Purpose: We present a novel technique to directly measure the eyelid upward force generation. This technique can be used during routine clinical examination using an inexpensive, portable force gauge. Methods: This prospective case series was conducted January to June 2015 in an ophthalmology clinic affiliated with a tertiary care medical center. A convenience sample of 42 patients (40–90 years of age) without known eyelid pathology participated. The eyelid upward net force generated was measured directly using a handheld dynamometer noninvasively attached to the upper eyelid. Comparison of the eyelid-brow upward force generated with eyelid upward net force generated allowed us to assess the contribution of levator and frontalis muscles to the force generated during upgaze. Data were evaluated with relation to gender and age. Results: Upper eyelid force generated was 53.3 g OD and 53.9 g OS; the generated force during frontalis muscle fixation was 38.4 g OD and 41.1 g OS. The levator and frontalis muscles showed a 3:1 ratio respectively in their contribution to the force generated during upgaze. Although no statistically significant differences were seen between eyes, gender, or within age groups, younger patients showed increased generating force which is attributed to the levator muscle. Interclass correlation coefficient showed virtually no correlation between clinical eyelid assessments and direct muscle force measurement. Reliability for repeated direct force measurements by the same physician was strong, with interclass correlation coefficient 0.951 to 0.969. No adverse events occurred. Conclusions: We describe a simple, reliable, inexpensive, new method for assessing upper eyelid upward force generation. Because the levator muscle serves as the primary contributor to eyelid elevation, this directly measurable eyelid assessment may help to increase understanding of its functional contribution and assessment when assessing eyelid pathologies. Accepted for publication July 11, 2017. Presented at Annual Conference of Ocular Microsurgery, January 8-10, 2015 in Eilat, Israel. The authors have no financial or conflicts of interest to disclose. Shay Ofir, Avner Belkin, and Arie Y. Nemet contributed to conception, design, analysis, writing, and literature search; Shay Ofir contributed to data collection, materials and patient recruitment; Arie Y. Nemet contributed to critical revision and final approval; and Shay Ofir had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Address correspondence and reprint requests to Shay Ofir, MD, Department of Ophthalmology, Meir Medical Center, 59 Tshernichovsky St., Kfar Saba 44281, Israel. E-mail: shayofirl@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
Δευτέρα 15 Ιανουαρίου 2018
Medial Buttressing in Orbital Blowout Fractures
Purpose: To study whether ethmoidectomy predisposes the orbit to medial wall fracture with lesser trauma. Methods: An interventional cadaver study of 5 heads (10 orbits); the left or right orbit was randomized to undergo endoscopic complete ethmoidectomy with the fellow orbit as control. Fractures were induced with direct globe trauma, and heads underwent CT scanning. Energy to induce fracture, peak orbital pressure at time of fracture, fracture pattern, and volume of herniated tissue were measured and analyzed. Results: Fractures were induced in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained orbital fracture at less energy required (2.14 ± 0.66 vs. 3.10 ± 0.19 J, mean difference: −0.96 ± 0.33 J, p
Seminoma Metastatic to the Orbit
Purpose: Seminomas are solid tumors in young men, but which rarely metastasize to the orbit. The authors review the known literature on seminoma metastatic to the orbit, and describe an additional case in a 33-year-old man. Methods: A literature search was performed on the MEDLINE database using keywords "seminoma," "testicular germ-cell tumors," "testicular cancer," "testicular neoplasm," "orbital metastasis," and "germ-cell neoplasms." Results: Malignant neoplasms of the testis account for only 1% of cancers in men. None-the-less, testicular germ cell seminoma is the most common solid tumor found in young men between the ages of 15 and 39. Only seven previous cases have been mentioned in the literature. The pathogenesis remains unclear although genetic, environmental, and maternal factors may play a role. The number of cases is too few to determine the best treatment options, but surgical excision and adjunctive orbital radiotherapy appear to be most appropriate. Conclusions: Although metastases to the orbit are rare, seminoma should be considered in the differential diagnosis of all young men with proptosis. Accepted for publication October 9, 2017. The authors have no financial or conflicts of interest to disclose. Dr. Carol Shields served as guest editor for this submission. Address correspondence and reprint requests to Jonathan J. Dutton, M.D., Ph.D., Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599. E-mail: jonathan_dutton@med.unc.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
Gelatin-Based Hemostatic Agents: Histopathologic Differences
Improved Long-term Volume Retention of SVF-gel Grafting with Enhanced Angiogenesis and Adipogenesis
Background The apoptosis of mature adipocytes after fat grafting can result in chronic inflammation, absorption, and fibrosis, leading to unpredictable outcomes. Selective elimination of mature adipocytes may result in better outcomes and a different underlying retention mode. We previously developed a mature-adipocyte-free product, SVF-gel, derived from lipoaspirate, which eliminates adipocytes while preserving the stromal vascular fraction. This study investigated the retention and regeneration mode of SVF-gel grafting. Methods Nude mice were grafted with human-derived SVF-gel or Coleman fat. Detailed cellular events over 3 months were investigated histologically and immunohistochemically. Results The retention rate 90 days after grafting was significantly higher for SVF-gel grafts than for standard Coleman fat (82% ± 15% vs. 42% ± 9%, P
Measurement of warping angle in human rib graft; Experimental study
To determine the warping angle of the costal cartilage in vivo. A nasal framework reconstruction with a rib graft was performed in a total of 130 patients. After the cartilage specimens were prepared, the remaining grafts were used for the experimental study. The angle of warping in all grafts was measured at 0, 30, and 60 minutes, after 24 hours and after one week. In this study, 8 subgroups of graft thicknesses from central and peripheral groups, which were determined according to the perichondral distance of the grafts, were evaluated, and the warping angles of a total of 48 osteochondral and chondral grafts were individually measured. Three-way analysis of variance was used to compare the change in warping over time to detect differences in the grafts. Significant differences were not observed in the 1-3 mm thick grafts of peripheral and central origin before 30 minutes(P>0.05), although significant differences were observed in these groups for all time periods after 30 minutes(P0.05). In the central origin grafts thinner than 1 mm, significant differences were not observed in the warping angle for all time periods(P>0.05), although significant differences were observed in the same grafts of peripheral origin(P
Cheek Volumization and Nasolabial folds
The impression that cheek filling results in longitudinal shortening ("lift") of the skin and elevation of the nasolabial crease(NLC) or nasolabial fold (NLF) has become common within the facial injection community, but remains unsubstantiated. In this study, seventy-seven patients were evaluated pre and post-injection injection of the cheeks with an Hyaluronic Acid filler using a 3-dimensional camera system. A constant pattern of skin expansion away from the center of the injection and perpendicular to the surface of the skin was observed. A subgroup of 37 patients without differences in their pre and post-injection facial expression were analyzed by direct comparison and failed to demonstrate lateral traction (or "pull") on the intervening skin from the cheek injection site to the nasolabial crease. Further, there was no photographic difference in the nasolabial fold or nasolabial crease. The only patients who demonstrated photographic improvement of the medial face were those who had filler placed directly in the transition between the lateral nasolabial fold and cheek (nasojugal crease). It is likely that expanding the nasojugal crease is the direct visual cue that leads to perceived improvement in the nasolabial fold. No disclosures Corresponding author Val Lambros, MD , Clinical professor of Plastic Surgery, University of California Irvine, 2121 E Coast Highway #200, Corona Del Mar Ca 92925, Lambrosone@aol.com ©2018American Society of Plastic Surgeons
Consequences of the F.D.A. Directed Moratorium on Silicone Gel Breast Implants – 1992-2006
The FDA silicone gel breast implant moratorium occurred 25 years ago. The immediate and long-term consequences of the moratorium are reviewed and assessed. Financial Disclosure Statement: Nothing to disclose. Corresponding Author: Norman M. Cole, M.D., 2208 Lake Ridge Drive, Belmont, NC 28012 USA ©2018American Society of Plastic Surgeons
“A fresh cadaver study on indocyanine green fluorescence lymphography: A new whole body imaging technique for investigating the superficial lymphatics.”
Background: Identification of the lymphatic system in cadavers is painstaking because lymphatic vessels have very thin walls and are transparent. Selection of appropriate contrast agents is a key factor for successfully visualizing the lymphatics. In this study, we introduce a new imaging technique of lymphatic mapping in whole body of fresh cadavers. Methods: Ten fresh human cadavers were used for this study. We injected 0.1 mL of indocyanine green fluorescence (ICG) solution subcutaneously at multiple spots along the watershed lines between lymphatic territories and hand and foot regions. After the body was scanned by the near infrared camera system, fluorescent tissues were harvested and histological examination was performed under the microscope equipped with the infrared camera system to confirm they were the lymphatics. Results: Subcutaneously injected ICG was immediately transported into the lymphatic vessels after gentle massage on the injection points. Sweeping massage along the lymphatic vessels facilitated ICG transport inside the lymphatic vessel to move towards the lymph nodes. The lymphatic system was visualized well in the whole body. Histological examinations confirmed that ICG was detected in the lymphatic lumens specifically, even when located far from the injected points. Conclusions: The lymphatic system could be visualized in whole body fresh cadavers, as in living bodies, using ICG fluorescence lymphography. Compatibility of ICG lymphography would be open to use cadaveric specimens for macro and microscopical analysis. Financial Disclosure Statement: The authors have no financial interest to declare in relation to the content of this article. Acknowledgments: This work was supported by the Japan Society for the Promotion of Science via Grants-in-Aid for Scientific Research (KAKENHI Award Number: 16K20358) and Research Foundation for the Electrotechnology of Chubu. Corresponding author: Akira Shinaoka, Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, 700-8558, Japan. Email: a-shinaoka@okayama-u.ac.jp ©2018American Society of Plastic Surgeons
Vitamin K5 is an efficient photosensitizer for ultraviolet A light inactivation of bacteria
Abstract
Photodynamic treatment combining light and a photosensitizer molecule can be an effective method to inactivate pathogenic bacteria. This study identified vitamin K5 as an efficient photosensitizer for ultraviolet light A (UVA)-induced bacterial inactivation. Six bacterial species, Bacillus cereus (vegetative form), Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, and two species of antibiotic-resistant bacteria, Pseudomonas aeruginosa* and Staphylococcus aureus*, were suspended in aqueous solutions with or without vitamin K5 and exposed to UVA irradiation. UVA irradiation (5.8 J cm−2) with vitamin K5 (1600 μmol l−1) reduced the colony forming units (CFU) of these bacteria by three to seven logs. Antibiotic resistant bacteria were also susceptible to the bactericidal effects of UVA and vitamin K5 combination treatment. Inactivation of bacteria in human plasma required higher doses of UVA light and vitamin K5. UVA irradiation (30 J cm−2) with vitamin K5 (2000 μ mol l−1) reduced Escherichia coli and Staphylococcus aureus spiked into human plasma by seven logs CFU/ml. Reactive oxygen species, such as superoxide anion radicals and hydroxyl radicals, were found to be generated in vitamin K5 aqueous solution after UVA irradiation, suggesting these oxygen species may mediate the inactivation of the bacteria.EsrB negatively regulates expression of the glutamine sythetase GlnA in the fish pathogen Edwardsiella piscicida
Abstract
Edwardsiella piscicida is a gram-negative bacterial pathogen invading a wide range of fish species. Response regulator EsrB is essential for activation of type III and type VI secretion systems (T3/T6SS). In this study, proteomes of the wild type E. piscicida EIB202 and a ΔesrB mutant strains were compared to identify the regulon components of EsrB cultured in DMEM allowing T3/T6SS expression. As a result, 19 proteins showed different expression, which were identified to be associated with T3/T6SS, related to amino acid transport and metabolism, and energy production. Particularly, GlnA, a glutamine synthetase essential for ammonia assimilation and glutamine biosynthesis from glutamate, was found to be regulated negatively by EsrB. Moreover, GlnA affected bacterial growth in vitro and bacterial colonization in vivo. Collectively, our results indicated that EsrB plays important roles in regulating the expression of metabolic pathways and virulence genes, including glutamine biosynthesis in E. piscicida during infection.Prevalence of metabolic syndrome in children with moderate to severe psoriasis treated with TNF inhibitors in comparison to conventional agents
Abstract
Association of childhood psoriasis with metabolic syndrome has not been studied well. TNF-alfa contributes to the inflammation seen in metabolic syndrome, and recently etanercept has shown to reduce the levels of inflammatory markers. Assessment of prevalence of metabolic syndrome in juvenile psoriasis patients in Kuwait. We included 236 patients with moderate to severe psoriasis below 18 years treated for at least 24 weeks with TNF inhibitors (Group A), and equal number of age and sex matched cases treated with conventional medications (Group B). The metabolic syndrome (MBS) was defined according to the International Diabetes Foundation (IDF 2007 criteria for children). Increased waist circumference was seen in 56.77% of cases in Group A. Triglyceridemia was less frequent in Group A. MBS was higher in Group B [41·52% vs. 50·42%, odds ratio (OR) 1·76, 95% CI 1.19–2.41; p = .005]. Psoriasis is associated with higher prevalence of metabolic syndrome in children. Six months of anti TNF treatment showed lesser association with metabolic syndrome. With fasting blood glucose, and serum TG seen in significantly lesser number of patients in this group.
Clinical evaluation of a novel fractional radiofrequency device for hair growth: Fractional radiofrequency for hair growth stimulation
Abstract
AGA is a common disorder. Different treatments are available to prevent hair loss and achieve hair growth with variable results. The purpose of the present study was to evaluate the efficacy and safety of a novel fractional radiofrequency (RF) device (HairLux, Innogen Technologies Ltd., Yokneam, Israel), to prevent hair loss and induce hair growth. Twenty-five patients received 10 fractional RF treatments every 2 weeks, and were followed up 2 months after the last treatment. All patients were evaluated by global photography. In 10 patients, blinded manual hair counts were performed. Patients demonstrated less hair shedding, fuller hair, and faster hair growth. There was an average increase of 31.6% in hair density (based on hair counts) and 18% increase in hair shaft thickness. All subjects tolerated the treatments well. The HairLux device is effective and safe for hair growth stimulation in AGA. Ten treatment sessions are recommended to maximize results.
PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?
HIVanti-PD-1CD4viral loadlung cancer
Unique Genetic Profiles from Cerebrospinal Fluid Cell-free DNA in Leptomeningeal Metastases of EGFR-mutant Non-Small Cell Lung Cancer: A New Medium of Liquid Biopsy
Abstract
Background
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Patients and methods
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. Results
28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26) and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared to those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; p < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% vs. 33.3%; p =0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. Conclusion
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR–mutant NSCLC.Final Results of a Multi-institutional Phase II Trial of Re-Irradiation with Concurrent Weekly Cisplatin and Cetuximab for Recurrent or Second Primary Squamous Cell Carcinoma of the Head and Neck
Abstract
Background
The optimal regimen of chemotherapy and re-irradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multi-center Phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Methods and Materials
Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS≥70 were eligible for this trial. Cetuximab 400mg/m2 was delivered as a loading dose in Week 1 followed by weekly cetuximab 250mg/m2 and cisplatin 30mg/m2 concurrent with 6 weeks of IMRT to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results
From 2009 to 2013, 48 patients enrolled on this trial. 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common Grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no Grade 5 acute toxicities. Eight Grade 3 late toxicities were observed, 4 of which were swallowing-related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (p=0.01). OS was not associated with radiation dose, surgery prior to re-XRT or interval from prior XRT. Conclusions
Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier
NCT00833261Activity and safety of afatinib in a window pre-operative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)
Abstract
Background
To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN).Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other endpoints included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic enhanced contrast (DCE)-MRI, diffusion weighted (DW)-MRI, safety and translational research (TR). Results
Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47-87%) had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI, 8-44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST.One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3 –hypoxia score expression and with TP53 wild type. Conclusion
Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration
ClinicalTrials.gov: NCT01538381Trichloroacetic acid (80%) as a chemical debridement method for chronic venous leg ulcers—A pilot study
Debridement is essential for the optimal care of venous leg ulcers. Several debridement methods with different limitations may be deployed. Trichloroacetic acid (TCA) is used for several dermatological purposes. Its application as a chemical debridement method for leg ulcers has never been explored. We designed a prospective study to determine the role of 80% TCA solution as a chemical debridement method for leg ulcers, regarding efficacy and procedure-associated pain. Chronic venous leg ulcers were treated with 3 cycles of 80% TCA solution or curettage over 1 week. Pain and the mean percentage of fibrin and devitalized tissue covering wound bed were evaluated. At the end of the study, a trend towards larger fibrin mean reduction among the TCA treated ulcers was observed, although this difference was not statistically significant (P = .35). The mean pain score after TCA application was significantly reduced compared to pain after curettage alone (P < 0.001). TCA presented several advantages over mechanical debridement: it is a more selective debridement method, has haemostatic properties, and a simpler and faster application. The 80% TCA solution may be a cheap, simple, and considerably less-painful chemical debridement method for venous leg ulcers compared to classical mechanical debridement.
The effect of 22.5 kHz low-frequency contact ultrasound debridement (LFCUD) on lower extremity wound healing for a vascular surgery population: A randomised controlled trial
The aim of this study was to compare changes in wound size and appearance and health complication rates in patients with vasculopathy and lower-extremity wounds treated with or without low-frequency contact ultrasound debridement (LFCUD) This study was a randomised controlled trial. The study was conducted in a vascular surgery service, including outpatient wound clinic and inpatient ward, in a tertiary care academic centre. In total, 70 patients with vasculopathy and lower-extremity wounds of mixed aetiology were enrolled in the trial; 68 completed the study. Patients were randomised to receive LFCUD plus usual care (n = 33) or usual care (n = 37) at 4 weekly visits, and were followed thereafter for up to 12 wk. The main outcome measures included closed wounds, change in wound surface area (WSA), and wound appearance by the revised Photographic Wound Assessment Tool (revPWAT). After 4 weekly LFCUD treatments, patients in the LFCUD group had significantly better wound appearance (total revPWAT score) compared with the control group treated only with usual care (P = <0.05). LFCUD-treated wounds also had a significant reduction in WSA over 4 wk that was not found in the UC group. LFCUD treatment was also associated with a greater number of healed wounds, odds ratio 5.00 (95% CI 1.24-20.25), and fewer instances of wound deterioration. Weekly LFCUD applications to patients with significant vasculopathy resulted in superior healing outcomes when compared with current usual wound care practice.
Direct repression of IGF2 is implicated in the anti-angiogenic function of microRNA-210 in human retinal endothelial cells
Abstract
Pathological angiogenesis leads to the development of retinal vasculopathies and causes severe vision impairment. Increased understanding of the mechanisms underlying the angiogenic behavior of retinal endothelial cells helps provide new insights for developing treatment of retinal vasculopathies. Pro-angiogenic function of miR-210 has previously been identified. However, the functional implication of miR-210 in retinal endothelial cells remains unknown. Human retinal microvascular endothelial cells (HRECs) were employed to investigate the impact of miR-210 on the angiogenic capacity of retinal endothelial cells. It was observed that without affecting the viability of HRECs, miR-210 significantly suppressed the migration and capillary-like tube formation in HRECs. Moreover, pro-angiogenic insulin growth factor 2 (IGF2) was newly identified as a direct target of miR-210 in HRECs. MiR-210 decreased the expression of IGF2 at both mRNA and protein levels in HRECs. IGF2-simulated activation of p38 MAPK was attenuated by miR-210 in HRECs. Recombinant IGF2 protein rescued miR-210-induced impairment of tube formation in HRECs. Therefore, in contrast to the previously reported pro-angiogenic function of miR-210, the current work reveals novel anti-angiogenic activity of miR-210 in HRECs. Furthermore, IGF2 is identified for the first time as a direct target of miR-210 in HRECs, adding new mechanistic insights into the expression regulation of pro-angiogenic IGF2 in human retinal endothelial cells. The current work helps increase the understanding of regulatory mechanisms underlying retinal endothelial cell physiology, justifying further evaluation for the therapeutic implications of miR-210/IGF2 interaction in the treatment of related retinal vasculopathies.
The Infinity from Nothing paradox and the Immovable Object meets the Irresistible Force
Abstract
In this paper I present a novel supertask in a Newtonian universe that destroys and creates infinite masses and energies, showing thereby that we can have infinite indeterminism. Previous supertasks have managed only to destroy or create finite masses and energies, thereby giving cases of only finite indeterminism. In the Nothing from Infinity paradox we will see an infinitude of finite masses and an infinitude of energy disappear entirely, and do so despite the conservation of energy in all collisions. I then show how this leads to the Infinity from Nothing paradox, in which we have the spontaneous eruption of infinite mass and energy out of nothing. I conclude by showing how our supertask models at least something of an old conundrum, the question of what happens when the immovable object meets the irresistible force.
Childhood alopecia areata—Data from the National Alopecia Areata Registry
Abstract
Background/Objectives
Alopecia areata may occur at any age and is the third-most-common dermatosis in children. The objective of this study was to investigate the clinical and epidemiologic features of children and adolescents with alopecia areata based on the data of the National Alopecia Areata registry on children and adolescents.
Methods
Two thousand two hundred eighteen children and adolescents with alopecia areata self-enrolled in the National Alopecia Areata Registry and completed a web-based, self-administered, short-intake screening questionnaire (first tier). In the second tier, 643 patients participated in a clinical examination and completed a long-form questionnaire.
Results
Mean age of onset was 5.9 ± 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was more prevalent in girls, but boys were significantly more likely to have a severe type (P = .009). One-fourth of all children had a positive family history, with 8% having more than three affected relatives. The disease most commonly associated with alopecia areata was atopic dermatitis (32.7%).
Conclusion
Childhood alopecia areata is more prevalent in girls than in boys, but boys have more extensive alopecia areata. Despite the low prevalence, congenital alopecia areata is an important differential diagnosis for neonatal hair loss. Alopecia areata runs in families, suggesting an underlying genetic background. One-quarter of the children reported at least one affected first-degree relative; 8% had more than three affected relatives.
Use of antiviral medications in drug reaction with eosinophilia and systemic symptoms (DRESS): A case of infantile DRESS
Abstract
A 3-month-old girl with Sturge-Weber syndrome presented with a morbilliform rash, eosinophilia, and fulminant liver failure to our tertiary pediatric hospital. She was diagnosed with drug reaction with eosinophilia and systemic symptoms complicated by viremia and evidence of viral hepatitis on liver biopsy. We discuss the role of viral reactivation in drug reaction with eosinophilia and systemic symptoms and the relevance of antiviral therapy in management.
A comprehensive next-generation sequencing assay for the diagnosis of epidermolysis bullosa
Abstract
Background
Historically, diagnosis of epidermolysis bullosa has required skin biopsies for electron microscopy, direct immunofluorescence to determine which gene(s) to choose for genetic testing, or both.
Methods
To avoid these invasive tests, we developed a high-throughput next-generation sequencing (NGS)-based diagnostic assay called EBSEQ that allows simultaneous detection of mutations in 21 genes with known roles in epidermolysis bullosa pathogenicity. Mutations are confirmed with traditional Sanger sequencing.
Results
We present our EBSEQ assay and preliminary studies on the first 43 subjects tested. We identified 11 cases of epidermolysis bullosa simplex, five cases of junctional epidermolysis bullosa, 11 cases of dominant dystrophic epidermolysis bullosa, 15 cases of recessive dystrophic epidermolysis bullosa, and one case that remains without diagnosis. We also found an additional 52 variants of uncertain clinical significance in 17 of the 21 epidermolysis bullosa-associated genes tested. Three of the variants of uncertain clinical significance were also found in three other patients, for a total of 49 unique variants of uncertain clinical significance. We found the clinical sensitivity of the assay to be 75% to 98% and the analytical sensitivity to be 99% in identifying base substitutions and small deletions and duplications. Turnaround time was 3 to 6 weeks.
Conclusions
EBSEQ is a sensitive, relatively rapid, minimally invasive, comprehensive genetic assay for the diagnosis of epidermolysis bullosa.
Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents and young adults
Abstract
Background/Objectives
There are no reliably effective, well-tolerated topical agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and tolerability of oxybutynin 3% gel in adolescents and young adults with primary focal hyperhidrosis.
Methods
Patients with severe axillary hyperhidrosis were treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was assessed by calculating change in Hyperhidrosis Disease Severity Score from baseline to weeks 1 and 4. Change in health-related quality of life was assessed using the Children's Dermatology Life Quality Index or the Dermatology Life Quality Index. Adverse effects were evaluated using patient diaries, investigator global review, and physical examination.
Results
Of 10 patients aged 13-24 enrolled, seven completed the study. Of those who completed the study, four (57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in Children's Dermatology Life Quality Index or Dermatology Life Quality Index score. Anticholinergic adverse effects were infrequent. The majority of treatment-related adverse events were mild to moderate in severity. One patient experienced a severe adverse event.
Conclusion
Oxybutynin 3% gel reduced hyperhidrosis severity and improved health-related quality of life in this small pilot study. Safety and efficacy should be further evaluated in a large, prospective, placebo-controlled study.
Severe ectropion in lamellar ichthyosis managed medically with oral acitretin
Abstract
Congenital ectropion is commonly associated with lamellar ichthyosis. Severe eyelid ectropion may cause corneal exposure, keratopathy, and permanent corneal scarring. We report a neonate with severe, bilateral, congenital ectropion and eclabium managed using oral retinoids. Both corneas were protected with topical antibiotics and lubricating eyedrops and eye ointments. At 12-month follow-up, the child was doing well, with no ectropion or corneal opacity.
Patient-Reported-Outcome-Messung (PROM) psychosozialer Belastung und Symptome für ambulante Patienten unter kurativer oder palliativer Tumortherapie
Zusammenfassung
Hintergrund
Palliative Unterstützung sollte früh in die Tumortherapie eingebunden werden, doch der Bedarf der Patienten bleibt oft unerkannt und unbehandelt. Die Autoren analysierten die Rücklaufquote einer quartalsweisen Patientenbefragung mit validierten Fragebögen und erfassten die Bedarfe der Tumorpatienten, die sich in kurativer oder palliativer Behandlung befanden.
Methoden
Bei der Entwicklung des Fragebogens wurden die 3 validierten Instrumente Hornheider Fragebogen (HSI), PHQ4 Fragebogen (Patient Health Questionnaire) und der MIDOS Fragebogen (MInimal DOcumentation System) kombiniert. 96 (13,6 %) kurativ und 609 (81,4 %) palliativ behandelte Patienten füllten einen Fragebogen aus.
Ergebnisse
Zwischen Oktober 2013 und März 2016 wurden 75 % der ausgeteilten Fragebögen ausgefüllt. Unter den kurativ und palliativ behandelten Patienten hatten 34 (35,8 %) und 272 (45,0 %) Patienten einen pathologischen HSI-Score (p = 0,094), bei 7 (11,3 %) und 51 (13,7 %) Patienten ergab der PHQ4 einen mittleren oder schlechten Score (p = 0,845) und 6 (6,5 %) und 70 (12,1 %) Patienten gaben ein schlechtes oder sehr schlechtes Allgemeinbefinden an (p = 0,388). 340 von 669 (50,8 %) Patienten wiesen auf die zusätzliche Belastung ihrer Angehörigen hin.
Schlussfolgerung
Die Analyse zeigt die Durchführbarkeit einer quartalsweise durchgeführten Patientenbefragung zur Erfassung des palliativen Bedarfs im Routinebetrieb einer onkologischen Ambulanz. Hauptsymptome beider Patientengruppen waren Müdigkeit und Schwäche. Weiterhin gab ein Großteil der Patienten eine Belastung der Angehörigen an.
Neue diagnostische und therapeutische Aspekte zu Chordomen
Zusammenfassung
Hintergrund
Chordome zählen zu den primären, malignen Knochentumoren und treten mit Schwerpunkt im Sakrum und Clivus entlang der Wirbelsäule auf (ICD-O: 9370/3). Man geht davon aus, dass sie aus Resten der Chorda dorsalis entstehen. Aufgrund des seltenen Auftretens zählen sie zu den sog. „orphan diseases".
Methoden
Es wurden eine Recherche und Auswertung aktueller Literatur und klinischer Studien durchgeführt.
Ergebnisse
Die primäre Therapie stellt heutzutage die Chirurgie dar; allerdings kann dies v. a. im Clivus problematisch sein. Zudem treten häufig Rezidive und nicht selten Metastasen auf. In der rezidivierten Situation wird die Hochdosisbestrahlung mit Protonen empfohlen. Aufgrund des generell langsamen Wachstums der Chordome ist eine konventionelle Chemotherapie problematisch. In den letzten Jahren konnten für Chordome molekularpathologische Signalwege mit entsprechenden Zielstrukturen identifiziert werden, die erste Ansätze für eine zielgerichtete Therapie bieten.
A photonumeric scale for the assessment of atrophic facial photodamage
Summary
Background
Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimising variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardised scale.
Objectives
To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication.
Methods
A pool of 393 facial photographs (en face and 45º oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades 0 through 8, where 0 is no photodamage and 8 is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 non-dermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated one week later.
Results
There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0.71 and 0.37 with standardised errors of 0.57 and 0.17 respectively) with no significant difference in repeatability between the two methods (p < 0.05).
Conclusions
The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.
This article is protected by copyright. All rights reserved.
Could conjunctivitis in dupilumab treated atopic dermatitis patients be caused by colonization with demodex and increased IL-17 levels?
Abstract
de Bruin-Weller et al., reported alarmingly high rates of unspecified and allergic conjunctivitis in trial patients with moderate-to-severe atopic dermatitis (AD) who underwent treatment with dupilumab; an antibody that inhibits signaling of IL-4 and IL-13.1 Importantly, the exact pathogenic mechanism behind incident conjunctivitis in dupilumab-treated patients is unclear. While all, but one case, were considered to be of mild or moderate severity, and most resolved after treatment discontinuation, ocular complications may ultimately deprive AD patients from effective treatment with dupilumab. For these reasons, the medical community needs to rapidly identify the pathogenic mechanism.
This article is protected by copyright. All rights reserved.
High-salt- and cholesterol diet-associated cognitive impairment attenuated by tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway
Abstract
Metabolic disorders are closely associated with dietary habits and seem to be related to neuroinflammation and neurodegenerative disease in humans. Emblica officinalis (EOT) fruits not only have good nutritional value but also have excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit with the expectation of controlling diet-induced neuroinflammation and cognitive impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce neuroinflammation and cognitive impairment in rats. The diet of the rats was then supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate the neuroprotective effects of EOT; in silico study, neurobehavioral tests, biochemical analyses, and immunohistochemical studies were performed. In silico study of p50 (NF-κB1) receptors with emblicanin (the main constituent of EOT) suggests that EOT has binds to NF-κB. EOT treatment reversed the HSCD-induced behavioral and memory disturbances in a step-down-type passive avoidance test. EOT treatment also inhibited HSCD-induced NF-κB upstream signaling, including the release of Th1, such as TNF-α, and downstream signaling Th2, such as IL-10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced increase in the level of cognitive impairment markers, such as amyloid β. Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal cell death by inhibiting the overexpression of NF-kB in brain. This study confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of HSCD; however further studies are warranted to elucidate the exact mechanism of action of EOT.
Κυριακή 14 Ιανουαρίου 2018
Pustular psoriasis and related pustular skin diseases
Summary
Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets.
Agricultural non-point source pollution management in a reservoir watershed based on ecological network analysis of soil nitrogen cycling
Abstract
The Miyun Reservoir plays a pivotal role in providing drinking water for the city of Beijing. In this research, ecological network analysis and scenario analysis were integrated to explore soil nitrogen cycling of chestnut and Chinese pine forests in the upper basin of the Miyun Reservoir, as well as to seek favorable fertilization modes to reduce agricultural non-point source pollution. Ecological network analysis results showed that (1) the turnover time was 0.04 to 0.37 year in the NH4+ compartment and were 15.78 to 138.36 years in the organic N compartment; (2) the Finn cycling index and the ratio of indirect to direct flow were 0.73 and 11.92 for the chestnut forest model, respectively. Those of the Chinese pine forest model were 0.88 and 29.23, respectively; and (3) in the chestnut forest model, NO3− accounted for 96% of the total soil nitrogen loss, followed by plant N (2%), NH4+ (1%), and organic N (1%). In the Chinese pine forest, NH4+ accounted for 56% of the total soil nitrogen loss, followed by organic N (34%) and NO3− (10%). Fertilization mode was identified as the main factor affecting soil N export. To minimize NH4+ and NO3− outputs while maintaining the current plant yield (i.e., 7.85e0 kg N/year), a fertilization mode of 162.50 kg N/year offered by manure should be adopted. Whereas, to achieve a maximum plant yield (i.e., 3.35e1 kg N/year) while reducing NH4+ and NO3− outputs, a fertilization mode of 325.00 kg N/year offered by manure should be utilized. This research is of wide suitability to support agricultural non-point source pollution management at the watershed scale.
Towards a Sedimentology of Information Infrastructures: a Geological Approach for Understanding the City
Abstract
Drawing primarily on ethnographic research performed in a city in Romania, this paper provides a thick description of police practices and information systems in that municipality. It shows various ways in which technologies mediate policing practitioners' perceptions, decisions and actions. Bringing some additional material from a case in the Dutch police in which they build risk profiles predicated on real-time data from a sensor network, the paper highlights new phenomena with ethical implications emerging at the intersection of information infrastructures and policing practices. In particular, it shows a solidifying effect of technologically mediated suspicion, a sedimentation process in technological infrastructures and the formation of pockets of prejudice in the layers of software code. To adequately account for these phenomena and others, the paper provides a set of arguments and conditions for a sedimentology of infrastructures. At the same time, it offers the first steps in a larger research project that would adapt and test the limits of a geological vocabulary and approach to understand smart urban environments.
Diagnostic and prognostic value of JC virus DNA in plasma in Progressive Multifocal Leukoencephalopathy
Abstract
Background
Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by the polyomavirus JC (JCV) affecting subjects with impaired immune system. While JCV-DNA detection in cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of plasma JCV-DNA is still uncertain. Methods
We retrospectively analyzed plasma samples drawn from patients with PML close to disease onset, and controls without PML. In PML patients, we compared plasma JCV DNA detection and levels to: JCV DNA in the other biological samples, clinical and laboratory parameters and patients' survival. Results
JCV-DNA was detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, HIV-negative; 29/79, 37%, HIV-positive) and of 4/144 (3%) controls without PML (0/95 HIV-negative; 4/49, 8%, HIV-positive), yielding a diagnostic sensitivity and specificity of, respectively, 48% and 97% (83% and 100% in HIV-negative; 37% and 92% in HIV-positive). Among 16 PML patients with undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA levels were independently associated with those in the CSF (p<0.0001) and previous corticosteroid treatment (p=0.012). Higher plasma JCV-DNA levels were associated with disease progression in HIV-negative patients (p=0.005), while among HIV-positive patients, they identified an increased risk of progression only in those treated with combined antiretroviral thearapy (cART)(p<0.0001). Conclusions
Testing JCV-DNA on plasma samples might complement PML diagnosis, especially when CSF is unavailable or JCV-DNA not detectable in CSF. In addition, JCV-DNA plasma levels could be useful as a marker of disease progression in both HIV-negative and cART-treated HIV-positive PML patients.Validation of the PIDS/IDSA Severity Criteria in Children with Community-Acquired Pneumonia
Abstract
Background
The Pediatric Infectious Diseases Society (PIDS)/Infectious Diseases Society of America (IDSA) guideline for community-acquired pneumonia (CAP) recommends intensive care unit (ICU) admission or continuous monitoring for children meeting severity criteria. Our objective was to validate these criteria. Methods
This was a retrospective cohort study of children age 3 months-18 years diagnosed with CAP in a pediatric Emergency Department (ED) from 9/2014-8/2015. Children with complex chronic conditions and recent ED visits were excluded. The primary predictor was the PIDS/IDSA severity criteria. Outcomes included disposition (i.e., admission vs. discharge) and interventions/diagnoses necessitating hospitalization (i.e., need for hospitalization [NFH]). Results
Of 518 children, 56.6% were discharged. 54.3% of discharged patients and 80.8% of those hospitalized <24 hours were classified as severe. Of those admitted, 10.7% did not meet severity criteria. Overall, 69.5% (n=360) met PIDS/IDSA severity criteria. Of these children, 73.1% did not demonstrate NFH. The areas under the receiver operator characteristic curves (AUC) for PIDS/IDSA major criteria were 0.63 and 0.51 for predicting disposition and NFH, respectively. For PIDS/IDSA minor criteria, the AUC was 0.81 and 0.56 for predicting disposition and NFH, respectively. The sensitivity, specificity, LR+ and LR- of the PIDS/IDSA criteria were 89%, 46%, 1.65, and 0.23 for disposition and 95%, 16%, 1.13, and 0.31 for NFH. Conclusions
More than half of children classified as severe by PIDS/IDSA criteria were not hospitalized. The PIDS/IDSA CAP severity criteria have only fair ability to predict need for hospitalization. New predictive tools specifically for children are required to improve clinical decision making.Increased sensitivity and high specificity of indirect immunofluorescence in detecting IgG subclasses for diagnosis of bullous pemphigoid
Summary
Background
Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively low sensitivity (60–80%) may be partly due to insufficient detection of minor IgG subclasses.
Aim
To determine the operating characteristics of an IgG subclass in IIF.
Methods
We designed a retrospective, dual-centre, controlled cohort study on sera from 64 BP sera that had been rated as false negatives by traditional IIF microscopy, and assessed circulating IgG1, IgG3 and IgG4 autoantibodies.
Results
The sensitivities of IIF in detecting IgG1, IgG3, IgG4 and all three in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities were > 97%.
Conclusion
Detection of IgG subclass (especially IgG1 and IgG4) autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic performance of IIF microscopy for diagnosis of BP.
Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a service setting
Summary
Background
Muir–Torre syndrome (MTS) is a subtype of Lynch syndrome, which encompasses the combination of sebaceous skin tumours or keratoacanthomas and internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous neoplasms (SNs) may occur before other malignancies, and may lead to the diagnosis, which allows testing of other family members, cancer surveillance, risk-reducing surgery or prevention therapies.
Aim
To evaluate the efficacy of universal immunohistochemistry (IHC) screening of SNs in a service setting.
Methods
Patients with SNs were ascertained by a regional clinical pathology service over a 3-year period. Results of tumour IHC, clinical genetics notes and germline genetic testing were retrospectively reviewed.
Results
In total, 62 patients presented with 71 SNs; 9 (15%) of these patients had previously diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins. Fifteen patients were referred to the Clinical Genetics department, and 10 patients underwent germline genetic testing. Two had a new diagnosis of MTS confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2 genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old woman with a sebaceous adenoma and history of endometrial cancer; to our knowledge, this is the first time a PMS2 mutation has been reported in MTS.
Conclusions
Universal IHC screening of SNs is an effective method to identify cases for further genetic evaluation. Rates of referral to clinical genetics were only moderate (58%). Increased awareness of MTS could help improve the rate of onward referral.
Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis
Summary
Background
Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory proteins upregulated in psoriasis, but their relation to atherosclerosis remains unclear.
Aim
To evaluate the role of serum psoriasin and koebnerisin as possible markers for subclinical atherosclerosis in patients with psoriasis.
Methods
Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients with psoriasis and in 45 healthy controls (HCs). Intima–media thickness (IMT) of the right and left common carotid arteries was measured to detect the presence of subclinical atherosclerosis. Clinical severity of psoriasis was estimated using the Psoriasis Area and Severity Index (PASI).
Results
Compared with HCs, patients with psoriasis had significantly higher levels of psoriasin (26.61 ± 22.45 ng/mL vs. 6.31 ± 1.68 ng/mL, P < 0.001) and koebnerisin (21.2 ± 13.12 ng/mL vs. 12.2 ± 4.67 ng/mL, P = 0.001), and significantly higher IMT values (1.07 ± 0.4 mm vs. 0.61 ± 0.1 mm, P < 0.001). A positive correlation was observed between IMT and PASI (r = 0.78, P < 0.001), serum psoriasin (r = 0.48, P > 0.01) and serum koebnerisin (r = 0.48, P < 0.01). Patients with psoriasis with subclinical atherosclerosis had higher serum levels of koebnerisin compared with patients without subclinical atherosclerosis (P = 0.04), which was not observed for psoriasin (P = 0.94).
Conclusion
Serum psoriasin and koebnerisin correlate with IMT, underlining their value as a potential link between psoriasis and atherosclerosis. In particular, koebnerisin seems to be a useful marker of subclinical atherosclerosis in patients with psoriasis.
Wierenga on theism and counterpossibles
Abstract
Several theists, including Linda Zagzebski, have claimed that theism is somehow committed to nonvacuism about counterpossibles. Even though Zagzebski herself has rejected vacuism, she has offered an argument in favour of it, which Edward Wierenga has defended as providing strong support for vacuism that is independent of the orthodox semantics for counterfactuals, mainly developed by David Lewis and Robert Stalnaker. In this paper I show that argument to be sound only relative to the orthodox semantics, which entails vacuism, and give an example of a semantics for counterfactuals countenancing impossible worlds for which it fails.
Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats
Abstract
The present study was conducted to evaluate the possible protective role of the algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the main secondary effects induced by the immunosuppressant drug CSA and/or ionizing radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25 mg/kg). Markers used to assess renal injury included serum creatinine, urea, glucose, albumin, protein, and lipid profile as well as kidney content of reduced glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by immunohistochemical estimation of caspase-3 expression in addition to histopathological examination. Results revealed that gamma radiation and/or CSA induced elevation in urea, creatinine, lipids, and glucose while decreasing albumin and protein levels. There was a noticeable increase in kidney content of GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was observed. Treatment with Sp significantly reversed the changes induced by CSA and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while increasing SOD activity. Histopathological examination further confirmed Sp protective efficacy. Moreover, kidney caspase-3 expression that was triggered by CSA and/or gamma radiation was decreased. In conclusion, spirulina can be regarded as a promising renoprotective natural agent against renal injury induced by CSA and/or gamma radiation.
Diurnal variations in personal care products in seawater and mussels at three Mediterranean coastal sites
Abstract
The presence of personal care products (PCPs) in the marine environment is of major concern. PCPs, UV filters, and musks can enter the marine environment indirectly through wastewater or directly via recreational activities. We conducted this study to document patterns in the occurrence of seven PCPs at three coastal sites impacted by recreational activities during 1 day. The study focused on diurnal variations in these seven PCPs in seawater and indigenous mussels. In seawater, UV filters showed diurnal variations that mirrored variations in recreational activities at the sites. Ethylhexyl methoxycinnamate (EHMC) and octocrylene (OC) water concentrations increased from under the limit of quantification in the morning to 106 and 369 ng/L, respectively, when recreational activities were the highest. In mussels, diurnal variations in OC were observed, with the lowest concentrations recorded in the morning and then increasing throughout the day. As Mytilus spp. are widely used as sentinels in coastal pollution monitoring programs (mussel watch), our findings on diurnal variations could enhance sampling recommendations for recreational sites impacted by PCPs.
Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid Cancer Through Ras/RAF/MEK/ERK Pathway Suppression
Publication date: February 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 179
Author(s): Saswata Chatterjee, Yunhee Rhee, Phil-Sang Chung, Rui-Feng Ge, Jin-Chul Ahn
Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has shown a potential anticancer effect against cervical and lung cancer. Palliative treatments like photodynamic therapy (PDT) are being implemented for a long time however, the results are still not promising in case of aggressive cancers like anaplastic thyroid cancer. The objective of this work is to establish an alternative method with the combination of photofrin-PDT and sulforaphene, a natural isothiocyanate from cruciferous vegetables, against human anaplastic thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle arrest, MMP depolarization and ROS generation, analyzed by flow cytometry. Western blot analysis of various proliferative proteins was performed to assess the activity of combination treatment against FRO cells. From the results, sulforaphene alone showed no cytotoxicity against normal cells, however, combination of sulforaphene and photofrin mediated PDT showed a noticeable decrease in cell proliferation against FRO cells. Combination treatment synergistically caused cell cycle arrest via ROS generation and MMP depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly modulated due to combination treatment. PDT and SFE can induce apoptosis in anaplastic thyroid cancer cells individually but while treated in combination, it enhanced the apoptotic and anti-proliferative effect, much higher than the individual doses. In summary, our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer.
Graphical abstract
Adequate vitamin D3 skin synthesis versus erythema risk in the Northern Hemisphere midlatitudes
Publication date: February 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 179
Author(s): Jakub Guzikowski, Janusz Krzyścin, Agnieszka Czerwińska, Weronika Raszewska
Health-optimum-exposure index (HOEI) is proposed to assess if the prescribed amount of vitamin D3 (target value) could be synthesized in the human skin without erythema appearance. It is defined as the ratio between the vitamin D3 quantity received during the maximum allowed outdoor exposure without erythema risk and the target value. Sunbathing is safe for HOEI>1 and 1/HOEI represents a part of minimal erythema dose (MED) necessary to obtain the target value. We examine the following targets: a vitamin D3 quantity equivalent to 1000 IU vitamin D3 taken orally, and an optimal vitamin D3 quantity defined by Krzyścin et al. (2016). The biologically weighted (previtamin D3 and erythemal) doses from the Northern Hemisphere midlatitudinal stations are analyzed to find HOEI dependence on personal and meteorological factors. HOEI depends mostly on the exposed skin area, person's age, and sun elevation at noon but not on the Fitzpatrick skin phototype. We found that only young adults (<21 yr) could safely obtain vitamin D3 quantity, which is equivalent to 1000 IU taken orally, almost throughout the whole year. Duration of such exposures appears <1 h only in the warm subperiods of the year (April–September) for a person with minimal erythema dose of 330 J m−2. Exposing larger part of the body (~30%) enables the oldest persons (>59 yr) to reach 1000 IU target during warm days in spring and summer. The optimal daily vitamin D3 quantity could only be synthesized only by young adults for about 40–60% of days in the May–August period if they expose at least 1/3 part of their body surface area. Vitamin D3 supplementation seems to be necessary over the whole year for the oldest persons with daily dosage of ~2000 IU but reduced to ~1000 IU in summer for sunseekers exposing significant part of the body.
Light quality affects flavonoid production and related gene expression in Cyclocarya paliurus
Publication date: February 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 179
Author(s): Yang Liu, Shengzuo Fang, Wanxia Yang, Xulan Shang, Xiangxiang Fu
Understanding the responses of plant growth and secondary metabolites to differential light conditions is very important to optimize cultivation conditions of medicinal woody plants. As a highly valued and multiple function tree species, Cyclocarya paliurus is planted and managed for timber production and medical use. In this study, LED-based light including white light (WL), blue light (BL), red light (RL), and green light (GL) were used to affect leaf biomass production, flavonoid accumulation and related gene expression of one-year C. paliurus seedlings in controlled environments. After the treatments of 60 days, the highest leaf biomass appeared in the treatment of WL, while the lowest leaf biomass was found under GL. Compared to WL, the total flavonoid contents of C. paliurus leaves were significantly higher in BL, RL, and GL, but the highest values of selected flavonoids (kaempferol, isoquercitrin and quercetin) were observed under BL. Furthermore, the greatest yields of total and selected flavonoids in C. paliurus leaves per seedling were also achieved under BL, indicating that blue light was effective for inducing the production of flavonoids in C. paliurus leaves. Pearson's correlation analysis showed that there were significantly positive correlations between leaf flavonoid content and relative gene expression of key enzymes (phenylalanine ammonia lyase, PAL; 4-coumaroyl CoA-ligase, 4CL; and chalcone synthase, CHS) in the upstream, which converting phenylalanine into the flavonoid skeleton of tetrahydroxy chalcone. It is concluded that manipulating light quality may be potential mean to achieve the highest yields of flavonoids in C. paliurus cultivation, however this needs to be further verified by more field trials.
Enzyme-mediated photoinactivation of Enterococcus faecalis using Rose Bengal-acetate
Publication date: Available online 11 January 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Daniel Manoil, Norbert Lange, Serge Bouillaguet
Rose Bengal-acetate (RB-Ac) is a pro-photosensitizer claimed to diffuse into target cells, where the acetate groups are hydrolyzed and the photosensitizing properties of Rose Bengal (RB) are restored. Despite promising results on tumor cells, the interaction of RB-Ac with bacteria has never been investigated. This study aimed to assess the interaction of RB-Ac with Enterococcus faecalis and to evaluate its potential use in antimicrobial photodynamic therapy (aPDT).Spectrofluorometry was used to assess the ability of E. faecalis to hydrolyze the RB-Ac compound. Fluorescence microscopy was employed to observe the distribution and to evaluate the cellular uptake of the RB produced. The antibacterial efficiency of RB-Ac-mediated aPDT was assessed by flow cytometry in combination with the LIVE/DEAD® staining.Results showed that RB-Ac was successfully hydrolyzed in the presence of E. faecalis cells. The RB produced appeared to incorporate the membrane of bacteria. Higher concentrations of RB-Ac resulted in higher incorporation of RB. The blue-light irradiation of RB-Ac-treated samples significantly reduced bacterial viability. <0.01% of E. faecalis survived after incubation with 200 μM RB-Ac during 900 min and blue-light activation.The current report indicates that E. faecalis cells can hydrolyze the RB-Ac compound to produce active RB. The use of RB-Ac did not appear to allow cytoplasmic internalization of the RB produced, which rather incorporated the membrane bilayers of E. faecalis. The use of RB-Ac did not provide additional advantages over RB in terms of PS localization. Nonetheless, sufficient RB was produced and incorporated into the membranes of bacteria to elicit effective aPDT.
Mixed microalgae consortia growth under higher concentration of CO2 from unfiltered coal fired flue gas: Fatty acid profiling and biodiesel production
Publication date: Available online 11 January 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Ambreen Aslam, Skye R. Thomas-Hall, Maleeha Manzoor, Faiza Jabeen, Munawar Iqbal, Qamar uz Zaman, Peer M. Schenk, M. Asif Tahir
Biodiesel is produced by transesterification of fatty acid methyl esters (FAME) from oleaginous microalgae feedstock. Biodiesel fuel properties were studied and compared with biodiesel standards. Qualitative analysis of FAME was done while cultivating mixed microalgae consortian under three concentrations of coal fired flue gas (1%, 3.0% and 5.5% CO2). Under 1% CO2 concentration (flue gas), the FAME content were 280.3 μg/mL, whereas lipid content was 14.03 μg/mL/D (day). Both FAMEs and lipid contents were low at other CO2 concentrations (3.0 and 5.5%). However, mixed consortia in the presence of phosphate buffer and flue gas (PB + FG) showed higher saturated fatty acids (SFA) (36.28%) and unsaturated fatty acids (UFA) (63.72%) versus 5.5% CO2 concentration, which might be responsible for oxidative stability of biodiesel. Subsequently, higher cetane number (52) and low iodine value (136.3 gI2/100 g) biodiesel produced from mixed consortia (PB + FG) under 5.5% CO2 along with 50 mM phosphate buffer were found in accordance with European (EN 14214) standard. Results revealed that phosphate buffer significantly enhanced the biodiesel quality, but reduce the FAME yield. This study intended to develop an integrated approach for significant improvement in biodiesel quality under surplus phosphorus by utilizing waste flue gas (as CO2 source) using microalgae. The CO2 sequestration from industrial flue gas not only reduced greenhouse gases, but may also ensure the sustainable and eco-benign production of biodiesel.
Graphical abstract
Preparation and characterization of biocompatible silver nanoparticles using pomegranate peel extract
Publication date: Available online 10 January 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Majid Nasiriboroumand, Majid Montazer, Hossein Barani
The potential application of any nanoparticles, including silver nanoparticles (AgNPs), strongly depends on their stability against aggregation. In the current study, an aqueous extract of pomegranate peel was used as a stabilizer during synthesis of AgNPs. Nanoparticles have been prepared by the chemical reduction method from an aqueous solution of silver nitrate in the presence of sodium borohydride as a reducing agent. The AgNPs were characterized by dynamic light scattering (DLS), zeta-potential measurements, UV–Vis spectroscopy and transmission electron microscopy (TEM). The antibacterial efficiency of AgNPs against Escherichia coli was investigated. The size, polydispersity index, FWHM, and colloidal stability of nanoparticles in dispersion depends on the extract concentrations. In the presence of pomegranate peel extract, the nanoparticles suspension shows colloidal stability at least for a week. Our studies show that AgNPs synthesized with the above described procedure were stable at pH = 3–12 and in the temperature range of 25–85 °C. Additionally, AgNPs exhibit antibacterial properties, especially at the lowest amount of extract to silver ratio (KExtract/Ag).
The importance of monochromatic lights in the production of phenolic acids and flavonoids in shoot cultures of Aronia melanocarpa, Aronia arbutifolia and Aronia × prunifolia
Publication date: Available online 10 January 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Agnieszka Szopa, Anna Starzec, Halina Ekiert
Shoot cultures of Aronia melanocarpa, A. arbutifolia and A. × prunifolia were maintained on Murashige and Skoog medium with 1 mg/l each of BA and NAA under monochromatic lights (far-red, red, blue lights, UV-A-irradiation), in darkness, and under white light (control). HPLC-DAD analyses of 19 phenolic acids and 11 flavonoids in methanolic extracts from the shoots revealed in all of them the presence of three depsides (chlorogenic, neochlorogenic and rosmarinic acids), protocatechuic acid, four flavonoid glycosides (cynaroside, quercitrin, hyperoside and rutoside), and additionally, in A. arbutifolia, 3,4-dihydroxyphenylacetic acid. Depending on light quality, the total amounts of these metabolites increased 1.8–5.9 times, reaching maximum values under blue light: 527.40 and 144.61 mg 100 g−1 DW (A. melanocarpa), 543.27 and 85.82 mg 100 g−1 DW (A. arbutifolia) and 1615.18 and 220.65 mg 100 g−1 DW (A. × prunifolia), respectively. The maximum total amounts were 1.3–3.6 times higher than under white light. The quantities of individual metabolites changed from 1.2 to 11.0 times, with high amounts of neochlorogenic acid and quercitrin in A. melanocarpa (243.35 and 75.64 mg 100 g−1 DW), and of chlorogenic and rosmarinic acids and quercitrin in A. arbutifolia (236.52, 219.35 and 51.01 mg 100 g−1 DW). Extremely high amounts of depsides (418.83, 644.68, 548.86 mg 100 g−1 DW) and quercitrin (165.88 mg 100 g−1 DW) were produced in cultures of the hybrid - A. × prunifolia. The results are potentially useful for practical applications. This is the first report documented the importance of light quality on the production of phenolic acids and flavonoids in three aronia in vitro cultures.
Editorial Board
Publication date: January 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 178
Professional quality of life, wellness education, and coping strategies among emergency physicians
Abstract
Professional quality of life (ProQOL) is affected by and affects professional well-being and performance. The objectives of this study are to identify risk factors of ProQOL among EM physicians in Zagazig University hospitals (ZUHs), to detect the relationship between ProQOL and coping strategies, and to measure the implication of the Worksite Wellness Education (WWE) program on improving knowledge skills, ProQOL, and coping. An intervention study was conducted among 108 EM physicians at ZUHs through two stages: assessing ProQOL subscales (CS, BO, and STS) and coping strategies and conducting the WWE program. A pre–post-test design was used in the evaluation. CS was higher among the older age group, smokers, nighttime sleepers, and hobbies' practitioners. Coping strategies carried out by EM physicians to overcome stress and their ProQOL scores were improved significantly post program. ProQOL has multiple factors that affect it. Applying the WWE program will address this concept and may raise awareness about how to cope with work stressors.
Σάββατο 13 Ιανουαρίου 2018
An integrated fuzzy-based advanced eutrophication simulation model to develop the best management scenarios for a river basin
Abstract
Assessment of water quality status of a river with respect to its discharge has become prerequisite to sustainable river basin management. The present paper develops an integrated model for simulating and evaluating strategies for water quality management in a river basin management by controlling point source pollutant loadings and operations of multi-purpose projects. Water Quality Analysis and Simulation Program (WASP version 8.0) has been used for modeling the transport of pollutant loadings and their impact on water quality in the river. The study presents a novel approach of integrating fuzzy set theory with an "advanced eutrophication" model to simulate the transmission and distribution of several interrelated water quality variables and their bio-physiochemical processes in an effective manner in the Ganges river basin, India. After calibration, simulated values are compared with the observed values to validate the model's robustness. Fuzzy technique of order preference by similarity to ideal solution (F-TOPSIS) has been used to incorporate the uncertainty associated with the water quality simulation results. The model also simulates five different scenarios for pollution reduction, to determine the maximum pollutant loadings during monsoon and dry periods. The final results clearly indicate how modeled reduction in the rate of wastewater discharge has reduced impacts of pollutants in the downstream. Scenarios suggesting a river discharge rate of 1500 m3/s during the lean period, in addition to 25 and 50% reduction in the load rate, are found to be the most effective option to restore quality of river Ganges. Thus, the model serves as an important hydrologic tool to the policy makers by suggesting appropriate remediation action plans.
Effects of Biologic Therapy on Cardiovascular Disease in Psoriasis
Abstract
Purpose of Review
The aim of this review is to summarize the literature on the effects of biologic treatment for psoriasis on the risk of cardiovascular (CV) disease (CVD) and adverse CV outcomes.
Recent Findings
Therapy with tumor necrosis factor-alpha (TNF-α) inhibitors has been associated with reduced risk of CV events in observational studies; however, data are conflicting. Data on interleukin (IL)-17 and IL-12/23 inhibitors are limited, and primary endpoints of studies on these drugs have not been focused on CV outcomes.
Summary
Psoriasis is a chronic inflammatory skin disease that has distinct pathogenetic overlaps with that of atherosclerosis. Patients with psoriasis, in particular moderate-to-severe disease, have an increased incidence and prevalence of CV risk factors and CVD. Biologic therapies targeted for treatment of psoriasis dampen the systemic inflammation and may therefore be effective in treating not only the cutaneous manifestations of psoriasis, but may also have beneficial or detrimental CV effects depending on the particular cytokine target and mode of action. Studies on TNF-α inhibitors have suggested that these may reduce the coronary artery calcium score, improve myocardial function, and reduce the risk of adverse CV events albeit that use of these drugs may also lead to weight gain. Studies of treatment with anti-IL-12/23 agents have yielded conflicting results, but ustekinumab, the only IL-12/23 inhibitor currently approved for psoriasis, appears to be effect neutral on CV parameters. Newer drugs such as IL-17 inhibitors have not demonstrated any notable CV safety signals based on pivotal clinical trials, but long-term data from real-life studies are lacking. As new treatment modalities emerge, there is a need for well-powered long-term observational studies to firmly establish the CV safety profile of these drugs in a real-life setting.
Hydrogeochemical processes and influence of seawater intrusion in coastal aquifers south of Chennai, Tamil Nadu, India
Abstract
Seawater intrusion promotes the salinity of groundwater, and it poses a great environmental impact on a global scale. The present study was carried out to determine the hydrogeochemical processes and influence of seawater intrusion in the coastal aquifers using geophysical, geochemical, and stable isotope techniques. The true resistivity value ranges from 0.5 to 8008.5 Ω-m which has been measured using vertical electrical sounding (VES) based on the Schlumberger method. About 33 groundwater samples were collected during post-monsoon (POM) (January 2012) and pre-monsoon (PRM) (June 2012) seasons from open and bore wells and were analyzed for major ions and stable isotopes. EC, Na+, and Cl− were high in groundwater of wells near salt pan, the Buckingham Canal, and backwater regions. Around 45% of the groundwater of this study area is of Na+-Cl− type due to salinisation. Reverse ion exchange and silicate weathering are the dominant processes controlling the geochemistry of groundwater. Saturation indexes (SI) of halite (SIhalite) and gypsum (SIgypsum) versus sulfate show an increasing trend line from > 0 to < 0, which implies higher dissolution of minerals and hints increasing salinization during both seasons. The value of Na+/Cl− ranges between 0.7 and 2.4 (POM) and from 0.6 to 2.8 (PRM). The molar ratio suggested that around 25% of the groundwater samples are with values similar to those of seawater. Further, the groundwater is also affected by saline backwater, salt pan activities, and Buckingham Canal. Some locations are also are affected by anthropogenic, agricultural activities and geochemical processes. Heavy stable isotopes were found to be dominant in the coastal region due to seawater intrusion. Stable isotopes of δ18O range from − 5.6 to − 2.9‰ during both periods. About 201 km2 of this area is affected by salinization. It is necessary to reduce pumping and plan for physical barriers to create freshwater ridges for controling the seawater intrusion.
Exposure to nanoscale and microscale particulate air pollution prior to mining development near a northern indigenous community in Québec, Canada
Abstract
This study serves as a baseline characterization of indoor and outdoor air quality in a remote northern indigenous community prior to the start of a major nearby mining operation, including measurements of nanoparticles, which has never been performed in this context before. We performed aerosol sample collection and real-time aerosol measurements at six different locations at the Cree First Nation of Waswanipi and the Montviel campsite, located 45 km west of the Cree First Nation of Waswanipi, in the south of the Nord-du-Québec region. High concentrations of airborne nanoparticles (up to 3.98 × 104 ± 8.9 × 103 cm−3 at 64.9-nm midpoint particle diameter) and fine particles (up to 1.99 × 103 ± 1.6 × 102 cm−3 at 0.3-μm midpoint particle diameter) were measured inside a residential home, where we did not find any ventilation or air filtration systems. The most abundant particle sizes by mass were between 0.19 and 0.55 μm. The maximum concentration of analyzed heavy metals was detected at the d50 cut-off particle size of 0.31 μm; and the most abundant heavy metals in the aerosol samples were Al, Ba, Zn, Cu, Hg, and Pb. We concluded that the sources of the relatively high indoor particle concentrations were likely laundry machines and cooking emissions in the absence of a sufficient ventilation system. However, the chemical composition of particles resulting from mining activities is expected to be different from that of the aerosol particles from indoor sources. Installation and proper maintenance of sufficient ventilation and air filtration systems may reduce the total burden of disease from outdoor and indoor air pollution and remediate infiltrated indoor particulate pollution from the mining sources as well.
Ecotoxicity thresholds for ametryn, diuron, hexazinone and simazine in fresh and marine waters
Abstract
Triazine and urea herbicides are two groups of photosystem II inhibiting herbicides frequently detected in surface, ground and marine waters. Yet, there are few water quality guidelines for herbicides. Ecotoxicity thresholds (ETs) for ametryn, hexazinone and simazine (triazine herbicides) and diuron (a urea herbicide) were calculated using the Australian and New Zealand method for deriving guideline values to protect fresh and marine ecosystems. Four ETs were derived for each chemical and ecosystem that should theoretically protect 99, 95, 90 and 80% of species (i.e. PC99, PC95, PC90 and PC80, respectively). For all four herbicides, the phototrophic species were significantly more sensitive than non-phototrophic species, and therefore, only the former data were used to calculate the ETs. Comparison of the ET values to measured concentrations in 2606 samples from 15 waterways that discharge to the Great Barrier Reef (2011–2015) found three exceedances of the simazine PC99, regular exceedances (up to 30%) of the PC99 in a limited number of rivers for ametryn and hexazinone and frequent (> 40%) exceedances of the PC99 and PC95 ETs in at least four waterways for diuron. There were no exceedances of the marine ETs in inshore reef areas. Further, ecotoxicity data are required for ametryn and hexazinone to fresh and marine phototrophic species, for simazine to marine phototrophic species, for tropical phototrophic species, repeated pulse exposures and long-term (2 to 12 months) exposures to environmentally relevant concentrations.
Efficient degradation of triclosan by an endophytic fungus Penicillium oxalicum B4
Abstract
Triclosan (TCS), a widely used antimicrobial and preservative agent, is an emerging contaminant in aqueous and soil environment. Microbial degradation of TCS has not been reported frequently because of its inhibition of microbe growth. To explore the new microbial resources for TCS biodegradation, fungal endophytes were isolated and screened for the degradation potential. The endophytic strain B4 isolated from Artemisia annua L. showed higher degradation efficiency and was identified as Penicillium oxalicum based on its morphology and ITS sequences of ribosomal DNA. In both medium and synthetic wastewater, TCS (5 mg/L) was almost completely degraded within 2 h by the strain B4. The high capacity of TCS uptake (127.60 ± 8.57 mg/g dry weight, DW) of fungal mycelium was observed during the first 10 min after TCS addition. B4 rapidly reduced initial content (5.00 mg/L) of TCS to 0.41 mg/L in medium in 10 min. Then, the accumulation of TCS in mycelium was degraded from 0.45 to 0.05 mg/g DW after 1-h treatment. The degradation metabolites including 2-chlorohydroquinone, 2, 4-dichloropheno, and hydroquinone were found to be restrained in mycelia. The end products of the biodegradation in medium showed no toxicity to Escherichia coli. The new characteristics of high adsorption, fast degradation, and low residual toxicity highlight the potential of endophytic P. oxalicum B4 in TCS bioremediation.
Variability and reliability of POP concentrations in multiple breast milk samples collected from the same mothers
Abstract
Risk assessment of infant using a realistic persistent organic pollutant (POP) exposure through breast milk is essential to devise future regulation of POPs. However, recent investigations have demonstrated that POP levels in breast milk collected from the same mother showed a wide range of variation daily and monthly. To estimate the appropriate sample size of breast milk from the same mother to obtain reliable POP concentrations, breast milk samples were collected from five mothers living in Japan from 2006 to 2012. Milk samples from each mother were collected 3 to 6 times a day through 3 to 7 days consecutively. Food samples as the duplicated method were collected from two mothers during the period of breast milk sample collection. Those were employed for POP (PCBs, DDTs, chlordanes, and HCB) analysis. PCB concentrations detected in breast milk samples showed a wide range of variation which was maximum 63 and 60% of relative standard deviation (RSD) in lipid and wet weight basis, respectively. The time course trend of those variations among the mothers did not show any typical pattern. A larger amount of PCB intake through food seemed to affect 10 h after those concentrations in breast milk in lipid weight basis. Intraclass correlation coefficient (ICC) analyses indicated that the appropriate sample size for good reproducibility of POP concentrations in breast milk required at least two samples for lipid and wet weight basis.
Consensus Recommendations for Treatment Strategies in Indians Using Botulinum Toxin and Hyaluronic Acid Fillers
Background: Indians constitute one of the largest population groups in the world. Facial anthropometry, morphology, and age-related changes in Indians differ from those of other ethnic groups, necessitating a good understanding of their facial structure and the required aesthetic treatment strategies. However, published recommendations specific to Indians are few, particularly regarding combination treatment. Methods: The Indian Facial Aesthetics Expert Group (19 dermatologists, plastic surgeons, and aesthetic physicians with a mean 15.5 years' aesthetic treatment experience) met to develop consensus recommendations for the cosmetic facial use of botulinum toxin and hyaluronic acid fillers, alone and in combination, in Indians. Treatment strategies and dosage recommendations (agreed by ≥ 75% of the group) were based on results of a premeeting survey, peer-reviewed literature, and the experts' clinical experience. Results: The need for combination treatment increases with age. Tear trough deficiency is the most common midface indication in Indian women aged 20–40 years. In older women, malar volume loss and jowls are the most common aesthetic concerns. Excess medial soft tissue on a relatively smaller midface precedes age-related sagging. Hence, in older Indians, fillers should be used peripherally to achieve lift and conservatively in the medial zones to avoid adding bulk medially. The shorter, wider lower face requires 3-dimensional correction, including chin augmentation, to achieve increased facial height and the oval shape desired by most Indian women. Conclusions: These recommendations give physicians treating Indians worldwide a better understanding of their unique facial characteristics and provide treatment strategies to achieve optimal aesthetic outcomes.Monobloc Reconstruction of Dome, Medial Crura, and Columella with Gamma-Shaped Costal Cartilage Graft
Summary: In severe nasal deformities, the original cartilages are removed, or they become unusable because of previous operations. Costal cartilage (CC) is one of the most important tools for the replacement of deficient nasal osteocartilaginous framework. In 4 secondary and 1 tertiary rhinoplasty cases with severe deformities of medial and lateral crura of the lower lateral cartilages, we have prepared a long strut graft from a CC and then split the graft tip 5–6 mm vertically into 2 equal halves to create a gamma (υ)-shaped strut graft. We have sutured the base of this graft to the nasal spine and/or the bases of the medial crural remnants. Then, we have prepared lateral crural grafts and secured the grafts over lateral crural remnants. Then we curved the split tip winglets of the υ-shaped strut graft to both sides and sutured them to lateral crural grafts in order to create a new dome. Splitting of the CC strut graft reduces the need for extensive suturing at the tip, obtains smoother contours and ensures graft economy, and provides an original and stable dome shape. The bending capacity of the CC is limited in middle-aged patients. Costal allografts from a young cadaver can be a good alternative. υ-shaped costal crural graft is useful for medial crural and domal monobloc reconstruction in secondary and tertiary cases.The Superiorly Based Partial Rectus Abdominis and External Oblique Flap: A New Technique for Breast Asymmetry Reconstruction
Summary: Breast asymmetry has a wide spectrum of presentations with several employable strategies for surgical correction. Historically, the external oblique muscle has proven to be a versatile flap option for the reconstruction of both local and distant defects. It has also been described for use in breast reconstruction for coverage of the lower pole of implant prostheses. The external oblique muscle flap can be harvested in several ways to capture overlying fat and skin. In this study, we describe the use of a superiorly based partial rectus and external oblique flap for surgical correction of lower pole breast hypoplasia. This flap provides vascularized autologous volume to the lower pole of the breast with minimal donor morbidity. Other advantages of this flap are that it can increase the nipple to inframammary fold distance and lower the inframammary fold. This technique represents an evolution of an under-utilized flap and is the first study describing the use of the external oblique flap in the management of breast asymmetry.Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis
Abstract
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNFα-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-α expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-κB by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-κB signaling in the development of pathologic corneal neovascularization.
Supplementing living kidney transplantees’ medical records with donor- and recipient-narratives
Abstract
Norway provides total social welfare coverage for organ transplantations, including free immunosuppressive medication and prepaid life-long follow up for both recipients and donors. Despite these benefits the proportion of living kidney donors (LKD) has in recent years declined from around 40% (2011) of all kidney transplantations to 24% (2016). This study suggests harnessing patient- and donor-narratives as a tool for addressing the current fall in donation rates. The hospital records of 18 recipient/donor dyads were compared with patient and donor accounts elicited in semi-structured interviews. Narratives afford a pertinent supplement to the primarily biomedical and technical information stored in medical records. Even in condensed form, the messages embedded in narratives contribute to a 'thicker' understanding of the complexity of living kidney donation (LKD)-decisions. Narratives represent a source of education for referring-nephrologists wishing to deepen their evaluation skills and avoid making decisions based on insufficient insight into patients' and potential donors' values and life-situation. Recipients' and donors' unedited accounts of their motivations, worries, doubts and expectations afford a revealing and edifying supplement to the primarily biomedical and technical information stored in medical records. In narratives, the predicaments and dilemmas surrounding LKD become visible and debatable and can serve as support for future donors, recipients and the nephrologists responsible for evaluation–conclusions. Generating narratives raises a number of practical, epistemic and normative challenges.
Callitriche cophocarpa (water starwort) proteome under chromate stress: evidence for induction of a quinone reductase
Abstract
Chromate-induced physiological stress in a water-submerged macrophyte Callitriche cophocarpa Sendtn. (water starwort) was tested at the proteomic level. The oxidative stress status of the plant treated with 1 mM Cr(VI) for 3 days revealed stimulation of peroxidases whereas catalase and superoxide dismutase activities were similar to the control levels. Employing two-dimensional electrophoresis, comparative proteomics enabled to detect five differentiating proteins subjected to identification with mass spectrometry followed by an NCBI database search. Cr(VI) incubation led to induction of light harvesting chlorophyll a/b binding protein with a concomitant decrease of accumulation of ribulose bisphosphate carboxylase (RuBisCO). The main finding was, however, the identification of an NAD(P)H-dependent dehydrogenase FQR1, detectable only in Cr(VI)-treated plants. The FQR1 flavoenzyme is known to be responsive to oxidative stress and to act as a detoxification protein by protecting the cells against oxidative damage. It exhibits the in vitro quinone reductase activity and is capable of catalyzing two-electron transfer from NAD(P)H to several substrates, presumably including Cr(VI). The enhanced accumulation of FQR1 was chromate-specific since other stressful conditions, such as salt, temperature, and oxidative stresses, all failed to induce the protein. Zymographic analysis of chromate-treated Callitriche shoots showed a novel enzymatic protein band whose activity was attributed to the newly identified enzyme. We suggest that Cr(VI) phytoremediation with C. cophocarpa can be promoted by chromate reductase activity produced by the induced quinone oxidoreductase which might take part in Cr(VI) → Cr(III) bioreduction process and thus enable the plant to cope with the chromate-generated oxidative stress.
Pollution and ecological risk assessment of nutrients associated with deposited sediments collected from roof and road surfaces
Abstract
Surface-deposited sediment in urban areas is an essential environmental medium for assessing nutrient contamination. The total nitrogen (TN) and total phosphorus (TP) pollution associated with surface-deposited sediments can be transported into urban water bodies by runoff and can cause eutrophication of those water bodies. By analyzing the samples collected on roof surfaces and road surfaces, this study provides a comparison of the differences in TN and TP pollution loading in sediments on these two different impervious surface materials. Also, an assessment of the ecological risk of nutrients in surface-deposited sediments with respect to grain size fraction was performed. The results indicate that the TN and TP pollution loading in both road-deposited sediments and roof-deposited sediments indicated an asymmetric "W" trend along with grain size fraction, and both road-deposited sediments and roof-deposited sediments had the highest TN and TP pollution contribution when the particle size is between 250 and 500 μm. TN in roof-deposited sediments has high ecological risk when the particle size is less than 250 μm. These findings help to provide guidance for the management of surface-deposited sediment pollution.
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