Antiwrinkle effect of topical adhesive pads on crow's feet: How long does the effect last for?

Summary

Background

Adhesive pads should reduce the action of the local muscle contraction on the skin leading to a decrease in the depth of existing wrinkles and the formation of new dynamic wrinkles.

Aim of the work

This study aims at assessing the antiwrinkles action of adhesive pads during time, and the temporary improvement of facial skin appearance by reducing the vision of linear wrinkles and improving skin elasticity.

Patients and methods

Thirty-nine subjects participated to a placebo-controlled study. In the short-term test, the measurements were taken 15, 30, and 60 minutes following 30 minutes application of the product; in the long-term test, the measurements were taken after wearing pads every night for 4 weeks. The roughness parameter of the skin surface was calculated by using a profilometry software 3D MEX^®.

Results

In the short- and long-term tests, analyzing the average of the elastomeric measurements, no significant change was observed in any of the parameters analyzed after 15, 30, and 60 minutes. The adhesive pad decreased significantly all roughness skin parameters 15 minutes after short-term application and until 60 minutes after long-term application. These changes did not occur in the contralateral untreated zone.

Conclusions

The use of topical adhesive pads improves wrinkles in the crow's feet area in the first hour after use. However, patient self-evaluation indicated that the use of topical adhesive pads for 3 weeks may offer subjective improvement in crow's feet zone over a 2 hour period. Topical adhesive pads are safe to use and tolerable for most users.

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Greenlandic water and sanitation—a context oriented analysis of system challenges towards local sustainable development

Abstract

Today, as Greenland focuses on more economic and cultural autonomy, the continued development of societal infrastructure systems is vital. At the same time, pressure is put on the systems by a lack of financial resources and locally based professional competences as well as new market-based forms of organization. Against this background, the article discusses the challenges facing Greenland's self-rule in relation to further develop the existing water and wastewater systems so that they can contribute to the sustainable development of Greenland. The article reviews the historical development of the water supply and wastewater system. This leads to an analysis of the sectorisation, which in recent decades has reorganized the Greenlandic infrastructures, and of how this process is influencing local sustainable development. The article discusses the socio-economic and human impacts and points to the need for developing the water and sanitation system to support not only hygiene and health, but also local sustainable development.

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Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells

Abstract

Background

Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute UV exposure to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines which modulate lipid homeostasis and secretion of adipokines.

Objectives

We aim to elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat.

Methods

Primary cultured adipocytes were treated with conditioned media from UV- or sham-irradiated skin cells. Young and old healthy subjects provided SC fat from sun-exposed and sun-protected skin. Another sun-protected skin was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via siRNA-mediated knockdown of cognate receptors.

Results

Specific adipochemokines, including C-X-C chemokines such as ENA-78/CXCL5, and C-C chemokines such as MIP-3α/CCL20 and RANTES/CCL5, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via down-regulation of lipogenic enzymes and sterol regulatory element-binding protein-1 (SREBP-1) through their respective cognate receptors, CXC-chemokine receptor (CXCR)2, CC-chemokine receptor (CCR)6, and CCR5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat.

Conclusions

These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity.

This article is protected by copyright. All rights reserved.

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Is UV-exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181

Abstract

Background

Squamous cell carcinoma (SCC) is among the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting UV-exposure during leisure time. However, the relative impact of occupational and non-occupational UV-exposure for SCC occurrence is unclear.

Objectives

To investigate the association between occupational and non-occupational UV-exposure with SCC in a multicenter population-based case-control study hypothesizing that high occupational UV-exposure increases the risk for SCC.

Methods

Consecutive patients with incident SCC (n=632) were recruited from a German national dermatology network. Population-based controls (n=996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV-exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and non-occupational UV-exposure dosages were estimated by blinded investigators using established reference values. Odds ratios (OR) and corresponding 95%-confidence intervals (95%-CI) were assessed using conditional logistic regression adjusting for relevant confounders.

Results

Total solar UV-exposure was significantly associated with an increased SCC. The OR (95%-CI) for high (>90^th percentile) vs. low (<40^th percentile) and moderate (40^th to 60^th percentile) occupational UV-exposure was 1.95 (1.19-3.18) and 2.44 (1.47-4.06) for SCC. Adjusting for occupational UV-exposure non-occupational UV-exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for non-occupational solar UV-exposure.

Conclusions

Solar occupational UV-exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

This article is protected by copyright. All rights reserved.

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Dupilumab treatment improves quality of life in adult patients with moderate-to-severe atopic dermatitis: Results from a randomized, placebo-controlled clinical trial

Abstract

Background

Dupilumab, a human anti-interleukin-4 receptor α monoclonal antibody, significantly improved clinical signs and symptoms in adults with moderate-to-severe atopic dermatitis (AD) in a randomized, double-blind, placebo-controlled, phase 2a trial.

Objectives

We evaluate health-related quality of life (HRQoL) and correlation of HRQoL with secondary clinical and patient-reported outcomes in a subset of patients from this trial of dupilumab.

Methods

Patients were randomized to 300 mg weekly subcutaneous dupilumab or placebo for 12 weeks (NCT01548404). The QoL Index for AD (QoLIAD) score (exploratory outcome) and its correlation with efficacy outcomes (Eczema Area and Severity Index [EASI; primary endpoint], SCORing Atopic Dermatitis [SCORAD], SCORAD visual analogue scale [VAS] scores for sleep and pruritus, pruritus numerical rating scale [NRS] and 5-dimensional pruritus) were assessed in 64 adults with moderate-to-severe AD.

Results

Mean QoLIAD scores at baseline (± standard error [SE]) were 13.3 (±1.34) and 11.3 (±1.09) for the placebo and dupilumab group, respectively. Dupilumab significantly improved QoLIAD score after 12 weeks of treatment vs. placebo (mean percent change from baseline in QoLIAD score [±SE]: −64.0 [±6.91] vs. –11.1 [±9.31]). Least squares mean % difference from baseline vs. placebo in QoLIAD score (±SE) was −52.0 (±11.43; P<0.0001). QoLIAD scores significantly correlated with changes in efficacy outcomes, including EASI (r=0.4355), 5-dimensional pruritus (r=0.4937), pruritus NRS (r=0.4064), total SCORAD (r=0.5559), and SCORAD VAS scores for sleep (r=0.4681) and pruritus (r=0.5400); all P<0.05.

Conclusions

Dupilumab improved QoLIAD scores in adults with AD and was significantly associated with improvements in study outcomes

This article is protected by copyright. All rights reserved.

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The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events

Publication date: Available online 26 August 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K.E. Kjørstad, S.T. Baksaas, D. Bundgaard, E. Halbakken, T. Hasselgård, T. Jonung, G.T. Jørgensen, J.J. Jørgensen, A.H. Krog, K. Krohg-Sørensen, E. Laxdal, S.R. Mathisen, G.V. Oskarsson, S. Seljeskog, I. Settemsdal, M. Vetrhus, B.A. Viddal, J. Wesche, F. Aasgaard, E. Mattsson
Objective/BackgroundThe objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery.MethodsThis was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated.ResultsThree hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%.ConclusionThis national study with almost complete inclusion and follow-up shows that the delays occurs mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.



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Autologous Latissimus Dorsi Breast Reconstruction Flap Salvage: Microvascular Anastomosis with Serratus Branch

Summary: Autologous breast reconstruction has become a standard option during the recovery of breast cancer survivors. Although pedicle damage is a rare complication of this procedure, extensive torsion or tension can lead to partial or total flap failure. We report a case of partial flap salvage after accidental transection of the pedicled blood supply within the intramuscular course of a latissimus dorsi musculocutaneous flap. This salvage technique involved microvascular anastomosis between the remaining vasculature of the latissimus dorsi pedicle and the serratus branch of the thoracodorsal artery and vein.

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Increased Epicardial Fat Volume Is Independently Associated with the Presence and Severity of Systemic Sclerosis

Publication date: Available online 26 August 2017
Source:Academic Radiology
Author(s): Benjamin D. Long, Jadranka Stojanovska, Richard K.J. Brown, Anil K. Attili, Eizabeth A. Jackson, Vladimir Ognenovski
Rationale and ObjectivesThe study aimed to determine if intrathoracic fat volumes are associated with the presence and severity of systemic sclerosis (SSc), defined by the presence of pulmonary arterial hypertension (PAH).Materials and MethodsA total of 265 patients were included in the study, 202 of whom had SSc (134 had SSc with no PAH and 68 had SSc-associated PAH) and who underwent high-resolution computed tomography, and 63 controls who underwent coronary computed tomography angiography with calcium scoring. Intrathoracic and epicardial (EFV) fat volumes were quantified by manual tracing of the mediastinum and the pericardium, the difference of which represents the extrapericardial fat volume. Associations between these three fat volumes and the presence and severity of SSc, adjusted for cardiovascular risk factors and interstitial lung disease, were evaluated by logistic regression analysis.ResultsOf the 202 patients with SSc, the mean age was 55 years (ranged from 20 to 86), and 79% (159 of 202) were women. Adjusted EFV (odds ratio [OR]: 1.065; 95% confidence interval [CI]: 1.046–1.084, P = < 0.0001), extrapericardial fat volume (OR: 1.028, 95% CI: 1.017–1.038, P = < 0.0001), and intrathoracic fat volume (OR: 1.033, 95% CI: 1.023–1.043, P = 0.001) were associated with the presence of SSc. Only EFV was associated with SSc severity (adjusted OR: 1.010, 95% CI: 1.003–1.018, P = 0.007).ConclusionIncreased epicardial fat volume is associated with the presence and severity of SSc, independent of cardiovascular risk factors and interstitial lung disease.



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Assumptions behind scoring source and item memory impact on conclusions about memory: a reply to Kellen and Singmann’s comment (2017)

Publication date: Available online 26 August 2017
Source:Cortex
Author(s): Elisa Cooper, Andrea Greve, Richard N. Henson




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The effect of working memory intervention on the gait patterns of the elderly

Publication date: Available online 26 August 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Elaheh Azadian, Mahdi Majlesi, Amir Ali Jafarnezhadgero
IntroductionThe purpose of this study was to evaluate the role of working memory (WM) training on walking patterns in elderly people.Methods20 elderly adults were selected and assigned randomly to two groups: WM training group and control group. WM training group received 6 weeks of computerized training on various spatial and verbal WM tasks. The spatial-temporal parameters, the ground reaction force and the timing activity of muscles in pre-posttest and in a follow-up were taken.ResultThe results indicated that a significant change in gait speed, double support time and stride time (p < 0.05). Alternations in ground reaction force (GRF) components were found significant. Timing of muscle activity also showed non-significant change after WM intervention.ConclusionBased on the results of this study, it can be concluded that WM intervention can be applied to improve gait parameters. The improvements in vertical ground reaction force after training may result in an increase upright stability and a decreased in rate falls.



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Mesenchymal cells are required for epithelial duct cell-to-beta cell maturation and function in an injured adult pancreas in the rat

Publication date: Available online 26 August 2017
Source:Acta Histochemica
Author(s): Juziel Kampando Manda, Benedict John Page, Venant Tchokonte-Nana
The islet, the endocrine portion of the pancreas − develops from an invagination of the pancreatic duct epithelial cells (PDECs) into the surrounding tissue. The contact of the PDECs with mesenchymal cells (MSCs) may be an essential drive for endocrine cell fate. During pancreatic development, cells that express Neurogenin-3 (Ngn3) biomarker are precursors of insulin- producing beta cells. These precursors have been reported in the neogenesis of islets from adult tissues following the surgical ligation of the main pancreatic duct (PDL). But the capacity of these precursors to induce the appropriate signals to complete the entire neogenesis program has been questioned. We studied the fate of co-culture of PDECs and MSCs from the ligated adult pancreas and established the exact location of adult stem- or progenitor-like cells that give rise to beta cells. PDECs were cultured in direct contact with or without MSCs in serum-containing culture media. The cytomorphology of the cells in co-cultures was determined and the immunocytochemical study of the cells was carried out using anti-Ngn3, anti-insulin and anti-cytokeratin-7 (CK7) antibodies. Both the PDEC/MSC- and PDEC/MSC+ cultures showed out- pocketing from duct epithelium by the end of the second week, which are distinct as cell clusters only in PDEC/MSC+ cells later in week four, exhibiting numerous branching ducts. Co-expression of Ngn3 with insulin was observed in both cultures from the second week. However, characterizations of these Ngn3+ cells in the PDEC/MSC+ culture revealed that these cells also co-expressed a CK7 biomarker. This study provides new evidence of the ductal epithelial nature of beta cells in injured adult pancreata; and that the mesenchymal stromal cells are required to sustain Ngn3 expression for beta cell maturation and function.



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Bioinformatics analyses of pathways and gene predictions in IL-1α and IL-1β knockout mice with spinal cord injury

Publication date: Available online 26 August 2017
Source:Acta Histochemica
Author(s): Zhuangchen Zhu, Defeng Wang, Wei Jiao, Guang Chen, Yan Cao, Qingfu Zhang, Junqin Wang
PurposeThis study aimed to explore the potential genes and pathways regulated in spinal cord injury (SCI) model mice with IL-1α and IL-1β knockout (KO).MethodsGene expression profile GSE70302, which includes data from injured spinal cord of 4 IL-1α-KO mice, 4 IL-1β-KO mice and 4 C57BL with 6 mice as controls was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) of the IL-1α-KO or IL-1β-KO vs. control, and IL-1α-KO vs. IL-1β-KO groups were screened, followed by function enrichment and protein–protein interaction (PPI) analyses. Finally, miRNAs associated with SCI that may target the DEGs were predicted.ResultsA total of 579 and 992 DEGs were selected from the IL-1α-KO vs. control group and the IL-1β-KO vs. control group, respectively, and 208 genes common between the 2 comparison groups were identified. Additionally, 526 DEGs were identified from the IL-1α-KO vs. IL-1β-KO groups. These DEGs were significantly enriched in functions and pathways associated with ion transport, neuron apoptotic processes and inflammatory responses. The common genes were enriched in the pathways for cytokine–cytokine receptor interaction. DEGs of IL-1α-KO vs. IL-1β-KO were significantly enriched in the immune system, hematopoietic cell lineage and PI3K-Akt signalling pathway-associated biological processes and pathways. The PPI network consisted of 76 nodes, such as Saa2, Kcna1, Scn8a, Ccl5, Ccl28 and Pink1. A total of 94 miRNAs, including mir-17-5P and mir-30a-5p were predicted that could target the DEGs.ConclusionIL-1α and IL-1β may play important roles in SCI by regulating ion transport, inflammation and neuron apoptotic processes and their associated genes or miRNAs. Compared with IL-1β-KO, IL-1α-KO may improve the outcome of SCI via the alteration of hematopoietic cell lineage and PI3K-Akt signalling pathways.



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Efficacy testing of novel chemical disinfectants on clinically relevant microbial pathogens

Publication date: Available online 26 August 2017
Source:American Journal of Infection Control
Author(s): Elaine Meade, Mary Garvey
BackgroundThere has been a dramatic increase in the number of hospital-acquired infections, which is linked to the pandemic of multidrug resistance. Clinical environments provide an ideal reservoir for the growth, proliferation, and transmission of pathogenic organisms, including bacterial and yeast species. Consequently, the need for improved, effective disinfectants is of paramount importance.MethodsStudies were conducted to assess the efficacy of chemical disinfectants—peracetic acid and triameen—on microbial strains. Testing included the assessment of antimicrobial and antisporicidal activity of disinfection solutions performed on a range of clinical isolates that pose a high risk for patient morbidity in clinical settings.ResultsBoth chemical disinfectants successfully inactivated all test strains, with peracetic acid showing a greater level of antimicrobial activity. Escherichia coli proved most susceptible when assessed by the Kirby disk diffusion, suspension, and medical suspension assays with the greatest reduction in cell viability achieved. Antibiotic-resistant Enterococcus and Staphylococcus aureus strains showed greatest resistance to both disinfectants.Discussion and conclusionsTest chemicals show potential to act as intermediate-level disinfectants inactivating vegetative microorganisms and bacterial spores on clinically relevant strains where they show potential as a preventative measure in relation to nosocomial infections.



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A Comprehensive Review of Cryogels and Their Roles in Tissue Engineering Applications

Publication date: Available online 26 August 2017
Source:Acta Biomaterialia
Author(s): Katherine R. Hixon, Tracy Lu, Scott A. Sell
The extracellular matrix is fundamental in providing an appropriate environment for cell interaction and signaling to occur. Replicating such a matrix is advantageous in the support of tissue ingrowth and regeneration through the field of tissue engineering. While scaffolds can be fabricated in many ways, cryogels have recently become a popular approach due to their macroporous structure and durability. Produced through the crosslinking of gel precursors followed by a subsequent controlled freeze/thaw cycle, the resulting cryogel provides a unique, sponge-like structure. Therefore, cryogels have proven advantageous for many tissue engineering applications including roles in bioreactor systems, cell separation, and scaffolding. Specifically, the matrix has been demonstrated to encourage the production of various molecules, such as antibodies, and has also been used for cryopreservation. Cryogels can pose as a bioreactor for the expansion of cell lines, as well as a vehicle for cell separation. Lastly, this matrix has shown excellent potential as a tissue engineered scaffold, encouraging regrowth at numerous damaged tissue sites in vivo. This review will briefly discuss the fabrication of cryogels, with an emphasis placed on their application in various facets of tissue engineering to provide an overview of this unique scaffold's past and future roles.Statement of SignificanceCryogels are unique scaffolds produced through the controlled freezing and thawing of a polymer solution. There is an ever-growing body of literature that demonstrates their applicability in the realm of tissue engineering as extracellular matrix analogue scaffolds; with extensive information having been provided regarding the fabrication, porosity, and mechanical integrity of the scaffolds. Additionally, cryogels have been reviewed with respect to their role in bioseparation and as cellular incubators. This all-inclusive view of the roles that cryogels can play is critical to advancing the technology and expanding its niche within biomaterials and tissue engineering research. To the best of the authors' knowledge, this is the first comprehensive review of cryogel applications in tissue engineering that includes specific looks at their growing roles as extracellular matrix analogues, incubators, and in bioseparation processes.

Graphical abstract

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Estrogen and progesterone signalling in the normal breast and its implications for cancer development

Publication date: Available online 26 August 2017
Source:Molecular and Cellular Endocrinology
Author(s): Heidi N. Hilton, Christine L. Clarke, J. Dinny Graham
The ovarian hormones estrogen and progesterone are master regulators of the development and function of a broad spectrum of human tissues, including the breast, reproductive and cardiovascular systems, brain and bone. Acting through the nuclear estrogen (ER) and progesterone receptors (PR), both play complex and essential coordinated roles in the extensive development of the lobular alveolar epithelial structures of the normal breast during puberty, the normal menstrual cycle and pregnancy. The past decade has seen major advances in understanding the mechanisms of action of estrogen and progesterone in the normal breast and in the delineation of the complex hierarchy of cell types regulated by ovarian hormones in this tissue. There is evidence for a role for both ER and PR in driving breast cancer, and both are favourable prognostic markers with respect to outcome. In this review, we summarize current knowledge of the mechanisms of action of ER and PR in the normal breast, and implications for the development and management of breast cancer.



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Distribution of genes encoding resistance to aminoglycoside modifying enzymes in methicillin-resistant Staphylococcus aureus (MRSA) strains

Publication date: Available online 26 August 2017
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Azar Dokht Khosravi, Atefeh Jenabi, Effat Abbasi Montazeri
Today Methicillin-Resistant Staphylococcus aureus (MRSA) have acquired multiple resistance to a wide range of antibiotics including aminoglycosides. So, this study was aimed to investigate the rate of aminoglycoside resistance and the frequency of aminoglycoside resistance mediated genes of aac(Ia)-2, aph(3)-IIIa and ant(4′)-Ia among MRSA strains. A total of 467 staphylococci isolates were collected from various clinical samples. S. aureus strains were identified by standard culture and identification criteria and investigating of presence of 16S rRNA and nuc genes. Cefoxitin disk diffusion, and oxacillin-salt agar screening methods were used to detect the MRSA strains with subsequent molecular identification for the presence of mecA gene. Antibiotic susceptibility of MRSA strains against aminoglycoside antibiotics was evaluated by using agar disk diffusion method. Multiplex PCR for the presence of aac(Ia)-2, aph(3)-IIIa and ant(4′)-Ia encoding genes for aminoglycosides were performed for MRSA strains. From total staphylococci tested isolates, 262 (56.1%) were identified as S. aureus, of which 161 (61.45%) were detected as MRSA and all comprised mecA gene. The resistance pattern of MRSA strains to aminoglycoside antibiotics were: gentamicin 136 (84.5%); amikacin 125 (77.6%); kanamycin 139 (86.3%); tobramycin 132 (82%); and neomycin 155 (96.3%). The frequency of aac(Ia)-2, aph(3)-IIIa, and ant(4′)-Ia genes among MRSA strains, were 64%, 42% and 11.8% respectively. In conclusion, as MRSA strains are of great concern in human infections, the results of present study could provide a useful resource for health sectors for choosing appropriate antibiotics for the effective treatment of infections due to MRSA strains.



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Charting the dynamic epigenome during B-cell development

Publication date: Available online 26 August 2017
Source:Seminars in Cancer Biology
Author(s): Jose I. Martin-Subero, Christopher C. Oakes
The epigenetic landscape undergoes a widespread modulation during embryonic development and cell differentiation. Within the hematopoietic system, B cells are perhaps the cell lineage with a more dynamic DNA methylome during their maturation process, which involves approximately one third of all the CpG sites of the genome. Although each B-cell maturation step displays its own DNA methylation fingerprint, the DNA methylome is more extensively modified in particular maturation transitions. These changes are gradually accumulated in specific chromatin environments as cell differentiation progresses and reflect different features and functional states of B cells. Promoters and enhancers of B-cell transcription factors acquire activation-related epigenetic marks and are sequentially expressed in particular maturation windows. These transcription factors further reconfigure the epigenetic marks and activity state of their target sites to regulate the expression of genes related to B-cell functions. Together with this observation, extensive DNA methylation changes in areas outside gene regulatory elements such as hypomethylation of heterochromatic regions and hypermethylation of CpG-rich regions, also take place in mature B cells, which intriguingly have been described as hallmarks of cancer. This process starts in germinal center B cells, a highly proliferative cell type, and becomes particularly apparent in long-lived cells such as memory and plasma cells. Overall, the characterization of the DNA methylome during B-cell differentiation not only provides insights into the complex epigenetic network of regulatory elements that mediate the maturation process but also suggests that late B cells also passively accumulate epigenetic changes related to cell proliferation and longevity.



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Thrombo-hemorrhagic liability in children with congenital heart diseases

Publication date: Available online 26 August 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Shebl Said Shebl, Walid Ahmed Naguib El-shehaby, Amira Hamed Darwish, Yasmin Shebl Said, Nabeh Helal Elfadaly, Eman Amer
BackgroundThe precise mechanisms of the increased incidence of hemostatic abnormalities in congenital heart disease (CHD) have not been determined. The aim of the study was to evaluate some indicators of activation of platelets and vascular endothelial cells in patients with CHD, evaluation of bleeding liability of these patients, and correlation with the clinical presentation of these patients.MethodsThis work was carried out on 20 patients with cyanotic congenital heart disease (CCHD), 20 patients with cyanotic congenital heart disease (ACHD), and 20 healthy children who served as the control group, aged between 1 and 10 years. All were subjected to full clinical examination, complete blood count, oxygen saturation, echocardiography, bleeding and coagulation times, PT, PTT, FDPs, plasma soluble P-selectin, E-selectin, and platelet factor 4 (PF4).ResultsThere was significant prolongation of PT and PTT, and there was a significant lowering of platelet counts. These results were obtained in CCHD and ACHD, but were more significant in CCHD patients. There was a significant elevation in PF4 (55.0 ± 25.5 ng/mL), P-selectin (128.9 ± 42.44 ng/dL), and E-selectin (9,461.5 ± 1,701.24 pg/mL) levels in children with CCHD as compared to those with ACHD (PF4, 21 ± 7.94 ng/mL; P-selectin, 80.1 ± 13.2 ng/mL; E-selectin, 7,969.6 ± 2,127.5 pg/mL), and significant increase in both groups when compared to the control group (PF4, 8.1 ± 4.7 ng/mL; P-selectin, 27.83 ± 9.73 ng/mL; E-selectin, 6,750.00 ± 3,204.00 pg/mL). There was a significant negative correlation between oxygen saturation, plasma P-selectin (r = –.865), E-selectin (r = –.401), and PF4 (r = –.792) in patients with CCHD.ConclusionPatients with CHD—both cyanotic and acyanotic—have variable degrees of increased liability for both thrombosis and hemorrhage that represents some sort of adaptation to preserve hemostasis and to protect these patients against the clinical presentation of both thrombosis and bleeding. This is to say that CHD patients have their own point of balance between thrombogenicity and bleeding liability. Wide-scale studies are needed to detect the normal levels of different thrombohemorrhagic parameters of these patients.



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Effects of glucocorticoids on stratum corneum lipids and function in human skin—a detailed lipidomic analysis

Publication date: Available online 26 August 2017
Source:Journal of Dermatological Science
Author(s): Mads A. Røpke, Cristina Alonso, Sora Jung, Hanne Norsgaard, Claudia Richter, Maxim E. Darvin, Thomas Litman, Annika Vogt, Jürgen Lademann, Ulrike Blume-Peytavi, Jan Kottner
BackgroundTopical glucocorticoids (GCs) are known to induce atrophy of human skin including thinning of epidermal and dermal compartments by influencing keratinocyte proliferation and synthesis of extracellular matrix proteins. GCs are also known to reduce skin barrier integrity but little is known about the changes in lipid composition in human skin following topical administration of GCs.ObjectiveThis study investigated the effects of GCs on stratum corneum (SC) function and lipid profile of human skin in vivo.MethodOver a period of 4 weeks, 16 healthy volunteers were treated on the forearms once daily with topical clobetasol proprionate (CP), betamethasone diproprionate (BDP) or vehicle. One day after last application (Day 29) SC lipids were collected by tape stripping and analysed by a high sensitivity liquid chromatography–mass spectrometry method. Gene expression was analysed in skin biopsies. The full skin, epidermal and SC thickness were assessed by ultrasound, optical coherence tomography and confocal microscopy, respectively, and barrier integrity was assessed by measuring transepidermal water loss (TEWL).ResultsCompared to vehicle controls, GCs induced significant alterations in SC lipid profiles. CP caused a reduction in 98 lipids of 226 analysed while BDP treatment only resulted in a significant change of 29 lipids. Most pronounced changes occurred among long chain, ester-linked, ceramide classes while other ceramide classes were much less affected. Almost the complete profile of triacylglycerols (TGs) was significantly decreased by CP while more modest changes were observed in free fatty acids. Topical GCs reduced the thickness of skin layers and increased TEWL. GC treatment also induced changes in expression of genes coding for extracellular markers and enzymes involved in lipids synthesis.ConclusionsThis study shows a reduction in specific SC lipid classes following topical GC treatment of human skin and contributes to the characterisation of the barrier disruption in human skin induced by topical steroids.



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Towards personalized medicine of colorectal cancer

Publication date: Available online 26 August 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Mohammad Azhar Aziz, Zeyad Yousef, Ayman Saleh, Sameer Mohammad, Bandar Al Knawy
Efforts in colorectal cancer (CRC) research aim to improve early detection and treatment for metastatic stages which could translate into better prognosis of this disease. One of the major challenges that hinder these efforts is the heterogeneous nature of CRC and involvement of diverse molecular pathways. New large-scale 'omics' technologies are making it possible to generate, analyze and interpret biological data from molecular determinants of CRC. The developments of sophisticated computational analyses would allow information from different omics platforms to be integrated, thus providing new insights into the biology of CRC. Together, these technological advances and an improved mechanistic understanding might allow CRC to be clinically managed at the level of the individual patient. This review provides an account of the current challenges in CRC management and an insight into how new technologies could allow the development of personalized medicine for CRC.



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Distance-delivered physical activity interventions for childhood cancer survivors: A systematic review and meta-analysis

Publication date: Available online 26 August 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): David Mizrahi, Claire E. Wakefield, Joanna E. Fardell, Veronica F. Quinn, Qishan Lim, Briana K. Clifford, David Simar, Kirsten K. Ness, Richard J. Cohn
This review aimed to determine the feasibility of distance-delivered physical activity (PA) interventions in childhood cancer survivors (CCS), and assess the effect on PA levels, and physical, physiological and psychological outcomes. We searched electronic databases until May 2016, including studies following intensive treatment. Meta-analyses were conducted on randomized controlled trials. We calculated the effect of interventions on PA levels and physical, physiological and psychological health outcomes. Thirteen studies (n=270 participants) were included in the systematic review and four (n=102 participants) in the meta-analysis. Most studies used telephone to deliver interventions with contact (1/day-1/month), duration (2 weeks–1year) and timing (maintenance therapy->20years following intensive treatment) varying between interventions. Interventions yielded a mean recruitment rate=64%, retention rate=85% and adherence rate=88%. Interventions did not increase PA levels (p=0.092), but had a positive effect on physical function (p=0.008) and psychological outcomes (p=0.006). Distance-delivered PA interventions are feasible in CCS. Despite not increasing PA levels, participation may improve physical and psychological health; however, larger randomized controlled trials are warranted.



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Skin Colonization by Staphylococcus Aureus Precedes the Clinical Diagnosis of Atopic Dermatitis in Infancy.

Related Articles

Skin Colonization by Staphylococcus Aureus Precedes the Clinical Diagnosis of Atopic Dermatitis in Infancy.

J Invest Dermatol. 2017 Aug 22;:

Authors: Meylan P, Lang C, Mermoud S, Johannsen A, Norrenberg S, Hohl D, Vial Y, Prod'hom G, Greub G, Kypriotou M, Christen-Zaech S

Abstract
Atopic dermatitis (AD) has a well-established association with skin colonization or infection by Staphylococcus aureus, which can exacerbate the disease. However, a causal relationship between specific changes in skin colonization during the first years of life and AD development still remains unclear. In this prospective birth cohort study, we aimed to characterize the association between skin colonization and AD development in 149 Caucasian infants with or without a family history of atopy. We assessed infants clinically and collected axillary and antecubital fossa skin swabs for culture-based analysis, at birth and at seven time points over the first two years of life. We found that at age three months, S. aureus was more prevalent on the skin of infants who developed AD later on. S. aureus prevalence was increased on infants' skin at the time of AD onset and also two months before it, when compared to age-matched unaffected infants. Furthermore, at AD onset, infants testing positive for S. aureus were younger than uncolonized subjects. In conclusion, our results suggest that specific changes in early-life skin colonization may actively contribute to clinical AD onset in infancy.

PMID: 28842320 [PubMed - as supplied by publisher]

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Ficolin-2 triggers antitumor effect by activating macrophages and CD8+ T cells

Publication date: Available online 26 August 2017
Source:Clinical Immunology
Author(s): Quanquan Ding, Yanying Shen, Dongqing Li, Juan Yang, Jing Yu, Zhinan Yin, Xiao-Lian Zhang
Ficolin-2 is an important serum complement lectin. Here, we describe novel findings indicating that serum ficolin-2 concentrations in multiple tumor patients are significantly lower than those in healthy donors. Administration of exogenous ficolin-2 or ficolin-A (a ficolin-2-like molecule in mouse), with only once, could remarkably inhibit the tumor cells growth in murine tumor models via early macrophages, dendritic cells (DCs) and CD8⁺ T cells, but not CD4⁺ T cells. Ficolin-A (FCN-A) knockout (KO) mice exhibits significantly increased tumor cell growth. Ficolin-2 induces macrophage activation, promotes M1 polarization and facilitates proliferation and antigen-specific cytotoxicity of CD8⁺ T cells. Ficolin-2 binds to Toll-like receptor 4 (TLR4) on macrophages and DCs and promotes their antigen-presenting abilities to CD8⁺ T cells. Our findings provide a new therapeutic strategy for tumors based on the triggering of immune-mediated antitumor effect by ficolin-2.



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CONTENTS 2

Publication date: July–August 2017
Source:Materials Today, Volume 20, Issue 6





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CONTENTS 1

Publication date: July–August 2017
Source:Materials Today, Volume 20, Issue 6





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Mitochondrial replacement techniques or therapies (MRTs) to improve embryo development and to prevent mitochondrial disease transmission

Publication date: Available online 26 August 2017
Source:Journal of Genetics and Genomics
Author(s): Xiang-Hong Ou, Qing-Yuan Sun




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Re-irradiation using Permanent Interstitial Brachytherapy (PIB): A Potentially Durable Technique for Salvaging Recurrent Pelvic Malignancies

Publication date: Available online 26 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jonathan Feddock, Dennis Cheek, Cole Steber, Jason Edwards, Stacey Slone, Wei Luo, Marcus Randall
PurposeWomen who develop recurrence of malignancy in a previously irradiated pelvis are often considered incurable. Permanent interstitial brachytherapy (PIB) is an under-utilized but well-tolerated and safe treatment option with significant curative potential when utilized in well-selected patients.Materials and methodsForty-two previously irradiated patients received curative or palliative intent PIB for a recurrent pelvic malignancy between January 2009 and August 2016. Minimum follow-up was 6 months following the PIB procedure. All patients had a biopsy-proven recurrence and were treated using PIB alone (n=32) or in combination with a short course of additional radiation therapy (n=10). Competing risk analyses were performed to assess the risk of failures in the presence of death without failure. Exploratory analyses were performed for factors related to failure using competing risk analyses and the Gray statistic.ResultsA total of 61 PIB implants were performed among 42 patients with a median follow up of 16.3 months. Fifty-two implants were performed as the first salvage re-irradiation to a solitary recurrence (8 patients had more than one lesion), and the success rate for initial re-irradiation using PIB was 73% (38 cases out of 52), and the median TTF was not reached. Nine patients underwent a second repeat PIB to the same recurrence as a form of salvage – 3 (33%) remain without evidence of recurrence. The median TTF after second salvage was 7.7 months. Even with the limited sample size, prolonged TTF was marginally associated with definitive intent (p=0.07) and the extent of disease at the time of PIB (p=0.08). Grade 3+ toxicities were seen in 8 patients (16.7%).ConclusionsPermanent interstitial brachytherapy is a feasible and potentially durable treatment modality that can be used to curatively salvage selected recurrent pelvic malignancies in a previously irradiated field.

Teaser

Permanent interstitial brachytherapy (PIB) is an often forgotten and underutilized brachytherapy technique that can be used to manage small volume recurrent gynecologic disease. The primary intent of this type of treatment is to manage local disease, and in nearly all cases, curative doses of radiation can be delivered in a single outpatient procedure. The median time to failure for re-irradiation was not identified in this series suggesting its effectiveness as a form of local therapy.


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Care for Patients, Not for Charts: A Future for Clinical Medical Physics

Publication date: Available online 26 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Todd F. Atwood, Derek W. Brown, James D. Murphy, Kevin L. Moore, Arno J. Mundt, Todd Pawlicki




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Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264.7 cells

Publication date: Available online 26 August 2017
Source:Journal of Ethnopharmacology
Author(s): Yi-Hong Zou, Liang Zhao, You-Kai Xu, Jing-Mei Bao, Xin Liu, Jun-Sheng Zhang, Wei Li, Abrar Ahmed, Sheng Yin, Gui-Hua Tang
Ethnopharmacological relevanceSalvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history.Aim of the studyThe aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases.Material and methodsThe aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C18, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay.ResultsSix new (1−6, salviplenoids A−F) and ten known (7−16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2.ConclusionsAmong all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.

Graphical abstract

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Syzygium cumini leaf extract inhibits LDL oxidation, but does not protect the liproprotein from glycation

Publication date: Available online 26 August 2017
Source:Journal of Ethnopharmacology
Author(s): Matheus M. dos Santos, Alessandro S. Prestes, Gabriel T. de Macedo, Assis Ecker, Rômulo P. Barcelos, Aline A. Boligon, Diego Souza, Andreza F. de Bem, João B.T. da Rocha, Nilda V. Barbosa
Etnopharmacological relevanceSyzygium cumini (L.) Skeels is a plant widely used in folk medicine to treat diabetes mellitus (DM). The tea from its leaves is frequently used by diabetics for lowering hyperglycemia. There is a close relationship between DM and atherosclerosis, a chronic immuno-inflammatory disease, were the early stages encompass oxidative and glycative modifications in the structure of low density lipoprotein (LDL).Aim of this studyTo investigate the potential protective effects of aqueous-leaf extract from Syzygium cumini (S.cExt) against CuSO4-induced oxidation and methylglyoxal (MG)-induced glycation of human LDL in vitro.Materials and methodsLDL oxidative changes were evaluated by measuring conjugated dienes (CD) formation, thiobarbituric acid reactive substances (TBARS) levels, quenching of tryptophan (Trp) fluorescence and structural modifications in LDL particle. In LDL glycated by MG (glyLDL), we determined the levels of fluorescent advanced glycation end products (AGEs) and mobility by agarose gel electrophoresis.ResultsS.cExt blocked oxidative events induced by CuSO4 in human LDL, plasma and serum. Fourier transform infrared spectroscopy (FT-IR) revealed that specific regions of ApoB100 were oxidized by CuSO4 in human LDL and that S.cExt reduced these oxidations. Unlike, the increased AGEs levels and eletrophoretic mobility observed in LDL MG-glycated were not modified by S.cExt.ConclusionThe findings herein indicate that S.cExt could be tested in atherogenesis models as potential protective agent against LDL oxidation.

Graphical abstract

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