Bimatoprost ophthalmic solution in facial vitiligo

Summary

Background

Vitiligo is one of the commonest pigmentary disorders characterized by destruction of melanocytes.

Aim

To evaluate the efficacy of topical bimatoprost ophthalmic solution in stable facial vitiligo.

Material and methods

Eight cases of stable facial vitiligo were treated with bimatoprost 0.03% ophthalmic solution once daily for 12 weeks. Photographic records were taken at 2 weeks follow-up along with dermoscopic (Polarized, 10×) evaluation.

Results

Four cases had excellent repigmentation, two cases had partial repigmentation and two cases had poor response.

Conclusion

Bimatoprost seems to be promising in treating stable vitiligo but large-scale studies are required.

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A retrospective analysis of biochemical and haematological parameters in patients with eating disorders

Abstract

Background

The objective of the study was to determine whether levels of biochemical and haematological parameters in patients with eating disorders (EDs) varied from the general population. Whilst dietary restrictions can lead to nutritional deficiencies, specific abnormalities may be relevant to the diagnosis, pathogenesis and treatment of EDs.

Methods

With ethics approval and informed consent, a retrospective chart audit was conducted of 113 patients with EDs at a general practice in Brisbane, Australia. This was analysed first as a total group (TG) and then in 4 ED subgroups: Anorexia nervosa (AN), Bulimia nervosa (BN), ED Not Otherwise Specified (EDNOS), and AN/BN. Eighteen parameters were assessed at or near first presentation: cholesterol, folate, vitamin B12, magnesium, manganese, zinc, calcium, potassium, urate, sodium, albumin, phosphate, ferritin, vitamin D, white cell count, neutrophils, red cell count and platelets. Results were analysed using IBM SPSS 21 and Microsoft Excel 2013 by two-tailed, one-sample t-tests (TG and 4 subgroups) and chi-square tests (TG only) and compared to the population mean standards. Results for the TG and each subgroup individually were then compared with the known reference interval (RI).

Results

For the total sample, t-tests showed significant differences for all parameters (p < 0.05) except cholesterol. Most parameters gave results below population levels, but folate, phosphate, albumin, calcium and vitamin B12 were above. More patients than expected were below the RI for most parameters in the TG and subgroups.

Conclusions

At diagnosis, in patients with EDs, there are often significant differences in multiple haematological and biochemical parameters. Early identification of these abnormalities may provide additional avenues of ED treatment through supplementation and dietary guidance, and may be used to reinforce negative impacts on health caused by the ED to the patient, their family and their treatment team (general practitioner, dietitian and mental health professionals). Study data would support routine measurement of a full blood count and electrolytes, phosphate, magnesium, liver function tests, ferritin, vitamin B12, red cell folate, vitamin D, manganese and zinc for all patients at first presentation with an ED.

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A review of patient-specific gastrointestinal parameters as a platform for developing in vitro models for predicting the in vivo performance of oral dosage forms in patients with Parkinson’s disease

Publication date: 25 November 2017
Source:International Journal of Pharmaceutics, Volume 533, Issue 1
Author(s): Erik Wollmer, Sandra Klein
Parkinson's disease (PD) is a progressive neurodegenerative disease that presents with visible motor symptoms, but that is accompanied by several additional symptoms, including gastrointestinal symptoms that may affect pharmacokinetics of oral medications. A detailed understanding of the nature of PD-specific gastrointestinal parameters and of how they may affect drug release of orally administered dosage forms seems to be essential information for developing better oral PD medications. The availability of bio-predictive drug release models simulating PD-specific gastrointestinal parameters would also be beneficial for this purpose. The focus of the present literature review was to determine PD-specific gastrointestinal parameters that will allow for the development of a test methodology simulating the gastrointestinal passage of orally administered medications in PD patients. Whereas for some gastrointestinal segments there is quite a reasonable set of data available on fluid volumes, motility and passage times, for others there is still a big lack in information that would be required for simulating a detailed gastrointestinal passage in a PD patient. The latter is particularly true for potential disease-related changes in gastrointestinal fluid composition. However, with the availability of novel non-invasive diagnostic options there is a chance of obtaining more information in the near future.

Graphical abstract

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Chapter 4 Chemical components and nutrition

Publication date: 2018
Source:Kent's Technology of Cereals
Author(s): Kurt A. Rosentrater, A.D. Evers




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Current mouse models of oral squamous cell carcinoma: Genetic and chemically induced models

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Kazuhisa Ishida, Hiroyuki Tomita, Takayuki Nakashima, Akihiro Hirata, Takauji Tanaka, Toshiyuki Shibata, Akira Hara
Oral squamous cell carcinoma (OSCC) patients have a low 5-year survival rate and poor prognosis. To improve survival and prognosis, the causes and processes involved in lesion development should be evaluated. For this purpose, the use of OSCC mouse models, such as chemically induced mouse models, genetically modified mouse models, and transplanted (xenograft) models, is crucial. These OSCC models exhibit both advantages and disadvantages when studying OSCC development and progression. Until a model resembling human OSCC is developed, both the advantages and disadvantages of each model should be carefully considered. In this review, we discuss OSCC mouse models and their use in cancer research worldwide.



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Post operative palatal cleft with synechia of tonsillar pillar and uvula – Could vascular ischemia be the etiology?

Publication date: Available online 6 October 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Surendra B. Patil, Shree Harsh
Post operative cleft of palate is a known complication of palatal split surgery. We present a post operative case of nasopharyngeal angiofibroma who presented with nasal twang in voice. Examination revealed cleft of soft palate with fusion of left side of uvula with the left tonsillar pillar. He underwent reconstruction of the left tonsillar pillar, left side of uvula and pushback palatoplasty. The aim of this article is to bring this unusual complication of palatal split surgery and it's management.



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Type I Dural Arteriovenous Fistula Mimicking Dural Venous Thrombosis-Related Intracranial Hypertension.

No abstract available

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Minimizing risk on the margins: Insights on Iron Age agriculture from stable isotope analyses in central Croatia

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Emily Zavodny, Brendan J. Culleton, Sarah B. McClure, Douglas J. Kennett, Jacqueline Balen




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Vanishing Act: Gorham-Stout Disease Leading to Dynamic Cerebrospinal Fluid Abnormalities.

No abstract available

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Moving things: Comparing lithic and bone refits from a Middle Paleolithic site

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Manuel Vaquero, M. Cristina Fernández-Laso, M. Gema Chacón, Francesca Romagnoli, Jordi Rosell, Pablo Sañudo
The refitting of both lithic and faunal remains is a basic field of research in Paleolithic archeology. In particular, the spatial dimension of lithic and faunal refitting is essential for resolving questions related to site formation processes and the organization strategies of hunter-gatherer bands. Unfortunately, although important insights can be gained by comparing the spatial patterns of faunal and lithic refits there are relatively few sites from which both types are available. Some processes causing the movement of archeological items are common to both bone and lithic remains, but others are specific to each. The similarities and differences between the lithic and faunal connections can be particularly informative when considering the type and timing of the archeological assemblage formation dynamics. This comparison may be especially useful for disentangling the roles of natural and cultural processes in these formation dynamics. To illustrate this, we will compare the refitting patterns of lithic and faunal remains in level M from Abric Romaní (Capellades, Barcelona, Spain), a Middle Paleolithic assemblage dated between 51 and 55kyrBP. The results of such a comparison provide new insights into various formation processes, including the intrasite movement of archeological items and the relationships between activity areas.



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Five-Year-Old Boy With Behavioral Changes and Papilledema.

A 5-year-old boy had initial symptoms of behavioral changes, nausea, vomiting, headache, weight loss, and progressive vision failure. Brain MRI revealed abnormal signal intensity in both optic nerves, the optic chiasm, the right medial temporal lobe, and tissues surrounding the right supraclinoid internal carotid artery with associated leptomeningeal and spinal cord enhancement. After nondiagnostic dural and spinal arachnoid biopsies, a temporal lobe biopsy was diagnostic for a rare malignant peripheral nerve sheath tumor. (C) 2017 by North American Neuro-Ophthalmology Society

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Burnt lime production and the Pre-Columbian Maya socio-economy: A case study from the northern Yucatán

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Kenneth Seligson, Tomás Gallareta Negrón, Rossana May Ciau, George J. Bey
Burnt lime has been crucial for architectural, dietary, and other purposes in Maya society since as far back as 1100 BCE. The recent identification of a series of pit-kilns used for lime production in the Puuc region of the northern Yucatán Peninsula allows for an unprecedented investigation of the socio-economic organization of the Pre-Columbian lime industry. This article reports on the importance of burnt lime to Maya society and presents the results of spatial analyses of the pit-kilns in relation to other archaeological and environmental features. The distribution of the lime production features indicate that the Pre-Columbian lime industry was decentralized and organized at the small corporate group level. Some of these groups likely incorporated limestone extraction and processing into a broader multi-crafting subsistence strategy. Those small corporate groups that did not produce their own lime would have had to acquire it from producing groups through an intra-community exchange system. Spatial analyses also indicate that lime production locations reflect a desire to limit both pre- and post-production material transportation efforts. The study provides a model for investigating the production and distribution of a perishable craft good that can be used for examining perishable goods in ancient societies beyond Mesoamerica. The small-scale, decentralized lime production organization identified in the northern Maya lowlands can now be compared with systems of production and exchange of perishable goods in other pre-modern societies around the world.



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Nonsurgical Management of Retained Needlefish Jaw.

While scuba diving, the left medial canthus of a 53-year-old man was pierced by a needlefish. He immediately lost vision in his left eye. An orbital computed tomographic scan showed the needlefish jaw in the left optic canal. The left medial orbit was explored surgically but no foreign object was removed. One month later, MRI confirmed the presence of the retained needlefish jaw. A conservative approach was taken and the patient remained stable over 3 months of follow-up. (C) 2017 by North American Neuro-Ophthalmology Society

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Editorial Board/ Publication Information

Publication date: October 2017
Source:Molecular Immunology, Volume 90





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Laughter-Induced Transient Vision Loss in a Patient With Silent Sinus Syndrome.

Background: To report a patient with silent sinus syndrome (SSS) who experienced transient ipsilateral monocular vision loss during intense laughter. Methods: Case report. Results: Our patient's transient vision loss completely resolved after maxillary sinus decompression and during 7 months of follow-up. Conclusions: Although the precise mechanism of our patient's vision loss remains undetermined, we suspect that the vascular supply to the eye and/or the optic nerve was compromised as the result of the combination of laughter (causing Valsalva maneuver and increased intrathoracic pressure) and SSS. (C) 2017 by North American Neuro-Ophthalmology Society

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A point mutation in the extracellular domain of CD4 completely abolishes CD4 T cell development in C57BL/6 mouse

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Huijie Wang, Saichao Li, Tianzhu Chao, Xugang Wang, Lijin Shi, Lichen Zhang, Yinming Liang, Qianqian Zheng, Liaoxun Lu
In this study, we performed ENU mutagenesis and multi-parameter flow cytometric analysis in C57BL/6 mice to uncover novel genes or alleles regulating immune cell development. We identified a novel mutant allele of Cd4 gene which completely blocked development of a major subset of T cells named CD4 T cell. Our data for the first time showed experimentally in mice the critical role of the first extracellular domain, by obtaining mice with a loss of function mutation from Ile to Asn at the position 99 of CD4 (I99N). Interestingly, such CD4^I99N mutant protein can be expressed on the surface of human cells, and the mRNA stability could be also affected by this point mutation, suggesting that absence of CD4 T cells in mice rooted in the deficiency in function and expression of CD4. In addition, we used this novel CD4 T cell deficient model as recipient mice for adoptive transfer experiment, and showed that it could be an optimal model for study of CD4 T cells.



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Why a One-Way Ticket to Mars May Result in a One-Way Directional Glymphatic Flow to the Eye.

No abstract available

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The archaic roles of the lamprey NF-κB (lj-NF-κB) in innate immune responses

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Peng Su, Xin Liu, Yue Pang, Chang Liu, Ranran Li, Qiong Zhang, Hongfang Liang, Hao Wang, Qingwei Li
The nuclear factor-kappa B (NF-κB) is a pleiotropic transcription factor regulating the expression of genes involved in various biological processes including the immune response and inflammation. Lamprey is regarded as a key species to provide meaningful clues for understanding the evolution of immune system; nevertheless, no information about lamprey NF-κB is reported. Thus, we have characterized a NF-κB homolog in lamprey (lj-NF-κB) for the deeper understanding of the role it played in lamprey immune system. The sequence and 3D structure analyses demonstrate that lj-NF-κB contained a Rel homology domain (RHD) and seven ankyrin repeats domains (ANKs), which would exhibit functional similarities to NF-κB superfamily proteins. This hypothesis was further proved by experiments. We found that the RHD of lj-NF-κB could interact with a mammalian κB response element, translocate to the nucleus to modulate gene (IL-6, IL-1β and TNF-α) expression, and the nuclear localization signals (NLS) was essential for the nuclear translocation. Furthermore, the ANKs of lj-NF-κB are the inhibition signal for the RHD of lj-NF-κB. The present results allow us to surmise that the lj-NF-κB should play a key role in immune response of lamprey, and the function of NF-κB has been maintained during evolution.



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Why a One-Way Ticket to Mars May Result in One-Way Directional Glymphatic Flow to the Eye: Response.

No abstract available

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Evaluation of the adjuvant effect of agonists of toll-like receptor 4 and 7/8 in a vaccine against leishmaniasis in BALB/c mice

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Mosayeb Rostamian, Hamid M. Niknam
There is no effective vaccine against human leishmaniasis. Achieving successful vaccines seems to need powerful adjuvants. Separate or combined use of toll like receptor (TLR) agonists as adjuvant is a promising approach in Leishmania vaccine research. In present study, we evaluated adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice. Mice were vaccinated three times by SLA with separate or combined TLR7/8 and TLR4 agonists and were then challenged by Leishmania major. Delay type hypersensitivity, lesion development, parasite load, and cytokines (interferon gamma, and interleukin-10) response were assessed. Results showed: 1) MPL can slightly assist SLA in parasite load reduction, but it is not able to increase SLA ability in evoking DTH and cytokine responses or decreasing lesion diameter. 2) R848 does not affect the DTH response and parasite load of mice vaccinated with SLA, but it decreases/inhibits cytokine responses induced by SLA, leading to increase lesion diameter. 3) MPL neutralized inhibitory effect of R848. In overall, these data emphasize that MPL slightly assists SLA to make a more potent vaccine, but R848 is not a good adjuvant to induce T cell-dependent immune response in BALB/c mice, and therefore combination of these TLR agonists in the current formulation, is not recommended for making a more powerful adjuvant.

Graphical abstract

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Clinical and Oculographic Analysis of Inferior Oblique Myokymia.

A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video-oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit. (C) 2017 by North American Neuro-Ophthalmology Society

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Structural characterization of the Man5 glycoform of human IgG3 Fc

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Ishan S. Shah, Scott Lovell, Nurjahan Mehzabeen, Kevin P. Battaile, Thomas J. Tolbert
Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined the crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.

Graphical abstract

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International Consensus Statement on the Clinical and Therapeutic Management of Leber's Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON. (C) 2017 by North American Neuro-Ophthalmology Society

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Identification of potential transcriptomic markers in developing asthma: An integrative analysis of gene expression profiles

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Fang Fang, Jian Pan, Yanhong Li, Yiping Li, Xing Feng, Jian Wang
The goal of this study was to identify potential transcriptomic markers in developing asthma by an integrative analysis of multiple public microarray data sets. Using the R software and bioconductor packages, we performed a statistical analysis to identify differentially expressed (DE) genes in asthma, and further performed functional interpretation (enrichment analysis and co-expression network construction) and classification quality evaluation of the DE genes identified. 3 microarray datasets (192 cases and 91 controls in total) were collected for this analysis. 62 DE genes were identified in asthma, among which 43 genes were up-regulated and 19 genes were down-regulated. The up-regulated gene with the highest Log2 Fold Change (LFC) was CLCA1 (LFC=2.81). The down-regulated gene with the highest absolute LFC was BPIFA1 (LFC=−1.45). Enrichment analysis revealed that those DE genes strongly associated with proteolysis, retina homeostasis, humoral immune response, and salivary secretion. A support vector machine classifier (asthma versus healthy control) was also trained based on DE genes. In conclusion, the consistently DE genes identified in this study are suggested as candidate transcriptomic markers for asthma diagnosis, and provide novel insights into the pathogenesis of asthma.



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The Visual Agnosias and Related Disorders.

Background: There are many disorders of higher visual processing that result from damage to specific areas of the cerebral cortex that have a specific role in processing certain aspects (modalities) of vision. These can be grouped into those that affect the ventral, or "what?", pathway (e.g., object agnosia, cerebral achromatopsia, prosopagnosia, topographagnosia, and pure alexia), and those that affect the dorsal, or "where?", pathway (e.g., akinetopsia, simultanagnosia, and optic ataxia). Evidence Acquisition: This article reviews pertinent literature, concentrating on recent developments in basic science research and studies of individual patients. Results: An overview of the current understanding of higher cerebral visual processing is followed by a discussion of the various disorders listed above. Conclusions: There has been considerable progress in the understanding of how the extrastriate visual cortex is organized, specifically in relation to functionally specialized visual areas. This permits a better understanding of the individual visual agnosias resulting from damage to these areas. (C) 2017 by North American Neuro-Ophthalmology Society

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A study on β-glucan binding protein (β-GBP) and its involvement in phenoloxidase cascade in Indian white shrimp Fenneropenaeus indicus

Publication date: December 2017
Source:Molecular Immunology, Volume 92
Author(s): Mahalingam Anjugam, Baskaralingam Vaseeharan, Arokiadhas Iswarya, Muthu Amala, Marimuthu Govindarajan, Naiyf S. Alharbi, Shine Kadaikunnan, Jamal M. Khaled, Giovanni Benelli
The present study reports the purification of novel immune molecule β-1, 3 glucan binding protein from the heamolymph of the Indian white shrimp, Fenneropenaeus indicus (Fiβ-GBP). The purified Fiβ-GBP had 95kDa molecular weight in SDS-PAGE analysis. MALDI-TOF/TOF analysis revealed that the purified Fiβ-GBP showed similarity to various crustacean proteins; 48 and 46% similarity was observed for β-1, 3 glucan binding protein of Chinese white shrimp Fenneropenaeus chinensis and banana shrimp Fenneropenaeus merguiensis, with MOWSE score of 3.11e+12 and 2.05e+8, respectively. The phenoloxidase activity (PO) of Fiβ-GBP was evaluated and, in the presence of laminarin, PO activity increased significantly. Substrate specificity assay demonstrated that Fiβ-GBP had the specific binding site for soluble or insoluble β-glucan (laminarin), since the PO activity increased in the presence of laminarin when compared to other sugars. Enzymatic activities revealed that the optimum temperature and pH for Fiβ-GBP activating PO were 40°C and pH 7–8. Moreover, even at 100°C Fiβ-GBP enhanced PO activity highlighting that Fiβ-GBP was thermostable and thermophilic in nature. Among various divalent metallic ions, Fiβ-GBP significantly promoted the PO activity in presence of Mg²⁺ and Ca²⁺. The breakdown of para nitroanilide from Nα−Benzoyl-l-Arginine 4-Nitroanilide hydrochloride showed that serine protease activity was induced by Fiβ-GBP and also increased concentration of Fiβ-GBP evoked the activity. Furthermore, hemolytic activity tests revealed that PO reaction product induced RBC membrane damage and cell shrinkage. Lastly, Baclight bacterial viability assays showed maximum killing effect of PO reaction product on both Gram positive and Gram negative bacteria.

Graphical abstract

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Anterior Ischemic Optic Neuropathy Due to Calciphylaxis.

A 72-year-old woman experienced anterior ischemic optic neuropathy in her left eye. The funduscopic and fluorescein angiographic findings were strongly suggestive of giant cell arteritis. Temporal artery biopsy revealed extensive calcification in the vessel wall consistent with calciphylaxis. This unusual disorder should be considered in the differential diagnosis of anterior ischemic optic neuropathy, particularly the arteritic form. (C) 2017 by North American Neuro-Ophthalmology Society

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Streptococcus gordonii lipoproteins induce IL-8 in human periodontal ligament cells

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): A Reum Kim, Ki Bum Ahn, Hyun Young Kim, Ho Seong Seo, Kee-Yeon Kum, Cheol‐Heui Yun, Seung Hyun Han
Streptococcus gordonii, a Gram-positive oral bacterium, is a life-threatening pathogen that causes infective endocarditis. It is frequently isolated from the periapical lesions of patients with apical periodontitis and has thus been implicated in inflammatory responses. However, little is known about the virulence factors of S. gordonii responsible for the induction of inflammatory responses in the periapical areas. Here, we investigated the role of S. gordonii cell wall-associated virulence factors on interleukin (IL)-8 induction in human periodontal ligament (PDL) cells using ethanol-inactivated wild-type S. gordonii, a lipoteichoic acid (LTA)-deficient mutant (ΔltaS), and a lipoprotein-deficient mutant (Δlgt). Wild-type S. gordonii induced IL-8 expression at both the protein and mRNA levels in human PDL cells in a dose- and time-dependent manner. A transient transfection and reporter gene assay demonstrated that wild-type S. gordonii activated Toll-like receptor 2 (TLR2). Additionally, IL-8 production induced by wild-type S. gordonii was substantially inhibited by anti-TLR2-neutralizing antibodies. Both wild-type S. gordonii and the ΔltaS mutant induced IL-8 production; however, this response was not observed when cells were stimulated with the Δlgt mutant. Interestingly, lipoproteins purified from S. gordonii induced IL-8 production, whereas purified LTA did not. In addition, purified lipoproteins stimulated TLR2 more potently than LTA. Furthermore, S. gordonii-induced IL-8 expression was specifically inhibited by blocking p38 kinase, while lipoprotein-induced IL-8 expression was inhibited by blocking p38 kinase, ERK, or JNK. Of particular note, exogenous addition of purified S. gordonii lipoproteins enhanced Δlgt-induced IL-8 production in human PDL cells to an extent similar to that induced by the wild-type strain. Collectively, these results suggest that lipoproteins are an important component of S. gordonii for the induction of IL-8 production in human PDL cells through TLR2 activation. Therefore, lipoproteins potentially contribute to inflammatory apical periodontitis.



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Repair of a Full-Thickness Defect of the Lower Eyelid Margin.

No abstract available

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Inflammatory cytokine of IL-1β is involved in T-2 toxin-triggered chondrocyte injury and metabolism imbalance by the activation of Wnt/β-catenin signaling

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Yanhai Chang, Xiao Wang, Zhengming Sun, Zhankui Jin, Ming Chen, Xiaoqing Wang, Mikko J. Lammi, Xiong Guo
Mycotoxin T-2 exerts a causative role in Kashin–Beck disease (KBD) suffering chondrocyte apoptosis and cartilage matrix homeostasis disruption. Recent research corroborated the aberrant levels of pro-inflammatory cytokine IL-1ß in KBD patients and mycotoxin environment. In the present study, we investigated the relevance of IL-1ß in T-2 toxin-evoked chondrocyte cytotoxic injury and aberrant catabolism. High levels of IL-1ß were detected in serum and cartilages from KBD patients and in T-2-stimulated chondrocytes. Moreover, knockdown of IL-1ß antagonized the adverse effects of T-2 on cytotoxic injury by enhancing cell viability and inhibiting apoptosis. However, exogenous supplementation of IL-1β further aggravated cell damage in response to T-2. Additionally, cessation of IL-1β rescued T-2-elicited tilt of matrix homeostasis toward catabolism by elevating the transcription of collagen II and aggrecan, promoting release of sulphated glycosaminoglycans (sGAG) and TIMP1, and suppressing matrix metalloproteinases production including MMP-1, MMP-3 and MMP-13. Conversely, IL-1β stimulation deteriorated T-2-induced disruption of matrix metabolism balance toward catabolism. Mechanistic analysis found the high activation of Wnt/β-catenin in KBD patients and chondrocytes upon T-2. Furthermore, this activation was mitigated after IL-1β inhibition, but further enhanced following IL-1β precondition. Importantly, blocking this pathway by transfection with β-catenin alleviated the adverse roles of IL-1β on cytotoxic injury and metabolism disorders under T-2 conditioning. Together, this study elucidates a new insight into how T-2 deteriorates the pathological progression of KBD by regulating inflammation-related pathways, indicating a promising anti-inflammation strategy for KBD therapy.



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Long-Pulsed Nd: YAG Laser Treatment for Nail Psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease in which lesions display angiogenesis and increased vascularity. OBJECTIVE: The long-pulsed 1,064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treats vascular lesions which suggests that it might also be used to treat nail psoriasis. METHODS: Sixteen patients (10 males and 6 females) with isolated nail psoriasis or nail with only mild cutaneous involvement were enrolled in the study. Nails were treated for 3 sessions with long-pulsed 1,064-nm Nd:YAG laser once monthly. During the course of the treatment, nail bed and matrix Nail Psoriasis Severity Index (NAPSI) scores were recorded. RESULTS: The mean baseline NAPSI score was 26 +/- 7.2. The means of total NAPSI scores after the first, second, and third treatment sessions were as follows: 22 +/- 6.6, 13 +/- 6, and 5.7 +/- 4.3, respectively. The decline in NAPSI score was statistically significant. At the end of the 3 treatment sessions, both nail bed and matrix lesions significantly responded to Nd:YAG laser treatment. CONCLUSION: The Nd:YAG laser is a promising treatment option for nail psoriasis. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

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Oligomeric proanthocyanidins attenuate airway inflammation in asthma by inhibiting dendritic cells maturation

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Yeshan Li, Qijun Yu, Wenxue Zhao, Jiaxiang Zhang, Wentao Liu, Mao Huang, Xiaoning Zeng
To date, although a promising anti-inflammatory activity of oligomeric proanthocyanidins (OPCs) has been observed in asthma, the mechanism responsible for these immunomodulatory properties remains obscure. Dendritic cells (DCs) that reside in the airway have been widely perceived as an important contributor to asthma. Our study was to demonstrate OPCs' effects on maturation and immunoregulation of pulmonary CD11c⁺ dendritic cells (DCs). BALB/c mice were exposed to ovalbumin (OVA) to induce murine model of asthma. In addition, pulmonary DCs and bone marrow-derived DCs (BMDCs) cultures were used to evaluate impacts of OPCs on DCs function. The results obtained here indicated that OPCs treatment dramatically reduced airway inflammation, such as the infiltration of inflammatory cells and the levels of allergen-specific serum IgE and Th2 cytokines. The expression of co-stimulatory molecules especially CD86 distributed on pulmonary DCs and bone marrow-derived DCs (BMDCs) also markedly declined. The phosphorylation of cAMP responsive element-binding protein (CREB) was significantly inhibited while no changes were observed in the expression of cAMP responsive element modulator (CREM). By transferring BMDCs into the airways of naïve mice, we found that OPCs-treated DCs (DC+OVA+OPC) were much less potent in promoting CD4⁺ T cells proliferation than OVA-pulsed DCs (DC+OVA), followed by the ameliorated eosinophilic inflammation in airway. Our findings tailor a novel profile of OPCs in the regulation of DCs function, shedding new light on the therapeutic potential of OPCs in asthma management.



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Healing Time Correlates With the Quality of Scaring: Results From a Prospective Randomized Control Donor Site Trial.

BACKGROUND: Scar formation remains a potential problem after surgery or trauma. Factors influencing scar tissue have been recognized, most notably healing time and wound depth. OBJECTIVE: To examine the association between healing time and the quality of scar tissue formation. MATERIALS AND METHODS: Scarring was assessed at 3 and 12 months after treatment in an RCT of 219 patients and consecutive 438 split-thickness skin graft donor sites. The primary end point of the study was healing time and the quality of scar tissue, which was scored by a validated scar scale evaluating scar height, surface, and color. RESULTS: The mean time of wound healing was 15.8 days, with a mean scar score of 6.89 at 3 months and 4.66 at 12 months. There was a significant (p

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Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Anna M. Gram, Chenglong Sun, Sanne L. Landman, Timo Oosenbrug, Hester J. Koppejan, Mark J. Kwakkenbos, Rob C. Hoeben, Søren R. Paludan, Maaike E. Ressing
Most cells are believed to be capable of producing type I interferons (IFN I) as part of an innate immune response against, for instance, viral infections. In macrophages, IFN I is potently induced upon cytoplasmic exposure to foreign nucleic acids. Infection of these cells with herpesviruses leads to triggering of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP (cGAMP) synthase (cGAS). Thereby, the stimulator of interferon genes (STING) and the downstream molecules TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are sequentially activated culminating in IFN I secretion.Human gamma-herpesviruses, such as Epstein-Barr virus (EBV), exploit B cells as a reservoir for persistent infection. In this study, we investigated whether human B cells, similar to macrophages, engage the cytoplasmic DNA sensing pathway to induce an innate immune response. We found that the B cells fail to secrete IFN I upon cytoplasmic DNA exposure, although they express the DNA sensors cGAS and IFI16 and the signaling components TBK1 and IRF3. In primary human B lymphocytes and EBV-negative B cell lines, this deficiency is explained by a lack of detectable levels of the central adaptor protein STING. In contrast, EBV-transformed B cell lines did express STING, yet both these lines as well as STING-reconstituted EBV-negative B cells did not produce IFN I upon dsDNA or cGAMP stimulation. Our combined data show that the cytoplasmic DNA sensing pathway is dysfunctional in human B cells. This exemplifies that certain cell types cannot induce IFN I in response to cytoplasmic DNA exposure providing a potential niche for viral persistence.



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Color Doppler Ultrasound Supports Early Diagnosis of Mixed High and Low Risk of Recurrence Subtypes in the Same Basal Cell Carcinoma Lesion.

No abstract available

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Human placental mesenchymal stem cells of fetal origins-alleviated inflammation and fibrosis by attenuating MyD88 signaling in bleomycin-induced pulmonary fibrosis mice

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Feng Li, Fei Han, Hui Li, Jia Zhang, Xia Qiao, Juan Shi, Li Yang, Jianda Dong, Meihui Luo, Jun Wei, Xiaoming Liu
Pulmonary fibrosis is a progressive lung disease that its pathogenic mechanism currently is incompletely understood. Toll-like receptor (TLR) signaling has recently been identified as a regulator of inflammation and pulmonary fibrosis. In addition, mesenchymal stem cells (MSCs) of different origins offer a great promise in treatment of idiopathic pulmonary fibrosis (IPF). However mechanisms of pathogenic roles of TLR signaling and therapeutic effects of MSCs in the IPF remain elusive. In present study, the involvement of TLR signaling and the therapeutic role of MSCs were interrogated in MyD88-deficient mice using human placental MSCs of fetal origins (hfPMSCs). The results showed an alleviated pulmonary inflammation and fibrosis in myeloid differentiation primary response gene 88 (MyD88)-deficient mice treated with bleomycin (BLM), accompanied with a reduced TGF-β signaling and production of pro-fibrotic cytokines, including TNF-α, IL-1β. An exposure of HLF1 lung fibroblasts, A549 epithelial cells and RAW264.7 macrophages to BLM led an increased expression of key components of MyD88 and TGF-β signaling cascades. Of interest, enforced expression and inhibition of MyD88 protein resulted in an enhanced and a reduced TGF-β signaling in above cells in the presence of BLM, respectively. However, the addition of TGF-β1 showed a marginally inhibitory effect on MyD88 signaling in these cells in the absence of BLM. Importantly, the administration of hfPMSCs could significantly attenuate BLM-induced pulmonary fibrosis in mice, along with a reduced hydroxyproline (HYP) deposition, MyD88 and TGF-β signaling activation, and production of pro-fibrotic cytokines. These results may suggest an importance of MyD88/TGF-β signaling axis in the tissue homeostasis and functional integrity of lung in response to injury, which may offer a novel target for treatment of pulmonary fibrosis.



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Deoxycholic Acid Injections for Bra-Line Lipolysis.

No abstract available

http://ift.tt/2wYDuNf

1,25(OH)2D3 induces regulatory T cell differentiation by influencing the VDR/PLC-γ1/TGF-β1/pathway

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Qiang Zhou, Shengying Qin, Jinyan Zhang, Lin Zhon, Zhihai Pen, Tonghai Xing
Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind. Results showed that 1,25(OH)2D3 induced the differentiation of T-regulatory cells (Treg cells), while inhibiting Th17 cell proliferation. In addition, 1,25(OH)2D3 promoted secretion of the anti-inflammatory cytokine, transforming Growth Factor beta1 (TGF-β1) but suppressed pro-inflammatory cytokines such as interleukin-17 (IL-17). Phospholipase C gamma 1 (PLC-γ1) is an indispensable signaling protein downstream of the classical TCR signaling pathway and was shown to play a crucial role in T cell activation, while Naive T cells expressed less PLC-γ1. Here we showed that Vitamin D could significantly upregulate PLC-γ1 expression, which then induced expression of TGF-β1. In summary, 1,25(OH)2D3 indirectly modulates the differentiation of Treg/Th17 cells by aff ;ecting the VDR/PLC-γ1/TGF-β1pathway. These results indicate that administration 1,25(OH)2D3 supplements may be a beneficial treatment for organ transplantation recipients.



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Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q. Yao, Charles E. McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs. Moreover, C/EBPβ-reconstituted myeloid cells expressed IL-10 and reduced T cell proliferation and function, similar to control MDSCs that express C/EBPβ. Exogenous expression of miR-21 and miR-181b in the C/EBPβ-deficient myeloid progenitors from septic mice produced similar results. Notably, NFI-A-dependent transactivation of NF-kB MDSC generating pathway was reversed in the C/EBPβ-deficient myeloid progenitors from septic mice. Together, these results support that decreasing C/EBPβ expression prevents MDSC generation and decreases immunosuppression in septic mice, providing a target for sepsis treatment.

Graphical abstract

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HLA-E regulatory and coding region variability and haplotypes in a Brazilian population sample

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Jaqueline Ramalho, Luciana C. Veiga-Castelli, Eduardo A. Donadi, Celso T. Mendes-Junior, Erick C. Castelli
The HLA-E gene is characterized by low but wide expression on different tissues. HLA-E is considered a conserved gene, being one of the least polymorphic class I HLA genes. The HLA-E molecule interacts with Natural Killer cell receptors and T lymphocytes receptors, and might activate or inhibit immune responses depending on the peptide associated with HLA-E and with which receptors HLA-E interacts to. Variable sites within the HLA-E regulatory and coding segments may influence the gene function by modifying its expression pattern or encoded molecule, thus, influencing its interaction with receptors and the peptide. Here we propose an approach to evaluate the gene structure, haplotype pattern and the complete HLA-E variability, including regulatory (promoter and 3′UTR) and coding segments (with introns), by using massively parallel sequencing. We investigated the variability of 420 samples from a very admixed population such as Brazilians by using this approach. Considering a segment of about 7kb, 63 variable sites were detected, arranged into 75 extended haplotypes. We detected 37 different promoter sequences (but few frequent ones), 27 different coding sequences (15 representing new HLA-E alleles) and 12 haplotypes at the 3′UTR segment, two of them presenting a summed frequency of 90%. Despite the number of coding alleles, they encode mainly two different full-length molecules, known as E*01:01 and E*01:03, which corresponds to about 90% of all. In addition, differently from what has been previously observed for other non classical HLA genes, the relationship among the HLA-E promoter, coding and 3′UTR haplotypes is not straightforward because the same promoter and 3′UTR haplotypes were many times associated with different HLA-E coding haplotypes. This data reinforces the presence of only two main full-length HLA-E molecules encoded by the many HLA-E alleles detected in our population sample. In addition, this data does indicate that the distal HLA-E promoter is by far the most variable segment. Further analyses involving the binding of transcription factors and non-coding RNAs, as well as the HLA-E expression in different tissues, are necessary to evaluate whether these variable sites at regulatory segments (or even at the coding sequence) may influence the gene expression profile.



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Irisin protects against neuronal injury induced by oxygen-glucose deprivation in part depends on the inhibition of ROS-NLRP3 inflammatory signaling pathway

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Juan Peng, Xian Deng, Wei Huang, Ji-hua Yu, Jian-xiong Wang, Jie-ping Wang, Shi-bin Yang, Xi Liu, Li Wang, Yun Zhang, Xiang-Yu Zhou, Hui Yang, Yan-Zheng He, Fang-yuan Xu
Recent studies found that irisin, a newly discovered skeletal muscle-derived myokine during exercise, is also synthesized in various tissues of different species and protects against neuronal injury in cerebral ischemia. The NOD-like receptor pyrin 3 (NLRP3) inflammasome play an important role in detecting cellular damage and mediating inflammatory responses to aseptic tissue injury during ischemic stroke. However, it is unclear whether irisin is involved in the regulation of NLRP3 inflammasome activation during ischemic stroke. In the present study, PC12 neuronal cells were exposed to oxygen-glucose deprivation (OGD), exogenous irisin (12.5, 25, 50nmol/L) or NLRP3 inhibitor glyburide (50, 100, 200μmol/L) were used as an intervention reagent, NLRP3 was over-expressed or suppressed by transfection with a NLRP3 expressing vector or NLRP3-specifc siRNA, respectively. Our data showed that both irisin and its precursor protein fibronectin type III domain containing 5 (FNDC5) expression were significantly down-regulated (p<0.05); but oxidative stress and ROS-NLRP3 inflammasome signaling were activated by OGD (p<0.05); treatment with irisin or inhibition of NLRP3 reversed OGD-induced oxidative stress and inflammation (p<0.05). However, these irisin-mediated effects were blunted by over-expression NLRP3 (p<0.05). Taken together, our results firstly revealed that irisin mitigated OGD-induced neuronal injury in part via inhibiting ROS-NLRP3 inflammatory signaling pathway, suggesting a likely mechanism for irisin-induced therapeutic effect in ischemic stroke.



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Neurosurgical management of brain metastases

Abstract

Brain metastases present a significant public health issue, affecting more than 100,000 patients per year in the U.S. and result in significant morbidity. Brain metastases can occur in a variety of clinical situations ranging from multiple brain metastases with uncontrolled systemic disease to a solitary metastasis in the setting of controlled systemic disease. Additionally, advances in genomics have broadened the opportunities for targeted treatment options and potentially more durable systemic responses. As such, the treatment of brain metastases is now more tailored and multimodal, involving systemic, radiation, and surgical therapies, often in combination. This review discusses the historical and current role of neurosurgical techniques in the treatment of brain metastases.

http://ift.tt/2xN7Y7C

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage

OBJECTIVES: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42; p<0.001). Among the stage D patients, the overall survival rate was worse in adherent patients than in non-adherent patients (hazard ratio=4.0, 95% CI: 1.67-9.88; p<0.001), whereas no differences were observed in patients in stages B or C. CONCLUSIONS: The rate of adherence to the Barcelona Clinic Liver Cancer staging system in clinical practice varies according to clinical disease stage. Adherence to the recommended guidelines positively impacts survival, especially in patients with early-stage disease.

http://ift.tt/2xWwogA

Independent early predictors of mortality in polytrauma patients: a prospective, observational, longitudinal study

OBJECTIVES: Trauma is an important public health issue and associated with substantial socioeconomic impacts and major adverse clinical outcomes. No single study has previously investigated the predictors of mortality across all stages of care (pre-hospital, emergency room, surgical center and intensive care unit) in a general trauma population. This study was designed to identify early predictors of mortality in severely injured polytrauma patients across all stages of care to provide a better understanding of the physiologic changes and mechanisms by which to improve care in this population. METHODS: A longitudinal, prospective, observational study was conducted between 2010 and 2013 in São Paulo, Brazil. Patients submitted to high-energy trauma were included. Exclusion criteria were as follows: injury severity score <16, <18 years old or insufficient data. Clinical and laboratory data were collected at four time points: pre-hospital, emergency room, and 3 and 24 hours after hospital admission. The primary outcome assessed was mortality within 30 days. Data were analyzed using tests of association as appropriate, nonparametric analysis of variance and generalized estimating equation analysis (p<0.05). ClinicalTrials.gov: NCT01669577. RESULTS: Two hundred patients were included. Independent early predictors of mortality were as follows: arterial hemoglobin oxygen saturation (p<0.001), diastolic blood pressure (p<0.001), lactate level (p<0.001), Glasgow Coma Scale score (p<0.001), infused crystalloid volume (p<0.015) and presence of traumatic brain injury (p<0.001). CONCLUSION: Our results suggest that arterial hemoglobin oxygen saturation, diastolic blood pressure, lactate level, Glasgow Coma Scale, infused crystalloid volume and presence of traumatic brain injury are independent early mortality predictors.

http://ift.tt/2jPxPqT

Sensitivity of caloric test and video head impulse as screening test for chronic vestibular complaints

OBJECTIVE: This study compared the results of the caloric test with those of the video head impulse test obtained during the same session and evaluated whether the former can be used to screen for non-acute vestibular dysfunction. METHODS: A total of 157 participants complaining of dizziness with vestibular characteristics of varying durations and clinical courses completed the caloric test and video head impulse test. RESULTS: Significantly more caloric test results than video head impulse test results were abnormal. CONCLUSIONS: The results of the caloric test and video head impulse test are distinct but complement each other. Within our sample, the caloric test was more sensitive for vestibular dysfunction. Therefore, the video head impulse test is not a suitable screening tool of the vestibular system in patients with chronic complaints.

http://ift.tt/2yr9vRA

High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population

OBJECTIVE: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). RESULTS: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002). CONCLUSIONS: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.

http://ift.tt/2gjXl6q

A Comparative Study of Sagittal Balance in Patients with Neuromuscular Scoliosis

OBJECTIVES: Spinopelvic alignment has been associated with improved quality of life in patients with vertebral deformities, and it helps to compensate for imbalances in gait. Although surgical treatment of scoliosis in patients with neuromuscular spinal deformities promotes correction of coronal scoliotic deformities, it remains poorly established whether this results in large changes in sagittal balance parameters in this specific population. The objective of this study is to compare these parameters before and after the current procedure under the hypothesis is that there is no significant modification. METHODS: Sampling included all records of patients with neuromuscular scoliosis with adequate radiographic records treated at Institute of Orthopedics and Traumatology of Clinics Hospital of University of São Paulo (IOT-HCFMUSP) from January 2009 to December 2013. Parameters analyzed were incidence, sacral inclination, pelvic tilt, lumbar lordosis, thoracic kyphosis, spinosacral angle, spinal inclination and spinopelvic inclination obtained using the iSite-Philips digital display system with Surgimap and a validated method for digital measurements of scoliosis radiographs. Comparison between the pre- and post-operative conditions involved means and standard deviations and the t-test. RESULTS: Based on 101 medical records only, 16 patients met the inclusion criteria for this study, including 7 males and 9 females, with an age range of 9-20 and a mean age of 12.9±3.06; 14 were diagnosed with cerebral palsy. No significant differences were found between pre and postoperative parameters. CONCLUSIONS: Despite correction of coronal scoliotic deformity in patients with neuromuscular deformities, there were no changes in spinopelvic alignment parameters in the group studied.

http://ift.tt/2yrhezk

Community Care Administration of Spinal Deformities in the Brazilian Public Health System

OBJECTIVE: Underfunding of the surgical treatment of complex spinal deformities has been an important reason for the steadily growing waiting lists in publicly funded healthcare systems. The aim of this study is to characterize the management of the treatment of spinal deformities in the public healthcare system. METHODS: A cross-sectional study of 60 patients with complex pediatric spinal deformities waiting for treatment in December 2013 was performed. The evaluated parameters were place of origin, waiting time until first assessment at a specialized spine care center, waiting time for the surgical treatment, and need for implants not reimbursed by the healthcare system. RESULTS: Ninety-one percent of the patients lived in São Paulo State (33% from Ribeirão Preto - DRS XIII). Patients waited for 0.5 to 48.0 months for referral, and the waiting times for surgery ranged from 2 to 117 months. Forty-five percent of the patients required implants for the surgical procedure that were not available. CONCLUSION: The current management of patients with spinal deformities in the public healthcare system does not provide adequate treatment for these patients in our region. They experience long waiting periods for referral and prolonged waiting times to receive surgical treatment; additionally, many of the necessary procedures are not reimbursed by the public healthcare system.

http://ift.tt/2gjXd6W

Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans

OBJECTIVE: The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system. METHOD: The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups. RESULTS: Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine. CONCLUSION: These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

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Systematic Review of Health Economic Evaluations of Diagnostic Tests in Brazil: How accurate are the results?

The aim of this study is to identify and characterize the health economic evaluations (HEEs) of diagnostic tests conducted in Brazil, in terms of their adherence to international guidelines for reporting economic studies and specific questions in test accuracy reports. We systematically searched multiple databases, selecting partial and full HEEs of diagnostic tests, published between 1980 and 2013. Two independent reviewers screened articles for relevance and extracted the data. We performed a qualitative narrative synthesis. Forty-three articles were reviewed. The most frequently studied diagnostic tests were laboratory tests (37.2%) and imaging tests (32.6%). Most were non-invasive tests (51.2%) and were performed in the adult population (48.8%). The intended purposes of the technologies evaluated were mostly diagnostic (69.8%), but diagnosis and treatment and screening, diagnosis, and treatment accounted for 25.6% and 4.7%, respectively. Of the reviewed studies, 12.5% described the methods used to estimate the quantities of resources, 33.3% reported the discount rate applied, and 29.2% listed the type of sensitivity analysis performed. Among the 12 cost-effectiveness analyses, only two studies (17%) referred to the application of formal methods to check the quality of the accuracy studies that provided support for the economic model. The existing Brazilian literature on the HEEs of diagnostic tests exhibited reasonably good performance. However, the following points still require improvement: 1) the methods used to estimate resource quantities and unit costs, 2) the discount rate, 3) descriptions of sensitivity analysis methods, 4) reporting of conflicts of interest, 5) evaluations of the quality of the accuracy studies considered in the cost-effectiveness models, and 6) the incorporation of accuracy measures into sensitivity analyses.

http://ift.tt/2gjX8QG

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

http://ift.tt/2yqPXNq

ERRATA

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

http://ift.tt/2gjWZg6

Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata and vitiligo

http://ift.tt/2wXMrGL

Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF

Summary

Background

We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM.

Methods

We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB).

Results

Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P < 0.001, Fisher exact test). The positive staining also colocalized with Junctional Adhesion Molecule 1 (JAM-A), a control antibody for gap cell junctions. No HC samples were positive. In 27 of the 30 patients, serum that was APM-positive also displayed IB colocalization of their autoantibody molecular weights with the Progen antibodies (P < 0.001, Fisher exact test).

Conclusions

Patients affected by El Bagre-EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4.

http://ift.tt/2ypOp4i

Melanoma arising from a plaque-type blue naevus with subcutaneous cellular nodules of the scalp

Summary

Plaque-type blue naevus (PTBN) is a very rare variant of blue naevus (BN). The potential malignancy of subcutaneous cellular nodules (SCN) in PTBN was discovered in 2012, and there is currently no clear consensus on prognostic factors or management guidelines of such lesions. PTBN on the scalp have not been described in the literature. We report the clinical, histopathological and immunohistological features of a 50-year-old man who presented with a 30-year history of scalp PTBN, with malignant proliferation of nodular elements and fatal outcome 8 years later. This case suggests that long-term monitoring of patients with PTBN is required. Early surgical removal of such lesions should be considered, especially in the presence of any case of enlargement or change.

http://ift.tt/2wZ0rA7

Amaranth seeds ( Amaranthus palmeri L.) as novel feedstock for biodiesel production by oleaginous yeast

Abstract

The potential of lipid accumulation by oleaginous yeast Cryptococcus vishniaccii grown on amaranth seed aqueous extract (AAE) media was assessed. Maximum cell biomass productivity of 104 mg/L/h, lipid productivity of 54 mg/L/h, and lipid content of 52.31% were recorded on AAE when carbon to nitrogen (C:N) ratio increased from 134 to 147 after removal of ammonia nitrogen. The lipid droplet (LD) size (2.32 ± 0.38 μm) was visualized by fluorescence microscopy using Nile red stain indicating maximum accumulated triacylglycerol (TAG) at C:N 147. Fatty acid methyl ester (FAME) profile obtained after transesterification of extracted lipid revealed the presence of palmitic acid (16:0), palmitoleic acid (16:1), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2). Data showed the presence of high monounsaturated fatty acid (MUFA) content (68.17%) depicting improved winter operating conditions of biodiesel. Various quality parameters of biodiesel were evaluated and compared to the American and European biodiesel standards specifications. Based on the lipid productivity, distribution of fatty acids, and evaluated properties obtained; the lipid accumulation by C. vishniaccii utilizing amaranth seeds as substrate could serve as a feasible feedstock for biodiesel production.

http://ift.tt/2gcJlYs

Performance evaluation of two Aspergillus spp. for the decolourization of reactive dyes by bioaccumulation and biosorption

Abstract

A biological method was adopted to decolourize textile dyes, which is an economic and eco-friendly technology for textile wastewater remediation. Two fungal strains, i.e. Aspergillus lentulus and Aspergillus fumigatus, were used to study the removal of low to high concentrations (25 to 2000 mg L⁻¹) of reactive remazol red, reactive blue and reactive yellow dyes by biosorption and bioaccumulation. The biosorption was successful only at the lower concentrations. A. lentulus was capable of removing 67–85% of reactive dyes during bioaccumulation mode of treatment at 500 mg L⁻¹ dye concentration with an increased biomass uptake capacity. To cope up with the high dye concentration of 2000 mg L⁻¹, a novel combined approach was successful in case of A. lentulus, where almost 76% removal of reactive remazol red dye was observed during bioaccumulation followed by biosorption. The scanning electron microscopy also showed the accumulation of dye on the surface of fungal mycelium. The results signify the application of such robust fungal strains for the removal of high concentration of dyes in the textile wastewaters.

http://ift.tt/2ymt7ad

Ultraviolet filters and heat shock proteins: effects in Chironomus riparius by benzophenone-3 and 4-methylbenzylidene camphor

Abstract

Benzophenone-3 (BP3) and 4-methylbenzylidene camphor (4MBC) are common ultraviolet filters (UV filters), compounds considered as emergent contaminants, used in different products like plastics and personal care products. The levels of these compounds are rising in the wild, but the effects they have on invertebrates are poorly understood. Chironomus riparius is a benthic insect widely used in toxicology, and several studies have been previously performed in our laboratory to determine the effects these compounds have on this organism at the molecular level. We have shown that UV filters can alter the mRNA levels of heat shock protein 70 (Hsp70), one of the most studied heat shock proteins. Although these proteins are crucial for the survival of organisms, little data is available on the effects these emergent contaminants have on them, especially in invertebrates. Here, we analyzed the transcriptional activity of 12 genes covering the different groups of heat shock protein [Hsp10, Hsp17, Hsp21, Hsp22, Hsp23, Hsp24, Hsp27, Hsp34, Hsp40, Hsp60, Hsc70 (3), and Hsc70 (4)] in response to 0.1 and 1 mg/L concentrations of BP3 and 4MBC at 8 and 24 h. The results showed that some small Hsp (sHsp) genes were altered by these compounds, while the genes of proteins present in mitochondria, Hsp10 and Hsp60, did not change. sHsps are also involved in developmental processes, so the observed variations could be due to the endocrine disruption activity described for these compounds rather than to a stress response.

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PD1 inhibitors and hair repigmentation: A desirable new side effect

http://ift.tt/2yofKDK

Refractory pityriasis rubra pilaris treated with etanercept, adalimumab, or ustekinumab: A retrospective investigation

Abstract

Pityriasis rubra pilaris (PRP) is a rare, difficult to treat papulosquamous disorder that responds variably to retinoids and immunosuppression. Successful use of biologics for treating PRP has been described in the literature by case reports and a limited number of case series. To provide additional data, we retrospectively analyzed cases of PRP treated with biologics at our institution. We identified seven patients with a clear diagnosis of PRP treated with adalimumab, etanercept, and/or ustekinumab at our institution from January 1, 2014 to April 1, 2017. Six of seven patients had type I, adult acquired PRP, and one had type V atypical juvenile PRP. In response to tumor necrosis factor (TNF)-α inhibition, two patients had marked responses (>75% improvement in involved body surface area), while three patients failed to show any improvement on a TNF-α inhibitor. In two cases of PRP refractory to TNF-α inhibition, ustekinumab resulted in a partial response (<75% improvement) in one patient and no response in the other. Compared to other published data, our cohort was substantially more resistant to treatment with biologics, a finding which may provide valuable perspective for dermatologists managing refractory PRP in the future.

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Abstracts Laser Florence 2017

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Inhibitory effects of Dianthi Herba ethanolic extract on inflammatory and nociceptive responses in murine macrophages and mouse models of abdominal writhing and ear edema

Publication date: 30 January 2018
Source:Journal of Ethnopharmacology, Volume 211
Author(s): You-Chang Oh, Yun Hee Jeong, Won-Kyung Cho, Youn-Hwan Hwang, Jin Yeul Ma
Ethnopharmacological relevanceDianthi Herba is a traditional herbal medicine used to treat inflammatory-related diseases including acute pyelonephritis, cystitis, laryngopharyngitis, and urethritis.Aim of the studyWe investigated the effects of Dianthi Herba ethanolic extract (DH) on lipopolysaccharide (LPS)-mediated inflammatory responses in murine macrophages including RAW 264.7 cell line and mouse peritoneal macrophages as well as nociceptive and edema mouse models.Materials and methodsThe biological effects of DH on inflammatory cytokine, mediator, and related protein production were assessed using enzyme-linked immunosorbent assay (ELISA), Western blotting, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). Additionally, Western blotting was performed to investigate intracellular signaling pathways, and the anti-nociceptive activity of three doses of DH (100, 200, and 300mg/kg) against acetic acid-induced writhing responses and its inhibitory effects on xylene-induced ear edema were researched in mice through oral administration.ResultsDH treatment significantly inhibited nitric oxide (NO) secretion and inflammatory cytokine production in RAW 264.7 cells and mouse peritoneal macrophages and induced heme oxygenase (HO)−1 expression. DH strongly inhibited the transcriptional activity of nuclear factor (NF)-κB and phosphorylation of mitogen-activated protein kinases (MAPK) in LPS-stimulated macrophages. Meanwhile, DH exerted anti-nociceptive effects on writhing responses and anti-edema effects in mice.ConclusionWe confirmed the anti-inflammatory activities and inhibitory mechanism of DH in macrophages and clarified its inhibitory effects in vivo. These findings illustrate the therapeutic potential of DH as a natural anti-inflammatory agent.

Graphical abstract

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Evaluations of the DMPP on organic and inorganic nitrogen mineralization and plant heavy metals absorption

Publication date: 15 February 2018
Source:Geoderma, Volume 312
Author(s): Yu Qiaogang, Ma Junwei, Sun Wanchun, Zou Ping, Lin Hui, Fu Changhuan, Fu Jianrong
The use of biochemical technologies to regulate soil nitrogen (N) transformations is an important strategy to improve plant nutrient uptake and its quality. Effect of organic and inorganic N fertilizers combined application supplemented with the nitrification inhibitor 3,4-dimethyl pyrazole phosphate (DMPP) on N transformations in the soil and heavy metal uptake of pakchoi cabbage (Brassica campestris L. ssp. chinensis) was studied in three different kinds of soils (purplish clayey soil, red soil, and sandy loam soil). The results demonstrated that DMPP addition in the organic and inorganic N combined fertilization extended ammonium N retention, and greatly reduced nitrate and nitrite N concentrations in three soils. Compared to the regular organic and inorganic-N combined fertilizers, DMPP addition in this fertilization increased the pakchoi biomass by 9.8% to 15.8% and reduced its nitrate concentrations by 15.7% to 40.8%. Furthermore, DMPP addition in the combined organic and inorganic fertilization decreased the heavy metal content of Cu (7.8% to 25.6%), Zn (10.4% to 20.3%), and Cd (12.8% to 22.2%) in the plant. The addition of DMPP to the organic and inorganic-N combined fertilizers could decrease the heavy metal counterion nitrate uptake in the plant, alter soil pH and decrease the activity of Cu, Zn and Cd in the soil, and weaken the plant heavy metal uptake of Cd and Zn in the three soils. It is proposed that DMPP could be used to regulate N transformation in the soil and decrease the heavy metal content in the plant in the organic and inorganic N combined fertilization, thus improving plant quality and yields.



http://ift.tt/2hJ7AOA

Influence of inoculating white-rot fungi on organic matter transformations and mobility of heavy metals in sewage sludge based composting

Publication date: 15 February 2018
Source:Journal of Hazardous Materials, Volume 344
Author(s): Chaosheng Zhang, Ying Xu, Meihua Zhao, Hongwei Rong, Kefang Zhang
White-rot fungi, Phanerochaete chrysosporium was inoculated to sewage sludge composting. Its effect on transformation of organic matter and mobility of heavy metals (Zn, Pb, Cu, and Ni) was studied. Detailed sampling was performed to measure C contents in humic extracts (HE), humic acids (HAs), fulvic acids (FAs), humin and distribution of heavy metals, including acid exchangeable fraction (AE), reducible fraction (RED), oxidization fraction (OXI) and residual fraction (RES). In our study, it is evident that the HE, HAs increased obviously and hydrolyzed humin decreased markedly in inoculation. The stabilization rate ((OXI+RES)/(AE+RED)) of Zn, Pb, Cu, and Ni was 20.31%, 7%, 14.3% and 19.79% higher in inoculating reactor. Additionally, the changes of heavy metals fractions could be explained by the organic variables. The results of this study demonstrated that Phanerochaete chrysosporium passivates the heavy metal by provoking the formation of humus.



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Conjugated microporous polymers bearing metallophthalocyanine moieties with enhanced visible-light photocatalytic activity

Publication date: February 2018
Source:Dyes and Pigments, Volume 149
Author(s): Qiang Li, Heng-guo Wang, Yanhui Li, Yanwei Li, Qian Duan
A series of metallophthalocyanine-based conjugated microporous polymers (MPc-CMPs, M = Co, Cu, Zn) were synthesized and used for the photodegradation of organic pollutants for the first time. The as-obtained MPc-CMPs were characterized by UV-vis spectroscopy, Fourier transform infrared spectra (FTIR), scanning electron microscope (SEM). Their photocatalytic activities were assessed by the photodegradation of RhB in the presence of H2O2 under visible light irradiation. Moreover, the possible mechanism to predict this reaction pattern was proposed. As a result, the as-obtained MPc-CMPs, especially CoPc-CMP, exhibit excellent photocatalytic efficiency, recyclability and stability. These results indicate that the MPc-CMPs are potentially applicable in the environmental purification of organic pollutants in the industrial wastewater.

Graphical abstract

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Zika virus and autoimmunity. One-step forward.

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Diana M. Monsalve, Yovana Pacheco, Yeny Acosta-Ampudia, Yhojan Rodríguez, Carolina Ramírez-Santana, Juan-Manuel Anaya
Zika virus (ZIKV) infection has been associated with the development of Guillain-Barré syndrome (GBS) and idiopathic thrombocytopenic purpura (ITP). Whether ZIKV infection is related to other autoimmune diseases is unknown. Therefore, an association study to evaluate rheumatic and thyroid autoimmunity in patients with ZIKV disease was conducted through a panel of 14 autoantibodies. In addition, a literature review on ZIKV, and GBS and ITP was performed. Our results disclosed a lack of rheumatoid and thyroid autoimmunity in patients with ZIKV disease. A total of 272 cases of GBS related to ZIKV were retrieved from the literature, the majority of them being males (54.8%). Electrophysiological findings indicated acute inflammatory demyelinating polyneuropathy as the most frequent subphenotype (75.7%). Up to date, twenty-four cases of ITP in patients with ZIKV disease have been published. Although a few fatal cases have been observed, most of the reported patients responded well to immunomodulatory treatment. A review of the mechanisms incriminated into the development of autoimmune phenomenon in ZIKV disease indicates molecular mimicry as the most plausible one. Nevertheless, more research aimed at deciphering ZIKV disease pathogenesis and its relationship with autoimmunity is warranted.



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Novelties in the field of autoimmunity – 1st Saint Petersburg congress of autoimmunity, the bridge between east and west

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Shani Dahan, Yahel Segal, Abdulla Watad, Shir Azrielant, Asaf Shemer, Dror Maymon, Yuri I. Stroev, Polina A. Sobolevskaya, Elena A. Korneva, Miri Blank, Boris Bilburd, Ora Shovman, Howard Amital, Michael Ehrenfeld, Amir Tanay, Shay Kivity, Elon Pras, Joav Chapman, Jan Damoiseaux, Ricard Cervera, Chaim Putterman, Iziaslav Shapiro, Luc Mouthon, Roberto Periconne, Nicola Bizzaro, Omry Koren, Gabriela Riemekasten, Valeriy A. Chereshnev, Vadim I. Mazurov, Mark Goloviznin, Victor Gurevich, Leonid P. Churilov, Yehuda Shoenfeld




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Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Charlotte Durtette, Eric Hachulla, Matthieu Resche-Rigon, Thomas Papo, Thierry Zénone, Bertrand Lioger, Christophe Deligny, Marc Lambert, Cédric Landron, Jacques Pouchot, Jean Emmanuel Kahn, Christian Lavigne, Benoit De Wazieres, Robin Dhote, Guillaume Gondran, Edouard Pertuiset, Thomas Quemeneur, Mohamed Hamidou, Pascal Sève, Thomas Le Gallou, Anne Grasland, Pierre-Yves Hatron, Olivier Fain, Arsène Mekinian
BackgroundCogan syndrome is mainly treated with corticosteroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.



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The inter-observer reading variability in anti-nuclear antibodies indirect (ANA) immunofluorescence test: a multicenter evaluation and a review of the literature

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): A. Rigon, M. Infantino, M. Merone, G. Iannello, A. Tincani, I. Cavazzana, N. Caraballese, A. Radice, M. Manfredi, P. Soda, A. Afeltra
Recently there has been an increase demand for computer-aided diagnosis (CAD) tools to sup- port clinicians in the field of Indirect ImmunoFluorescence (IIF), as the novel digital imaging reading approach can help to overcome the reader subjectivity. Nevertheless, a large multicenter evaluation of the inter-observer reading variability in this field is still missing. This work fills this gap as we evaluated 556 consecutive samples, for a total of 1679 images, collected in three laboratories with IIF expertise using HEp-2 cell substrate (MBL) at 1:80 screening dilution ac- cording to conventional procedures. In each laboratory, the images were blindly classified by two experts into three intensity classes: positive, negative, and weak positive. Positive and weak pos- itive ANA-IIF results were categorized by the predominant fluorescence pattern among six main classes. Data were pairwise analyzed and the inter-observer reading variability was measured by Cohen's kappa test, revealing a pairwise agreement little further away than substantial both for fluorescence intensity and for staining pattern recognition (k=0.602 and k=0.627, respec- tively). We also noticed that the inter-observer reading variability decreases when it is measured with respect to a gold standard classification computed on the basis of labels assigned by the three laboratories. These data show that laboratory agreement improves using digital images and comparing each single human evaluation to potential reference data, suggesting that a solid gold standard is essential to properly make use of CAD systems in routine work lab.



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Autoimmune comorbidity in chronic spontaneous urticaria: a systematic review

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Pavel Kolkhir, Elena Borzova, Clive Grattan, Riccardo Asero, Dmitry Pogorelov, Marcus Maurer
Background and ObjectiveNumerous autoimmune diseases (AIDs) have been linked to chronic spontaneous urticaria (CSU). Here, we provide the first extensive and comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice versa.MethodsA Pubmed and Google Scholar search was performed to identify studies reporting the prevalence of various AIDs in CSU and vice versa published before April 2017.ResultsThe prevalence of individual AIDs in CSU is increased (≥1% in most studies vs ≤1% in general population). AIDs with relatively high prevalence in the general population are also quite common in CSU patients, whereas those with low prevalence remain a rare finding in CSU. The rates of comorbidity in most studies were ≥1% for insulin-dependent diabetes mellitus, rheumatoid arthritis (RA), psoriasis and celiac disease (CD), ≥2% for Graves' disease, ≥3% for vitiligo, and ≥5% for pernicious anemia and Hashimoto's thyroiditis. Organ-specific AIDs are more prevalent in CSU than systemic (multiorgan or non organ-specific) AIDs. More than 2% of CSU patients have autoimmune polyglandular syndromes encompassing autoimmune thyroid disease (ATD) and vitiligo or pernicious anemia. Antithyroid and antinuclear antibodies are the most prevalent AID-associated autoantibodies in CSU. More than 15% of CSU patients have a positive family history for AIDs. The prevalence of urticarial rash in AID patients is >1% in most studies. This rash is more prevalent in eosinophilic granulomatosis with polyangiitis, ATD, systemic lupus erythematosus, RA and CD.ConclusionsCSU patients have an increased risk of AIDs, especially adult female patients with a positive family history and a genetic predisposition for AIDs, who should be screened for signs and symptoms of AIDs.



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Interleukin-22 in human inflammatory diseases and viral infections

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Arezoo Gowhari Shabgah, Jamshid Gholizadeh Navashenaq, Omid Gohari Shabgah, Hamed Mohammadi, Amirhossein Sahebkar
Interleukin-22 (IL22) is one of the members of IL10 family. Elevated levels of this cytokine can be seen in diseases caused by T lymphocytes, such as Psoriasis, Rheumatoid arthritis, interstitial lung diseases. IL22 is produced by different cells in both innate and acquired immunities. Different types of T cells are able to produce IL22, but the major IL22-producing T-cell is the TCD4. TH22 cell is a new line of TCD4 cells, which differentiated from naive T cells in the presence of TNFα and IL6; 50% of peripheral blood IL22 is produced by these cells. IL22 has important functions in host defense at mucosal surfaces as well as in tissue repair. In this review, we assess the current understanding of this cytokine and focus on the possible roles of IL-22 in autoimmune diseases.



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Uveitis: diagnostic work-up. A literature review and recommendations from an expert committee

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Pascal Sève, Patrice Cacoub, Bahram Bodaghi, Salim Trad, Jérémie Sellam, David Bellocq, Philip Bielefeld, Damien Sène, Gilles Kaplanski, Dominique Monnet, Antoine Brézin, Michel Weber, David Saadoun, Christophe Chiquet, Laurent Kodjikian
PurposeDiagnosis of uveitis is difficult. Etiologic investigations should take into account the epidemiology of uveitis and should focus on the most severe forms of the disease and those which can be treated. This study was undertaken to establish recommendations for the diagnosis of uveitis.MethodsRecommendations were developed by a multidisciplinary panel of 14 experts, including internists, ophthalmologists, and rheumatologists, and are based on a review of the literature and the results of the ULISSE study, which was the first prospective study to assess the efficacy of a standardized strategy for the etiologic diagnosis of uveitis. The following groups of patients are not included in these recommendations: children, immunocompromised patients, patients with severe retinal vasculitis, and those with specific eye diseases diagnosed by ophthalmologic examination only.ResultsDiagnosis should be guided by the medical history of the patient and physical examination. Serologic screening for syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at this stage, investigations oriented by the anatomic characteristics of uveitis are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma release, chest computed tomography (chronic uveitis), cerebral magnetic resonance imaging and anterior chamber tap with interleukin-10 analysis (intermediate or posterior uveitis in patients >40 years-old). Other investigations prescribed in the absence of orientation are usually unhelpful.ConclusionsA strategy is proposed for the etiologic diagnosis of uveitis. The benefit of more invasive investigations remains to be determined.



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Rheumatic diseases and autoimmune vascular dementia

Publication date: Available online 14 October 2017
Source:Autoimmunity Reviews
Author(s): Fabiola Atzeni, Nicolò Pipitone, Luca Iaccarino, Ignazio Francesco Masala, Ronen Weiss, Alessandra Alciati, Andrea Doria, Joab Chapmanand, Piercarlo Sarzi-Puttini
Vascular dementia (VD) comes second after Alzheimer's disease (AD) as a cause of impaired cognition. VD is not a specific nosological entity, but rather a syndrome encompassing a number of diseases caused by impaired supply of blood to the brain. Systemic autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis and antiphospholipid syndrome (APS) can be associated with dementia. VD is often related to the presence of traditional cardiovascular risk factors, but it may also be associated with a host of disorders affecting the brain blood vessels, neuronal cells, or both. It is important to entertain in the differential diagnosis of VD, to recognize and to cure them accurately in order to preserve life's quality of our patients.



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Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats

Publication date: 15 February 2018
Source:Behavioural Brain Research, Volume 338
Author(s): Molly J. Goodfellow, Youn Ju Shin, Derick H. Lindquist
Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4–9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction.



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Reassessing the significance of the PAH c.158G>A (p.Arg53His) variant in patients with hyperphenylalaninemia

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Effect of MRI on breast tissue expanders and recommendations for safe use

Ferromagnetic port-containing breast tissue expanders are currently labeled MRI-unsafe because of the presumption that magnets should not enter the machine. However, designating these devices as MRI-unsafe can lead to unnecessary procedures or suboptimal imaging choices. This study provides an ex vivo analysis of how breast tissue expanders behave when subjected to strong magnetic fields to determine which variables might affect clinical risk.

http://ift.tt/2zpnUMr

Toxicity studies of nanofabricated palladium against filariasis and malaria vectors

Abstract

The present study was carried out to establish the biofabrication of palladium nanoparticles (PdNPs) using the plant leaf extract of Tinospora cordifolia Miers and its toxicity studies on the larvae of filariasis vector, Culex quinquefasciatus Say and malaria vector, Anopheles subpictus Grassi. The biofabricated PdNPs were characterized by using UV–visible spectrum, FTIR, XRD, FESEM, EDX and HRTEM. HRTEM confirmed the PdNPs were slightly agglomerated and spherical in shape and the average size was 16 nm. Gas chromatography and mass spectrometry analysis result revealed that the major constituent present in the T. cordifolia leaf extract is 2,4-di-tert-butylphenol (31.79%) whereas the minor compounds are 1-hexadecanol (7.97%), 1-octadecanol (7.70%), 1-eicosanol (6.85%), behenic alcohol (5.36%), 1-tetradecene (6.22%), cyclotetradecane (6.23%), 1-hexadecene (7.97%), 1-octadecene (7.70%), 1-eicosene (6.85%), and 1-docosene (5.36%). T. cordifolia leaf extract exhibited the larvicidal activity against the fourth instar larvae of C. quinquefasciatus and A. subpictus with the values of LC₅₀ = 59.857 and 54.536 mg/L; LC₉₀ = 113.445 and 108.940 mg/L, respectively. The highest toxicity was observed in the biofabricated PdNPs against the fourth instar larvae of C. quinquefasciatus and A. subpictus with the values of LC₅₀ = 6.090 and 6.454 mg/L; LC₉₀ = 13.689 and 13.849 mg/L, respectively. Concerning non-target effects, Poecilia reticulata were exposed to PdNPs for 24 h and did not exhibit any noticeable toxicity. Overall, our findings strongly suggest that PdNPs is a perfect ecological and inexpensive approach for the control of filariasis and malaria vectors.

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