Capability of Secale montanum trusted for phytoremediation of lead and cadmium in soils amended with nano-silica and municipal solid waste compost

Abstract

The purpose of this study is to evaluate the capability of Secale montanum trusted for phytoremediation of contaminated soils with lead (Pb) and cadmium (Cd). To conduct this study, soil samples were taken from contaminated rangelands soils around National Lead & Zinc Factory, Zanjan, Iran. In this study, which was performed in a greenhouse, after preparing the pot and treating soils with nano-silica (NS) and municipal solid waste compost (MSWC) amendments, 20 Secale seeds were cultured in each pot. The translocation factor (TF), the bio-concentration factor (BCF), and remediation factor (RF) were calculated to determine the phytoremediation capability of Secale. Six months after establishment, plant organs were harvested and Pb and Cd concentrations were measured in shoot and roots of Secale. For statistical analysis and to compare the obtained means, ANOVA and Tukey's tests were performed, respectively. The pot experiment results showed that Pb uptake and accumulation by roots of S. montanum were highest in pots amended with NS500. In comparison, Pb concentration in shoots of Secale was highest in pots amended with MSWC 2%. In general, it seems that NS500 and MSWC 2% help phytoremediation capability of Secale in the Pb-contaminated soils.

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Knowledge, behavior and attitudes of dental practitioners towards photodynamic therapy use in dental practice

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Fahim Vohra, Ishfaq A Bukhari, Saeed A Sheikh, Refal Albaijan, Abdul Hakeem Qureshi, Zaeem Arif, Zohaib Akram
BackgroundThe aim of the present study was to assess knowledge, behavior and attitudes of dental practitioners (DPs) towards photodynamic therapy (PDT) in dental clinical practice.MethodsA cross-sectional study was performed and a 13-item survey questionnaire was given to DPs practicing in 13 different teaching hospitals in Karachi, Pakistan. Questions were aimed at exploring the knowledge of DPs regarding PDT and their attitude towards PDT and perceptions that may influence clinical practices. Chi-square and spearman coefficient were conducted to compare subgroups and correlate factors with the knowledge score of DPs.ResultsA total of 509 questionnaires were completed (response rate=82%). Median age of participants was 34 years and 70% were females. Most DPs demonstrated good knowledge related to PDT, and nearly 77%, 69% and 62% were aware of the mechanism of action and the role of photosensitizers in PDT respectively. It was reported that 74% of the respondents expressed that they are comfortable to know about PDT in detail for their clinical practice. A cumulative 54% disagreed that discussing the option for PDT with their patients was peripheral to their role as clinicians. A striking 82% would like to attend seminars and workshops on PDT. Significant difference was found among senior lecturers and assistant professors for the knowledge items (p <0.05). No statistical correlation was found between the knowledge items score of DPs and their behavior (r=0.18; p=0.762), attitude (r=0.04; p=0.594) and self-rated knowledge (r=0.42; p=0.854).ConclusionDental practitioners showed adequate knowledge regarding PDT and its use in dentistry. However, expertise with regards to handling and training is warranted so that DPs could use PDT in their dental practice.



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Combination Vismodegib and Photodynamic Therapy for Multiple Basal Cell Carcinomas

Publication date: Available online 1 November 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Jason M. Rizzo, Robert J. Segal, Nathalie C. Zeitouni
BackgroundOral vismodegib therapy and photodynamic therapy (PDT) are non-invasive treatments for basal cell carcinoma (BCC) with overlapping utility in widespread BCCs and patients who are poor surgical candidates. There is no published study to date investigating the combination use of PDT with vismodegib to optimize individual response rates.ObjectiveTo evaluate the combination of red light PDT and vismodegib therapy in patients with multiple nodular BCCs. The primary objective was to determine the safety of this combination therapy. Secondary outcomes included evaluation of the overall response rate, treatment-related pain, and cosmesis.MethodsAn open label pilot study of immunocompetent patients with multiple BCCs treated with 3 months of continuous vismodegib therapy (150 mg daily) and 3 consecutive ALA PDT sessions. Outcomes were assessed following each PDT session and 30 days post-treatment.ResultsFour patients with multiple nodular BCC (median=5) were enrolled in the trial between January and August of 2016. Three patients completed the full intervention phase trial and a total of 19 lesions were treated. One patient completed 2 months of vismodegib and 2 PDT sessions. One PDT session was sufficient for small lesions, whereas larger lesions required all 3 sessions. The fifteen evaluable lesions at the end of the 3 PDT sessions showed complete responses. At 30-day follow-up, one of the treated lesions was noted to have clinical evidence of disease. Overall response rate showed 90% complete response and 10% partial response for the study. Combination therapy was well tolerated and yielded a similar or superior side effect profile to that of individual therapies with excellent cosmesis.ConclusionCombination PDT-vismodegib is a potential safe & effective therapy for the treatment of multiple BCCs that may enhance efficacy of individual therapies.



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Short-term effects of adjunctive antimicrobial photodynamic therapy in obese patients with chronic periodontitis: A randomized controlled clinical trial

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Fahim Vohra, Zohaib Akram, Ishfaq A. Bukhari, Saeed A. Sheikh, Fawad Javed
BackgroundThe aim of the present study was to assess the effect of antimicrobial photodynamic therapy (aPDT) as an adjunct to scaling and root planing (SRP) on clinical periodontal and immunological parameters in obese patients with chronic periodontitis (CP).MethodsFifty-three obese with CP patients were divided into 2 groups receiving aPDT with SRP and SRP only respectively. Full-mouth plaque index (PI), bleeding on probing (BOP), pocket depth (PD) and clinical attachment level (CAL) were assessed at baseline, 6 and 12 weeks post-therapy. Gingival crevicular fluid (GCF) levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were evaluated using enzyme linked immunosorbent assay at baseline and 12 weeks.ResultsThere was a significant improvement in all periodontal variables in both study groups at 6 weeks and 12 weeks with respect to the baseline visit (p<0.001). Significant reduction in PD of 4–6mm and ≥7mm was observed for aPDT group as compared to SRP group (p<0.01) at both 6 weeks and 12 weeks of follow-up. At 6 weeks, a significant (p<0.001) gain in CAL was observed in both groups, which remained stable at 12 weeks. IL-6 and TNF-α levels decreased significantly (p=0.001) at 12 weeks after therapy in both the groups. Inter-group comparison showed significant difference for TNF-α (p=0.024) and IL-6 (p=0.044) levels for aPDT group at 12 week follow-up.ConclusionWithin the limits of this clinical trial, adjunctive aPDT showed improvement in clinical and immunological parameters in obese patients with CP. Antimicrobial PDT showed additional benefit in moderate and deep periodontal pockets in obese patients with CP.



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A new screening method to detect proximal dental caries using fluorescence imaging

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Eun-Soo Kim, Eun-Song Lee, Si-Mook Kang, Eun-Ha Jung, Elbert de Josselin de Jong, Hoi-In Jung, Baek-Il Kim
ObjectivesThis study aimed to assess the screening performance of the quantitative light-induced fluorescence (QLF) technology to detect proximal caries using both fluorescence loss and red fluorescence in a clinical situation. Moreover, a new simplified QLF score for the proximal caries (QS-Proximal) is proposed and its validity for detecting proximal caries was evaluated as well.MethodsThis clinical study included 280 proximal surfaces, which were assessed by visual-tactile and radiographic examinations and scored by each scoring system according to lesion severity. The occlusal QLF images were analysed in two different ways: (1) a quantitative analysis producing fluorescence loss (ΔF) and red fluorescence (ΔR) parameters; and (2) a new QLF scoring index. For both quantitative parameters and QS-Proximal, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) were calculated as a function of the radiographic scoring index at the enamel and dentine caries levels.ResultsBoth ΔF and ΔR showed excellent AUROC values at the dentine caries level (ΔF=0.860, ΔR=0.902) whereas a relatively lower value was observed at the enamel caries level (ΔF=0.655, ΔR=0.686). The QS-Proximal also showed excellent AUROC ranged from 0.826 to 0.864 for detecting proximal caries at the dentine level.ConclusionThe QS-Proximal, which represents fluorescence changes, showed excellent performance in detecting proximal caries using the radiographic score as the gold standard.



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Secretion of the angiogenic factor VEGF after photodynamic therapy with ALA under hypoxia-like conditions in colon cancer cells

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Aleksandra Kawczyk-Krupka, Beata Kwiatek, Zenon P. Czuba, Anna Mertas, Wojciech Latos, Thomas Verwanger, Barbara Krammer, Aleksander Sieroń
BackgroundPhotodynamic therapy (PDT), eliminates not only the tumor, but also modulates signaling factors release, e.g. vascular endothelial growth factor (VEGF), which plays a crucial role in cancer progression. Assessment of the VEGF-secreting activity of resistant colon cancer cells in different degree of malignancy: SW480 and SW620 under hypoxia-like conditions during δ- aminolevulinic acid (ALA) PDT was the objective of our study.MethodsThe colon cancer cell lines SW480 and SW620 were treated in sublethal doses with ALA PDT in hypoxia- like conditions with cobalt chloride (CoCl2). To assess cell viability, MTT assays were performed and the discrimination of the cell death mode was monitored via fluorescence microscopy. The cells cytotoxicity using LDH test was assessed. Determination of VEGF was carried out using the Bio- Plex Assay Pro™ kit on the Bio- Plex Suspension Array System.ResultsALA PDT used in sublethal doses decreases release of VEGF in more aggressively growing SW620 colon cancer cell line in hypoxia-like conditions. In addition the level of secretion of VEGF in SW620 was much higher than in SW480 cells, which correlates with the grade of aggressive growth of colon cancer cells.ConclusionOur outcomes offer evidence, that in hypoxia mimic condition sublethal ALA-PDT- mediated VEGF inhibition could be clinically relevant.



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Antimicrobial photodynamic therapy for infectious stomatitis in snakes: Clinical views and microbiological findings

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Kathleen Fernandes Grego, Marcelo Pires Nogueira de Carvalho, Marcos Paulo Vieira Cunha, Terezinha Knöbl, Fabio Celidonio Pogliani, José Luiz Catão-Dias, Sávio Stefanini Sant'Anna, Martha Simões Ribeiro, Fábio Parra Sellera
BackgroundAntimicrobial photodynamic therapy (APDT) has been broadly investigated as an alternative to treat localized infections, without leading to the selection of resistant microorganisms. Infectious stomatitis is a multifactorial disease frequently reported in captive snakes characterized by infection of the oral mucosa and surrounding tissues. In this study, we investigated methylene blue (MB)-mediated APDT to treat infectious stomatitis in snakes and verified the resistance phenotype and genotype before and after APDT.MethodsThree Boid snakes presented petechiae, edema and caseous material in their oral cavities. MB (0.01%) was applied on the lesions and after 5min they were irradiated using a red laser (λ=660nm), fluence of 280J/cm², 8J and 80s per point, 100mW, spot size 0.028cm² and fluence rate of 3.5W/cm². APDT was repeated once a week during 3 months. Samples of the lesions were collected to identify bacteria and antibiotic resistance profiles. To analyze the clonality of bacterial isolates before and after APDT, isolates were subjected to ERIC PCR analysis.ResultsSnakes presented clinical improvement such as reduction of inflammatory signs and caseous material. Pseudomonas aeruginosa and Escherichia coli were present in all snakes; Klebsiella pneumoniae and Morganella morganii were also identified in some animals. We also observed that the oral microbiota was completely replaced following APDT. However, K. pneumoniae isolates before and after APDT were a single clone with 100% of genetic similarity that lost resistance phenotype for seven antibiotics of four classes.ConclusionsThese results show that APDT can be used to treat infectious stomatitis in snakes.



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Photodynamic therapy using a cytotoxic photosensitizer porphyrus envelope that targets the cell membrane

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Mizuho Inai, Norihiro Honda, Hisanao Hazama, Sharmin Akter, Shinichiro Fuse, Hiroyuki Nakamura, Tomoyuki Nishikawa, Yasufumi Kaneda, Kunio Awazu
BackgroundSubcellular localization of a photosensitizer is known to determine the therapeutic efficacy of photodynamic therapy (PDT). Cell membrane is an optimal target that promises an effective treatment outcome.ObjectivesWe previously developed a novel photosensitizer named porphyrus envelope (PE) by combining hemagglutinating virus of Japan envelope (HVJ-E) with lipidated protoporphyrin IX (PpIX lipid). In the current study, the cellular localization of PE and its ability to induce multiple anti-tumor effect were characterized.Materials and MethodsThe localization and uptake of PpIX lipid in cells were evaluated with confocal laser scanning microscopy and a cell-based fluorescent assay, respectively. The ability of PE to suppress the migration and proliferation of cancer cells was assessed using a scratch-wound assay. The synergistic effect of PDT and HVJ-E treatment was evaluated using an in vitro experiment with PC-3 cells.ResultsPE localized along the cell membrane and PpIX lipid accumulated selectively in the prostate cancer cells within 10min. Also, PE maintained the ability to undergo fusion and induce cancer cell death even after light irradiation at the dose for PDT. Incubation with PE resulted in delayed migratory and proliferative activity of PC-3 cells. PE-mediated PDT was twice as effective when cells were further incubated with PE following PDT.ConclusionsPE allows rapid drug delivery targeting the cell membrane. Because the cytotoxicity of HVJ-E was maintained, synergistic effect of HVJ-E and the photochemical reactions resulted in highly effective killing of prostate cancer cells in vitro and thus represents a promising treatment for prostate cancer.



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IDIOPATHIC ELASTOSIS PERFORANS SERPIGINOSA WITH SATISFACTORY RESPONSE AFTER 5-ALA PHOTODYNAMIC THERAPY

Publication date: Available online 10 November 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): S Alique-García, J. Company-Quiroga, C. Horcajada-Reales, B. Echeverría-García, J.C. Tardío-Dovao, J. Borbujo
Photodynamic therapy (PDT) involves the use of photochemical reactions mediated through the interaction of photosensitizing agents, light, and oxygen for the treatment of malignant or benign diseases. Topical photosensitizers employed in dermatology are 5-aminolevulinic acid (5 ALA) and methyl aminolevulinate, classically used for the treatment of superficial non-melanoma skin cancer and their precursors. Recently the efficacy of PDT has been introduced in other benign diseases. Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibers. Management of this condition is complicated, various methods have been used but with limited success. We report a case of EPS in a 30-yeard-old woman treated with 5 ALA-PDT. After 4 sessions the lesions have almost completely disappeared with no residual side effects. Therefore we present an effective and safe alternative for the treatment of EPS.



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Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant dermatosis: Report of 4 cases

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Calvina Theresia, Jie Zheng, Xiao-Ying Chen
BackgroundTopical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases.ObjectivesTo determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis.ObservationsWe presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects.ConclusionsTopical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated.



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Photodynamic therapy for the treatment of peri-implant diseases: A network meta-analysis of randomized controlled trials

Publication date: March 2018
Source:Photodiagnosis and Photodynamic Therapy, Volume 21
Author(s): Gowri Sivaramakrishnan, Kannan Sridharan
BackgroundPhotodynamic therapy in peri-implantitis has been tested in randomized clinical trials. Though systematic review and meta-analysis on human and animal studies, identifies the utility of photodynamic therapy, a comparison of other interventions with photodynamic therapy for peri-implantitis does not exist. Hence the aim of this network meta-analysis is to identify the role of photodynamic therapy for peri-implantitis compared with other interventions tested in randomized human clinical trials.MethodRandomized controlled trials comparing photodynamic therapy and other interventions in patients with peri- implantitis was searched for in electronic databases. The risk of bias was calculated using Cochrane risk of Bias tool. The heterogeneity between the studies in direct comparison was assessed using Chi-square and I² tests. GRADE working group approach was used to assess the quality of evidence. Publication bias was assessed using Funnel plot and Trim and Fill method was used to identify the number of missing studies.ResultsWe observed a significant reduction in the level of attachment scores with the use of combined photodynamic therapy with mechanical debridement when compared with other interventions tested. For bleeding on probing, pocket depth and plaque scores no statistically significant results were obtained.ConclusionThe use of photodynamic therapy with mechanical debridement will definitely bring about significant improvement in patients with peri-implantitis. Further trials on the use of photodynamic therapy with other treatment modalities need to be tested to arrive at the best possible treatment option for peri-implantitis.



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Effect of methylene blue-induced photodynamic therapy on a Streptococcus mutans biofilm model

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Mariana Alencar Nemezio, Sofia Sampaio de Souza Farias, Maria Cristina Borsatto, Carolina Patrícia Aires, Silmara Aparecida Milori Corona
BackgroundSeveral studies have reported the use of antimicrobial photodynamic therapy (aPDT) to control biofilm but its efficacy depends on several factors, such as biofilm model used. This study aims to examine whether exposure to diode laser combined with methylene blue affects the bacterial viability and polysaccharide content in a Streptococcus mutans cariogenic biofilm model, which simulated 'feast-famine' episodes of exposure to sucrose that occur in the oral cavity.Materials and methodsS. mutans biofilms were formed on acrylic resin discs and exposed to a 10% sucrose solution for 1min, eight times/day. After growing for 48h, the biofilms were submitted to the following treatments, twice daily (n=4): (i) 0.9% NaCl (NaCl) as the negative control; (ii) 0.12% chlorhexidine digluconate (CHX) as the positive antibacterial control; (iii) diode laser combined with methylene blue, using an energy density of 320J/cm² (aPDT). After 120h of growth, the biofilm formed on each disc was collected to determine the viable bacterial counts and concentration of insoluble exopolysaccharides (IEPS) and intracellular polysaccharides (IPS).ResultsBacterial counts in the biofilms formed differed among the treatments. Compared with NaCl, aPDT significantly destabilized biofilm (p<0.0001). aPDT and CHX equally lowered the concentration of IEPS and IPS in biofilms.ConclusionUnder the experimental conditions assessed, our findings indicate that a twice-daily treatment with diode laser combined with methylene blue effectively decreased bacterial viability and the intra- and extracellular polysaccharide concentration in biofilms of S. mutans, a cariogenic bacterium.



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Treatment of oral refractory large area mucosal leukoplakia with CO2 laser combined with photodynamic therapy: Case report

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Yunfeng Zhang, Linglin Zhang, Degang Yang, Guolong Zhang, Xiuli Wang




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Clinical study on clinical operation and post-treatment reactions of HMME-PDT in treatment of PWS

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Yunjie Zhang, Xianbiao Zou, Hongxia Chen, Yuguang Yang, Hui Lin, Xiaojuan Guo
ObjectiveTo analyze the clinical efficacy of hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) in treating port-wine stains (PWS), and its clinical operation skills and operation essentials.MethodA total of 16 cases of PWS with negative HMME skin test results were included in this study. Their treated areas were exposed and injected with 5mg/kg HMME, and then irradiated under 532nm LED green light (produced by Wuhan YaGe LED1 modified machines), with the irradiation power density between 80 and 100mW/cm². Each light spot was irradiated for 20–25min. After one treatment, the clinical efficacy and post-treatment reactions at each treated area were observed.ResultUnder standard operation, two of the 16 cases were cured (12.5%) after one HMME-PDT treatment, eight cases indicates a good efficacy (50.0%), four cases showed alleviation (25.0%), while two cases displayed no efficacy (12.5%), indicating an one-time response rate of 87.5%. Pain was reported during treatment, and significant post-treatment edema was observed at the treated areas; And no allergy or other adverse reaction were reported.ConclusionIn adherence to operation standards and operation essentials during treatment, HMME-PDT shows a satisfactory clinical efficacy in treating PWS.



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Antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM – 660nm) in a dog with chronic gingivostomatitis

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Paula Abreu Villela, Naiá de Carvalho de Souza, Juliana Durigan Baia, Marco Antonio Gioso, Ana Cecília Corrêa Aranha, Patrícia Moreira de Freitas
Chronic gingivostomatitis in dogs is an inflammatory syndrome of the oral cavity, which treatment and control of concomitant periodontitis allow healing in most of the cases. In the presence of recurrent lesions, invasive methods are necessary to treat lesions and pain. As a conservative adjuvant method, photobiomodulation (PBM) with low power laser is able to promote reduction of tissue pain and tissue inflammation besides increasing vascularization and healing, restoring the normal function of the irradiated organ in a shorter time. In veterinary medicine, there is no standardization of technique for its use in oral tissue for treating gingivostomatitis in dogs. In the present case, a dog was submitted to aPDT (7.2J/point, 3min/point, 180J/cm²) and PBM (1.6J/point, 40s/point, 25J/cm²), using a semiconductor diode laser, with wavelength of 660nm, spot size of ​​0.04cm² and output power of 40mW. The established protocol proved to be effective as coadjutant treatment for chronic gingivostomatitis, restoring the integrity of dog's affected mucosa and gingiva.



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Effects of LED —Based Photodynamic Therapy using Red and Blue Lights, with Natural Hydrophobic Photosensitizers on Human Glioma Cell Line

Publication date: Available online 7 November 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Zahra Jamali, Sedigheh Marjaneh Hejazi, Seyed Mohsen Ebrahimi, Hemen Moradi-sardareh, Maliheh Paknejad
Photodynamic therapy (PDT) has received high attention in cancer treatment due to its minimal side effects, specific cancer-targeting, non-invasion and low cost. It utilizes a specific group of anti-cancer drugs called photosensitizers (PS), which can be only activated under a certain wavelength light illumination and kills cancer cells. To screen the potential of PS and setup of PDT treatment protocol, it is essential to assess the PDT efficacy in vitro.In this study, a light-emitting diode- (LED-) based illumination system at two wavelengths (red & blue) with homogeneous and stable irradiation, and constant temperature conditions in 96-well plates was provided. The photodynamic effect of curcumin (CUR) and methyl ester of 5-aminolevulinic acid (MAL) using LED light on human glioma cell line was investigated. The obtained results indicate that this homemade LED-based illumination system is a favorable light source for in vitro PDT in 96-well plates. The PDT using CUR and MAL was efficient at final concentrations of 25μM and 2mM, and light doses of 60J/cm2 and 40J/cm2 respectively. The blue PDT efficiency was dependent on the light and PS doses. MAL-PDT and CUR-PDT using blue LED significantly decreased cell viability in the treatment groups compared with control groups. Furthermore, MAL-PDT using blue LEDs was more effective in comparison with conventional red LEDs on the human glioma cell line.



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The diagnostic value of the native fluorescence visualization device for early detection of premalignant/malignant lesions of the oral cavity

Publication date: Available online 24 October 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Maryam Amirchaghmaghi, Nooshin Mohtasham, Zahra Delavarian, Mohammad Taghi Shakeri, Masoud Hatami, Pegah Mosannen Mozafari
PurposeThe present study aimed to determine the diagnostic value of a native fluorescence visualization device in the identification of oral malignant/dysplastic lesions.MethodsThis study involved 45 patients who had oral lesions that were suspected to be malignant, potentially malignant, or benign. The patients visited the Oral Medicine Department of the Mashhad Dental School. The sensitivity, specificity, positive and negative predictive values, and likelihood ratio of this device were determined.ResultsThe histopathological assessment of samples showed 9 cases of oral squamous cell carcinoma and 12 lesions with dysplasia. Ten samples of dysplastic lesions and all malignant lesions appeared dark or red/orange when examined with the native fluorescence visualization device. In 90% of the dysplastic/malignant lesions, the label-free fluorescence results were positive. The sensitivity, specificity, and positive and negative predictive values of this device were 90%, 15%, 40%, and 71%, respectively.ConclusionsThe native fluorescence visualization device can be used in specialized centers as an adjunctive device to increase the sensitivity of a clinical examination, but is not capable of distinguishing benign lesions from malignant and dysplastic ones due to its low specificity.



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Treatment of peritoneal carcinomatosis with photodynamic therapy: Systematic review of current evidence

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Muhammad Qutayba Almerie, Gemma Gossedge, Kathleen E. Wright, David G. Jayne
BackgroundPeritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis.MethodsWe systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017).ResultsThree human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15–300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0–4 [4=highest]: PDT 3.4±1.0 vs. control 0.4±0.6, p<0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p<0.001).ConclusionPDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.



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Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Yusei Shinohara, Yoshio Endo, Chiaki Abe, Ikkyu Shiba, Masahiro Ishizuka, Tohru Tanaka, Yutaka Yonemura, Shun-Ichiro Ogura, Masahide Tominaga, Hisatsugu Yamada, Yoshihiro Uto
5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers.



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Programmable LED-based integrating sphere light source for wide-field fluorescence microscopy

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Aziz ul Rehman, Ayad G. Anwer, Ewa M. Goldys
Wide-field fluorescence microscopy commonly uses a mercury lamp, which has limited spectral capabilities. We designed and built a programmable integrating sphere light (PISL) source which consists of nine LEDs, light-collecting optics, a commercially available integrating sphere and a baffle. The PISL source is tuneable in the range 365–490nm with a uniform spatial profile and a sufficient power at the objective to carry out spectral imaging. We retrofitted a standard fluorescence inverted microscope DM IRB (Leica) with a PISL source by mounting it together with a highly sensitive low- noise CMOS camera. The capabilities of the setup have been demonstrated by carrying out multispectral autofluorescence imaging of live BV2 cells.



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Assessing daylight & low-dose rate photodynamic therapy efficacy, using biomarkers of photophysical, biochemical and biological damage metrics in situ

Publication date: December 2017
Source:Photodiagnosis and Photodynamic Therapy, Volume 20
Author(s): Ana Luiza Ribeiro de Souza, Ethan LaRochelle, Kayla Marra, Jason Gunn, Scott C. Davis, Kimberley S. Samkoe, M. Shane Chapman, Edward V. Maytin, Tayyaba Hasan, Brian W. Pogue
BackgroundSunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused byconventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure.MethodsNude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery.ResultsOf the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm²) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R=0.74, and comparison of keratinocyte nuclear damage R=0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage.ConclusionsDaylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process.

Graphical abstract

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Stress response of a clinical Enterococcus faecalis isolate subjected to a novel antimicrobial surface coating

Publication date: Available online 12 November 2017
Source:Microbiological Research
Author(s): Emanuel Clauss-Lendzian, Ankita Vaishampayan, Anne de Jong, Uwe Landau, Carsten Meyer, Jan Kok, Elisabeth Grohmann
Emerging antibiotic resistance among pathogenic bacteria, paired with their ability to form biofilms on medical and technical devices, represents a serious problem for effective and long-term decontamination in health-care environments and gives rise to an urgent need for new antimicrobial materials. Here we present the impact of AGXX^®, a novel broad-spectrum antimicrobial surface coating consisting of micro-galvanic elements formed by silver and ruthenium, on the transcriptome of Enterococcus faecalis. A clinical E. faecalis isolate was subjected to metal stress by growing it for different periods in presence of the antimicrobial coating or silver-coated steel meshes. Subsequently, total RNA was isolated and next-generation RNA sequencing was performed to analyze variations in gene expression in presence of the antimicrobial materials with focus on known stress genes. Exposure to the antimicrobial coating had a large impact on the transcriptome of E. faecalis. After 24minutes almost 1/5 of the E. faecalis genome displayed differential expression. At each time-point the cop operon was strongly up-regulated, providing indirect evidence for the presence of free Ag⁺-ions. Moreover, exposure to the antimicrobial coating induced a broad general stress response in E. faecalis. Genes coding for the chaperones GroEL and GroES and the Clp proteases, ClpE and ClpB, were among the top up-regulated heat shock genes. Differential expression of thioredoxin, superoxide dismutase and glutathione synthetase genes indicates a high level of oxidative stress. We postulate a mechanism of action where the combination of Ag⁺-ions and reactive oxygen species generated by AGXX^® results in a synergistic antimicrobial effect, superior to that of conventional silver coatings.



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Evaluation of the serum zinc level in adult patients with melasma: Is there a relationship with serum zinc deficiency and melasma?

Summary

Background

Melasma is a common acquired hypermelanosis of sun-exposed skin, particularly on the face, which presents as symmetric, light- to gray-brown-colored macules and patches. There are several studies of serum zinc levels in cutaneous disorders. So far, no studies have been carried out to assess the serum zinc level in patients with melasma. The aim of this study is to determine the serum zinc level in patients with melasma compared to healthy subjects.

Materials and methods

A total of 118 patients with melasma and 118 healthy controls were enrolled in this prospective cross-sectional study. The two groups were matched for age and sex. Atomic absorption spectrophotometry was used to measure serum zinc levels. The statistical analysis was performed using SPSS software.

Results

The mean serum level of zinc in melasma patients and controls was 77.4±23.2 μg/dL and 82.2±23.9 μg/dL, respectively (P-value=.0001). Serum zinc deficiency was found in 45.8% and 23.7% of melasma patients and control subjects, respectively. A positive family history of melasma in first-degree relatives was present in 46 (39%) of the cases, and a history of taking oral contraceptive pill was found in 95 (81%) of women with melasma. The aggravating factors for melasma were stated as: sun exposure (11.1%), pregnancy (15.3%), nutrition (2.5%), oral contraceptive pills (18.6%), and emotional stress (5.9%). The malar and centrofacial patterns were seen in 3.4% and 72% of cases, respectively, whereas 24.6% of the patients had both centrofacial distribution and malar distribution, and there was no patient with mandibular pattern. Among patients with melasma, 20.3% had thyroid dysfunction, while in the control subjects, 8.4% had thyroid dysfunction (P=.001).

Conclusion

There is a significant relationship between low levels of zinc and melasma. Zinc deficiency may be involved in the pathogenesis of melasma. Also, treatment with oral zinc supplements can be tried in these patients to see the outcome. However, to make recommendations on screening for zinc deficiency in patients with melasma, future research of good methodological quality is needed.

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Influences of age, ethnic group, and skin sites on a provisory skin marking, experimentally induced, in vivo

Abstract

Background

To study capacity of skin to being imprinted by a marking head rapidly applied (10 seconds) onto the skin under a standardized pressure (15 kPa).

Material and Methods

Referential photographs of skin markings, resulting from different times of application serve at grading the extent of skin imprints. The imprinting tool, equipped with 5 linear bulbs of different sizes but same thickness (1 mm), was applied onto the cheeks of 641 women of different ages (18-80 years) of 3 different ethnic groups. In the cohort of 198 Caucasian women, the marking head was pressed onto 3 different sites (outer arm, cheek, and dorsal forearm) and the kinetics of skin recovery from cheek marking was recorded on a smaller and younger part of this Caucasian cohort, ie, 141 Caucasian women, aged 18-59 years.

Results

The recorded intensities of skin markings were found highly correlated with age in all 3 studied ethnic groups (Chinese, African-American, and Caucasian). Caucasian women seem more sensitive to the marking and the kinetics of recovery from such imprint was found highly dependent from its intensity, ie, the higher the grades, the slower the recovery. In Caucasian women, intensities were different between skin sites, where arm showed higher resistance to marking. Possible impact of photo-aging on the decreased skin resistance to such provoked deformation is likely of minor amplitude, as compared to the one induced by chronological aging.

Conclusion

This method offers a new vision on skin aging, in its variable response to a standard deformation that appears mostly driven by chronological aging.

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Characterization of sweat induced with pilocarpine, physical exercise, and collected passively by metabolomic analysis

Abstract

Background/purpose

The elimination of the pain associated with needle picking is a strong motivation for the development of clinical non-invasive diagnostic methods. Sweat has been described as an alternative biological sample that may have a direct relation to the plasma composition.

Materials and methods

In this study, analysis of sweat of human volunteers obtained by induction with pilocarpine is compared with sweat samples obtained by physical exercise and by passive collection along 7 hours. The sweat samples have been analyzed by 1H nuclear magnetic resonance spectroscopy.

Results

A range of 34 different metabolites has been detected in sweat samples, including lactate, several amino acids, pyroglutamate, and urocanate. Most of the metabolites identified were quantified. The majority of the amino acids detected in sweat seem to have origin in the epidermis surface. No significant differences in sweat samples from female and male were observed by 1H NMR metabolomic analysis.

Conclusions

Principal component analysis (PCA) shows that both physical exercise and pilocarpine methods seem to be equally reproducible methods in terms of sweat metabolite composition presenting better repeatability than natural sweat collection. Nevertheless, this difference is mainly originated from amino acids with origin from the skin surface.

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Ultrasound with neurostimulation compared with ultrasound guidance alone for lumbar plexus block: A randomised single blinded equivalence trial

BACKGROUND Ultrasound-guided lumbar plexus blocks usually require confirmatory neurostimulation. A simpler alternative is to inject local anaesthetic inside the posteromedial quadrant of the psoas muscle under ultrasound guidance. OBJECTIVE We hypothesised that both techniques would result in similar total anaesthesia time, defined as the sum of performance and onset time. DESIGN A randomised, observer-blinded, equivalence trial (equivalence margin = 7.4 min). SETTING Ramathibodi Hospital and Maharaj Nakorn Chiang Mai Hospital (Thailand) from 12 May 2016 to 10 January 2017. PATIENTS A total of 110 patients undergoing total hip or knee arthroplasty, who required lumbar plexus block for postoperative analgesia. INTERVENTION In the combined ultrasonography-neurostimulation group, quadriceps-evoked motor response was sought at a current between 0.2 and 0.8 mA prior to local anaesthetic injection (30 ml of lidocaine 1% and levobupivacaine 0.25% with epinephrine 5 μg ml−1 and 5 mg of dexamethasone). In the ultrasound guidance alone group, local anaesthetic was simply injected inside the posteromedial quadrant of the psoas muscle. MAIN OUTCOMES MEASURES We measured the total anaesthesia time, the success rate (at 30 min), the number of needle passes, block-related pain, cumulative opioid consumption (at 24 h) and adverse events (vascular puncture, paraesthesia, local anaesthetic spread to the epidural space). RESULTS Compared with ultrasound guidance alone, combined ultrasonography-neurostimulation resulted in decreased mean (±SD) total anaesthesia time [15.3 (±6.5) vs. 20.1 (±9.0) min; mean difference, −4.8; 95% confidence interval, −8.1 to −1.9; P = 0.005] and mean (±SD) onset time [10.2 (±5.6) vs. 15.5 (±9.0) min; P = 0.004). No inter-group differences were observed in terms of success rate, performance time, number of needle passes, block-related pain, opioid consumption or adverse events. CONCLUSION Although the ultrasonography-neurostimulation technique results in a shorter total anaesthesia time compared with ultrasound guidance alone, this difference falls within our accepted equivalence margin (±7.4 min). TRIAL REGISTRATION www.clinicaltrials in the (Study ID: TCTR20160427003). Correspondence to De Q. Tran, MD, FRCPC, Professor, Department of Anaesthesia, Montreal General Hospital, McGill University, 1650 Ave Cedar, Montreal, QC, Canada H3G-1A4 Tel: +1 514 934 1934x43261; fax: +1 514 934 8249; e-mail: de_tran@hotmail.com © 2017 European Society of Anaesthesiology

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Prevalence of obesity among adults in Issele-Uku, Delta State Nigeria

Publication date: Available online 12 November 2017
Source:Alexandria Journal of Medicine
Author(s): Otovwe Agofure
BackgroundObesity is gradually assuming an epidemic dimension among adults in Nigeria. Unfortunately, this has led to the increase in the prevalence of chronic diseases.ObjectiveThe study was designed to assess the prevalence of obesity among adults in Issele-uku, Aniocha North Local Government Area of Delta State, Nigeria.Materials and MethodsThe study employed a cross-sectional study design conducted among 201 respondents utilizing a simple random sampling technique. A validated semi-structured questionnaire was administered to obtain information from respondents; while descriptive and inferential statistics was used to analyze the data.ResultsThe results show that more of the respondents were between the ages of 18–40 years, while about half 101(50.50%) were females and 104(52.0%) were married. Furthermore, only 46(23.0%) were overweight while 17.50% and 5.50% were pre-obese and obese respectively. The mean Body Mass Index of the respondents was 23.02±4.42 while the respondents demonstrated positive attitude towards prevention of obesity. In addition, only eating akpu/fufu significantly predicted obesity (R²=0.034) while both sex (P=.350) and educational status (P=0.165) did not significantly influence obesity and some of the respondents' 82(41.0%) exercises once in a while.ConclusionThe study recommended more awareness campaign on the dangers of obesity across communities in Nigeria.



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Oleanonic acid ameliorates pressure overload-induced cardiac hypertrophy in rats: The role of PKCζ-NF-κB pathway

Publication date: Available online 11 November 2017
Source:Molecular and Cellular Endocrinology
Author(s): Hui Gao, Hui Liu, Tiexin Tang, Xiaofei Huang, Dongxiu Wang, Yan Li, Pan Huang, Yingfu Peng
It has been reported that inflammation is closely related with cardiac hypertrophy. Some inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6 directly induce cardiac hypertrophy, which is associated with the activation of nuclear factorkappa B (NF-κB). Thus, NF-κB is an attractive target for cardiac hypertrophy. In the present study, oleanonic acid inhibited the elevation of transcriptional activity of NF-κB and reduced the mRNA expressions of hypertrophic genes such as atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) in a concentration-dependent manner in phenylephrine (PE)-treated cardiomyocytes. Furthermore, we found that oleanonic acid inhibited the phosphorylation of protein kinase C ζ (PKCζ) at Thr410 site and then reduced the activation of NF-κB using gain- and loss-of-function approaches in PE-treated cardiomyocytes. In vivo, similar results were observed in abdominal aortic constriction (AAC) rats that were intragastrically administered with oleanonic acid, and the pathological changes accompanying cardiac hypertrophy were relieved. In conclusion, oleanonic acid can effectively ameliorate cardiac hypertrophy by inhibiting PKCζ-NF-κB signaling pathway.



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Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg-AD mouse model by attenuating neuroinflammation

Publication date: February 2018
Source:Neurobiology of Aging, Volume 62
Author(s): Ronit Shapira, Beka Solomon, Shai Efrati, Dan Frenkel, Uri Ashery
There is a real need for new interventions for Alzheimer's disease (AD). Hyperbaric oxygen therapy (HBOT), the medical administration of 100% oxygen at conditions greater than 1 atmosphere absolute, has been used successfully to treat several neurological conditions, but its effects on AD pathology have never been thoroughly examined. Therefore, we exposed old triple-transgenic (3xTg) and non-transgenic mice to HBOT followed by behavioral, histological, and biochemical analyses. HBOT attenuated neuroinflammatory processes by reducing astrogliosis, microgliosis, and the secretion of proinflammatory cytokines (IL-1β and TNFα) and increasing expression of scavenger receptor A, arginase1, and antiinflammatory cytokines (IL-4 and IL-10). Moreover, HBOT reduced hypoxia, amyloid burden, and tau phosphorylation in 3xTg mice and ameliorated their behavioral deficits. Therefore, we suggest that HBOT has multifaceted effects that reduce AD pathologies, even in old mice. Given that HBOT is used in the clinic to treat various indications, including neurological conditions, these results suggest HBOT as a novel therapeutic intervention for AD.

Graphical abstract

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Resource forecasting: Differential effects of glucose taste and ingestion on delay discounting and self-control

Publication date: 1 February 2018
Source:Appetite, Volume 121
Author(s): X.T. Wang, Ryan N. Reed, Lee A. Baugh, Kelene A. Fercho
We tested a novel hypothesis that glucose taste acts as a signal for resource acquisition, motivating preference for immediate rewards while actual glucose ingestion prompts resource conservation, promoting future-orientated self-regulation. In Study 1, participants were engaged in a delay-discounting task and a grip-control task before and after a beverage intervention (glucose drink, water drink, or glucose mouth-rinse). Glucose ingestion decreased delay discounting, making larger-and-later rewards more attractive. In contrast, glucose rinse increased delay discounting. Water ingestion had none of the effects. In the grip-control task, only glucose ingestion improved the performance. Study 2 using fMRI revealed that glucose rinse and glucose ingestion resulted in distinct brain activational patterns. Compared to glucose rinse, glucose ingestion deactivated a few brain regions (e.g., the anterior cingulate gyrus and inferior frontal gyrus) that are previously shown to be more active when making more difficult intertemporal choices, suggesting that glucose ingestion eases the process of making intertemporal choice. In sum, our behavioral and neuroimaging findings together suggest a dual signaling role of glucose sensation and ingestion in regulating delay discounting and self-control.



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Feminist approaches to Anorexia Nervosa: a qualitative study of a treatment group

Abstract

Background

Eating disorders (EDs) are now often approached as biopsychosocial problems. But it has been suggested by scholars interested in sociocultural factors that all is not equal within this biospsychosocial framework, with the 'social' aspects of the equation relegated to secondary factors within ED treatment contexts. Although sociocultural influences are well-established as risk factors for EDs, the exploration of whether or how such perspectives are useful in treatment has been little explored. In responding to this context, this article seeks to discuss and evaluate a 10 week closed group intervention based on feminist approaches to EDs at a residential eating disorder clinic in the East of England.

Methods

The data was collected via one-to-one qualitative interviews and then analysed using thematic discourse analysis.

Results

The participants suggested that the groups were helpful in enabling them to situate their problem within a broader cultural and group context, that they could operate as a form of 'protection' from ideologies regarding femininity, and that a focus on the societal contexts for EDs could potentially reduce feelings of self-blame. At the same time, the research pointed to the complexities of participants considering societal rather than individualised explanations for their problems, whilst it also confronted the implications of ambivalent responses toward feminism.

Conclusions

Highly visible sociocultural factors in EDs – such as gender - may often be overlooked in ED clinical contexts. Although based on limited data, this research raises questions about the marginalisation of sociocultural factors in treatment, and the benefits and challenges including the latter may involve.

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Aportación de la PET/TC con 11C-colina en la recidiva bioquímica del cáncer de próstata con antígeno específico prostático sérico inferior a 1 ng/ml

Publication date: Available online 12 November 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): F.J. Gómez-de la Fuente, I. Martínez-Rodríguez, M. de Arcocha-Torres, R. Quirce, J. Jiménez-Bonilla, N. Martínez-Amador, I. Banzo
ObjetivoLa PET/TC con ¹¹C-colina ha mostrado buenos resultados en la reestadificación del cáncer de próstata (CP) con antígeno específico prostático (PSA) elevado. Su uso con niveles bajos es controvertido. Nuestro objetivo fue evaluar la aportación de la ¹¹C-colina PET/TC en pacientes con CP, recidiva bioquímica y PSA <1ng/ml.Material y métodoSe evaluaron retrospectivamente 50 pacientes consecutivos (edad: 65,9±5,6 años) con recidiva bioquímica de CP y PSA <1ng/ml (media: 0,4±0,2). La PET/TC fue adquirida a los 20 min de la administración intravenosa de 555-740 MBq de ¹¹C-colina. El seguimiento mínimo fue de 30 meses.ResultadosDe los 50 pacientes, 21 (42%) mostraron una ¹¹C-colina PET/TC anormal. En 7 (14%) se confirmó la afectación tumoral (4 en lecho prostático, 4 en ganglios pélvicos, 2 en ganglios mediastínicos y un tumor síncrono sigmoide) y se modificó en todos ellos el tratamiento inicialmente previsto. En 2 pacientes (4%) se confirmó enfermedad benigna (uno con sarcoidosis, otro con secuelas de TBC) y en 3 pacientes (6%) ausencia de enfermedad. En los otros 9 pacientes (18%) los hallazgos no fueron estudiados (7 en ganglios mediastínicos y 4 en pélvicos). La ¹¹C-colina PET/TC fue normal en 29 pacientes (58%). Solo en 2 de ellos se confirmó recidiva a los 30 meses.ConclusiónLa ¹¹C-colina PET/TC demostró su utilidad en la recidiva bioquímica de CP y PSA <1 ng/ml en el 14% de los pacientes al mostrar enfermedad tumoral, lo que tuvo implicaciones terapéuticas. En un 4% se detectó enfermedad benigna. Una ¹¹C-colina PET/TC normal se asoció a una tasa de recurrencia muy baja a los 30 meses.Objective¹¹C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of ¹¹C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml.Material and methodFifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of ¹¹C-choline. Minimum follow up time was 30 months.ResultsTwenty-one out of 50 patients (42%) had an abnormal ¹¹C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients.Conclusions¹¹C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal ¹¹C-choline PET/CT was associated with a very low rate of recurrence at 30 months.



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An ultrasonographic investigation of deep neck flexor muscles cross-sectional area in forward and normal head posture

Publication date: Available online 12 November 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Roya Eshaghi Moghadam, Leila Rahnama, Noureddin Karimi, Mohsen Amiri, Mahsa Rahnama
BackgroundAs one of the most common work-related musculoskeletal disorders and postural deviations, forward head posture (FHP), is considered to lead to muscle imbalance.ObjectivesTherefore, the aim of this study is to investigate the bilateral cross-sectional area (CSA) of the deep neck flexor muscles at rest and during five stages of the craniocervical flexion (CCF) test in individuals with FHP and the controls with normal head posture.MethodsEighteen students with FHP and 18 controls with normal head posture, all females aged 18–35 years, participated in this study. Participants were categorized into two groups based on their craniovertebral angle. The CSA of the deep neck flexors was measured using ultrasonography while participants lay supine on the table with a pressure biofeedback unit placed under their necks in order to let the examiner measure the CSA of the muscles during rest and five stages of the CCF test including 22, 24, 26, 28, and 30 mmHg of the pressure biofeedback unit.ResultsA significant effect of contraction level was observed in both groups, indicating significant increases of the CSA of the deep neck flexors during contraction (F = 64.37, P < 0.001). No significant difference was evident for the CSA of the deep neck flexors between the groups, although the increase in the CSA of the deep neck flexors was up to 28 mmHg in the normal head posture group compared to 26 mmHg in the FHP group.ConclusionsThe results of the present study showed no significant difference between the performance of the deep neck flexors during the CCF test in FHP and normal head posture individuals, which challenge the common belief of the deep neck flexors weakness in individuals sustaining from FHP.



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Effect of noisy galvanic vestibular stimulation on center of pressure sway of static standing posture

Publication date: Available online 17 October 2017
Source:Brain Stimulation
Author(s): Yasuto Inukai, Naofumi Otsuru, Mitsuhiro Masaki, Kei Saito, Shota Miyaguchi, Sho Kojima, Hideaki Onishi
BackgroundThe vestibular system is involved in the control of standing balance. Galvanic vestibular stimulation (GVS) is a noninvasive technique that can stimulate the vestibular system. In recent years, noisy GVS (nGVS) using noise current stimulation has been attempted, but it has not been clarified whether it affects postural sway in open-eye standing.ObjectiveThe purpose of this study was to clarify the influence of nGVS on the center of pressure (COP) sway measurement in open-eye standing postural control and identify the responders of nGVS.MethodsnGVS (0.1–640 Hz) was delivered at 0.4 and 1.0 mA over the bipolar mastoid. COP sway root mean square area, sway path length, medio-lateral (ML) mean velocity, and antero-posterior (AP) mean velocity before and during nGVS in an open-eye standing posture was measured.ResultsnGVS at 0.4 and 1.0 mA significantly reduced sway path length, mean velocity. The stimulation effect of nGVS was also large in subjects with a long sway path. For subjects with high COP sway of Baseline, nGVS was effective even with stimulation for a short duration (5 s).ConclusionsThese findings suggest that nGVS improves postural sway in an open-eye standing posture among young subjects.



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Global structural integrity and effective connectivity in patients with disorders of consciousness

Publication date: Available online 11 November 2017
Source:Brain Stimulation
Author(s): Olivier Bodart, Enrico Amico, Francisco Gomez, Adenauer G. Casali, Sarah Wannez, Lizette Heine, Aurore Thibaut, Jitka Annen, Melanie Boly, Silvia Casarotto, Mario Rosanova, Marcello Massimini, Steven Laureys, Olivia Gosseries
BackgroundPrevious studies have separately reported impaired functional, structural, and effective connectivity in patients with disorders of consciousness (DOC). The perturbational complexity index (PCI) is a transcranial magnetic stimulation (TMS) derived marker of effective connectivity. The global fractional anisotropy (FA) is a marker of structural integrity. Little is known about how these parameters are related to each other.ObjectiveWe aimed at testing the relationship between structural integrity and effective connectivity.MethodsWe assessed 23 patients with severe brain injury more than 4 weeks post-onset, leading to DOC or locked-in syndrome, and 14 healthy subjects. We calculated PCI using repeated single pulse TMS coupled with high-density electroencephalography, and used it as a surrogate of effective connectivity. Structural integrity was measured using the global FA, derived from diffusion weighted imaging. We used linear regression modelling to test our hypothesis, and computed the correlation between PCI and FA in different groups.ResultsGlobal FA could predict 74% of PCI variance in the whole sample and 56% in the patients' group. No other predictors (age, gender, time since onset, behavioural score) improved the models. FA and PCI were correlated in the whole population (r = 0.86, p < 0.0001), the patients, and the healthy subjects subgroups.ConclusionWe here demonstrated that effective connectivity correlates with structural integrity in brain-injured patients. Increased structural damage level decreases effective connectivity, which could prevent the emergence of consciousness.



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International randomized-controlled trial of transcranial Direct Current Stimulation in depression

Publication date: Available online 27 October 2017
Source:Brain Stimulation
Author(s): Colleen K. Loo, Mustafa M. Husain, William M. McDonald, Scott Aaronson, John P. O'Reardon, Angelo Alonzo, Cynthia Shannon Weickert, Donel M. Martin, Shawn M. McClintock, Adith Mohan, Sarah H. Lisanby
BackgroundEvidence suggests that transcranial Direct Current Stimulation (tDCS) has antidepressant effects in unipolar depression, but there is limited information for patients with bipolar depression. Additionally, prior research suggests that brain derived neurotrophic factor (BDNF) Val66Met genotype may moderate response to tDCS.ObjectiveTo examine tDCS efficacy in unipolar and bipolar depression and assess if BDNF genotype is associated with antidepressant response to tDCS.Methods130 participants diagnosed with a major depressive episode were randomized to receive active (2.5 milliamps (mA), 30 min) or sham (0.034 mA and two 60-second current ramps up to 1 and 0.5 mA) tDCS to the left prefrontal cortex, administered in 20 sessions over 4 weeks, in a double-blinded, international multisite study. Mixed effects repeated measures analyses assessed change in mood and neuropsychological scores in participants with at least one post-baseline rating in the unipolar (N = 84) and bipolar (N = 36) samples.ResultsMood improved significantly over the 4-week treatment period in both unipolar (p = 0.001) and bipolar groups (p < 0.001). Among participants with unipolar depression, there were more remitters in the sham treatment group (p = 0.03). There was no difference between active and sham stimulation in the bipolar sample. BDNF genotype was unrelated to antidepressant outcome.ConclusionsOverall, this study found no antidepressant difference between active and sham stimulation for unipolar or bipolar depression. However, the possibility that the low current delivered in the sham tDCS condition was biologically active cannot be discounted. Moreover, BDNF genotype did not moderate antidepressant outcome.Clinical Trials Registrationwww.clinicaltrials.gov, NCT01562184.



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Report of seizure induced by 10 Hz rTMS over M1

Publication date: Available online 8 November 2017
Source:Brain Stimulation
Author(s): Valentina Bruno, Carlotta Fossataro, Francesca Garbarini




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Number of pulses or number of sessions? An open-label study of trajectories of improvement for once-vs. twice-daily dorsomedial prefrontal rTMS in major depression

Publication date: Available online 7 November 2017
Source:Brain Stimulation
Author(s): Laura Schulze, Kfir Feffer, Christopher Lozano, Peter Giacobbe, Zafiris J. Daskalakis, Daniel M. Blumberger, Jonathan Downar
BackgroundRepetitive transcranial magnetic stimulation (rTMS) shows efficacy in the treatment of major depressive episodes (MDEs), but can require ≥4–6 weeks for maximal effect. Recent studies suggest that multiple daily sessions of rTMS can accelerate response without reducing therapeutic efficacy. However, it is unresolved whether therapeutic effects track cumulative number of pulses, or cumulative number of sessions.ObjectiveThis open-label study reviewed clinical outcomes over a 20–30 session course of high-frequency bilateral dorsomedial prefrontal cortex (DMPFC)-rTMS among patients receiving 6000 pulses/day delivered either in twice-daily sessions 80 min apart (at 20 Hz) or single, longer, once-daily sessions (at 10 Hz).MethodsA retrospective chart review identified 130 MDD patients who underwent 20–30 daily sessions of bilateral DMPFC-rTMS (Once-daily, n = 65; Twice-daily, n = 65) at a single Canadian clinic.ResultsMixed-effects modeling revealed significantly faster improvement (group-by-time interaction) for twice-daily versus once-daily DMPFC-rTMS. Across both groups, the pace of improvement showed a consistent relationship with number of cumulative sessions, but not with cumulative number of pulses. Although the twice-daily group completed treatment in half as many days, final clinical outcomes did not differ significantly between groups on dichotomous measures (response/remission rates: once-daily, 35.4%/33.8%; twice-daily, 41.5%/35.4%), or continuous measures, or on overall response distribution.ConclusionsTwice-daily rTMS appears feasible, tolerable, and capable of achieving comparable results to once-daily rTMS, while also reducing course length approximately twofold. Therapeutic gains tracked the cumulative number of sessions, not pulses. Future randomized studies comparing once-daily to multiple-daily rTMS sessions, while controlling for number of pulses, may be warranted.



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Accelerated HF-rTMS in the elderly depressed: A feasibility study

Publication date: Available online 31 October 2017
Source:Brain Stimulation
Author(s): Alexandre Dardenne, Chris Baeken, Cleo L. Crunelle, Chris Bervoets, Frieda Matthys, Sarah C. Herremans




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tDCS changes in motor excitability are specific to orientation of current flow

Publication date: Available online 7 November 2017
Source:Brain Stimulation
Author(s): Vishal Rawiji, Matteo Ciocca, André Zacharia, David Soares, Dennis Truong, Marom Bikson, John Rothwell, Sven Bestmann
BackgroundMeasurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the folded cortex results in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS.MethodsHere we test this idea by using Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP) to measure changes in corticospinal excitability following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus.ResultsCurrent flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces non-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is thought to select different afferent pathways to M1.ConclusionsOur results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.



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Early symptom improvement at 10 sessions as a predictor of rTMS treatment outcome in major depression

Publication date: Available online 19 October 2017
Source:Brain Stimulation
Author(s): Kfir Feffer, Hyewon Helen Lee, Farrokh Mansouri, Peter Giacobbe, Fidel Vila-Rodriguez, Sidney H. Kennedy, Zafiris J. Daskalakis, Daniel M. Blumberger, Jonathan Downar
BackgroundPredicting rTMS nonresponse could be helpful in sparing patients from futile treatment, and in improving use of limited rTMS resources. While several predictive biomarkers have been proposed, few are accurate for individual-level prediction; none have entered routine use. An alternative approach in pharmacotherapy predicts outcome from early response; patients showing minimal (e.g., ≤20%) improvement at 2 weeks can be predicted as nonresponders with negative predictive values (NPV) > 80–90%. This approach has recently been extended to ECT, but never before to rTMS.ObjectiveTo assess the accuracy of 2-week clinical response in predicting rTMS treatment outcome.MethodsWe reviewed clinical symptom scores for 101 patients who underwent 20 sessions of dorsomedial prefrontal rTMS for unipolar major depression in a naturalistic retrospective case series, defining nonresponders both at the conventional <50% improvement criterion and at a more stringent <35% criterion.ResultsPatients achieving <20% improvement at session 10 were correctly predicted as nonresponders with NPVs of 88.2% by the conventional and 80.4% by the stringent criterion. Achieving <10% improvement at session 10 predicted nonresponse with NPVs of 89.5% and 86.8% by conventional and stringent criteria, respectively. Using the least-depressed score of either session 5 or 10, <20% improvement predicted nonresponse with NPVs of 91.3% and 82.6%, and <10% improvement predicted nonresponse with NPVs of 93.5% and 93.5%, by conventional and stringent criteria.ConclusionFor DMPFC-rTMS, a '<20% improvement at 2 weeks' rule concurred with previous pharmacotherapy and ECT studies on predicting nonresponse, and could prove useful for treatment decision-making in clinical settings.



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Vagus nerve magnetic modulation facilitates dysphagia recovery in patients with stroke involving the brainstem - A proof of concept study

Publication date: Available online 7 November 2017
Source:Brain Stimulation
Author(s): Wang-Sheng Lin, Chen-Liang Chou, Miao-Hsiang Chang, Yuh-Mei Chung, Fu-Gong Lin, Po-Yi Tsai
Background & aimsStroke involving the brainstem (SBS) causes severe oropharyngeal dysphagia (OD). Research on the therapeutic efficacy of vagus nerve modulation (VNM) by using repetitive transcranial magnetic stimulation (rTMS) in SBS patients with OD has been limited thus far. We aimed to assess the effect of VNM by using rTMS in improving swallowing function after SBS.MethodWe conducted a sham-controlled, double-blinded, parallel pilot study in 28 SBS patients with OD randomly allocated to a real rTMS group (n = 13; TMSreal) or a sham group (n = 15; TMSsham). For VNM, 5-Hz rTMS was applied to the left mastoid in 10 sessions. We evaluated all patients for swallowing function before and after rTMS conditioning, assessed on the 8-point Penetration–Aspiration Scale (PAS) through videofluoroscopy and the Australian Therapy Outcome Measures–Swallowing scale (AusTOMs). We measured the amplitude and latency of cricopharyngeal motor evoked potentials (CP-MEPs) as the neurophysiological parameters.ResultsTMSreal exhibited significant improvement in all swallowing outcomes—neurophysiological, radiological, and functional—compared with TMSsham: We noted higher CP-MEP amplitude (p = 0.004), shorter CP-MEP latency (p = 0.004), a lower PAS score (p = 0.001), and a higher AusTOMs score (p < 0.001) following rTMS in TMSreal. Moreover, the neurophysiological improvements were significantly correlated with the functional outcomes (p < 0.05).ConclusionsOur results encourage the application of VNM by using rTMS for improving swallowing function after SBS. The immediate therapeutic effects suggest that this novel intervention can be an effective complementary therapy to traditional oropharyngeal rehabilitation.Clinical trial registrationURL: http://ift.tt/1xHjpsE. Unique identifier: NCT02893033.



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Simultaneous rTMS and psychotherapy in major depressive disorder: Clinical outcomes and predictors from a large naturalistic study

Publication date: Available online 11 November 2017
Source:Brain Stimulation
Author(s): Lana Donse, Frank Padberg, Alexander T. Sack, A. John Rush, Martijn Arns
BackgroundRepetitive transcranial magnetic stimulation (rTMS) is considered an efficacious non-invasive neuromodulation treatment for major depressive disorder (MDD). However, little is known about the clinical outcome of combined rTMS and psychotherapy (rTMS + PT). Through common neurobiological brain mechanisms, rTMS + PT may exert enhanced antidepressant effects compared to the respective monotherapies.ObjectiveThe current naturalistic study aimed to evaluate feasibility and clinical outcome of rTMS + PT in a large group of MDD patients. The second aim was to identify clinical predictors of response and remission.MethodsA total of 196 patients with MDD were treated with at least 10 sessions of simultaneous rTMS and PT. rTMS was applied over the DLPFC, either 10 Hz left or 1 Hz right. Psychotherapy was based on principles of cognitive behavioral therapy (CBT). Symptoms were measured using the BDI each fifth session until end of treatment and at 6-month follow-up. Comparisons were made between responders and non-responders, as well as between the 10 Hz and 1 Hz protocol. Additionally, baseline variables and early BDI change were evaluated as predictors of response/remission.Major findings and conclusions1) Combining rTMS and PT resulted in a 66% response and a 56% remission rate at the end of treatment with 60% sustained remission at follow-up. Compared to previous findings in RCTs, these rates are relatively high; 2) No differences were found between the 10 Hz and 1 Hz TMS regarding clinical outcome; 3) Clinical baseline variables were not predictive of treatment outcomes; 4) Early symptom improvement (at session 10) was highly predictive of response, and may therefore be used to guide rTMS + PT continuation; 5) Based on the current findings in a large naturalistic study, future studies employing a more standardized method are warranted to draw solid conclusions on the unique effect of rTMS + PT.



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Masthead

Publication date: November–December 2017
Source:Brain Stimulation, Volume 10, Issue 6





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Editorial Board

Publication date: November–December 2017
Source:Brain Stimulation, Volume 10, Issue 6





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Table of Contents

Publication date: November–December 2017
Source:Brain Stimulation, Volume 10, Issue 6





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Safety of repeated sessions of transcranial direct current stimulation: A systematic review

Publication date: Available online 31 October 2017
Source:Brain Stimulation
Author(s): Stevan Nikolin, Christina Huggins, Donel Martin, Angelo Alonzo, Colleen K. Loo
BackgroundRepeated sessions of transcranial direct current stimulation (tDCS) are increasingly used for therapeutic applications. However, adverse events (AEs) associated with repeated sessions have not been comprehensively evaluated.ObjectiveThe aim of this study was therefore to evaluate the safety of repeated sessions of tDCS, examining AE risk relative to tDCS exposure. Further, to identify whether certain participant populations are particularly at risk from tDCS.MethodsA systematic review and meta-analysis included sham-controlled studies (up to June 2017) involving two or more tDCS sessions, spaced not more than a day apart. Data was extracted on AEs reported, total tDCS exposure (cumulative charge), and diagnostic groups (Healthy, Pain Disorder, Stroke, Neurocognitive Disorder, Neuropsychiatric Disorder, and Other). Univariate simple linear meta-regression analyses examined AE likelihood, comparing active and sham tDCS, with increasing exposure. Rates of AEs were compared for diagnostic groups.Results158 studies (total 4130 participants) met inclusion criteria and were included for quantitative analyses. The incidence of AEs (examined per session, by proportion of participants, and by the number of studies reporting AEs) did not increase with higher levels of tDCS exposure. Furthermore, AE rates were not found to be greater for any diagnostic group.ConclusionsLittle evidence was found to suggest that repeated sessions of active tDCS pose increased risk to participants compared to sham tDCS within the limits of parameters used to date. Increased risks associated with greater levels of exposure to tDCS, or rare and under-reported AEs, however, cannot be ruled out.



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Information for Authors

Publication date: November–December 2017
Source:Brain Stimulation, Volume 10, Issue 6





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Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders

Publication date: Available online 27 October 2017
Source:Brain Stimulation
Author(s): N.W. Bailey, K.E. Hoy, N.C. Rogasch, R.H. Thomson, S. McQueen, D. Elliot, C.M. Sullivan, B.D. Fulcher, Z.J. Daskalakis, P.B. Fitzgerald
BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction.Primary hypothesesWe expected higher theta and alpha activity in responders compared to non-responders to rTMS.MethodsFifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5–8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4–8 Hz), upper alpha (10–12.5 Hz), and gamma (30–45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately.ResultsResponders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm.ConclusionBaseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression.



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Electroconvulsive therapy, depression, the immune system and inflammation: A systematic review

Publication date: Available online 19 October 2017
Source:Brain Stimulation
Author(s): Antoine Yrondi, Marie Sporer, Patrice Péran, Laurent Schmitt, Christophe Arbus, Anne Sauvaget
BackgroundThe management and treatment of major depressive disorder are major public health challenges, the lifetime prevalence of this illness being 4.4%–20% in the general population. Major depressive disorder and treatment resistant depression appear to be, in part, related to a dysfunction of the immune response. Among the treatments for depression ECT occupies an important place. The underlying cerebral mechanisms of ECT remain unclear.Objectives/HypothesisThe aim of this review is to survey the potential actions of ECT on the immuno-inflammatory cascade activated during depression.MethodsA systematic search of the literature was carried out, using the bibliographic search engines PubMed and Embase. The search covered articles published up until october 2017.The following MESH terms were used: Electroconvulsive therapy AND (inflammation OR immune OR immunology).ResultsOur review shows that there is an acute immuno-inflammatory response immediately following an ECT session. There is an acute stress reaction. Studies show an increase in the plasma levels of cortisol and of interleukins 1 and 6. However, at the end of the course of treatment, ECT produces, in the long term, a fall in the plasma level of cortisol, a reduction in the levels of TNF alpha and interleukin 6.LimitationsOne of the limitations of this review is that a large number of studies are relatively old, with small sample sizes and methodological bias.ConclusionAdvances in knowledge of the immuno-inflammatory component of depression seem to be paving the way towards models to explain the mechanism of action of ECT.



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Stochastic resonance in the human vestibular system – Noise-induced facilitation of vestibulospinal reflexes

Publication date: Available online 31 October 2017
Source:Brain Stimulation
Author(s): M. Wuehr, J.C. Boerner, C. Pradhan, J. Decker, K. Jahn, T. Brandt, R. Schniepp
BackgroundThere is strong evidence that the presence of noise can enhance information processing in sensory systems via stochastic resonance (SR).ObjectivesTo examine the presence of SR in human vestibulospinal reflex function.MethodsHealthy subjects were stimulated with 1 Hz sinusoidal GVS of varying amplitudes (0–1.9 mA). Coherence between GVS input and stimulation-induced motion responses was determined and psychometric function fits were subsequently used to determine individual vestibulospinal reflex thresholds. This procedure was repeated with additional application of imperceptible white noise GVS (nGVS).ResultsnGVS significantly facilitated the detectability of weak subthreshold vestibular inputs (p < 0.001) and thereby effectively lowered the vestibulospinal threshold in 90% of participants (p < 0.001, mean reduction: 17.5 ± 14.6%).ConclusionThis finding provides evidence for the presence of SR-dynamics in the human vestibular system and gives a functional explanation for previously observed ameliorating effects of low-intensity vestibular noise stimulation on balance control in healthy subjects and patients with vestibular hypofunction.



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Simultaneous aerobic exercise and rTMS: Feasibility of combining therapeutic modalities to treat depression

Publication date: Available online 31 October 2017
Source:Brain Stimulation
Author(s): Ryan E. Ross, Catherine J. VanDerwerker, Jennifer H. Newton, Mark S. George, E. Baron Short, Gregory L. Sahlem, A.J. Manett, James B. Fox, Chris M. Gregory




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Sensory percepts induced by microwire array and DBS microstimulation in human sensory thalamus

Publication date: Available online 27 October 2017
Source:Brain Stimulation
Author(s): Brandon D. Swan, Lynne B. Gasperson, Max O. Krucoff, Warren M. Grill, Dennis A. Turner
BackgroundMicrostimulation in human sensory thalamus (ventrocaudal, VC) results in focal sensory percepts in the hand and arm which may provide an alternative target site (to somatosensory cortex) for the input of prosthetic sensory information. Sensory feedback to facilitate motor function may require simultaneous or timed responses across separate digits to recreate perceptions of slip as well as encoding of intensity variations in pressure or touch.ObjectivesTo determine the feasibility of evoking sensory percepts on separate digits with variable intensity through either a microwire array or deep brain stimulation (DBS) electrode, recreating "natural" and scalable percepts relating to the arm and hand.MethodsWe compared microstimulation within ventrocaudal sensory thalamus through either a 16-channel microwire array (∼400 kΩ per channel) or a 4-channel DBS electrode (∼1.2 kΩ per contact) for percept location, size, intensity, and quality sensation, during thalamic DBS electrode placement in patients with essential tremor.ResultsPercepts in small hand or finger regions were evoked by microstimulation through individual microwires and in 5/6 patients sensation on different digits could be perceived from stimulation through separate microwires. Microstimulation through DBS electrode contacts evoked sensations over larger areas in 5/5 patients, and the apparent intensity of the perceived response could be modulated with stimulation amplitude. The perceived naturalness of the sensation depended both on the pattern of stimulation as well as intensity of the stimulation.ConclusionsProducing consistent evoked perceptions across separate digits within sensory thalamus is a feasible concept and a compact alternative to somatosensory cortex microstimulation for prosthetic sensory feedback. This approach will require a multi-element low impedance electrode with a sufficient stimulation range to evoke variable intensities of perception and a predictable spread of contacts to engage separate digits.



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TLR8 activation and inhibition by guanosine analogs in RNA: importance of functional groups and chain length

Publication date: Available online 11 November 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Tiannan Hu, Scott R. Suter, Madeline M. Mumbleau, Peter A. Beal
Toll-like receptor 8 (TLR8) is an important component of the human innate immune system that recognizes single stranded RNA (ssRNA). Recent x-ray crystal structures of TLR8 bound to ssRNA revealed a previously unrecognized binding site for a 5'-UpG-3' dinucleotide. Here we use an atomic mutagenesis strategy coupled with a cellular TLR8 activation assay to probe the importance of specific functional groups present on the guanine base in RNA-mediated receptor agonism and antagonism. Results from RNA analogs containing 7-deazaguanosine, 2-aminopurine and inosine confirm the importance of guanine N7, O6 and N2, respectively, in TLR8 activation. Nevertheless, these RNAs each retained TLR8 antagonism activity. RNA containing 7-deaza-8-azainosine (7d8aI) was prepared from a novel phosphoramidite and found to be a weaker TLR8 activator than guanosine-containing RNA. However, 7d8aI-containing RNA also retained TLR8 antagonism activity indicating that removal of multiple TLR8 H-bonding sites on guanine is insufficient for blocking TLR8 antagonism by guanine-containing RNA. We also identified an oligoribonucleotide length dependence on both TLR8 activation and antagonism. These studies extend our understanding of the effects of nucleobase modification on immune stimulation and will inform the design of novel RNA-based therapeutics.

Graphical abstract

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Defining the Role of Free Flaps in Partial Breast Reconstruction

J reconstr Microsurg
DOI: 10.1055/s-0037-1607363

Background Free flaps have a well-established role in breast reconstruction after mastectomy; however, their role in partial breast reconstruction remains poorly defined. We reviewed our experience with partial breast reconstruction to better understand indications for free tissue transfer. Methods A retrospective review was performed of all patients undergoing partial breast reconstruction at our center between February 2009 and October 2015. We evaluated the characteristics of patients who underwent volume displacement procedures versus volume replacement procedures and free versus pedicled flap reconstruction. Results There were 78 partial breast reconstructions, with 52 reductions/tissue rearrangements (displacement group) and 26 flaps (replacement group). Bra cup size and body mass index (BMI) were significantly smaller in the replacement group. Fifteen pedicled and 11 free flaps were performed. Most pedicled flaps (80.0%) were used for lateral or upper pole defects. Most free flaps (72.7%) were used for medial and inferior defects or when there was inadequate donor tissue for a pedicled flap. Complications included hematoma, cellulitis, and one aborted pedicled flap. Conclusion Free and pedicled flaps are useful for partial breast reconstruction, particularly in breast cancer patients with small breasts undergoing breast-conserving treatment (BCT). Flap selection depends on defect size, location, and donor tissue availability. Medial defects are difficult to reconstruct using pedicled flaps due to arc of rotation and intervening breast tissue. Free tissue transfer can overcome these obstacles. Confirming negative margins before flap reconstruction ensures harvest of adequate volume and avoids later re-operation. Judicious use of free flaps for oncoplastic reconstruction expands the possibility for breast conservation.
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Recent advances in melanoma research via “omics” platforms

Publication date: Available online 11 November 2017
Source:Journal of Proteomics
Author(s): Carmen Rodríguez-Cerdeira, Alberto Molares-Vila, Miguel Carnero-Gregorio, Alberte Corbalán-Rivas
Melanoma has a high mortality rate and metastatic melanoma is highly resistant to conventional therapies. "Omics" fields such as proteomics and microRNA and exosome studies have provided new knowledge to complement the information generated by genomic studies. This work aimed to review the current status of biomarker discovery for melanoma through multi-"omics" platforms. A few sets of novel microRNAs and proteins are described, some of them with important implications in suppressing melanoma at different stages. Upregulation of genes involved in angiogenesis, immunosuppressive factors, modification of stroma, capture of melanoma cells in lymph nodes and factors responsible for tumour cell recruitment have been identified in exosomes, among molecules with other functions. A remarkable series of proteins involved in epithelial-mesenchymal/mesenchymal-epithelial transitions, inflammation, motility, proliferation and progression processes, centrosome amplification, aneuploidy, inhibition of CD8+ effector T-cells, and metastasis in general were identified. Genomic and protein-protein interactions or metabolome levels were not analysed.Proteomics tools such as Orbitrap shotgun mass spectrometry or deep mining proteomic analysis utilizing high-resolution reversed phase nanoseparation in combination with mass spectrometry are also discussed. The application of these tools together with bioinformatics approaches applied to the clinical setting will enable the implementation of personalized medicine in the near future.

Graphical abstract

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CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: putative roles for IGF-1R and TLR4

Publication date: Available online 11 November 2017
Source:Brain Research Bulletin
Author(s): O.M. Ogundele, C.C. Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-D-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice. Although CaMKIIα is involved in modulation of NMDAR activity, it is equally linked to inflammatory and neurotropin signaling in neurons. Based on these propositions, we speculate that non-neurotransmitter upstream receptors associated with neurotropic and inflammatory signaling activities of CaMKIIα may alter its synaptic function. Besides, how these receptors (i.e. inflammatory and neurotropic receptors) alter CaMKIIα function (phosphorylation) relative to hippocampal NMDAR activity in schizophrenia is poorly understood. Here, we examined the relationship between toll-like receptor (TLR4; inflammatory), insulin-like growth factor receptor 1 (IGF-1R; neurotropic) and CaMKIIα expression in the hippocampus of behaviorally deficient schizophrenic mice after we induced schizophrenia through NMDAR inhibition.Schizophrenia was induced in WT (C57BL/6) mice through intraperitoneal administration of 30mg/Kg ketamine (NMDAR antagonist) for 5days (WT/SCZ). Five days after the last ketamine treatment, wild type schizophrenic mice show deficiencies in sociability and social novelty behavior. Furthermore, there was a significant decrease in hippocampal CaMKIIα (p <0.001) and IGF-1R (p <0.001) expression when assessed through immunoblotting and confocal immunofluorescence microscopy. Additionally, WT schizophrenic mice show an increased percentage of phosphorylated CaMKIIα in addition to upregulated TLR4 signaling (TLR4, NF-κB, and MAPK/ErK) in the hippocampus. To ascertain the functional link between TLR4, IGF-1R and CaMKIIα relative to NMDAR hypofunction in schizophrenia, we created hippocampal-specific TLR4 knockdown mouse using AAV-driven Cre-lox technique (TLR4 KD). Subsequently, we inhibited NMDAR function in TLR4 KD mice in an attempt to induce schizophrenia (TLR4 KD SCZ). Interestingly, IGF-1R and CaMKIIα expressions were preserved in the TLR4 KD hippocampus after attenuation of NMDAR function. Furthermore, TLR4 KD SCZ mice showed no prominent defects in sociability and social novelty behavior when compared with the control (WT).Our results show that a sustained IGF-1R expression may preserve the synaptic activity of CaMKIIα while TLR4 signaling ablates hippocampal CaMKIIα expression in NMDAR hypofunction schizophrenia. Together, we infer that IGF-1R depletion and increased TLR4 signaling are non-neurotransmitter pro-schizophrenic cues that can reduce synaptic CaMKIIα activity in a pharmacologic mouse model of schizophrenia.



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Sarcopenia in Peripheral Arterial Disease: Prevalence and Impact on Functional Status

Publication date: Available online 11 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Odessa Addison, Steven J. Prior, Rishi Kundi, Monica C. Serra, Leslie I. Katzel, Andrew W. Gardner, Alice S. Ryan
ObjectivesTo determine the prevalence of sarcopenia in older men with peripheral arterial disease (PAD) and to compare to a subset of the group to age, race, sex, and body mass index (BMI)-matched non-PAD control counterparts. We also sought to compare the functional status of those with PAD with and without sarcopenia.DesignCohort study.SettingA Veterans Affairs medical center.ParticipantsSedentary, community dwelling men age 50+ years with a confirmed diagnosis of PAD (N=108; 44% black; BMI 27.8 ± 0.4 kg/m²; ABI:0.62 ± 0.01; mean ±SEM).InterventionsNot applicable.Main OutcomesDual-energy x-ray absorptiometry scans were used to assess appendicular lean mass (ALM) and determine the prevalence of sarcopenia by ALM/height² (ALM/ht²). Treadmill tests were used to determine claudication onset time (COT), peak walking time (PWT), and claudication recovery time (CRT). Six-minute walk distance (6MWD) was also measured.ResultsSarcopenia prevalence in our PAD cohort was 25%. The PAD subset (N=42) matched with control counterparts for race, sex, age, and BMI had higher prevalence rates compared with their non-PAD counter parts (23.8% vs 2.4%, P<0.05). Individuals with sarcopenia (N=28) had lower 6MWD (p<0.05; 326± 18.8 vs 380 ± 9.7 meters) and higher CRT (p<0.05; 592 ± 98 vs 395 ± 29 seconds) compared to individuals with PAD but without sarcopenia (N=80). There was no difference in COT or PWT between the PAD groups.ConclusionsMen with PAD demonstrate a high prevalence of sarcopenia. Those with sarcopenia and PAD demonstrate decreased mobility function.



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Pain Neurophysiology Education and Therapeutic Exercise for Patients With Chronic Low Back Pain: A Single-Blind Randomized Controlled Trial.

Publication date: Available online 11 November 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bodes Pardo Gema., Lluch Girbés Enrique., Roussel Nathalie A., Gallego Izquierdo Tomás., Jiménez Penick Virginia., Pecos Martín Daniel.
AimTo assess the effect of a pain neurophysiology education program plus therapeutic exercise for patients with chronic low back pain (CLBP).DesignSingle-blind randomized controlled trial.SettingPrivate clinic (Clínica Bonn) and Alcalá de Henares University, Madrid, Spain.Participants56 patients with CLBP for 6 months or more.InterventionParticipants were randomized to receive either a therapeutic exercise (TE) program consisting of motor control, stretching, and aerobic exercises (TE group, n=28) or the same therapeutic exercise program in addition to a pain neurophysiology education program (PNE+TE group, n=28), conducted in two 30 to 50 minute sessions in groups of 4 to 6 participants.Main outcomes measuresThe primary outcome was pain intensity rated on the Numeric Pain Rating Scale which was completed immediately following treatment and at a 1-month and 3-month follow-up. Secondary outcome measures were pressure pain threshold, finger-to-floor distance, Roland-Morris Disability Questionnaire, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and the Patient Global Impression of Change.ResultsAt the 3-month follow-up, a large change in pain intensity (-2.2 (-2.93,-1.28), p<0.001; d=1.37) was observed for the PNE+TE group, and a moderate effect size was observed for the secondary outcome measures.ConclusionCombining pain neurophysiology education plus therapeutic exercise resulted in significantly better results for participants with CLBP, with a large effect size, compared to therapeutic exercise alone.



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