% CI: 22.0-26.8). After forward, step-wise multivariate modeling, studies with higher mean preoperative SNOT-22 score and higher asthma prevalence were associated with greater changes in SNOT-22 score after ESS, whereas studies with longer mean follow-up had smaller changes in SNOT-22 score.

Conclusions

Studies evaluating quality-of-life outcomes after sinus surgery using the SNOT-22 instrument universally show significant improvement after ESS. Across the published literature, the magnitude of change is quite variable and appears to be influenced by a number of factors including baseline SNOT-22 score, asthma prevalence, and length of follow-up. Laryngoscope, 2017

http://ift.tt/2iEYcNa

Determining Candidate Single Nucleotide Polymorphisms in Acquired Laryngotracheal Stenosis

Objectives/Hypothesis

Despite wide adoption of strategies to prevent injury from prolonged intubation and tracheotomy, acquired laryngotracheal stenosis (ALTS) has not disappeared. ALTS' persistence may be due to patient factors that confer unique susceptibility for some. We sought to identify genetic markers in genes associated with wound healing that could be associated with ALTS.

Study Design

Case-control study.

Methods

One hundred thirty-eight patients were recruited, 53 patients with ALTS and 85 control patients who underwent intubation or tracheotomy without evidence of ALTS. The patients' DNA was isolated from whole blood. Custom primers were designed, and the TaqMan assay employing allele-specific polymerase chain reaction was used to interrogate single nucleotide polymorphisms (SNPs) rs1799750, rs522616, rs2276109, rs2569190, rs1800469, and rs1024611 of candidate wound healing genes MMP1, MMP3, MMP12, CD14, TGFβ1, and MCP1, respectively. A logistic regression model was used to examine the association of candidate gene polymorphisms with the presence or absence of ALTS.

Results

All 138 patients were successfully genotyped. No significant association was found between candidate SNPs and development of ALTS in the overall group. However, subgroup analysis within each ethnicity identified SNPs that are associated with ALTS depending upon the ethnic background.

Conclusions

Patient factors such as variations in wound healing due to functional SNPs may shed light on the development of ALTS. There may be a difference in susceptibility to developing ALTS in different ethnic backgrounds. These preliminary findings need to be corroborated in larger population studies.

Level of Evidence

3b Laryngoscope, 2017

http://ift.tt/2B2suAh

Sino-Nasal outcome test-22 outcomes after sinus surgery: A systematic review and meta-analysis

Objectives/Hypothesis

The goal of the study was to perform a systematic review with meta-analysis to determine the mean change in the 22-item Sino-Nasal Outcome Test (SNOT-22) across patients who have had endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) in the literature.

Methods

A literature search was performed to identify studies that assessed SNOT-22 scores before and after ESS in adult patients with CRS. A random effects model with inverse variance weighting was used to generate the mean change after surgery, along with the forest plot and 95% confidence interval (CI). The impact of patient-specific factors across studies was assessed using a mixed-effects meta-regression.

Results

The final study list included 40 unique patient cohorts published from 2008 to 2016. All studies showed a statistically significant change in mean SNOT-22 scores between baseline and postoperative time points (P < .001), ranging from 12.7 to 44.8, at an average follow-up of 10.6 months. The summary change in mean SNOT-22 across all studies was 24.4 (95% CI: 22.0-26.8). After forward, step-wise multivariate modeling, studies with higher mean preoperative SNOT-22 score and higher asthma prevalence were associated with greater changes in SNOT-22 score after ESS, whereas studies with longer mean follow-up had smaller changes in SNOT-22 score.

Conclusions

Studies evaluating quality-of-life outcomes after sinus surgery using the SNOT-22 instrument universally show significant improvement after ESS. Across the published literature, the magnitude of change is quite variable and appears to be influenced by a number of factors including baseline SNOT-22 score, asthma prevalence, and length of follow-up. Laryngoscope, 2017

http://ift.tt/2iEYcNa

Determining Candidate Single Nucleotide Polymorphisms in Acquired Laryngotracheal Stenosis

Objectives/Hypothesis

Despite wide adoption of strategies to prevent injury from prolonged intubation and tracheotomy, acquired laryngotracheal stenosis (ALTS) has not disappeared. ALTS' persistence may be due to patient factors that confer unique susceptibility for some. We sought to identify genetic markers in genes associated with wound healing that could be associated with ALTS.

Study Design

Case-control study.

Methods

One hundred thirty-eight patients were recruited, 53 patients with ALTS and 85 control patients who underwent intubation or tracheotomy without evidence of ALTS. The patients' DNA was isolated from whole blood. Custom primers were designed, and the TaqMan assay employing allele-specific polymerase chain reaction was used to interrogate single nucleotide polymorphisms (SNPs) rs1799750, rs522616, rs2276109, rs2569190, rs1800469, and rs1024611 of candidate wound healing genes MMP1, MMP3, MMP12, CD14, TGFβ1, and MCP1, respectively. A logistic regression model was used to examine the association of candidate gene polymorphisms with the presence or absence of ALTS.

Results

All 138 patients were successfully genotyped. No significant association was found between candidate SNPs and development of ALTS in the overall group. However, subgroup analysis within each ethnicity identified SNPs that are associated with ALTS depending upon the ethnic background.

Conclusions

Patient factors such as variations in wound healing due to functional SNPs may shed light on the development of ALTS. There may be a difference in susceptibility to developing ALTS in different ethnic backgrounds. These preliminary findings need to be corroborated in larger population studies.

Level of Evidence

3b Laryngoscope, 2017

http://ift.tt/2B2suAh

Multilevel lumbar spine infection due to poor dentition in an immunocompetent adult: a case report

Although spinal infections have been reported following dental procedures, development of a spinal infection attributed to poor dentition without a history of a dental procedure in an immunocompetent adult has...

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Detection of Hepatitis C antibodies without viral transmission in Hepatitis C negative recipients receiving kidneys from Hepatitis C positive donors treated with Direct Acting Anti-Viral Therapy

No abstract available

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Use of organs from hepatitis C virus positive donors for uninfected recipients: a potential cost-effective approach to save lives?

Background Organs from hepatitis C virus (HCV) seropositive (HCVpos) individuals are seldom used for transplantation because of the risk of disease transmission. Because transmitted HCV is now amenable to effective treatment we estimated the potential impact of using HCVpos deceased donor organs for transplantation. Methods The Potential Donor Audit (PDA) of patients (

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Analysis of biomarkers within the initial 2 years posttransplant and 5-year kidney transplant outcomes: results from Clinical Trials in Organ Transplantation-17

ABSTRACT Background An early posttransplant biomarker/surrogate marker for kidney allograft loss has the potential to guide targeted interventions. Previously published findings, including results from the Clinical Trials in Organ Transplantation (CTOT)-01 study, showed that elevated urinary chemokine CXCL9 levels and elevated frequencies of donor-reactive interferon gamma-(IFNγ)-producing T cells by enzyme linked immunosorbent spot (ELISPOT) assay associated with acute cellular rejection within the first year and with lower 1-year posttransplant estimated glomerular filtration rate (eGFR). How well these biomarkers correlate with late outcomes, including graft loss, is unclear. Methods In CTOT-17, we obtained 5-year outcomes in the CTOT-01 cohort and correlated them with a) biomarker results and b) changes in eGFR (Chronic Kidney Disease Epidemiology Collaboration formula) over the initial 2 years posttransplant using univariable analysis and multivariable logistic regression. Results Graft loss occurred in 14/184 subjects (7.6%) 2 to 5 years posttransplant. Neither IFNγ ELISPOTs nor urinary CXCL9 were informative. In contrast, a ≥40% decline in eGFR from 6 months to 2 years posttransplant independently correlated with thirteen-fold odds of 5-year graft loss [adjusted odds ratio (aOR) 13.1; 95% CI 3.0-56.6], a result that was validated in the independent Genomics of Chronic Allograft Rejection cohort (n=165, aOR: 11.2). Conclusions We conclude that while pre and early posttransplant ELISPOT and chemokine measurements associate with outcomes within 2-years posttransplant, changes in eGFR between 3 months or 6 months and 24 months are better surrogates for 5-year outcomes, including graft loss. Corresponding author: Peter S Heeger, MD, Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai, New York, USA, Email: peter.heeger@mssm.edu, Phone: 212 241 6324, Fax: 212 987 0389 Authorship Geovani Faddoul, M.D. Participated in data analysis and writing/editing of the manuscript Girish N Nadkarni, M.D. Participated in data analysis and writing/editing of the manuscript Nancy D. Bridges, M.D. Participated in study design and writing/editing of the manuscript Jens Goebel, M.D. Participated in writing/editing of the manuscript Donald E. Hricik, M.D. Participated in study design, data analysis and writing/editing of the manuscript Richard Formica, M.D. Participated in study design and writing/editing of the manuscript Madhav C Menon, M.D. Participated in study design, data analysis and writing/editing of the manuscript Yvonne Morrison, Participated in study design and writing/editing of the manuscript Barbara Murphy, M.D. Participated in study design and writing/editing of the manuscript Kenneth Newell, M.D. Participated in study design and writing/editing of the manuscript Peter Nickerson, M.D. Participated in study design and writing/editing of the manuscript Emilio D. Poggio, M.D. Participated in study design and writing/editing of the manuscript David Rush, M.D. Participated in study design and writing/editing of the manuscript Peter S. Heeger, M.D. Participated in study design, data analysis and writing/editing of the manuscript Disclosure The authors of this manuscript have no conflicts of interest to disclose. Funding The study was supported by National Institutes of Health U01 grant AI63594 awarded to P Heeger and K23DK107908 to G Nadkarni Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Heme Oxygenase 1 Attenuates Hypoxia-Reoxygenation Injury in Mice Liver Sinusoidal Endothelial Cells

ABSTRACT Background Heme oxygenase 1 (HO-1), a heat shock protein, can be involved in the resolution of inflammation by modulating cytokine expression and apoptotic cell death. Based on recent evidence that liver sinusoidal endothelial cells (LSECs) is the critical target in early period of liver ischemia-reperfusion injury (IRI), this study aims to clarify whether overexpression of HO-1 gene provides a protective effect on mice LSECs. Method LSECs were transfected with adenovirus vectors encoding mice HO-1 gene (Ad-HO-1) or green fluorescent protein (Ad-EGFP). Controls were not infected with any vector. LSECs were then treated with hypoxic or normoxic culture. We used low serum culture medium and hypoxia-reoxygenation (H-R) conditions to cause IRI in vitro. The transfection efficiency of HO-1 gene in LSECs, after 48 hours of transfection, and the effect of HO-1 on the model of H-R injury in LSECs were observed. Results Transfection of LSECs with Ad-HO-1 was at an optimal dose (MOI=80) to markedly express HO-1 mRNA and protein. Groups of overexpressed HO-1 showed lower levels of inflammatory factor mediators IL-6 and TNF-α. Survival rate of the cells after H-R injury was higher and attributed to overexpressed HO-1. In contrast, the control adenovirus expressing the EGFP failed to induce HO-1 expression, and stimulated cell apoptosis. HO-1 expression was down-regulated in all H-R groups compared to normoxia groups, which may be related to the disruption of the LSEC structure. Conclusion Up-regulation of HO-1 can attenuate H-R injury in LSECs by inhibiting proinflammatory cytokine release and diminishing apoptotic cell death. Corresponding author: Zhong Zeng, MD, PhD, Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical College, 295 Xichang Road, Kunming 650032, Yunnan Province, China. Telephone: +86-871-65359202; Fax: +86-871-65359202; Email: zzong@medmail.com.cn Authorship: Siming Qu, Bo Yuan, and Zhong Zeng contributed equally to this work; Siming Qu and Bo Yuan performed the majority of experiments; Hongbin Zhang participated in the performance of the research; Hanfei Huang participated in data analysis; Shikun Yang, Jie Lin, Li Jin, and Pu Wu participated in the writing of the paper. Disclosure: The authors declare no conflicts of interest. Funding: National Nature Science Foundation of China, No. 81660113 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comparison of BQ123, Epoprostenol, and Verapamil as Vasodilators During Normothermic Ex Vivo Liver Machine Perfusion

Background The optimal vasodilator to avoid hepatic artery (HA) vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), Epoprostenol (prostacyclin analogue), and Verapamil (calcium channel antagonist). Methods Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: Group 1: livers perfused with a dose of 1.25 mg of BQ123 at baseline and at 2 hours of perfusion, Group 2: Epoprostenol at a continuous infusion of 4mg/hr, Group 3: Verapamil 2.5mg at baseline and at 2 hours of perfusion, Group 4: No vasodilator used during ex vivo perfusion. Liver injury and function were assessed during perfusion, and daily post transplantation until postoperative day 3. All groups were compared to a cold storage group for post operative graft function. Results Hepatic artery flow during NEVLP was significantly higher in BQ123 compared to Verapamil, Epopostenol, and no vasodilator treated livers. AST levels were significantly lower with BQ123 and Verapamil compared to Epoprostenol and control group during perfusion. Peak AST levels were lower in pigs receiving BQ123 and Verapamil perfused grafts compared to Epoprostenol and control group. INR, alkaline phosphatase, and total bilirubin levels were lower in the BQ123 and Verapamil groups compared to Epoprostenol group. Cold storage group had increased markers of ischemia reperfusion injury and slower graft function recovery compared to machine perfused grafts. Conclusion The use of BQ123, Epoprostenol, and Verapamil during NEVLP is safe. Livers perfused with BQ123 and Verapamil have higher HA flow and reduced hepatocyte injury during perfusion compared to Epoprostenol. Hepatic artery flow is significantly reduced in the absence of vasodilators during NEVLP. Authors Contributions. Juan Echeverri: Conception and design of the study, completion of experiments, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Nicolas Goldaracena: Completion of experiments, acquisition of data, data analysis and interpretation, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Johan Moritz Kaths: Completion of experiments, acquisition of data, data analysis and interpretation, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Ivan Linares: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Roizar Rosales: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Dagmar Kollmann: Completion of experiments, acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Matyas Hamar: Acquisition of data, data analysis and interpretation final approval for publication, and agreement to be accountable for all aspects of the work. Peter Urbanellis: Analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Sujani Ganesh: Acquisition of data, analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Oyedele Adeyi: Analysis and interpretation of data, revised manuscript critically for important intellectual content, final approval for publication, and agreement to be accountable for all aspects of the work. Mahmood Tazari: Statistical analysis and interpretation of data, revised manuscript critically, final approval for publication, and agreement to be accountable for all aspects of the work. Markus Selzner: Conception and design of the study, completion of experiments, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Nazia Selzner: Conception and design of the study, acquisition of data, data analysis and interpretation, drafted manuscript, final approval for publication, and agreement to be accountable for all aspects of the work. Disclosure: The authors declare no conflicts of interest. Correspondence: Nazia Selzner, MD, PhD, Toronto General Hospital, NCSB 11C-1244, 585 University Avenue, Toronto, ON M5G2N2, Phone: 1-416-340-5230, Fax: 1-416-340-5242, e-mail: nazia.selzner@uhn Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Myeloid-Derived Suppressor Cells and their Potential Application in Transplantation

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells of the myeloid lineage upregulated by mediators of inflammation such as IL-2, GCSF, and S100A8/A9. These cells have been studied extensively by tumor biologists. Because of their robust immunosuppressive potential, MDSCs have stirred recent interest among transplant immunologists as well. MDSCs inhibit T cell responses through, among other mechanisms, the activity of arginase-1 and iNOS, and the expansion of T regulatory (Treg) cells. In the context of transplantation, MDSCs have been studied in several animal models, and to a lesser degree in humans. Here, we will review the immunosuppressive qualities of this important cell type and discuss the relevant studies of MDSCs in transplantation. It may be possible to exploit the immunosuppressive capacity of MDSCs for the benefit of transplant patients. Disclosure: The authors have no financial disclosures. Grant support: This work was supported by a grant (to JRS) from the American Surgical Association Foundation and by the Living Legacy Foundation of Maryland. Author contributions: JRS – read the literature, developed the concept/hypotheses, wrote the manuscript, lead the project, revised the paper YSL – read the literature, contributed to hypotheses, edited the paper ED – read the literature, edited the paper, contributed to manuscript's structure JSB – read the literature, edited the paper, contributed to manuscript's structure, mentored the project Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Association of Cardiac Abnormalities to the Frail Phenotype in Cirrhotic Patients on the Waitlist: From the Functional Assessment in Liver Transplantation (FrAILT) Study.

ABSTRACT Background Frailty is a syndrome of decreased physiologic reserve that results from compromise of multiple physiologic systems including cardiovascular. We aimed to determine the association between the frail phenotype and cardiac abnormalities in liver transplant (LT) candidates through evaluation of transthoracic echocardiography (TTE) indices. Methods Included were consecutive outpatients listed for LT who underwent a frailty assessment from 1/1/14-6/30/16 (using the Liver Frailty Index) and a 2-dimensional/doppler TTE exam. Patients were categorized as robust, intermediate frail, or frail by the Liver Frailty Index based on scores of 34cc/m2 (p= 0.001). In linear regression adjusted for age, sex, hypertension and diabetes, the Liver Frailty Index was positively associated with LA dimension (coeff 0.20, 95%CI 0.07-0.34), LAVIcc/m2 (coeff 0.01, 95%CI 0.005-0.02), ejection fraction (coeff 1.59, 95%CI 0.32-2.85) and pulmonary artery systolic pressure (coeff 0.01, 95%CI 0.003-0.02) and negatively associated with LV hypertrophy (coeff -0.22, 95%CI -0.37, -0.06). Conclusion In LT candidates, frailty is associated with cardiac structural and functional changes, independent of known risk factors. Our study provides evidence to support that measures of frailty in cirrhotic patients encompass abnormalities of the cardiovascular system and may inform assessments of cardiovascular reserve in this population. CORRESPONDENCE INFORMATION: Jennifer C. Lai, MD, MBA, Department of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA, 513 Parnassus Avenue, UCSF Box 0538, San Francisco, CA 94143, Email: Jennifer.lai@ucsf.edu, Academic office: (415) 476-2777 AUTHORSHIP Puchades:Study concept and design; acquisition of data; analysis and interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content. Chau: Study design; acquisition of data, interpretation of data; critical revision of the manuscript for important intellectual content. Dodson: Study design; interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content. Mohamad: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Mustain: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Lebsack: Study design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. Aguilera: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Prieto: Study design; interpretation of data; critical revision of the manuscript for important intellectual content. Lai: Study concept and design; analysis and interpretation of data; drafting of manuscript; critical revision of the manuscript for important intellectual content; statistical analysis and study supervision. DISCLOSURE: The authors of this manuscript have no conflicts of interest to disclose. FUNDING: This study was funded by the Spanish Transplantation Society (Puchades), an American College of Gastroenterology Junior Faculty Development Award (Lai), P30AG044281 (UCSF Older Americans Independence Center; Lai), and K23AG048337 (Paul B. Beeson Career Development Award in Aging Research; Lai). These funding agencies played no role in the analysis of the data or the preparation of this manuscript. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Rituximab and Therapeutic Plasma Exchange in Recurrent Focal Segmental Glomerulosclerosis Postkidney Transplantation

Background Focal segmental glomerulosclerosis (FSGS) is a common cause of end stage renal disease (ESRD) with a high rate of recurrence after kidney transplantation. Several factors such as white race, rapid progression, and previous allograft failure due to recurrence were found to be risks of recurrence. Data are limited on the benefits of rituximab and/or therapeutic plasma exchange (TPE) in preventing recurrence. In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS post kidney transplantation. Methods We enrolled 66 patients with FSGS in this prospective observational study and followed their outcomes. Patients with high risk for recurrence received preventative therapy with TPE and/or rituximab. Results Twenty three of the thirty seven (62%) who received preventative therapy developed recurrence compared to fourteen recurrences out of the twenty seven (51%) who did not receive any therapy (p=0.21). There was a trend for less relapse when rituximab was used as a therapy for recurrent FSGS, (6/22 versus 9/18, p=0.066). We utilized a clinical score of 5 values to assess the prediction of FSGS recurrence. A score of 3 or more had a predictive Receiver Operating Characteristic (ROC) curve of 0.72. Treatment with TPE and/or rituximab resulted in better allograft survival than historical studies. Allograft failure due to recurrent FSGS occurred in only 6 patients (9%). Conclusion Preventative therapies do not decrease the recurrence rate of recurrent FSGS. However, prompt treatment of recurrence with these therapies may result in improved outcomes. Corresponding Author: Nada Alachkar, MD, 600 Wolfe St. Brady 502, Baltimore, MD. Email: nalachk1@jhmi.edu Authorship Page: Sami Alasfar: data collection, data analysis and interpretation, drafting the article Dany Matar: data collection Robert A Montgomery: critical revision of the article Niraj Desai: critical revision of the article Bonnie Lonze: critical revision of the article Vikas Vujjini: data collection Michelle M. Estrella: critical revision of the article John Manllo Dieck: data collection, critical revision of the article Gebran Khneizer: data collection Sanja Sever: critical revision of the article Jochen Reiser: critical revision of the article Nada Alachkar: design of the work, data collection, data analysis and interpretation, drafting the article, final approval of the version to be published Disclosures: JR and SS are cofounders and stock holders of Trisaq, a biotechnological company developing novel therapeutics for chronic kidney diseases and FSGS, and have pending and issued patents in the therapeutic and diagnostic space regarding kidney diseases. Sources of support: NIH R01DK101350-04, Nada Alachkar Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: Long-term results after 7 years of a randomized clinical trial

Background The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety and long-term graft outcome in CMV-positive (R+) renal transplant recipients. Methods Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2x450 mg/day oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2x900 mg/day valganciclovir was initiated at a viral load of ≥400 CMV copies/mL (PCR) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (D+/R+, D-/R+). Results The 12-month-results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared to preemptive group experienced a CMV infection or disease up to month 84 (11.5% [95% CI: 6.8%,17.8%] vs. 39.7% [31.9%,48.0%], p

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Procedural sedation and analgesia for adults in Europe: Safety first

No abstract available

http://ift.tt/2zrV01A

Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review

BACKGROUND Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S) The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) 25% of baseline), or that a recovery time longer than 15 min be accepted. Correspondence to Thomas Fuchs-Buder, MD, Department of Anaesthesia and Critical Care, University Hospital of Nancy, Rue du Morvan, F-54511 Vandoeuvre-Les-Nancy, France. Cedex E-mail: t.fuchs-buder@chru-nancy.fr © 2017 European Society of Anaesthesiology

http://ift.tt/2mRaTJj

Procedural sedation and analgesia for adults in Europe: Safety first

No abstract available

http://ift.tt/2zrV01A

Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review

BACKGROUND Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S) The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) 25% of baseline), or that a recovery time longer than 15 min be accepted. Correspondence to Thomas Fuchs-Buder, MD, Department of Anaesthesia and Critical Care, University Hospital of Nancy, Rue du Morvan, F-54511 Vandoeuvre-Les-Nancy, France. Cedex E-mail: t.fuchs-buder@chru-nancy.fr © 2017 European Society of Anaesthesiology

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A systematic review of group work interventions in UK high secure hospitals

Publication date: Available online 20 November 2017
Source:Aggression and Violent Behavior
Author(s): Michaela Sturgeon, Nichola Tyler, Theresa A. Gannon
BackgroundRehabilitating high secure hospital patients poses significant challenges. Group work is thought to play a key role in patient recovery; however, there have been no reviews conducted specifically assessing group work interventions for high secure hospital patients.ObjectivesTo review the focus of group work interventions that are being implemented and evaluated with high secure hospital patients in the UK and to examine the effectiveness of these interventions and the methods used to assess intervention effectiveness.MethodA systematic literature search combined with reference screening was conducted examining group work interventions with high secure hospital patients in the UK.ResultsIn total, 29 manuscripts were identified for review inclusion. Across these, ten focuses of group work intervention emerged: anger/aggression, offence-specific, enhancing insight and understanding of mental illness, thinking skills/problem solving, substance misuse, self-harm, relationships, self-esteem and well-being, relapse prevention, and moving on. Positive outcomes were generally reported across all ten areas.ConclusionsStudies assessing the impact of group work interventions could be improved by increasing sample sizes, reducing sole reliance on self-report measures, employing clear statistical and clinical significance testing, and increasing the use of follow-up assessments and control groups.



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Sixty years of child-to-parent abuse research: What we know and where to go

Publication date: Available online 16 November 2017
Source:Aggression and Violent Behavior
Author(s): Melanie Simmons, Troy E. McEwan, Rosemary Purcell, James R.P. Ogloff




http://ift.tt/2zYdNAX

Editorial Board

Publication date: November 2017
Source:Aggression and Violent Behavior, Volume 37





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Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment

Summary

Background

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction.

Aim

To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability.

Patients/Methods

Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit.

Results

Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure.

Conclusions

The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability.

http://ift.tt/2zaeVOD

Comparative study of buffered 50% glycolic acid (pH 3.0) + 0.5% salicylic acid solution vs Jessner's solution in patients with acne vulgaris

Summary

Background

Superficial chemical peels are frequently used in acne vulgaris treatment. Although glycolic acid (GA) has been widely used in clinical practice, its pH ranges from 0.08-2.75 and thus should be neutralized after application to avoid burns.

Objective

To evaluate treatment efficacy and safety of chemical peeling using buffered 50% GA (pH 3.0) + 0.5% salicylic acid (SA) solution that does not need to be neutralized in the treatment of acne vulgaris compared to the conventional peeling using Jessner's solution.

Methods

We performed a prospective, randomized, evaluator-blind, split-face clinical trial. Twenty patients were randomized by assigning one side of each patient's face to receive a 50% GA (pH 3.0) + 0.5% SA peel (GA side) and the other side to receive the Jessner's solution (Jessner's solution side). All patients underwent 2 sessions of treatment spaced 2 weeks apart. Lesion count, acne severity, subjective efficacy assessment, and side effects were evaluated.

Results

The total lesion count was significantly reduced for the GA and Jessner's solution sides (P < .001). However, there was no significant difference in the total lesion count, acne severity, or subjective efficacy assessment between the 2 sides (P > .05). The GA side had fewer side effects than the Jessner's solution side.

Conclusion

The results of this study suggest that chemical peeling using the 50% GA (pH 3.0) + 0.5% SA solution can be as effective and convenient as the conventional peeling using Jessner's solution in the treatment of acne vulgaris and may show fewer adverse events than the conventional peeling.

http://ift.tt/2BcHyfq

Open-label study assessing the efficacy and tolerability of topical skincare and sun protection products following intense pulsed light treatment

Summary

Background

The visible signs of photodamage can be improved by intense pulsed light (IPL). Active ingredients in cosmeceuticals also have effects on skin quality and pigmentation, and can camouflage post-treatment side effects. Combination therapies utilizing different treatment modalities have been shown to optimize clinical outcomes for skin rejuvenation and patient satisfaction.

Aim

To evaluate the efficacy of a combination of IPL with a daily topical skincare and sunscreen regimen for the treatment of facial photodamage and for the improvement of IPL treatment tolerability.

Patients/Methods

Twenty female subjects with moderate-to-severe facial photodamage, with past history of IPL treatments, received one IPL treatment followed by the use of the topical skincare regimen for 8 weeks. An investigator assessed facial photodamage and hyperpigmentation at baseline, week 4, and week 8, and postprocedure erythema. Subject questionnaires were also administered at each visit.

Results

Compared to baseline, there was a significant improvement in photodamage and hyperpigmentation of bare facial skin. The application of the skincare regimen resulted in a significant reduction in post-IPL erythema, stinging/burning, and itching. The majority of patients were very satisfied or satisfied and felt the treatment regimen improved various aspects of skin quality and the tolerability of the procedure.

Conclusions

The addition of a topical skincare regimen after IPL treatment to the face resulted in significant improvements in facial photodamage and pigmentation, decreased post-treatment side effects, and increased tolerability.

http://ift.tt/2zaeVOD

Comparative study of buffered 50% glycolic acid (pH 3.0) + 0.5% salicylic acid solution vs Jessner's solution in patients with acne vulgaris

Summary

Background

Superficial chemical peels are frequently used in acne vulgaris treatment. Although glycolic acid (GA) has been widely used in clinical practice, its pH ranges from 0.08-2.75 and thus should be neutralized after application to avoid burns.

Objective

To evaluate treatment efficacy and safety of chemical peeling using buffered 50% GA (pH 3.0) + 0.5% salicylic acid (SA) solution that does not need to be neutralized in the treatment of acne vulgaris compared to the conventional peeling using Jessner's solution.

Methods

We performed a prospective, randomized, evaluator-blind, split-face clinical trial. Twenty patients were randomized by assigning one side of each patient's face to receive a 50% GA (pH 3.0) + 0.5% SA peel (GA side) and the other side to receive the Jessner's solution (Jessner's solution side). All patients underwent 2 sessions of treatment spaced 2 weeks apart. Lesion count, acne severity, subjective efficacy assessment, and side effects were evaluated.

Results

The total lesion count was significantly reduced for the GA and Jessner's solution sides (P < .001). However, there was no significant difference in the total lesion count, acne severity, or subjective efficacy assessment between the 2 sides (P > .05). The GA side had fewer side effects than the Jessner's solution side.

Conclusion

The results of this study suggest that chemical peeling using the 50% GA (pH 3.0) + 0.5% SA solution can be as effective and convenient as the conventional peeling using Jessner's solution in the treatment of acne vulgaris and may show fewer adverse events than the conventional peeling.

http://ift.tt/2BcHyfq

Revisiting in vitro release test for topical gel formulations: The effect of osmotic pressure explored for better bio-relevance

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Soorin Jeong, Seonghee Jeong, Sungyoon Chung, Aeri Kim
Release test methods for topical dosage forms including pharmacopeial tests require a large volume of release media, with limited application for high throughput screening. In the present study, we evaluated Transwell assay to miniaturize the release test method for optimization of thermoreversible topical gel formulations. We also explored the osmotic effect on the in vitro release rates from gel formulations to understand the bio-relevance of release media. An extreme vertices type of mixture design in Minitab®16 generated eleven formulations composed of poloxamer 407, poloxamer 188, and phosphate buffered saline (PBS). A quadratic equation adequately described the composition dependence of gelation temperature. Epidermal growth factor (EGF) and trypan blue were used as model drugs for proteins and small molecules, respectively. Cumulative release in PBS containing 30% sucrose exhibited linear correlation with respect to the gel compositions, while PBS without sucrose did not differentiate various compositions. Higher release rates in PBS than in sucrose media are attributable to the osmotic water flow from PBS into the donor phase, and subsequent increase in diffusivity. The time course of in vivo near-infrared fluorescence imaging of topical EGF gels on the wound sites were consistent with the in vitro release profiles measured with PBS as the release media. To the best of our knowledge, this is the first study to propose a release test method suitable for high throughput screening of topical formulations with emphasis on the osmotic pressure effect. Bio-relevant release media composition for a topical formulation would vary depending on its clinical application because the osmotic water flow through the normal skin would be negligible compared to compromised skin.

Graphical abstract

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Characterization of the IPEC-J2 MDR1 (iP-gp) cell line as a tool for identification of P-gp substrates

Publication date: 15 January 2018
Source:European Journal of Pharmaceutical Sciences, Volume 112
Author(s): Burak Ozgür, Lasse Saaby, Kristine Langthaler, Birger Brodin
Recently, we transfected the porcine intestinal cell line IPEC-J2, with human P-glycoprotein (P-gp, ABCB1). The resulting cell line, iP-gp, has a high expression of functional human P-gp in the apical membrane, and a low expression of nonhuman ATP-binding cassette (ABC) transporters. The aim of the present work was to investigate the usability of iP-gp cell line for determining transepithelial transport kinetics of the prototypical P-gp substrates digoxin and rhodamine 123.The cell line generated tight monolayers after 16days of culture, reflected by high transepithelial electrical resistance values (TEER>15,000Ω·cm²), immunocytochemistry and low fluxes of the paracellular flux marker [¹⁴C]-mannitol. Monolayer integrity was not affected the common solvents dimethyl sulfoxide (DMSO), methanol and ethanol in concentrations up to 2% (v/v).Transepithelial fluxes of [³H]-labeled digoxin and rhodamine 123 were measured at varying donor concentrations, and kinetic parameters were estimated. Km and Vmax of P-gp mediated basolateral-to-apical (B-A) flux of rhodamine 123 were estimated to 332±124μM and 111±16pmol·cm⁻²·min⁻¹ (n=3, total N=6), respectively. Vmax and Km of digoxin B-A flux could not be estimated due to the low aqueous solubility of digoxin. The half maximal inhibitory concentrations (IC50) of the selective P-gp inhibitor, zosuquidar (LY-335979), were estimated to 0.05±0.01μM (n=3, total N=6) and 0.04±0.01μM (n=3, total N=6) in transport experiments with digoxin and rhodamine 123 as substrates, respectively. Bidirectional fluxes of digoxin and rhodamine 123 were measured in transfected Madin Darby canine kidney cells (MDCK II MDR1) and compared with the fluxes obtained with the iP-gp cell monolayers. Efflux ratios were highest in the iP-gp cells, due to a tighter paracellular pathway. In conclusion, both digoxin and rhodamine 123 could be used to obtain IC50 values of inhibition, Ki values were only possible to obtain using rhodamine 123. The observed tightness, robustness towards solvents and the high efflux ratios confirmed that the iP-gp cell line may serve as a useful screening tool for investigations of substrate-P-gp interactions and modulation of P-gp function.



http://ift.tt/2zabKGH

Speckled acral hypopigmentation in an adolescent

Abstract

We report a case of speckled acral hypopigmentation in a 12-year-old girl. She presented with asymptomatic hypopigmented macules on the hands and feet. This rare entity is a proposed variant of reticulate acropigmentation and of unknown etiology.

http://ift.tt/2jKVGZ8

Urticarial vasculitis after meningococcal serogroup B vaccine in a 6-year-old girl

Abstract

The first vaccine that shows significant potential in providing broad coverage against serogroup B meningococcal disease has recently been approved. Because of its newness, potential adverse events need to be reported. Here we report a case of urticarial vasculitis, a rare disease in children, in probable relationship with the novel vaccine.

http://ift.tt/2hRrBXa

Erythromelanosis follicularis faciei et colli: A clinicoepidemiologic study

Abstract

We describe 25 cases of erythromelanosis follicularis faciei et colli from India. The male:female ratio was 5.25:1 and the average age of onset was 12.3 years. The cheeks, preauricular area, and submandibular region were the sites most commonly affected. Keratosis pilaris was seen in 22 (88%) of the patients.

http://ift.tt/2jKURzt

Comparison of prostate distortion by inflatable and rigid endorectal MRI coils in permanent prostate brachytherapy imaging

Publication date: Available online 21 November 2017
Source:Brachytherapy
Author(s): Geoffrey V. Martin, Rajat J. Kudchadker, Teresa L. Bruno, Steven J. Frank, Jihong Wang
PurposeTo study the deformation of the prostate by a rigid reusable endorectal coil and a balloon-type endorectal coil (BTC) during MRI of the prostate in brachytherapy imaging.Methods and MaterialsThe prostate gland was contoured on 157 MRI scans from 52 prostate cancer patients undergoing brachytherapy. The curvature of the posterior prostate surface deformation was computed as a measure of prostate distortion and compared between scans with a BTC, rigid endorectal coil (REC), or no endorectal coil. For the nine patients who had MRIs with all three endorectal scenarios, a mean prostate deformation vector was also calculated between scenarios using deformable image registration. These measures of prostate distortion were compared with the prostate anterior-to-posterior to left-to-right ratio (AP/LR) on the largest prostate axial slice.ResultsSignificant differences in prostate curvature were found between scans without an endorectal coil versus a REC versus a BTC (p < 0.001). The mean prostate deformation was 3.9 mm due to the BTC and 2.0 mm for the REC (p = 0.012). The mean AP/LR ratio was 0.62 with a BTC versus 0.76 without a coil or 0.73 with a REC (p < 0.001), but no difference existed between scans with a REC versus no coil (p = 0.7). The AP/LR ratio showed moderate correlation with prostate curvature (r = 0.48), and with mean prostate deformation (r = −0.64 to 0.68).ConclusionsThe REC caused minimal deformation of the prostate compared with a BTC with adequate MR image quality, and calculation of the cross-sectional AP/LR ratio on the largest axial prostate slice can serve as a simple measure of prostate distortion.



http://ift.tt/2zYetGc

Status and progress of hepatitis B control through vaccination in the South-East Asia Region, 1992–2015

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Lana Childs, Sigrun Roesel, Rania A. Tohme
In 2016, the Immunization Technical Advisory Group of the South-East Asia Region (SEAR) endorsed a regional goal to achieve ≤1% prevalence of hepatitis B surface antigen (HBsAg) among 5-year-old children by 2020. Chronic hepatitis B virus (HBV) infection is largely preventable with a birth dose of hepatitis B vaccine (HepB-BD) followed by two to three additional doses. We reviewed the progress towards hepatitis B control through vaccination in SEAR during 1992–2015. We summarized hepatitis B vaccination data and reviewed the literature to determine the prevalence of chronic HBV infection pre- and post-vaccine introduction. We used a mathematical model to determine post-vaccine prevalence of HBsAg among 5 year olds in countries lacking national serosurvey data and estimated the impact of vaccination on disease burden. Regional coverage with three doses of hepatitis B vaccine (HepB3) increased from 56% in 2011 to 87% in 2015. By 2016, 7 of 11 countries had introduced universal HepB-BD. Regional HepB-BD coverage increased from 9% in 2011 to 34% in 2015. In 2015, estimated HBsAg among 5 year olds was 1.1% with variability among countries. Myanmar (3.8%), Timor-Leste (2.7%), Indonesia (1.8%), and India (1%) had the highest prevalence of HBsAg. During 1992–2015, vaccination prevented approximately 16 million chronic HBV infections and 2.6 million related deaths. In 2015, around 197,640 perinatal HBV infections occurred in SEAR with majority occurring in India (62%), Bangladesh (24%), and Myanmar (8%). Myanmar had the highest rate of perinatal chronic HBV infections at 16 per 1000 live births. Despite significant progress in the control of HBV, SEAR needs to secure political commitment for elimination and consider additional strategies, such as promoting health facility births, universal birth dose administration, developing strong coordination between health sectors, and using alternative vaccine delivery methods, to improve HepB-BD coverage and subsequently achieve HBV control and elimination.



http://ift.tt/2zZDcKv

The effect of cool water pack preparation on vaccine vial temperatures in refrigerators

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Geneva Goldwood, Steven Diesburg
Cool water packs are a useful alternative to ice packs for preventing unintentional freezing of vaccines during outreach in some situations. Current guidelines recommend the use of a separate refrigerator for cooling water packs from ambient temperatures to prevent possible heat degradation of adjacent vaccine vials. To investigate whether this additional equipment is necessary, we measured the temperatures that vaccine vials were exposed to when warm water packs were placed next to vials in a refrigerator. We then calculated the effect of repeated vial exposure to those temperatures on vaccine vial monitor status to estimate the impact to the vaccine. Vials were tested in a variety of configurations, varying the number and locations of vials and water packs in the refrigerator. The calculated average percentage life lost during a month of repeated warming ranged from 20.0% to 30.3% for a category 2 (least stable) vaccine vial monitor and from 3.8% to 6.0% for a category 7 (moderate stability) vaccine vial monitor, compared to 17.0% for category 2 vaccine vial monitors and 3.1% for category 7 vaccine vial monitors at a constant 5 °C. The number of vials, number of water packs, and locations of each impacted vial warming and therefore percentage life lost, but the vaccine vial monitor category had a higher impact on the average percentage life lost than any of the other parameters. The results suggest that damage to vaccines from repeated warming over the course of a month is not certain and that cooling water packs in a refrigerator where vaccines are being stored may be a useful practice if safe procedures are established.



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Association of Corynebacterium pseudotuberculosis recombinant proteins rCP09720 or rCP01850 with rPLD as immunogens in caseous lymphadenitis immunoprophylaxis

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Mara Thais de Oliveira Silva, Francisco Silvestre Brilhante Bezerra, Rodrigo Barros de Pinho, Karine Rech Begnini, Fabiana Kommling Seixas, Tiago Collares, Ricardo Dias Portela, Vasco Azevedo, Odir Dellagostin, Sibele Borsuk
Caseous lymphadenitis (CLA) is a chronic disease responsible for significant economic losses in sheep and goat breeding worldwide. The treatment for this disease is not effective, and an intense vaccination schedule would be the best control strategy. In this study, we evaluated the associations of rCP09720 or rCP01850 proteins from Corynebacterium pseudotuberculosis with recombinant exotoxin phospholipase D (rPLD) as subunit vaccines in mice. Four experimental groups (10 animals each) were immunized with a sterile 0.9% saline solution (G1), rPLD (G2), rPLD + rCP09720 (G3), and rPLD + rCP01850 (G4). The mice received two doses of each vaccine at a 21-day interval and were challenged 21 days after the last immunization. The animals were evaluated daily for 40 days after the challenge, and mortality rate was recorded. The total IgG production level increased significantly in the experimental groups on day 42 after the first vaccination. Similarly, higher levels of specific IgG2a were observed in experimental groups G2, G3, and G4 compared to the IgG1 levels on day 42. G4 showed a significant (p < .05) humoral response against both antigens of the antigenic formulations. The cellular immune response induced by immunization was characterized by a significant (p < .05) production of interferon-γ compared to that in the control, while the concentrations of interleukin (IL)-4 and IL-12 were not significant in any group. A significant increase of tumor necrosis factor was observed only in G4. The survival rates after the challenge were 30% (rPLD), 40% (rPLD + rCP09720), and 50% (rPLD + rCP01850). Thus, the association of rCP01850 with rPLD resulted in the best protection against the challenge with C. pseudotuberculosis and induced a more intense type 1 T-helper cell immune response.



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A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Shirin Kalimuddin, Limin Wijaya, Yvonne F.Z. Chan, Abigail W.L. Wong, Helen M.L. Oh, Lin-Fa Wang, Julaihabee A. Kassim, Jing Zhao, Zhongkai Shi, Jenny G. Low
BackgroundHuman Rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. The PIKA Rabies vaccine adjuvant is a TLR3 agonist and has been shown to be safe and immunogenic in clinical phase I studies.MethodsWe conducted a phase II, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA rabies vaccine under an accelerated regimen. 126 subjects were randomized into two groups: control vaccine classic regimen ("control-classic") and PIKA vaccine accelerated regimen ("PIKA-accelerated"). Subjects were followed up for safety and rabies virus neutralizing antibodies (RVNA).ResultsBoth the control and PIKA vaccines were generally well tolerated. 57.6% of subjects in the PIKA vaccine group, compared with 43.8% of subjects in the control-classic group, achieved the target RVNA titer of ≥0.5 IU/mL by Day 7. All subjects achieved the target RVNA titer by Day 14. The RVNA geometric mean titer at Day 7 was 0.60 IU/ml in the PIKA vaccine group and 0.39 IU/ml in the control-classic group. At Day 14, the RVNA geometric mean titer was 18.25 IU/ml in the PIKA-accelerated group and 19.24 IU/ml in the control-classic group. The median time taken to reach the target RVNA titer level of ≥0.5 IU/mL was 7.0 days (95% CI: 7.0–42.0 days) in the PIKA-accelerated group and 14.0 days (95% CI: 7.0–42.0 days) in the control-classic group.ConclusionThe accelerated regimen using the investigational PIKA Rabies vaccine was well-tolerated and demonstrated non-inferior immunogenicity compared to the classic regimen using the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov (NCT02956421).



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Development of a broadly protective modified-live virus vaccine candidate against porcine reproductive and respiratory syndrome virus

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Haiyan Sun, Aspen Workman, Fernando A. Osorio, David Steffen, Hiep L.X. Vu
Modified-live virus (MLV) vaccines are widely used to protect pigs against porcine reproductive and respiratory syndrome virus (PRRSV). However, current MLV vaccines do not confer adequate levels of heterologous protection, presumably due to the substantial genetic diversity of PRRSV isolates circulating in the field. To overcome this genetic variation challenge, we recently generated a synthetic PRRSV strain containing a consensus genomic sequence of PRRSV-2. We demonstrated that our synthetic PRRSV strain confers unprecedented levels of heterologous protection. However, the synthetic PRRSV strain at passage 1 (hereafter designated CON-P1) is highly virulent and therefore, is not suitable to be used as a vaccine in pigs. In the present study, we attenuated CON-P1 by continuously passaging the virus in MARC-145 cells, a non-natural host cell line. Using a young pig model, we demonstrated that the synthetic virus at passages 90 and 122 (designated as CON-P90 and CON-P122, respectively) were fully attenuated, as evidenced by the significantly reduced viral loads in serum and tissues and the absence of lung lesion in the infected pigs. Most importantly, CON-P90 confers similar levels of heterologous protection as its parental strain CON-P1. Taken together, the results indicate that CON-P90 is an excellent candidate for the formulation of next generation of PRRSV MLV vaccines with improved levels of heterologous protection.



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Factors influencing on influenza vaccination and its trends of coverage in patients with diabetes in Korea: A population-based cross-sectional study

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Hyun-Young Shin, Jae Ho Chung, Hee-Jin Hwang, Tae Ho Kim
BackgroundInfluenza infection is a contagious disease and annual influenza vaccination is recommended to the patients with chronic diseases. Although diabetes is an indication for influenza vaccination, the global rate of influenza vaccination is insufficient. Therefore, our study aimed to elucidate influenza vaccination statuses among patients with diabetes and the related factors in Korea.MethodsA total of 32,268 subjects (4,540 with and 27,728 without diabetes) from the Korea National Health and Nutrition Examination Survey III–VI (2005–2015) were included. Socioeconomic factors and health-related factors were analyses for the relation of influenza vaccination by Student's t-test, the chi-squared test and a multivariate logistic regression analysis.ResultsThe influenza vaccination coverage rates were 50.0% in the diabetes mellitus (DM) group and 38.2% in the non-DM group. The trends in influenza vaccination rates during KNHANES III–VI were not significant in each group (P trend  =  0.24 in the DM group, 0.30 in the non-DM group). Socioeconomic (older age, female sex, higher family income, and medical aid insurance) and health-related factors (lack of risky alcohol consumption, obesity, and recent health check-ups) were associated with influenza vaccination among patients with DM.ConclusionsThe rate of influenza vaccination among patients with diabetes is insufficient in Korea. More efforts are needed to increase the influenza vaccination rates among vulnerable at-risk populations.



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Workshop report: Nucleic acid delivery devices for HIV vaccines: Workshop proceedings, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA, May 21, 2015

Publication date: Available online 22 November 2017
Source:Vaccine
Author(s): Bruce G. Weniger, Ian E. Anglin, Tina Tong, Michael Pensiero, Jeffrey K. Pullen
On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities. Meeting participants presented the results and experience of representative clinical trials of NA vaccines using a variety of alternative delivery devices, as well as a broader group of methods studied in animal models and at bench top, to improve upon the performance and/or avoid the drawbacks of conventional needle-syringe (N–S) delivery. The subjects described and discussed included (1) delivery targeted into oral, cutaneous/intradermal, nasal, upper and lower respiratory, and intramuscular tissues; (2) devices and techniques for jet injection, solid, hollow, and dissolving microneedles, patches for topical passive diffusion or iontophoresis, electroporation, thermal microporation, nasal sprayers, aerosol upper-respiratory and pulmonary inhalation, stratum-corneum ablation by ultrasound, chemicals, and mechanical abrasion, and kinetic/ballistic delivery; (3) antigens, adjuvants, and carriers such as DNA, messenger RNA, synthesized plasmids, chemokines, wet and dry aerosols, and pollen-grain and microparticle vectors; and (4) the clinical experience and humoral, cellular, and cytokine immune responses observed for many of these target tissues, technologies, constructs, and carriers. This report summarizes the presentations and discussions from the workshop (http://ift.tt/2hJjQPp), which was webcast live in its entirety and archived online (http://ift.tt/1HPlZxC).



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Development of an intelligent surgical training system for Thoracentesis

Publication date: Available online 21 November 2017
Source:Artificial Intelligence in Medicine
Author(s): Hirenkumar Nakawala, Giancarlo Ferrigno, Elena De Momi
Surgical training improves patient care, helps to reduce surgical risks, increases surgeon's confidence, and thus enhances overall patient safety. Current surgical training systems are more focused on developing technical skills, e.g. dexterity, of the surgeons while lacking the aspects of context-awareness and intra-operative real-time guidance. Context-aware intelligent training systems interpret the current surgical situation and help surgeons to train on surgical tasks. As a prototypical scenario, we chose Thoracentesis procedure in this work. We designed the context-aware software framework using the surgical process model encompassing ontology and production rules, based on the procedure descriptions obtained through textbooks and interviews, and ontology-based and marker-based object recognition, where the system tracked and recognised surgical instruments and materials in surgeon's hands and recognised surgical instruments on the surgical stand. The ontology was validated using annotated surgical videos, where the system identified "Anaesthesia" and "Aspiration" phase with 100% relative frequency and "Penetration" phase with 65% relative frequency. The system tracked surgical swab and 50mL syringe with approximately 88.23% and 100% accuracy in surgeon's hands and recognised surgical instruments with approximately 90% accuracy on the surgical stand. Surgical workflow training with the proposed system showed equivalent results as the traditional mentor-based training regime, thus this work is a step forward a new tool for context awareness and decision-making during surgical training.



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An EEG-based functional connectivity measure for automatic detection of alcohol use disorder

Publication date: Available online 21 November 2017
Source:Artificial Intelligence in Medicine
Author(s): Wajid Mumtaz, Mohamad Naufal b Mohamad Saad, Nidal Kamel, Syed Saad Azhar Ali, Aamir Saeed Malik
BackgroundThe abnormal alcohol consumption could cause toxicity and could alter the human brain's structure and function, termed as alcohol used disorder (AUD). Unfortunately, the conventional screening methods for AUD patients are subjective and manual. Hence, to perform automatic screening of AUD patients, objective methods are needed. The electroencephalographic (EEG) data have been utilized to study the differences of brain signals between alcoholics and healthy controls that could further developed as an automatic screening tool for alcoholics.MethodIn this work, resting-state EEG-derived features were utilized as input data to the proposed feature selection and classification method. The aim was to perform automatic classification of AUD patients and healthy controls. The validation of the proposed method involved real-EEG data acquired from 30 AUD patients and 30 age-matched healthy controls. The resting-state EEG-derived features such as synchronization likelihood (SL) were computed involving 19 scalp locations resulted into 513 features. Furthermore, the features were rank-ordered to select the most discriminant features involving a rank-based feature selection method according to a criterion, i.e., receiver operating characteristics (ROC). Consequently, a reduced set of most discriminant features was identified and utilized further during classification of AUD patients and healthy controls. In this study, three different classification models such as Support Vector Machine (SVM), Naïve Bayesian (NB), and Logistic Regression (LR) were used.ResultsThe study resulted into SVM classification accuracy=98%, sensitivity=99.9%, specificity=95%, and f-measure=0.97; LR classification accuracy=91.7%, sensitivity=86.66%, specificity=96.6%, and f-measure=0.90; NB classification accuracy=93.6%, sensitivity=100%, specificity=87.9%, and f-measure=0.95.ConclusionThe SL features could be utilized as objective markers to screen the AUD patients and healthy controls.



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Sensory Constraints on Perceptual Simulation During Sentence Reading.

Author: Gao, Xuefei; Jiang, Ting

DOI: 10.1037/xhp0000475

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2AlgYDP

Emergent Perception of Gaze Direction Across Time.

Author: Mihalache, Diana; Gaeddert, Laurel A.; Sweeny, Timothy D.

DOI: 10.1037/xhp0000479

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zWesD5

How Does "Not Left" Become "Right"? Electrophysiological Evidence for a Dynamic Conflict-Bound Negation Processing Account.

Author: Dudschig, Carolin; Kaup, Barbara

DOI: 10.1037/xhp0000481

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2Alt3ca

Automatic Imitation of Multiple Agents: Simultaneous or Random Representation?.

Author: Cracco, Emiel; Brass, Marcel

DOI: 10.1037/xhp0000489

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zVeT0F

Cognitive Control Over Prospective Task-set Interference.

Author: Whitehead, Peter S.; Egner, Tobias

DOI: 10.1037/xhp0000493

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2AmLLA3

Alertness and Cognitive Control: Testing the Early Onset Hypothesis.

Author: Schneider, Darryl W.

DOI: 10.1037/xhp0000497

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zWemeH

Task Demands Determine Comparison Strategy in Whole Probe Change Detection.

Author: Udale, Rob; Farrell, Simon; Kent, Chris

DOI: 10.1037/xhp0000490

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2Ak6q7G

Disentangling Inhibition-Based and Retrieval-Based Aftereffects of Distractors: Cognitive Versus Motor Processes.

Author: Singh, Tarini; Laub, Ruth; Burgard, Jan Pablo; Frings, Christian

DOI: 10.1037/xhp0000496

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zVy7mF

Attentional Effect on Contrast Appearance: From Enhancement to Attenuation.

Author: Zhou, Liu-Fang; Buetti, Simona; Lu, Shena; Cai, Yong-Chun

DOI: 10.1037/xhp0000499

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

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Auditory Over Visual Advantage of Sensorimotor Synchronization in 6- to 7-Year-Old Children but Not in 12- to 15-Year-Old Children and Adults.

Author: Mu, Yan; Huang, Yingyu; Ji, Chao; Gu, Li; Wu, Xiang

DOI: 10.1037/xhp0000500

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zWedYH

Time-Based Expectancy in Temporally Structured Task Switching.

Author: Aufschnaiter, Stefanie; Kiesel, Andrea; Dreisbach, Gesine; Wenke, Dorit; Thomaschke, Roland

DOI: 10.1037/xhp0000494

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2AnezIP

The Contribution of Perceptual Factors and Training on Varying Audiovisual Integration Capacity.

Author: Wilbiks, Jonathan M. P.; Dyson, Benjamin J.

DOI: 10.1037/xhp0000503

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zVxWaZ

Distinct Kinematic Markers of Demonstration and Joint Action Coordination? Evidence From Virtual Xylophone Playing.

Author: McEllin, Luke; Knoblich, Gunther; Sebanz, Natalie

DOI: 10.1037/xhp0000505

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2Amd5y7

You 'Have' to Hear This: Using Tone of Voice to Motivate Others.

Author: Weinstein, Netta; Zougkou, Konstantina; Paulmann, Silke

DOI: 10.1037/xhp0000502

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zX75LP

The Bandwidth of VWM Consolidation Varies With the Stimulus Feature: Evidence From Event-Related Potentials.

Author: Hao, Renning; Becker, Mark W.; Ye, Chaoxiong; Liu, Qiang; Liu, Taosheng

DOI: 10.1037/xhp0000488

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2Amd5hB

Seeing It Both Ways: Using a Double-Cuing Task to Investigate the Role of Spatial Cuing in Level-1 Visual Perspective-Taking.

Author: Michael, John; Wolf, Thomas; Letesson, Clement; Butterfill, Stephen; Skewes, Joshua; Hohwy, Jakob

DOI: 10.1037/xhp0000486

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2zX6WIh

Optimal Task-Sets Override Attentional Capture by Rare Cues.

Author: Schonhammer, Josef G.; Kerzel, Dirk

DOI: 10.1037/xhp0000483

Publication Date: POST AUTHOR CORRECTIONS, 20 November 2017

http://ift.tt/2Am9bFM

Propofol attenuates myocardial ischemia reperfusion injury partly through inhibition of resident cardiac mast cell activation

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Xiaoqian Yu, Xiaotong Sun, Meng Zhao, Yonghao Hou, Jingxin Li, Jingui Yu, Yuedong Hou
Cardiac mast cell activation is involved in the process of myocardial ischemia reperfusion (I/R) injury and exacerbates myocardial infarction. Propofol, an anesthetic with antioxidant property, can reduce myocardial infarct size in I/R injury. The present study was designed to investigate whether propofol can attenuate myocardial I/R injury by inhibiting resident cardiac mast cell activation by a Langendorff model. Thirty rats were randomly assigned to 5 groups (n=6 per group): control group and four test groups (I/R, I/R+compound 48/80, I/R+propofol, I/R+compound 48/80+propofol). Cultured RBL-2H3 cells were pretreated with propofol and subjected to mast cell degranulator compound48/80 (C48/80).Microscopically, degradation of myofibrillar and degranulation of mast cells were studied using hematoxylin-eosin toluidine blue staining techniques. After the effluent was assayed for tryptase, LDH, CK-MB and cTnI, myocardial tissue was evaluated for cytokine levels and infarct area. Heart subjected to I/R showed significantly increased expression of cytokines (TNF-α and IL-6), LDH, CK-MB and cTnI. In addition, the I/R-induced heart also showed greater histopathological injury and a larger infarction zone, following increased mast cell degranulation with concomitant rise in tryptase. Mast cell degranulation by C48/80 further aggravated I/R injury. However, all of these effects were suppressed by propofol pretreatment, which also abrogated C48/80-mediated exacerbation of I/R injury. Also, propofol attenuated the C48/80-evoked tryptase and histamine release in RBL-2H3 cells. It is concluded that pretreatment of propofol confers protection against I/R injury partly by inhibiting resident cardiac mast cell activation.



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Esculentoside A specifically binds to ribosomal protein S3a and impairs LPS-induced signaling in macrophages

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Ying-Hua Li, Jing Wang, Ying Liu, Lie Qiu, Jian-Zhong Li, Hong-Gang Hu, Zhen-Lin Hu, Wen Zhang, Bin Lu, Jun-Ping Zhang
Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, is reported as a potent suppressor of pro-inflammatory functions of macrophages. However, little is known about the target proteins of EsA for its anti-inflammatory activity. In the present study, to identify the intracellular target for EsA, affinity resins bearing immobilized EsA were used to capture binding proteins of EsA from RAW264.7 cell lysates. Mass spectrography and Western blot analysis of captured proteins indicated that ribosomal protein S3a preferentially bound to EsA affinity resin. Competition experiment further demonstrated that free EsA can disturb the specific interaction between recombinant RPS3a and affinity resin. Surface Plasmon Resonance analysis confirmed that EsA directly bound to RPS3a. Lentivirus-mediated RNAi RPS3a resulted in suppression of TNF-α and IL-6 production and impediment of signal transduction in LPS-stimulated RAW264.7 cells, indicating that RPS3a is required for LPS-triggered signaling during induction of pro-inflammatory cytokines. In addition, EsA inhibited the expression of inflammatory factors more strongly in the case of RPS3a interference. These results suggest that EsA exerts its anti-inflammatory activity by targeting RPS3a and impairing its signaling function. These new findings not only extended our understanding on the intracellular mechanisms of EsA, but also indicated RPS3a as an essential component for LPS-mediated pro-inflammatory signaling, thus implying RPS3a as a novel therapeutic target for anti-inflammatory therapy.



http://ift.tt/2zXnFv1

Protective effect of catechin on humoral and cell mediated immunity in rat model

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Aditya Ganeshpurkar, Ajay K. Saluja
The present study was focused on examining the effect of catechin on the cellular and humoral immunity in rat model. Immunomodulatory effect of catechin was determined by delayed-type hypersensitivity (DTH) response, carbon clearance assay, leucocyte mobilization test and cyclophosphamide-induced myelosuppression and hemagglutinating antibody (HA) titer assay. Catechin in experimental dose (25, 50 and 100mg/kg, p.o.) elevated a significant increase in antibody titer in the hemagglutination test with increased levels of immunoglobulin. There was an enhancement in the delayed-type hypersensitivity reaction produced by sheep red blood cells. There was also restoration in the functioning of leucocytes in cyclophosphamide-treated rats with an increased clearance of carbon particles. The results of the present study signify that catechin possesses sufficient potential for modulating immune activity by cellular and humoral mechanisms.



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Family Caregivers Need Our Help-And Now It's the Law.

Author: Kennedy, Maureen Shawn MA, RN, FAAN

Page: 7

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Social Determinants of Health: The Role of Nursing.

Author: Olshansky, Ellen F. PhD, RN, WHNP-BC, FAAN

Page: 11

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Nurses' Use of On-the-Job Workarounds.

Author: H., Wendie via ajnoffthecharts.com

Page: 13

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Nurses' Use of On-the-Job Workarounds.

Author: W., Amy via Facebook

Page: 13

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Palliative Care for Advanced Dementia.

Author: M., Nomi via ajnoffthecharts.com

Page: 13

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Staying Professional on Social Media.

Author: Griffith, Linda RN-ONC

Page: 13

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The Need to Improve Student Writing.

Author: Lanier, Regina MAEd, BSN, RN

Page: 13

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Women in Rural America Are Losing Hospital-Based Obstetric Services.

Author: Sofer, Dalia

Page: 14-15

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Repeal of the ACA Could Lead to RN Job Cuts.

Author: Potera, Carol

Page: 15

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NewsCAP: The Affordable Care Act (ACA) has increased health care access for adults with mental illness.

Author:

Page: 15

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Study Finds Overall Prostate Cancer Mortality Decreases with PSA Screening.

Author: Zolot, Joan

Page: 16

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NewsCAP: Some addicts abuse opioids prescribed for pets.

Author:

Page: 16

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