Recent investigations are focused on the potential antitumor effect of neurokinin-1 receptor (NK1R) antagonists in different neoplastic diseases1. Consequently, Kwatra et al. raised an interesting observation about the possible influence of aprepitant on CTCL outcome2.
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Itch pathogenesis involves modulation of the neuroimmune axis, with several immunosuppressants such as azathioprine1 and mycophenolate mofetil2 demonstrating significant anti-pruritic activity in subsets of patients with pruritus. These immunosuppressive agents are contraindicated in patients with malignancy, and thus there is a need for novel anti-pruritic agents without significant immunosuppressive effects in neoplastic conditions such as cutaneous T cell lymphoma (CTCL).
This article is protected by copyright. All rights reserved.
Recent investigations are focused on the potential antitumor effect of neurokinin-1 receptor (NK1R) antagonists in different neoplastic diseases1. Consequently, Kwatra et al. raised an interesting observation about the possible influence of aprepitant on CTCL outcome2.
This article is protected by copyright. All rights reserved.
Itch pathogenesis involves modulation of the neuroimmune axis, with several immunosuppressants such as azathioprine1 and mycophenolate mofetil2 demonstrating significant anti-pruritic activity in subsets of patients with pruritus. These immunosuppressive agents are contraindicated in patients with malignancy, and thus there is a need for novel anti-pruritic agents without significant immunosuppressive effects in neoplastic conditions such as cutaneous T cell lymphoma (CTCL).
This article is protected by copyright. All rights reserved.
BACKGROUND: To assess whether use of low-chloride solutions in unselected critically ill or perioperative adult patients for maintenance or resuscitation reduces mortality and renal replacement therapy (RRT) use when compared to high-chloride fluids. METHODS: Systematic review and meta-analysis with random-effects inverse variance model. PubMed, Cochrane library, EMBASE, LILACS, and Web of Science were searched from inception to October 2016. Published and unpublished randomized controlled trials in any language that enrolled critically ill and/or perioperative adult patients and compared a low- to a highchloride solution for volume maintenance or resuscitation. The primary outcomes were mortality and RRT use. We conducted trial sequential analyses and assessed risk of bias of individual trials and the overall quality of evidence. Fifteen trials with 4067 patients, most at low risk of bias, were identified. Of those, only 11 and 10 trials had data on mortality and RRT use, respectively. A total of 3710 patients were included in the mortality analysis and 3724 in the RRT analysis. RESULTS: No statistically significant impact on mortality (odds ratio, 0.90; 95% confidence interval, 0.69–1.17; P = .44; I2 = 0%) or RRT use (odds ratio, 1.12; 95% confidence interval, 0.80–1.58; P = .52; I2 = 0%) was found. Overall quality of evidence was low for both primary outcomes. Trial sequential analyses highlighted that the sample size needed was much larger than that available for properly powered outcome assessment. CONCLUSIONS: The current evidence on low- versus high-chloride solutions for unselected critically ill or perioperative adult patients demonstrates no benefit, but suffers from considerable imprecision. We noted a limited exposure volume for study fluids and a relatively low risk of the populations in each study. Together with the relatively small pooled sample size, these data leave us underpowered to detect potentially important differences. Results from well-conducted, adequately powered randomized controlled trials examining sufficiently large fluid exposure are necessary.
BACKGROUND: There is limited data on prehospital administration of tranexamic acid (TXA) in civilian trauma. The aim of this study was to evaluate changes in coagulation after severe trauma from on-scene to the hospital after TXA application in comparison to a previous study without TXA. METHODS: The study protocol was registered at ClinicalTrials.gov (NCT02354885). A prospective, multicenter, observational study investigating coagulation status in 70 trauma patients receiving TXA (1 g intravenously) on-scene versus a control group of 38 patients previously published without TXA. To account for potential differences in patient and trauma epidemiology, crystalloid and colloidal resuscitation fluid, 2 propensity score matched groups (n = 24 per group) were created. Measurements included ROTEM, standard coagulation tests and blood gas analyses on-scene and emergency department admission. Presented values are mean and [standard deviation], and difference in means and 95% confidence intervals. RESULTS: Patient epidemiology was not different between groups. Coagulation assays on-scene were comparable between the TXA and C. Prehospital hyperfibrinolysis was blunted in all 4 patients in the TXA group. Viscoelastic FIBTEM maximum clot firmness (MCF), representing functional fibrinogen levels, did not change from on-scene to the emergency department in the TXA group, whereas MCF decreased −3.7 [1.8] mm in the control group. Decrease of MCF was significantly reduced in the TXA group in EXTEM by 9.2 (7.2–11.2) mm (P
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Epstein–Barr virus (EBV)-associated T- or natural killer (NK)-cell lymphoproliferative disease (LPD) is a heterogeneous group of disorders characterized by chronic proliferation of EBV-infected lymphocytes. Patients may present with severe skin manifestations, including hypersensitivity to mosquito bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized by blister formation and necrotic ulceration. Skin biopsy specimens show inflammatory reactions comprising EBV-infected lymphocytes. However, blister fluids have not been fully assessed in patients with this disease. Blister fluids were collected from three patients with EBV-associated LPD: two with HMB and one with HV. Immunophenotyping of blister lymphocytes and measurement of tumor necrosis factor (TNF)-α in blister fluids were performed. The patients with HMB and HV exhibited markedly increased percentages of NK and γδ T cells, respectively, in both peripheral blood and blister fluids. These NK and γδ T cells strongly expressed the activation marker human leukocyte antigen-DR and were considered to be cellular targets of EBV infections. TNF-α was highly elevated in all blister fluids. Severe local skin reactions of EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes and a high TNF-α concentration in blister fluids.
Type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone, has been characterized as a defective protein in dystrophic epidermolysis bullosa and as an autoantigen in epidermolysis bullosa acquisita. Although COL7 is produced and secreted by both epidermal keratinocytes and dermal fibroblasts, the role of COL7 with regard to the epidermis is rarely discussed. This review focuses on COL7 physiology and pathology as it pertains to epidermal keratinocytes. We summarize the current knowledge of COL7 production and trafficking, its involvement in keratinocyte dynamics, and epidermal carcinogenesis in COL7 deficiency and propose possible solutions to unsolved issues in this field.
Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment opinion for advanced melanoma and non-small-cell lung cancer, as well as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1 antibody result in a unique side-effect profile, commonly described as immune-related adverse events (irAE). These irAE affect the skin, gastrointestinal tract, liver, endocrine system and other organ systems. We report two cases of oral lichenoid reaction showing multiple ulcers associated with nivolumab treatment. Both patients presented with multiple ulcers covered with fibrinous plaque over the entire oral mucosa, lips and tongue. Histopathological examination of ulceration showed epithelial necrosis and subepidermal clefts with dense band-like layers of lymphohistiocytic infiltrate within the upper dermis. Nivolumab was interrupted in both cases. Case 1 responded well to topical corticosteroids. Case 2 required oral corticosteroids, however, nivolumab could be restarted without recurrence of oral ulcers. We provide a comprehensive review of reported cases of lichenoid reaction showing multiple oral ulcers associated with anti-PD-1 therapy to date. Early recognition and management may improve treatment, avoid discontinuation of life-saving therapy and maintain quality of life in these patients.
Publication date: 15 March 2018
Source:Materials & Design, Volume 142
Author(s): W.W. Xu, S.L. Shang, C.P. Wang, T.Q. Gang, Y.F. Huang, L.J. Chen, X.J. Liu, Z.K. Liu
The discovery of γ′-Co3(Al,W) opens up a pathway to exploit novel Co-Al-based alloys as candidates of the next generation of superalloys. Inspired by the unexpected finding of γ′-Co3(Al,W), we present a comprehensive investigation concerning the effect of alloying elements on phase stabilities and mechanical properties of Co3Al. Up to 22 transition metal elements, e.g. Sc, Ti, V, Cr, Mn, Fe, Ni, Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd, Hf, Ta, W, Re, Os, Ir, and Pt, are considered. Results show that W, Ti, Re, V, and Ta favor to occupy the Al-sublattice. Pd, Pt, Rh, Ni, Ir, Fe, and Ru favor to occupy the Co-sublattice. The others can occupy both the Co- and Al-sublattices. W, Ta, V, Ti, Nb, Re, Mo, Pt, and Cr are shown to stabilize Co3Al. It verifies that elastic properties are roughly in inverse proportional to the volume change induced by alloying elements within each group of 3d, 4d, or 5d. Based on the analysis of electronic configurations, the influence mechanism of alloying elements is traceable from the chemical bonding and the geometry of charge density. The present calculations are in favorable accord with available experimental data in the literature.
Violence and Gender , Vol. 0, No. 0.
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AbstractBackground.Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long‐term cognitive functioning (CogF) in germ‐cell tumor (GCT) survivors.Subjects, Materials, and Methods. GCT survivors (n = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow‐up (range: 5–32). The study group consisted of survivors receiving a cisplatin‐based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only.Results.Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p < .05). Overall long‐term cognitive impairment was independent of age in the multivariable analysis.Conclusion.This prospective study shows that GCT survivors suffer from a long‐term CogF impairment. These results may help guide clinicians' decisions in treatment and follow‐up of GCTs.Implications for Practice.In this study, long‐term survivors of germ‐cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided.
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In this short review, the most common non-invasive neuromodulatory techniques will be described, along with their advantages and disadvantages and their application in headache. Available preventive treatments can be unhelpful or may have unpleasant side effects; moreover, the rate of response to preventive drugs does not exceed 50%, lower in chronic migraine; alternative options would be welcome. Though the concept of neuromodulation was originally developed with invasive methods, newer non-invasive techniques are appearing.
The novel neuromodulatory techniques have been developed with encouraging results: compared with traditional pharmacotherapy, advantages of non-invasive neuromodulation include reduced incidence of adverse effects, improved adherence, and safety and ease of use. The results are encouraging for acute or preventive treatment of different kinds of headache.
A variety of neuromodulatory approaches is expanding fastly and has opened new possibilities for treatment of patients suffering from many forms of headache, especially those who have failed traditional pharmacotherapy. The non-invasive treatments can be seen as supplementing traditional management in refractory patients. Current study results are encouraging but preliminary and larger and more rigorous trials are needed to clarify benefit and mode of action.
Progestogen hypersensitivity (PH) is a rare disorder which usually occurs in women of childbearing age with symptoms ranging from urticaria with or without angioedema, multiple organ involvement consistent with allergic anaphylaxis, to a spectrum of other non-evanescent skin eruptions. In this review, we present a clinical vignette of PH and discuss the clinical presentation and proposed pathomechanisms, diagnosis, and treatment of PH.
The hypersensitivity symptoms are associated with exogenous progestin exposure (e.g., contraceptive medicines, in vitro fertilization therapy) or endogenous progesterone from progesterone surges during the luteal phase of the menstrual cycle and pregnancy. Recognition of this condition can be challenging to the clinician due to its heterogeneous clinical presentation. It has been recently proposed to use the new term "progestogen hypersensitivity" to replace "autoimmune progesterone dermatitis" due to the lack of evidence supporting an autoimmune mechanism for this disorder. In addition, diagnostic and treatment algorithms are now available that can lead to successful management of this condition. More new developments of Progesterone desensitization protocols are now available which appear to be the safest and most effective long-term treatment option for PH.
With the extensive use of oral contraceptives and increased use of supra-physiologic doses of progesterone to support pregnancy in in vitro fertilization, there is likely to be a higher prevalence of PH in the future than currently recognized. Therefore, the allergist-immunologist will be required to collaborate with gynecologists and reproductive endocrinologists to diagnose and treat this condition.
Publication date: 1 July 2018
Source:Microporous and Mesoporous Materials, Volume 264
Author(s): Jingze Sun, Liya Semenchenko, Woo Taik Lim, Maria Fernanda Ballesteros Rivas, Victor Varela-Guerrero, Hae-Kwon Jeong
Zeolitic-imidazole framework ZIF-8 has attracted tremendous interests for the high-resolution kinetic separation of propylene/propane mixture due to its effective aperture size in between the sizes of propylene and propane molecules. It is of great interest to fine-tune the effective aperture size of ZIF-8 either to improve its propylene/propane separation performances or to extend its use to the separation of other gas mixtures. It has been shown that substituting Zn with other metal nodes (e.g. Co) is a potential means to fine-tune the effective aperture size of ZIF-8. Here, we attempt to introduce another metal center, Cd, into ZIF-8 in a facile and scalable manner. Phase-pure Cd-ZIF-8 was successfully synthesized in methanol using a conventional solvothermal method, although it showed a narrow synthesis window. The presence of an organic base (triethylamine, TEA) was found critical not only for the facile synthesis of phase-pure Cd-ZIF-8 but also for the suppression of its phase transformation. A battery of characterizations including single-crystal X-ray structure solutions confirmed that the effective aperture size of Cd-ZIF-8 is the largest among its iso-structures (Zn-ZIF-8 and Co-ZIF-8). Finally, for the first time, mixed-metal CdZn-ZIF-8 crystals with various Cd/Zn ratios were solvothermally synthesized, demonstrating a further opportunity for varying the effective aperture sizes of ZIF-8 and its iso-structures.
We investigated the significance of tropospheric ozone as a factor explaining recent tree health (in terms of defoliation) and productivity (in terms of basal area increment, BAI) in 15 ICP Forests level I and one level II plots in alpine forests in Trentino (N. Italy). Mean daily ozone summer concentrations varied between 30 and 72 parts per billion (ppb) leading to large exceedance of concentration-based critical levels set to protect forest trees. Phytoxic ozone dose (POD0) estimated at the level II plot over the period 1996–2009 was 31–61 mmol m−2 projected leaf area (PLA). The role of ozone was investigated taking into account other site and environmental factors. Simple linear regression, multiple linear regression (MLR, to study mean periodical defoliation and mean periodical BAI), and linear mixed models (LMM, to study annual defoliation data) were used. Our findings suggest that—regardless of the metric adopted—tropospheric ozone is not a significant factor in explaining recent status and trends of defoliation and BAI in the alpine region examined. Both defoliation and BAI are in turn driven by biotic/abiotic damage, nutritional status, DBH (assumed as a proxy for age), and site characteristics. These results contrast with available ozone-growth dose response relationships (DRRs) and other observational studies. This may be due to a variety of concurrent reasons: (i) DRRs developed for individual saplings under controlled condition are not necessarily valid for population of mature trees into real forest ecosystems; (ii) some observational studies may have suffered from biased design; and (iii) since alpine forests have been exposed to high ozone levels (and other oxidative stress) over decades, possible acclimation mechanisms cannot be excluded.
The development of environmentally sustainable control strategies to fight insect pests is a key challenge nowadays. Pheromone-mediated mating disruption (MD) is based on the release of synthetic sex attractants into a crop, interfering with mate finding of a given pest species. However, a limited number of research items have been published on the optimization of MD strategies against the European grapevine moth, Lobesia botrana, as well as on the use of biodegradable dispensers to reduce waste production in vineyards, despite the high economic importance of this pest. Therefore, the present study evaluated the efficacy of the MD products Isonet® L TT and the biodegradable Isonet® L TT BIO, applied at various densities, in reducing L. botrana damage on grapevine in comparison to an untreated control and the reference MD product Isonet® L. Experiments were conducted in three different areas of grapevine cultivation, located in Central and Northern Italy, over three different years. Our MD approach allowed a reliable control of the three generations of L. botrana during the whole grape growing season, leading to a significant reduction in the infested flower clusters and bunches, as well as in the number of nests per flower cluster and bunch, if compared to the untreated control. The performances of Isonet® L TT BIO, Isonet® LTT, and Isonet® L did not differ in terms of infested flower clusters/bunches, as well as nests per flower cluster/bunch. This was confirmed in all experimental sites over 3 years of field experiments. Overall, the present research provides useful information for the optimization of MD programs against L. botrana, highlighting the interesting potential of biodegradable pheromone dispensers that can be easily applied at low densities in vineyards, reducing the use of chemical pesticides to control moth pests.
Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 25-29.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 3-6.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 33-35.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 10-14.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 21-24.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 15-17.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 18-20.
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Clinical Thyroidology Jan 2018, Vol. 30, No. 1: 36-41.
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Publication date: March 2018
Source:Journal of Anthropological Archaeology, Volume 49
Author(s): Blanca Ochoa, Marcos García-Diez
The objective of the paper is to determine convergences or divergences in the placement of cave art through the combined study of parietal art and the specific space in which it was executed.The proposed methodology is based on the definition of the concepts of graphic space, visibility, access and capacity. Through these, a series of variables have been created to analyse in the cave: the presence of an archaeological context, the specific location of the figures, divided into three levels of study –graphic unit, panel and topographic unit–, the cave transit, the selected spaces and the potential visibility and observer capacity at each level.This methodology has been applied to Chufín Cave (Cantabria, Spain). By studying the location of the different panels, two potential uses for the cave were determined: some panels are located on highly visible surfaces in large spaces of the cave using the techniques of deep engraving and drawing with red pigments. In contrast, other panels are situated in low visibility areas of more difficult access, with the technique of shallow engraving. This evidence might point towards a more widespread use of cave art in the first case, possibly including all the community, and a restricted use in the second case.
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In the United States, an increasing number of individuals are identifying as transgender. Males at birth who identify as females are called male-to-female (MTF) transgender individuals or trans women, and females at birth who identify as males are called female-to-male (FTM) transgender individuals or trans men. The transgender patient population possess unique health concerns disparate from those of the general populace. Exogenous hormone therapy for transgender patients leads to changes in the distribution and pattern of hair growth. Exogenous testosterone can lead to male pattern hair loss and hirsutism, while estrogen therapy usually results in decreased facial and body hair growth and density. A thorough understanding of the hormonal treatments that may be used in transgender individuals as well the unique and complex biologic characteristics of the hair follicle is required for appropriate diagnosis, counseling and treatment of patients. The aim of this article is to provide a framework for understanding hair disorders in transgender individuals and effective treatment options.
The PD-1 inhibitor nivolumab was recently approved by the FDA for adjuvant use in completely resected stage III or IV melanoma, a move welcomed by experts in the field.
Medscape Medical News
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Publication date: Available online 18 January 2018
Source:Cancer Cell
Author(s): Amanda Balboni Iniguez, Björn Stolte, Emily Jue Wang, Amy Saur Conway, Gabriela Alexe, Neekesh V. Dharia, Nicholas Kwiatkowski, Tinghu Zhang, Brian J. Abraham, Jaume Mora, Peter Kalev, Alan Leggett, Dipanjan Chowdhury, Cyril H. Benes, Richard A. Young, Nathanael S. Gray, Kimberly Stegmaier
Many cancer types are driven by oncogenic transcription factors that have been difficult to drug. Transcriptional inhibitors, however, may offer inroads into targeting these cancers. Through chemical genomics screening, we identified that Ewing sarcoma is a disease with preferential sensitivity to THZ1, a covalent small-molecule CDK7/12/13 inhibitor. The selective CDK12/13 inhibitor, THZ531, impairs DNA damage repair in an EWS/FLI-dependent manner, supporting a synthetic lethal relationship between response to THZ1/THZ531 and EWS/FLI expression. The combination of these molecules with PARP inhibitors showed striking synergy in cell viability and DNA damage assays in vitro and in multiple models of Ewing sarcoma, including a PDX, in vivo without hematopoietic toxicity.
Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 μg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days.
A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 μg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review.
Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis).
Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP.
Recent compelling epidemiological studies indicate a strong association of obesity with thyroid cancer. Obesity has been shown to promote thyroid cancer progression and exacerbate poor outcome in thyroid cancer patients. However, the molecular mechanisms by which obesity increases thyroid cancer risk and facilitates cancer progression are not completely understood. Obesity induces complex pathological changes including hyperglycemia, hyperinsulinemia, hyperlipidemia, oxidative stress, adipokines, and inflammatory responses. These changes can affect the development and progression of cancer through highly complex interactions in vivo. The deleterious effect of obesity may differ according to the different cancer types. In view of the increased incidence of thyroid cancer in parallel with the widespread occurrence of obesity in the past decades, it is imperative to clarify how obesity affects thyroid carcinogenesis. This review focuses on molecular mechanisms by which obesity aggravates thyroid carcinogenesis as elucidated by mouse models of thyroid cancer.
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB. We show that active cofilin, LIMK1, LIMK2, and SSH1 are overexpressed in human CRC and are associated with tumor progression parameters. SSH1 is an independent predictor of lymph node metastasis by multivariate analysis. LIMK1 and SSH1 expression is also higher in non-responders to chemotherapy, and SSH1 is shown by multivariate analysis to independently predict response of metastatic disease to chemotherapy. Active cofilin, LIMK1, LIMK2, and SSH1 also correlated with the EMT markers examined. In addition, immunofluorescence analysis showed increased expression of active cofilin, LIMK1, LIMK2, and SSH1 in HT29 colon cancer cells resistant to 5-fluorouracil compared to parental HT29 cells. Our results suggest that F-actin regulators LIMK/cofilin pathway and SSH1 are associated with CRC progression and chemoresistance representing promising tumor biomarkers and therapeutic targets in CRC.
Allergic sensitization is associated with eczema, asthma, and rhinitis. However, it is unknown whether and how allergic sensitization is associated over time with acquisition, remission, and persistence of these diseases and their comorbidity.
To gain a better understanding of factors including allergic sensitization transitions that influence the temporal pattern of asthma, eczema, and rhinitis and their comorbidity during childhood.
In the Isle of Wight birth cohort information on allergic sensitization to common allergens was collected at ages 4, 10, and 18 years along with asthma, rhinitis, and eczema status determined by clinical diagnosis. Logistic regressions were used to estimate subsequent and concurrent odds-ratios of diseases transition with allergic sensitization transition status as the main independent variable. Two transition periods were considered, 4 to 10 years of age, and 10 to 18 years of age.
The odds of new diagnosis of allergic disease (no-yes) was increased among subjects with acquired or persistent allergic sensitization to common allergens compared to subjects with no sensitization (acquisition of sensitization odds ratio [OR]=3.22, p <0.0001; persistence of sensitization, OR=6.33, p <0.0001). The odds of remission of allergic diseases (yes-no) was lower among subjects with acquired or sustained allergic sensitization (acquisition, OR=0.18, p =0.0001; persistence, OR=0.085, p <0.0001), compared to subjects not sensitized. Subjects with acquired or persistent allergic sensitization were also had higher odds for persistence of disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, p =0.0001; persistence, OR=11.79, p <0.0001).
Transition of allergic sensitizations to common allergens is a prognostic factor for subsequent or concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction of allergic sensitization has a potential to lead to remission of these conditions.
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Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma.
To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AEC) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children.
Primary AEC were obtained from children with and without asthma, differentiated into Air Liquid Interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; RT) and permeability to fluorescent dextran.
Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics, however no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction of TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed.
This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.
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Companion animals are also affected by IgE-mediated allergies, but the eliciting molecules are largely unknown. We aimed at refining an allergen microarray to explore sensitization in horses and compare it to the human IgE reactivity profiles.
Custom-designed allergen microarray was produced on the basis of the IimmunoCAP ISAC technology containing 131 allergens. Sera from 51 horses derived from Europe or Japan were tested for specific IgE reactivity. The included horse patients were diagnosed for eczema due to insect bite hypersensitivity, chronic coughing, recurrent airway obstruction, urticaria, or were clinically asymptomatic.
Horses showed individual IgE binding patterns irrespective of their health status, indicating sensitization. In contrast to European and Japanese human sensitization patterns, frequently recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass, likely due to specific respiratory exposure around paddocks and near the ground. The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S-albumin Fag e 2 from buckwheat, which recently gained importance not only in human but also in horse diet.
In line with the One Health concept, covering human health, animal health and environmental health, allergen microarrays provide novel information on the allergen sensitization patterns of the companion animals around us, which may form a basis for allergen-specific preventive and therapeutic concepts.
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Publication date: 30 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 115
Author(s): Christian Siewert, Regina Moog, Rainer Alex, Philipp Kretzer, Benno Rothenhäusler
Wet media milling is a well-established unit operation for the manufacturing of suspension formulations during early phase pharmaceutical development. However, knowledge about the kinetics of particle breakage is limited, although the impact of hydro-mechanical process parameters on the mean particle size of finished suspensions has been thoroughly investigated. We performed in this work milling trials with two different compounds on two milling devices with different mechanical design and volume scale. We analyzed our data in terms of a kinetic milling model where we included the milling speed as an explicit process parameter in addition to the process duration. We show, that the milling kinetics can be fairly well predicted for a wide range of these operating parameters. The proposed milling model may therefore be useful for rational process planning and scale-up considerations in the industrial setting.
Treatment Outcomes and Adverse Events Following In-Office Angiolytic Laser With or Without Concurrent Polypectomy for Vocal Fold Polyps.
JAMA Otolaryngol Head Neck Surg. 2018 Jan 18;:
Authors: Lin YH, Wang CT, Lin FC, Liao LJ, Lo WC, Cheng PW
Abstract
Importance: In-office angiolytic laser procedures have been used successfully as an alternative treatment for vocal fold polyps; little is known in detail about the treatment outcomes and adverse events.
Objective: To examine the outcomes and incidence rates of adverse events associated with in-office angiolytic laser procedures with or without concurrent polypectomy as an alternative treatment for vocal fold polyps.
Design, Setting, and Participants: Retrospective cohort study at a tertiary medical center. We identified 114 consecutive patients with vocal polyps who underwent in-office angiolytic laser treatments between January 1, 2014, and August 31, 2016. After the exclusion of 17 with missing or incomplete data, 97 were enrolled.
Interventions: In-office 532-nm laser procedures with or without concurrent polypectomy.
Main Outcomes and Measures: Between 1 and 2 months after the surgical procedures, we collected the following outcome data: videolaryngostroboscopy, perceptual rating of voice quality, acoustic analysis, maximal phonation time, and subjective rating of voice quality using a visual analogue scale and 10-item voice handicap index.
Results: This study enrolled 97 patients (mean [SD] age, 45.6 [11.3] years; 48 [49%] male). The mean duration of symptoms was 10.1 months (range, 1-60 months). Twenty-nine patients (30%) had angiolytic laser procedures only, while 68 (70%) received laser with concurrent polypectomy. Both treatment modalities offered significant improvements. Only 1 patient (1%) receiving angiolytic laser with concurrent polypectomy underwent another treatment session, so this group had significantly less need for multiple treatments than those receiving laser treatment alone (6 [21%]; effect size, -1.57; 95% CI, -2.77 to -0.36). We identified 8 adverse events (8% of the cases): vocal fold edema (n = 5), vocal hematoma (n = 2), and vocal ulceration (n = 1). Patients treated with laser plus concurrent polypectomy had significantly fewer adverse events than those treated with angiolytic laser alone (2 [3%] vs 6 [21%]; effect size, 1.20; 95% CI, 0.26 to 2.13).
Conclusions and Relevance: In-office angiolytic laser procedures can be an effective alternative treatment for vocal polyps, although with possible need for multiple treatment sessions and occasional occurrence of minor postoperative adverse events. Concurrent polypectomy following laser coagulation allows less laser energy delivery and reduces the risk of postoperative adverse events and the need for additional treatment sessions.
PMID: 29346486 [PubMed - as supplied by publisher]
