The prevalence of affective disorders such as depression and anxiety is particularly high in patients with autoimmune diseases, including inflammatory skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. A dysregulated immune response has been linked to the precipitation of depression in many patient populations. However, studies examining the extent to which the underlying skin disease inflammatory processes contribute to depression and a subsequent decline in quality of life are limited. The published literature over the past 5 years was reviewed for evidence of a relationship between depression and inflammatory processes in the context of skin pathology. The findings, particularly the evidence from interventional clinical trials of targeted anti-cytokine therapies, suggest that pro-inflammatory cytokines associated with several skin diseases may be causally linked with the coexistent depressive symptomology.
Skin Pharmacol Physiol 2018;31:246–251
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Τετάρτη 27 Ιουνίου 2018
Inflammation: A Contributor to Depressive Comorbidity in Inflammatory Skin Disease
An Autonomic Network: Synchrony Between Slow Rhythms of Pulse and Brain Resting State Is Associated with Personality and Emotions
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Table of Contents
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
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Information for Authors
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
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Mepolizumab in the treatment of severe eosinophilic asthma
Publication date: July 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
Author(s): Ronald A. Strauss, Nesreen Jawhari
https://ift.tt/2KhY2Le
Editorial Board
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
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A march by any other name
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
Author(s): David A. Hill, Carlos A. Camargo, Amy S. Paller, Jonathan M. Spergel
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Information for Readers
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
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Meat reintroduction in a patient with α-gal allergy
Publication date: July 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
Author(s): Teresa Pelletier, Santiago Alvarez-Arango, F.N.U. Sameeta, Ellen Manos, Elina Jerschow
https://ift.tt/2KgLUdG
Children & Environment Toxins: What Everyone Needs to Know
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
Author(s): Anita Sivam
https://ift.tt/2KpN5Dt
Leaving the nest
Publication date: July 2018
Source:Annals of Allergy, Asthma & Immunology, Volume 121, Issue 1
Author(s): Ashley A. Dyer, Amy O'Keefe, Madeleine K. Kanaley, Lauren M. Kao, Ruchi S. Gupta
BackgroundThe transition from adolescence to young adulthood marks a developmental period in which responsibility for management of chronic conditions such as food allergy shifts from the caregiver to the young adult. Fatal food-induced anaphylaxis is most common among adolescents and young adults. However, colleges are currently not well positioned to provide integrated support for students with food allergies.ObjectiveThe study objective was to explore the systems, structures, and policies that currently support students with food allergies at college, assess unmet needs, and develop pilot interventions through the use of patient-centered design processes.MethodsKey informant interviews were conducted with stakeholders in the campus management of food allergies (n = 26) between April and May 2016. Data were coded and assessed for relative frequencies of each code to determine challenges and potential solutions.ResultsThe convergence of stakeholder-identified themes indicated that the transition to college for students with food allergy would be improved by providing support for: (1) Notification of others in the student's campus network about food allergy; (2) Establishing clearly defined roles/responsibilities; and (3) Increasing campus awareness of food allergy signs, symptoms, and lethality. To better provide comprehensive support for students, 5 interventions—collectively called Spotlight—were developed.ConclusionThe use of qualitative research methods, patient-centered design processes, and collaborations with diverse stakeholders—including pediatricians that care for adolescents—can provide a framework for designing coordinated systems and policies to provide comprehensive support to college students with food allergy. Next steps include rigorously testing implementation of the Spotlight intervention prototypes.
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Congenital nevus comedonicus complicated by a hidradenitis suppurativa‐like lesion: Report of a childhood case
Pediatric Dermatology, EarlyView.
https://ift.tt/2lGg0bP
RuO2/graphene nanoribbon composite supported on screen printed electrode with enhanced electrocatalytic performances toward ethanol and NADH biosensing
Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Vesna Vukojević, Sladjana Djurdjić, Miloš Ognjanović, Bratislav Antić, Kurt Kalcher, Jelena Mutić, Dalibor M. Stanković
In this work, we aimed to propose a newly synthesized composite material with enhanced electrocatalytic properties as a novel screen-printed sensor for the quantification of NADH. Additionally, the surface was modified with alcohol dehydrogenase for the preparation of an amperometric biosensor for analysis of ethanol. Synthesized material was characterized using several microstructural (FE-SEM, HR-TEM, XRD) and electrochemical (CV, EIS) techniques. The electrochemical response of the tested analytes was investigated as a function of important parameters. Under optimal conditions, the working linear range and limit of detection for ethanol sensing was 1–1800 µM and 0.19 µM, respectively. For NADH, the linear range was from 1 to 1300 µM with limit of detection of 0.52 µM. Moreover, effects of some possible interfering compounds were investigated and the developed procedure was applied to commercial alcoholic beverages. The results obtained showed satisfactory precision and accuracy of the developed method and confirm the proposed approach could be a possible replacement for the currently used techniques for ethanol and NADH quantification.
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Biosensors for determination of D and L- amino acids: A review
Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): C.S. Pundir, Suman Lata, Vinay Narwal
Amino acids (AAs) of nutritional importance exist as L-isomers, while D-isomeric form of AAs is common constituent of bacterial cell wall. The presence of D-amino acids in foods is promoted by harsh technological processes (e.g., high temperature, extreme pH, adulteration or microbial contamination). The detection of free AAs in different brain disorders is also very important. Among the various methods available for detection of AAs, most are complicated and require time-consuming sample pre-treatment, expensive instrumental set-up and trained persons to operate, specifically for chromatographic methods. The biosensing methods overcome these drawbacks, as these are simple, fast, specific and highly sensitive and can also be applied for detection of AAs in vivo. This review presents the principles, merits and demerits of various analytical methods for AA determination with special emphasis on D-amino acids (DAA) and L-amino acids (LAA) biosensors. The electrochemical AA biosensors work optimally within 2–900 s, pH range, 5.3–9.5; temperature range, 25–45 °C; AA concentration range, 0.0008–8000 mM, limit of detection(LOD) between 0.02 and 1250 µM and working potential from −0.05 to 0.45 V. These biosensors measured AA level in fruit juices, beverages, urine, sera and were reused 200 times over a period of 7–120 days. The use of various nanostructures and electrochemical microfluidic paper based analytical device (EμPAD) are suggested for further development of AA biosensors.
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Modelling of magnetoimpedance response of thin film sensitive element in the presence of ferrogel: Next step toward development of biosensor for in-tissue embedded magnetic nanoparticles detection
Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): N.A. Buznikov, A.P. Safronov, I. Orue, E.V. Golubeva, V.N. Lepalovskij, A.V. Svalov, A.A. Chlenova, G.V. Kurlyandskaya
In-tissue embedded magnetic nanoparticle (MNPs) detection is one of the most interesting cases for cancer research. In order to understand the origin, the limits and the way of improvement of magnetic biosensor sensitivity for the detection of 3D mezoscopic distributions of MNPs, we have developed a magnetoimpedance biosensor prototype with a [Cu (3 nm)/FeNi(100 nm)]5/Cu(500 nm)/[FeNi(100 nm)/Cu(3 nm)]5 rectangular sensitive element. Magnetoimpedance (MI) responses were measured with and without polyacrylamide ferrogel layer mimicking natural tissue in order to evaluate stray fields of embedded MNPs of γ-Fe2O3 iron oxide. A model for MI response based on a solution of Maxwell equations with Landau-Lifshitz equation was developed in order to understand the origin of the prototype sensitivity which reached 1.3% of ΔZ/Z per 1% of MNPs concentration by weight. To make this promising technique useful for magnetically labeled tissue detection, a synthesis of composite gels with MNPs agglomerates compactly located inside pure gel and their MI testing are still necessary.
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Highly sensitive paper-based immunoassay using photothermal laser speckle imaging
Publication date: 15 October 2018
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Seungri Song, Seoyeon Choi, Suho Ryu, Soocheol Kim, Tongwha Kim, Joonchul Shin, Hyo-Il Jung, Chulmin Joo
Paper-based lateral-flow assay (LFA) is a simple and inexpensive point-of-care device that has become commonplace in medicine, environmental monitoring, and over-the-counter personal use. Some LFAs have demonstrated comparable analytical performance with laboratory-based methods, but the detection limit or sensitivity of most LFAs is significantly inferior to other molecular techniques by 10–100 × . Consequently, LFAs are not viable for the early detection of disease-relevant biomarkers that are present in extremely small amounts in clinical specimens. Herein, we present a simple, cost-effective, and highly sensitive LFA sensor based on photothermal laser speckle imaging (PT-LSI). Under the illumination of a photothermal excitation light, gold nanoparticles (AuNPs), a common signal transduction medium in LFAs, absorb the light energy to produce heat, which subsequently induces modulation of the optical property and thermal deformation of the membrane. We measured these fluctuations through laser speckle imaging to quantify the concentration of AuNP-biomarker complexes. We experimentally demonstrate that the detection limit of our technique is superior to that of colorimetric detector by 68–125 × . The capability of our sensor for highly sensitive detection of disease biomarkers is validated by using U.S. FDA-approved LFA kits for cryptococcal antigens (CrAg).
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Combined percutaneous radiofrequency ablation and cementoplasty for the treatment of extraspinal painful bone metastases: A prospective study
Publication date: Available online 27 June 2018
Source:Journal of the Egyptian National Cancer Institute
Author(s): Andrew Fares, Mohamed H. Shaaban, Raafat M. Reyad, Ahmed S. Ragab, Mohga A. Sami
IntroductionAbout 50% of patients with cancer develop bone metastasis mainly presenting with distressing, drug-resistant pain.Aim of the workThe study evaluated efficacy and safety of combined cementoplasty and bony radiofrequency ablation in palliation of intractable pain and disability in cancer patients with bony metastases.Patients and methodsThe study included 30 adult patients suffering from localized bony metastases causing refractory moderate to severe pain. Radiofrequency bony ablation performed followed by cementoplasty were done under computed tomography (CT) guidance with conscious sedation and local anesthesia. Final CT check was done to ensure adequate lesion filling and to exclude any cement leakage. Pain, hemodynamic variables, and neurological status were checked for a minimum of 2 h before discharge. The patients were followed up weekly in the pain clinic. The primary outcome measures pain severity and daily opioid consumption. The secondary outcome measures were quality of life and the degree of disability, and procedure-related adverse outcomes.ResultsPain score, daily morphine consumption, and Oswestry Disability Index score decreased significantly after 1 day, and 1, 4 and 12 weeks. None of the patients had serious complications during the postoperative follow up visits. Only 4 patients (13.3%) experienced discomfort during, and few days after the procedure, 3 patients (10%) suffered from local infection, and 2 patients (6.7%) reported cement leakage.ConclusionCombined radiofrequency ablation and cementoplasty is a safe and effective pain relief modality in patients suffering from extraspinal painful bone metastases with improvement of the quality of life.
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Mannitol in Critical Care and Surgery Over 50+ Years: A Systematic Review of Randomized Controlled Trials and Complications With Meta-Analysis
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A pilot split‐scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss
Clinical and Experimental Dermatology, EarlyView.
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Pandemic influenza vaccines: what they have taught us about B cell immunology
David J Topham | Phuong Nguyen | Mark Y Sangster
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Fat spectral modeling on triglyceride composition quantification using chemical shift encoded magnetic resonance imaging
Publication date: October 2018
Source:Magnetic Resonance Imaging, Volume 52
Author(s): Gregory Simchick, Amelia Yin, Hang Yin, Qun Zhao
PurposeTo explore, at a high field strength of 7T, the performance of various fat spectral models on the quantification of triglyceride composition and proton density fat fraction (PDFF) using chemical-shift encoded MRI (CSE-MRI).MethodsMR data was acquired from CSE-MRI experiments for various fatty materials, including oil and butter samples and in vivo brown and white adipose mouse tissues. Triglyceride composition and PDFF were estimated using various a priori 6- or 9-peak fat spectral models. To serve as references, NMR spectroscopy experiments were conducted to obtain material specific fat spectral models and triglyceride composition estimates for the same fatty materials. Results obtained using the spectroscopy derived material specific models were compared to results obtained using various published fat spectral models.ResultsUsing a 6-peak fat spectral model to quantify triglyceride composition may lead to large biases at high field strengths. When using a 9-peak model, triglyceride composition estimations vary greatly depending on the relative amplitudes of the chosen a priori spectral model, while PDFF estimations show small variations across spectral models. Material specific spectroscopy derived spectral models produce estimations that better correlate with NMR spectroscopy estimations in comparison to those obtained using non-material specific models.ConclusionAt a high field strength of 7T, a material specific 9-peak fat spectral model, opposed to a widely accepted or generic human liver model, is necessary to accurately quantify triglyceride composition when using CSE-MRI estimation methods that assume the spectral model to be known as a priori information. CSE-MRI allows for the quantification of the spatial distribution of triglyceride composition for certain in vivo applications. Additionally, PDFF quantification is shown to be independent of the chosen a priori spectral model, which agrees with previously reported results obtained at lower field strengths (e.g. 3T).
Graphical abstract
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Background field removal technique based on non-regularized variable kernels sophisticated harmonic artifact reduction for phase data for quantitative susceptibility mapping
Publication date: October 2018
Source:Magnetic Resonance Imaging, Volume 52
Author(s): Hirohito Kan, Nobuyuki Arai, Masahiro Takizawa, Kazuyoshi Omori, Harumasa Kasai, Hiroshi Kunitomo, Yasujiro Hirose, Yuta Shibamoto
PurposeWe developed a non-regularized, variable kernel, sophisticated harmonic artifact reduction for phase data (NR-VSHARP) method to accurately estimate local tissue fields without regularization for quantitative susceptibility mapping (QSM). We then used a digital brain phantom to evaluate the accuracy of the NR-VSHARP method, and compared it with the VSHARP and iterative spherical mean value (iSMV) methods through in vivo human brain experiments.Materials and methodsOur proposed NR-VSHARP method, which uses variable spherical mean value (SMV) kernels, minimizes L2 norms only within the volume of interest to reduce phase errors and save cortical information without regularization. In a numerical phantom study, relative local field and susceptibility map errors were determined using NR-VSHARP, VSHARP, and iSMV. Additionally, various background field elimination methods were used to image the human brain.ResultsIn a numerical phantom study, the use of NR-VSHARP considerably reduced the relative local field and susceptibility map errors throughout a digital whole brain phantom, compared with VSHARP and iSMV. In the in vivo experiment, the NR-VSHARP-estimated local field could sufficiently achieve minimal boundary losses and phase error suppression throughout the brain. Moreover, the susceptibility map generated using NR-VSHARP minimized the occurrence of streaking artifacts caused by insufficient background field removal.ConclusionOur proposed NR-VSHARP method yields minimal boundary losses and highly precise phase data. Our results suggest that this technique may facilitate high-quality QSM.
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A pilot split‐scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss
Clinical and Experimental Dermatology, EarlyView.
https://ift.tt/2KpnlqP
Combined Ex Vivo Hypothermic and Normothermic Perfusion for Assessment of High-Risk Deceased Donor Human Kidneys for Transplantation
https://ift.tt/2Iw301u
Androgen insensitivity syndrome
OBJECTIVE: We provide a review of the literature about the Androgen Insensitivity Syndrome (AIS), its onset and associated developmental anomalies and the genetic alterations causing it.
MATERIALS AND METHODS: We searched PubMed with a larger emphasis on the physiology, genetics and current management of AIS.
RESULTS: AIS is an X-linked recessive Disorder of Sex Development (DSD). It is caused by mutations of the Androgen Receptor, and their large amount and heterogeneity (missense and nonsense mutations, splicing variants, deletions, and insertions) are responsible for the wide spectrum of possible phenotypes of patients, divided into Partial AIS (PAIS) and Complete AIS (CAIS). Once the clinical and laboratory investigations have laid the foundation for a diagnostic hypothesis, it is important to identify the actual karyotype of the individual and search for the mutation in the Androgen Receptor to diagnose with certainty the syndrome. Alternatively, in the absence of such evidence, the diagnosis should more properly be an AIS-like condition, which we describe as well in our report.
CONCLUSIONS: The management of this DSD is based on pharmacotherapies, surgery and psychological support: all of them must be directed to facilitate the patient's life, considering his/her sexual identity.
L'articolo Androgen insensitivity syndrome sembra essere il primo su European Review.
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Attentional ERPs distinguish aging and early Alzheimer's dementia
Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Colin T. Lockwood, William Vaughn, Charles J. Duffy
The early detection of Alzheimer's disease requires our distinguishing it from cognitive aging. Here, we test whether spatial attentional changes might support that distinction. We engaged young normal (YN), older normal (ON), and patients with early Alzheimer's dementia (EAD) in an attentionally cued, self-movement heading discrimination task while we recorded push-button response times and event related potentials. YNs and ONs show the behavioral effects of attentional shifts from the cue to the target, whereas EAD patients did not (p < 0.001). YNs and ONs also show the shifting lateralization of a newly described attentional event related potentials component, whereas EAD patients did not (p < 0.001). Our findings suggest that spatial inattention in EAD patients may contribute to heading direction processing impairments that distinguish them from ONs and undermine their navigational capacity and driving safety.
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Erratum: Use of Social Media and an Online Survey to Discuss Complex Reconstructive Surgery: A Case of Upper Lip Reconstruction with 402 Responses from International Microsurgeons
J reconstr Microsurg 2018; 34: e1-e1
DOI: 10.1055/s-0038-1667022
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Full text
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Effects of a homogeneous polysaccharide from Sijunzi decoction on human intestinal microbes and short chain fatty acids in vitro
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Beibei Gao, Ruijun Wang, Ying Peng, Xiaobo Li
Ethnopharmacological relevanceSijunzi decoction (SJZD) is a classic recipe in traditional Chinese medicine (TCM) to strengthen the spleen and replenish Qi. It is well known for treating disorders of gastrointestinal function manifested in poor appetite, reduced food intake and loose stools. Polysaccharide is the most abundant constituent and the major effective component in SJZD.Aim of the studyThe present study aimed to understand the immunomodulatory mechanism of S-3–1, a homogeneous polysaccharide purified from SJZD with immune-enhancement activity, by investigating its effects on human intestinal microbes and short chain fatty acids.Materials and methodsS-3–1 was incubated with simulated gastric juice, intestinal juice, and human fecal microflora independently and sequentially. The concentrations of total polysaccharide and reducing sugar were measured to identify the stability of independently and sequentially incubated S-3–1 in three in vitro fermentation models. Gas chromatograph (GC) analysis was used to measure the short chain fatty acid (SCFA) contents in human fecal samples. The human gut microbiota composition was measured by 16S rRNA gene Illumina MiSeq sequencing (V3-V4 region).ResultsS-3–1 was degraded in three in vitro fermentation models separately and sequentially. Both S-3–1 and incubated S-3–1 could regulate the abundances of Lactobacillus, Pediococcus, Streptococcus, Bacteroides, Enterococcus, Clostridium and Dorea in human intestinal microflora samples. Specifically, S-3–1 could only regulate the abundances of Paraprevotella and Oscillospira, while the influenced flora changed to Butyricimonas, Coprococcus, Dialister, Sutterella, Ruminococcus and Parabacteroides after sequential incubation of S-3–1. In contrast to S-3–1 showing no influence on the content of SCFA, incubated S-3–1 showed increased contents of acetic acid and total acid that were associated with its effects on the abundances of Enterococcus, Sutterella, Butyricimonas and Streptococcus.ConclusionS-3–1 plays an immunomodulatory role by regulating the abundances of 9 intestinal bacteria genera. Incubated S-3–1 can regulate more bacteria genera, a total of 13 kinds, and can adjust the SCFA content to affect immunomodulation. Incubation with gastric and intestinal juices enhanced S-3–1′s capability of modulating the intestinal flora composition and decreased the bacteria's need for a carbon source. This study could provide new insights for studies on the pharmacological mechanisms of polysaccharides in vitro.
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Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Yen-Cheng Chen, Chung-Yi Cheng, Chung-Te Liu, Yuh-Mou Sue, Tso-Hsiao Chen, Yung-Ho Hsu, Pai-An Hwang, Cheng-Hsien Chen
Ethnopharmacological relevanceBrown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism.Materials and methodsThe fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice.ResultsLJE inhibited doxorubicin-induced apoptosis and upregulated Na+/H+ exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice.ConclusionWe demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.
Graphical abstract
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Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: Muscarinic receptor-linked vasorelaxant and cardiotonic effects
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Umme Salma, Taous Khan, Abdul Jabbar Shah
Ethnopharmacological relevanceEruca sativa Mill., (Brassicaceae) is a popular remedy for the treatment of hypertension in Pakistan. However, direct effect of the extract and its fractions on blood pressure and vascular tone are unknown.Aim of the studyThis investigation was aimed to explore the pharmacological base for the traditional use of E. sativa in hypertension.Materials and methodsIn-vivo blood pressure study was carried out using normotensive and high salt-induced hypertensive rats under anaesthesia. The cardiovascular mechanisms were explored using rat aorta and atria in-vitro. Preliminary phytochemical analysis, spectrophotometric detection of total phenols, flavonoids and HPLC analysis of crude extract were performed using quercetin and erucin as marker compounds.ResultsIntravenous injection of crude extract induced a fall in mean arterial pressure (MAP) in both normotensive (max fall: 41.79 ± 1.55% mmHg) and hypertensive (max fall: 58.25 ± 0.91% mmHg) rats. Atropine (1 mg/kg) pretreatment attenuated this effect significantly (p < 0.001), suggesting the involvement of muscarinic receptor in its antihypertensive effect. Fractions also induced atropine-sensitive antihypertensive effect. Similarly, oral administration of crude and aqueous extracts resulted a fall in MAP in the hypertensive rats. In isolated rat aortic rings from normotensive rats, crude extract and fractions induced an endothelium-dependent relaxation. This relaxation was partially inhibited with L-NAME and atropine pretreatment and with denudation of aortic rings, indicating involvement of muscarinic receptor-linked nitric oxide (NO). In aorta from the hypertensive rats, crude extract and fractions induced endothelium-independent relaxation. This relaxation was not affected by pretreatment with L-NAME or atropine. Crude extract and fractions also suppressed phenylephrine contractions in Ca+2 free/EGTA medium. In isolated rat atrial preparations, crude extract and fractions induced negative inotropic and chronotropic effects with a positive inotropic effect by the n-hexane fraction, which were not affected with atropine pretreatment. Phytochemical screening and spectrophotometric analysis indicated the presence of phenols and flavonoids, whereas HPLC analysis of crude extract revealed the presence of quercetin (flavonoid) and erucin (isothiocyanate).ConclusionThe results suggest that E. sativa is an antihypertensive remedy which is mainly due to its vasodilatory and partly cardiac effects. Muscarinic receptors-linked NO release and dual inhibitory effect on Ca+2 influx and release underlie the vasodilation. This finding provides pharmacological base to the traditional use of E. sativa in hypertension. The presence of quercetin and erucin further support this finding.
Graphical abstract
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Ephedra gerardiana aqueous ethanolic extract and fractions attenuate Freund Complete Adjuvant induced arthritis in Sprague Dawley rats by downregulating PGE2, COX2, IL-1β, IL-6, TNF-α, NF-kB and upregulating IL-4 and IL-10
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Ambreen Malik Uttra, Alamgeer, Muhammad Shahzad, Arham Shabbir, Shah Jahan
Ethnopharmacological relevanceThe whole plant, roots and stems of Ephedra gerardiana (Family Ephedraceae) have long been used as a folk remedy to treat rheumatism and painful joints in Northern Areas of Pakistan.Aim of the studyThe purpose of study was to observe the preventive efficacy of Ephedra gerardiana (EG) aerial parts in treating rheumatoid arthritis using Freund's complete adjuvant (FCA) induced arthritis in rat model and to determine its possible mechanism of action.Material and methodsArthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. EG aqueous ethanolic extract (30:70) and its aqueous, n-butanol and ethyl acetate fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) while, PGE2 and TNF-α levels in serum samples were measured by Enzyme linked immunosorbent assay (ELISA). Moreover, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. In addition, anti-oxidant activity of plant extract and fractions was also evaluated using DPPH and reducing power assays. Also, preliminary phytochemistry and total phenolic and flavonoid contents were investigated in most active fraction (aqueous fraction).ResultsEG extract and fractions (notably aqueous fraction) significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, the overproduction of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α were remarkably attenuated in all EG treated rats, however, IL-4 and 10 were markedly increased. The radiographic and histopathologic improvement in joint architecture was also observed in EG treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, tannins, saponins and glycosides.ConclusionThese results indicate that EG extract and fractions significantly attenuated adjuvant arthritis in rats by decreasing the levels of aforementioned pro-inflammatory and increasing the levels of anti-inflammatory mediators. This suggests that Ephedra gerardiana aerial parts might be used as a therapeutic agent for treating human arthritis.
Graphical abstract
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Systematic investigation of the Erigeron breviscapus mechanism for treating cerebrovascular disease
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Jiangmei Wang, Lulu Zhang, Baoshi Liu, Qian Wang, Yangyang Chen, Zhenzhong Wang, Jun Zhou, Wei Xiao, Chunli Zheng, Yonghua Wang
Ethnopharmacological relevanceCerebrovascular diseases (CBVDs), characterized by striking morbidity and mortality, have become the most common life-threatening diseases. The existing drugs of CBVDs target one or a few of pathogenic factors, the efficacy of which is limited because of the complexity of CBVDs. Traditional Chinese medicine (TCM), featured by multi-component and multi-target endows the great effectiveness in CBVDs treatment. For instance, Erigeron breviscapus (vant.) Hand. Mazz. （Erigeron breviscapus) has been used to treat CBVDs for a long time and the efficacy has been verified through years' of practice. Nevertheless, the mechanisms of Erigeron breviscapus for treating CBVDs are still unclear.The aim of the studySystematically decipher the mechanisms of Erigeron breviscapus for treating CBVDs.Materials and methodsThe systems pharmacology approach is utilized by integrating ADME pharmacokinetic screening, target fishing, protein-protein interaction (PPI), network analysis and in vitro experiments verification.ResultsFirst, 14 potentially active molecules were screened out through in silico ADME pharmacokinetic evaluation, most of which have been reported with excellent biological activities. Then 169 targets of active molecules were read out using our in-house softwares, systems drug targeting (sysDT) and Weighted Ensemble Similarity(WES). We found that the targets of the active compounds were significantly enriched to the CBVDs therapeutic targets by analyzing their biological processes and protein-protein interactions (PPIs). A multi-layer network analysis including compound-target network, target-pathway network and "CBVDs pathway" indicated that the Erigeron breviscapus exerts a protective effect on CBVDs via regulating multiple pathways and hitting on multiple targets. Meanwhile in vitro experiments confirmed that the stigmasterol, scutellarein, and daucosterol from Erigeron breviscapus increased the MEK and PLCγ proteins levels, and decreased the expression of Bax, PI3K, and eNOS, which led to the cell survival, proliferation and contraction.ConclusionThe approach used in this work offers a new exemplification for systematically understanding the mechanisms of herbal medicines, which will give an impulse to the CBVDs drug development.
Graphical abstract
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Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout
Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Mayuri Napagoda, Jana Gerstmeier, Hannah Butschek, Sybille Lorenz, Dinusha Kanatiwela, Mallique Qader, Ajith Nagahawatte, Sudhara De Soyza, Gaya Bandara Wijayaratne, Aleš Svatoš, Lalith Jayasinghe, Andreas Koeberle, Oliver Werz
Ethnopharmacological relevanceLeucas zeylanica (L.) W.T. Aiton is a popular, multi-purpose medicinal plant in Sri Lanka but the pharmacological potential and the chemical profile have not been systematically investigated to understand and rationalize the reported ethnobotanical significance.Aim of the studyThe present study was undertaken to scientifically validate the traditional usage of this plant for the treatment of inflammatory conditions, gout and microbial infections. Inhibition of 5-lipoxygenase (5-LO), microsomal prostaglandin E2 synthase (mPGES)−1 and xanthine oxidase (XO) by different extracts of L. zeylanica was investigated to determine the anti-inflammatory and anti-gout activity, respectively. The antibacterial and antifungal activities were also studied and the relevant constituents in the bioactive extracts were tentatively identified.Materials and methodsCell-free and/or cell-based assays were employed in order to investigate the effects of the extracts against the activity of human 5-LO, mPGES-1 and XO as well as to assess antioxidant properties. The antibacterial activity of the extracts was determined by the broth micro-dilution method against Gram positive and Gram negative bacteria including methicillin-resistant Staphylococcus aureus while the agar dilution method was employed to determine the anti-Candida activity. Gas chromatography coupled to mass spectrometric (GC-MS) analysis enabled the characterization of secondary metabolites in the extracts.ResultsThe dichloromethane extract of L. zeylanica efficiently inhibited 5-LO activity in stimulated human neutrophils (IC50 = 5.5 µg/mL) and isolated human 5-LO and mPGES-1 (IC50 = 2.2 and 0.4 µg/mL). Potent inhibition of XO was observed by the same extract (IC50 = 47.5 μg/mL), which is the first report of XO-inhibitory activity of a Sri Lankan medicinal plant. Interestingly, significant radical scavenging activity was not observed by this extract. Only the n-hexane extract exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus saprophyticus with a MIC of 250 µg/mL while the anti-Candida activity was moderate. GC-MS analysis revealed the presence of phytosterols, fatty acids, sesquiterpenes, diterpenes and several other types of secondary metabolites.ConclusionsPotent inhibition of 5-LO, mPGES-1 and XO rationalizes the ethnopharmacological use of L. zeylanica as anti-inflammatory and anti-gout remedy. Interestingly, the antimicrobial activities were not prominent, despite its wide utility as an antimicrobial medication.
Graphical abstract
https://ift.tt/2tIwd3L
Regional Anesthesiology and Acute Pain Medicine in the Era of Value-Based Health Care
Source:Anesthesiology Clinics
Author(s): Edward R. Mariano, Nabil M. Elkassabany
https://ift.tt/2MsG9pK
FDA Approves New Targeted Combo Therapy for Melanoma
Survival advantages are unprecedented, says expert. Encorafenib and binimetinib are a late-stage BRAF and MEK inhibitor combination for metastatic disease.
FDA Approvals
https://ift.tt/2MufXeu
Ketogenic diet for schizophrenia: Nutritional approach to antipsychotic treatment
Publication date: September 2018
Source:Medical Hypotheses, Volume 118
Author(s): Adam Włodarczyk, Mariusz S. Wiglusz, Wiesław Jerzy Cubała
Schizophrenia is a mental disorder that mostly appears in the second or third decade of life with no consistent appearance. The first-line pharmacological treatment are antipsychotic drugs, which mainly act by suppressing the activity of dopamine. Unfortunately many of schizophrenic patients suffer from persistent positive or negative symptoms that cannot be fully treated with available medication. With exploration on the possible causes of the disease there is evidence on dopaminergic transmission defects, there is a need to find more holistic way in treating the disease and a diet regimen could be one of them. Ketogenic diet, which is a popular diet regimen that consists in low-carbohydrate (about 30–50 g/day), medium-protein (up to 1 g/kg daily) and high-fat intake (around 80% of daily calories) mainly known for its helpful role in weight-loss. The key mechanism is to generate ketosis. A state in which ketones bodies in the blood provides energy part of the body's energy comes from ketone bodies in the blood. Possible hypothesis can be that ketogenic diet changes the ratio of GABA:glutamate in favor of GABA, by suppressing the catabolism and increasing the synthesis of GABA as well as glutamate metabolism, which could help to compensate the disrupted GABA levels in schizophrenic brain, leading to possible better outcome of the disease regarding symptomatology and preventing the weight-gain regarding some medications used and the correlating diseases responsible for weight gain.
https://ift.tt/2IBAWKc
Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood
Publication date: September 2018
Source:Medical Hypotheses, Volume 118
Author(s): Martiniano Bello, Concepción Guadarrama-García, Luz M. Velasco-Silveyra, Eunice D. Farfán-García, Marvin A. Soriano-Ursúa
Boron is increasingly added to food supplements due to multiple effects that have been reported in mammals after boric acid administration. Among these effects are inflammatory process control, bone and muscle strength enhancement, protein expression regulation, and a decreased risk of developing some pathologies in which these processes are key, such as osteoporosis, dermatological inflammatory non-infectious maladies and diseases affecting the central nervous system. Experimental data have suggested that steroid hormone levels in plasma change after boric acid administration, but a clear mechanism behind these variations has not been established. We analyzed possibilities for these changes and hypothesized that boric acid disrupts the interactions between steroid hormones and several carriers in plasma. In particular, we proposed that there is an uncoupling of the interactions between sex hormone binding globulin (SHBG) and estrogens and testosterone and that there are alterations in the binding of hydrophobic ligands by other carrier proteins in plasma. Further experimental and computational studies are required to support the hypothesis that boric acid and probably other boron-containing compounds can displace steroid hormones from their plasma carriers. If such phenomena are confirmed, boron administration with a clear mechanism could be employed as a therapeutic agent in several diseases or physiological events that require modulation of steroid hormone levels in plasma.
https://ift.tt/2KdZTAU
Regional Anesthesiology and Acute Pain Medicine in the Era of Value-Based Health Care
Source:Anesthesiology Clinics
Author(s): Edward R. Mariano, Nabil M. Elkassabany
https://ift.tt/2MsG9pK
Travel distance: Impact on stage of presentation and treatment choices in head and neck cancer
The objective was to examine the impact of travel distance on stage of presentation and treatment choices in head and neck squamous cell carcinoma in the rural setting.
https://ift.tt/2lBEClM
Part I: Onychomycosis: Clinical Overview and Diagnosis
Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. In the following continuing medical education manuscript, we review the epidemiology, risk factors, and clinical presentation of onychomycosis and demonstrate current and emerging diagnostic strategies.
https://ift.tt/2tDtys6
Part II: Onychomycosis: Treatment and Prevention of Recurrence
Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, Food and Drug Administration approved medications for onychomycosis, as well as, off-label therapies and devices.
https://ift.tt/2N5GZtO
A comparison of patient satisfaction (using the Breast-Q questionnaire) with bilateral breast reconstruction following risk-reducing or therapeutic mastectomy
Patients undergoing mastectomy and immediate breast reconstruction for cancer may be expected to have different perceptions of long term outcomes compared with those who have this operation prophylactically.
https://ift.tt/2N3qpKU
Effect of local application of transcutaneous carbon dioxide on survival of random pattern skin flaps
Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, these outcomes remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow of skin flaps and increase angiogenesis.
https://ift.tt/2tJFGIe
Response to: Time course of improvement after re-repair procedure for VPI management
I read with interest the paper by Elsherbiny et al.1 I think this adds some important information about the time scale of change and the need for patience. It is unfortunate that the speech assessments were not made blindly and independently (as acknowledged by the authors). However, the improvement with time seems to be impressive.
https://ift.tt/2N1IMzX
Acute skin allergy to thermoplastic mask used for patient immobilization during radiation therapy: a case report
Radiosurgical treatments of brain tumors, vascular malformations, and functional disorders are more and more frequently used. Gamma Knife irradiation with the Icon system necessitates the use of a thermoplasti...
https://ift.tt/2lCFYNd
Successful treatment following early recognition of a case of Fournier’s scrotal gangrene after a perianal abscess debridement: a case report
Fournier's gangrene is an acute surgical emergency characterized by high mortality rates ranging from approximately 13% to 45%. Therefore, aggressive multidisciplinary management is necessary.
https://ift.tt/2yQxBHq
Who are the smokers who never plan to quit and what do they think about the risks of using tobacco products?
Source:Addictive Behaviors, Volume 87
Author(s): Lucy Popova, Ban Majeed, Daniel Owusu, Claire Adams Spears, David L. Ashley
IntroductionSmoking cigarettes is the most harmful way to use tobacco. Smokers who do not plan to quit present a particular challenge in reducing the morbidity and mortality from tobacco use. Switching to a lower harm product might encourage them to end their use of combusted cigarettes. This study aimed to better understand smokers who do not intend to quit (including their demographic and worldviews as indicators of their social, cultural, and political dispositions) and their perceived risks of cigarettes and possible lower-risk products such as e-cigarettes.MethodsParticipants were 2572 current smokers. Data were pooled from 2015 and 2016 cross-sectional surveys of national probability samples of U.S. adults and analyzed with multivariable logistic regressions.ResultsSmokers who never plan to quit comprise 14.3% of current U.S. smokers and are more likely to be older (24.2% among 65+ years old vs. 9.8% among 18–24) and less likely to have ever used e-cigarettes. A one-unit increase in hierarchical worldview (measured on a 1–6 scale) was associated with a 20% increase in the odds of never planning to quit. Those who denied that cigarettes cause disease or death (aORs between 1.6 and 2.0) or were uncertain (aORs: 2.5–2.7) were more likely to never plan to quit compared to those who agreed. They did not view risks of e-cigarettes substantially different compared to smokers who plan to quit.ConclusionOne in seven U.S. smokers never plans to quit and might benefit from interventions which reflect their hierarchical worldviews and increase their risk perceptions of combustible cigarettes.
https://ift.tt/2Mv5yzj
Evaluation of heterogeneous catalytic ozonation process for diclofenac degradation in solutions synthetically prepared
Abstract
Sodium diclofenac (DCF) is a common analgesic and anti-inflammatory drug, which has become an environmental problem due to its growth and accumulation into water bodies. In this work, commercial (with excipients) and analytical (pure) DCF mineralization was studied by means of heterogeneous catalytic ozonation. The process was carried out with magnetite (Fe3O4) as a catalyst, which preserves its physical and chemical properties during the process. The best results of mineralization were obtained after a 40-min treatment of 35 mg/L analytical DCF solution, with a 0.5 g/L catalyst concentration. These results showed the highest organic load decrease, measured as dissolved organic carbon (DOC) and chemical oxygen demand (COD), with 94 and 89%, respectively. In addition, the percentage of organic load decrease was compared between the conventional and the catalyzed process. Besides, reaction products were identified by gas chromatography–mass spectrometry (GC-MS) and the catalytic properties were identified by Mössbauer spectroscopy, which showed the catalyst maintained its nature after the process. Finally, the results obtained show that the heterogeneous catalytic process could be an efficient degradation treatment for emerging contaminants such as DCF.
https://ift.tt/2KqVDgz
Isolating infectious patients: organizational, clinical, and ethical issues
Source:American Journal of Infection Control
Author(s): Dinah J. Gould, Nicholas S. Drey, Jane Chudleigh, Marco-Felipe King, Neil Wigglesworth, Edward Purssell
BackgroundIsolating infectious patients is essential to reduce infection risk. Effectiveness depends on identifying infectious patients, transferring them to suitable accommodations, and maintaining precautions.MethodsOnline study to address identification of infectious patients, transfer, and challenges of maintaining isolation in hospitals in the United Kingdom.ResultsForty-nine responses were obtained. Decision to isolate is made by infection prevention teams, clinicians, and managers. Respondents reported situations where isolation was impossible because of the patient's physical condition or cognitive status. Very sick patients and those with dementia were not thought to tolerate isolation well. Patients were informed about the need for isolation by ward nurses, sometimes with explanations from infection prevention teams. Explanations were often poorly received and comprehended, resulting in complaints. Respondents were aware of ethical dilemmas associated with isolation that is undertaken in the interests of other health service users and society. Organizational failures could delay initaiting isolation. Records were kept of the demand for isolation and/or uptake, but quality was variable.ConclusionIsolation has received the most attention in countries with under-provision of accommodations. Our study characterizes reasons for delays in identifying patients and failures of isolation, which place others at risk and which apply to any organization regardless of availability. It also highlights the ethical dilemmas of enforcing isolation.
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Priors-guided slice-wise adaptive outlier cleaning for arterial spin labeling perfusion MRI
Source:Journal of Neuroscience Methods
Author(s): Yiran Li, Sudipto Dolui, Dan-Feng Xie, Ze Wang
BackgroundDue to the low signal-to-noise-ratio (SNR) and unavoidable head motions, the pairwise subtraction perfusion signal extraction process in arterial spin labeling (ASL) perfusion MRI can produce extreme outliers.Comparison with existing methodsWe previously proposed an adaptive outlier cleaning (AOC) algorithm for ASL MRI. While it performed well even for clinical ASL data, two issues still exist. One is that if the reference is already dominated by noise, outlier cleaning using low correlation with the mean as a rejection criterion will actually reject the less noisy samples but keep the more noisy ones. The other is that it is sub-optimal to reject the entire outlier volumes without considering the quality of each constituent slices. To address both problems, a prior-guided and slice-wise AOC algorithm was proposed in this study.New MethodsThe reference of AOC was initiated to be a pseudo cerebral blood flow (CBF) map based on prior knowledge and outlier rejection was performed at each slice. ASL data from the ADNI database (www.adni-info.org) were used to validate the method. Image preprocessing was performed using ASLtbx.ResultsThe proposed method outperformed the original AOC and SCORE in terms of higher SNR and test-retest stability of the resultant CBF maps.ConclusionASL CBF can be substantially improved using prior-guided and slice-wise outlier rejection. The proposed method will benefit the ever since increasing ASL user community for both clinical and scientific brain research.
https://ift.tt/2Ku6i7j
The effects of exposure to appetitive cues on inhibitory control: A meta-analytic investigation
Publication date: 1 September 2018
Source:Appetite, Volume 128
Author(s): Andrew Jones, Eric Robinson, Jay Duckworth, Inge Kersbergen, Natasha Clarke, Matt Field
Inhibitory control refers to the ability to stop, change or delay a response, and is often used in order to protect higher order goals. Theoretical models suggest that appetitive cues such as pictures of alcoholic drinks or food evoke strong automatic appetitive responses which lead to transient impairments in inhibitory control, and that these effects of cues may be related to individual differences (e.g. in body mass index, or alcohol consumption). In order to investigate these claims we conducted a random effects meta-analysis of 66 effect sizes (35 alcohol, 31 food) from 37 articles that tested the effect of exposure to appetitive (alcohol/food) cues on indices of inhibitory control. The overall effect of cue exposure was small, but robust (SMD = −0.12 [95% CI −0.23, −0.02]; Z = 2.34, p = .02, I2 = 84%). Exposure to alcohol-related cues significantly impaired inhibitory control (SMD = −0.21 [95% CI = −0.32, −0.11]; Z = 4.17, p < .001), however exposure to food-related cues did not lead to impairments (SMD = −0.03 [95% CI = −0.21, 0.15]; Z = 0.36, p = .720). There was no evidence that drinking or weight status significantly moderated the effects of cues on inhibitory control. Similarly, cue modality (words, pictures, or smells) did not significantly moderate the effects. Trim and Fill analysis suggested bias in the literature, which when corrected, made the overall effect of cues non-significant. Overall, these findings provide some tentative support for theoretical claims that exposure to appetitive cues prompts transient impairments in inhibitory control. Further research is required to determine the clinical significance of these observations. However, care should be taken when drawing conclusions from a potentially biased evidence base.
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Breastfeeding experience, challenges and service demands among Chinese mothers: A qualitative study in two cities
Publication date: 1 September 2018
Source:Appetite, Volume 128
Author(s): Yan Zhang, Yi Jin, Carel Vereijken, Bernd Stahl, Hong Jiang
Breastfeeding rates remain low in China despite decades of efforts at improving breastfeeding practices. The study aimed to explore mothers' breastfeeding experience throughout the breastfeeding period and to understand their challenges and support service needs at each stage. Qualitative research methods, individual in-depth interviews and focus group discussions were carried out with mothers and people who played various roles regarding breastfeeding such as service provider, researcher and policy maker. Mothers' breastfeeding practices can be categorized into five stages. In the 'preparatory stage', pregnant women had high intention towards breastfeeding but had inadequate knowledge and skills preparation. In the 'initial stage' in hospital for childbirth, mothers received inadequate support from hospital professionals due to the short hospital stay. In the 'self-exploratory stage' after being discharged from hospital, mothers mostly relied on non-professionals' support. In the 'transitional stage' between four and six months postpartum, most mothers gave up exclusive breastfeeding due to the lack of a supportive environment at workplace. At the 'complementary feeding stage', most mothers stopped breastfeeding and switched to formula between six and 12 months for reasons such as perceived non-nutritious value of breast milk after six months, returning to work, desiring returning to former lifestyle. This study shows that mothers encounter different problems and have specific needs for support at different stages of breastfeeding. Tailored support could be provided to encourage exclusive breastfeeding for the first six months and continued breastfeeding for up to 2 years.
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Neuronal, astroglial and locomotor injuries in subchronic copper intoxicated rats are repaired by curcumin: A possible link with Parkinson’s disease
Source:Acta Histochemica
Author(s): Abdellatif Abbaoui, Halima Gamrani
We aim herein to assess the neurotoxic effects of subchronic Cu-exposition (0125%) for 6 weeks on dopaminergic and astroglial systems then locomotor activity in rats as well as the probable therapeutic efficiency of curcumin-I (30 mg/kg B.W.). We found that intoxicated rats showed a significant impairment of Tyrosine Hydroxylase (TH) within substantia nigra pars compacta (SNc), ventral tegmental area (VTA) and the striatal outputs together with loss expression of GFAP in these structures. This was linked with an evident decrease in locomotor performance. Co-treatment with curcumin-I inverted these damages and exhibited a significant neuroprotective potential, thus, both TH expression and locomotor performance was reinstated in intoxicated rats. These results prove a profound dopaminergic and astroglial damages following subchronic Cu exposition and new beneficial curative potential of curcumin against subchronic Cu-induced astroglial and dopaminergic neurotoxicity. Consequently, we suggest that Cu neurotoxicity may be strengthened in vivo firstly by attacking and weaking the astroglial system, and curcumin could be prized as a powerful and preventive target for the neurodegenerative diseases related metal element, especially Parkinson's disease.
https://ift.tt/2N182X3
Is substance P a nasal epithelial neuropeptide?
Source:Journal of Allergy and Clinical Immunology
Author(s): Steven D. Douglas, Susan E. Leeman
https://ift.tt/2N2KPnv
RNA Sequencing of Carboplatin- and Paclitaxel-Resistant Endometrial Cancer Cells Reveals New Stratification Markers and Molecular Targets for Cancer Treatment
Abstract
Despite advances in surgical technique and adjuvant treatment, endometrial cancer has recently seen an increase in incidence and mortality in the USA. The majority of endometrial cancers can be cured by surgery alone or in combination with adjuvant chemo- or radiotherapy; however, a subset of patients experience recurrence for reasons that remain unclear. Recurrence is associated with chemoresistance to carboplatin and paclitaxel and consequentially, high mortality. Understanding the pathways involved in endometrial cancer chemoresistance is paramount for the identification of biomarkers and novel molecular targets for this disease. Here, we generated the first matched pairs of carboplatin-sensitive/carboplatin-resistant and paclitaxel-sensitive/paclitaxel-resistant endometrial cancer cells and subjected them to bulk RNA sequencing analysis. We found that 45 genes are commonly upregulated in carboplatin- and paclitaxel-resistant cells as compared to controls. Of these, the leukemia inhibitory factor, (LIF), the protein tyrosine phosphatase type IVA, member 3 (PTP4A3), and the transforming growth factor beta 1 (TGFB1) showed a highly significant correlation between expression level and endometrial cancer overall survival (OS) and can stratify the 545 endometrial cancer patients in the TCGA cohort into a high-risk and low-risk-cohorts. Additionally, four genes within the 45 upregulated chemoresistance-associated genes are ADAMTS5, MICAL2, STAT5A, and PTP4A3 codes for proteins for which small-molecule inhibitors already exist. We identified these proteins as molecular targets for chemoresistant endometrial cancer and showed that treatment with their correspondent inhibitors effectively killed otherwise chemoresistant cells. Collectively, these findings underline the utility of matched pair of chemosensitive and chemoresistant cancer cells to identify markers for endometrial cancer risk stratification and to serve as a pharmacogenomics model for identification of alternative chemotherapy approaches for treatment of patients with recurrent disease.
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Clinical and Laboratory Markers of Relapse in Cutaneous Polyarteritis Nodosa
https://ift.tt/2txYNFB
Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib
https://ift.tt/2KpGysm
Cutavirus Infection in Primary Cutaneous B- and T-Cell Lymphoma
https://ift.tt/2N2NbTj
Strengthening the Case for the Role of Thrombophilia in Calciphylaxis
https://ift.tt/2N2MVUl
Decision Tree Model vs Traditional Measures for Associations of Sun-Protective Behaviors
https://ift.tt/2KueqnW
Assessing the Competence of Aging Physicians Who Are Young at Heart
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Understanding and Assessing Nontechnical Skills in Robotic Urological Surgery: A Systematic Review and Synthesis of the Validity Evidence
Source:Journal of Surgical Education
Author(s): Jethro CC Kwong, Jason Y Lee, Mitchell G Goldenberg
OBJECTIVERobotic urological surgery (RUS) has seen widespread adoption across institutions in the last decade. To match this rapid growth, it is imperative to develop a structured RUS curriculum that addresses both technical and nontechnical competencies. Emerging evidence has shown that nontechnical skills form a critical component of RUS training. The purpose of this review is to examine the validity evidence of available nontechnical skills assessment tools in RUS.METHODSA literature search of MEDLINE, EMBASE, and PsycINFO was conducted to identify primary articles using nontechnical skills assessment tools in RUS. Messick's validity framework and the Medical Education Research Study Quality Instrument were utilized to evaluate the quality of the validity evidence of the abstracted articles.RESULTSOf the 566 articles identified, 12 used nontechnical skills assessment tools in RUS. The metrics used ranged from self-assessment using global rating scales, to objective measures such as electroencephalography. The setting of these evaluations ranged from immersive and virtual reality-based simulators to live surgery.CONCLUSIONSLimited effort has been made to develop nontechnical skills assessment tools in RUS. Recently, there has been a shift from subjective to objective measures of nontechnical performance, as well asthe development of assessments specific to RUS. However, the validity evidence supporting these nontechnical assessments is limited at this time, including their relationship to technical skills, and their impact on surgical outcomes.
https://ift.tt/2yNBxsx
Properties and effects of organic additives on performance and emission characteristics of diesel engine: a comprehensive review
Abstract
Fast depletion of conventional automobile fuels and environmental pollution due to exhaust emission are the issues of great importance. Improvement in engine performance and emission control is quite difficult to handle simultaneously. The fuel properties can be improved substantially by incorporation of additives in different proportions to get better emission standard without deteriorating the engine performance. The aim of current study is to review/summarize the effects of various organic additives on the engine performance (i.e., brake thermal efficiency, brake specific fuel consumption, volumetric efficiency, etc.) and emissions (i.e., carbon dioxide, carbon monoxide, nitrogen oxides, hydrocarbons, particulate matter, and other harmful compounds). The physico-chemical and combustion properties (i.e., density, latent heat, dynamic viscosity, flash point, boiling point, cetane number, oxygen content, lower heating value, auto-ignition temperature, etc.) of various additives were also discussed to check the suitability of additives with diesel. Finally, limitations and opportunities using organic additives with respect to engine performance and combustion were discussed to guide future research and improvement in this field.
https://ift.tt/2KfF1JB
Measles control in Australia – threats, opportunities and future needs
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): C. Raina MacIntyre, Elizabeth Kpozehouen, Mohana Kunasekaran, Kathleen Harriman, Stephen Conaty, Alexander Rosewell, Julian Druce, Nicolee Martin, Anita E. Heywood, Heather F. Gidding, James Wood, Sonya Nicholl
Control of measles was the focus of a national workshop held in 2015 in Sydney, Australia, bringing together stakeholders in disease control and immunisation to discuss maintaining Australia's measles elimination status in the context of regional and global measles control.The global epidemiology of measles was reviewed, including outbreaks in countries that have achieved elimination, such as the Disneyland outbreak in the United States and large outbreaks in Sydney, Australia. Transmission of measles between Australia and New Zealand occurs, but has not been a focus of control measures. Risk groups, the genetic and seroepidemiology of measles as well as surveillance, modelling and waning vaccine-induced immunity were reviewed. Gaps in policy, research and practice for maintaining measles elimination status in Australia were identified and recommendations were developed.Elimination of measles globally is challenging because of the infectiousness of measles and the need for 2-dose vaccine coverage rates in excess of 95% in all countries to achieve it. Until this occurs, international travel will continue to permit measles importation from endemic countries to countries that have achieved elimination. When measles cases are imported, failure to diagnose and isolate cases places the health system at risk of measles outbreaks. Vaccine funding models can result in gaps in vaccine coverage for adults and migrants. Australia introduced a whole-of-life immunisation register in 2016 and catch-up vaccination for at-risk communities, which will improve measles control. Research on diagnosis, immunology, case management and modelling of vaccination strategies are important to ensure continued control of measles.
https://ift.tt/2yKdJWw
Receipt of other routinely recommended vaccines relative to receipt of seasonal influenza vaccines: Trends from medicare administrative data, 2013–2015
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Angela K. Shen, Rob Warnock, Steve Chu, Jeffrey A. Kelman
Annual influenza vaccination campaigns emphasize the importance of getting vaccinated against influenza. These campaigns offer potential opportunities to raise awareness of all vaccines. We explored the peak timing of the receipt of influenza and other routinely recommended vaccinations.We examined administrative claims data of 31 million Medicare fee-for-service beneficiaries, eligible to receive vaccinations administered from 2013 to 2015 from Medicare Part B (medical insurance) and Medicare Part D (prescription drug benefit).From 2013 to 2015, 88% of over 50 million influenza vaccination claims occurred in September, October, and November. Claims for pneumococcal (42%), herpes zoster (36%), and tetanus-containing (32%) vaccines were also concentrated during these months. For pneumococcal vaccines, this concentration occurred across various provider settings, including traditional doctor's offices, pharmacies, and hospitals. Herpes zoster (92%) and tetanus-containing (72%) vaccines were largely administered in the pharmacy.Annual influenza vaccination efforts offer additional opportunities to assess, recommend, and administer other recommended vaccinations.
https://ift.tt/2lBD4Z9
Increased leaching and addition of amendments improve the properties of seawater-neutralized bauxite residue as a growth medium
Abstract
Laboratory and greenhouse experiments were carried out to investigate the chemical, physical, and microbial properties of seawater-neutralized bauxite residues and the effects of additional leaching (1 pore volume of deionized water versus an additional 6 pore volumes) and amendment with gypsum (5%) and/or cattle manure (6%) on its properties and on the growth of Rhodes grass (Chloris gayana). Additional leaching resulted in a decrease in EC, exchangeable Na, SAR, and ESP. For unamended control treatments, additional leaching induced a rise in pHSE from 8.5 to 9.6 and pH1:5 from 9.1 to 10.1 due to dissolution of residual alkalinity. Addition of gypsum arrested this pH increase resulting in a final pHSE of 7.5 and pH1:5 of 8.8. In control treatments, additional leaching resulted in a pronounced decrease in Rhodes grass yields. However, in gypsum and cattle manure-amended treatments, it led to substantial yield increases and decreases in tissue Al and Na concentrations and increased K/Na ratios. Upon drying for the first time, bauxite residue was shown to contract and form a solid massive structure. The aggregates formed from crushing this material were water stable (as measured by wet sieving). Additions of cattle manure or gypsum to residue aggregates did not affect pore size distribution. Addition of cattle manure increased organic C and microbial biomass C content and basal respiration rate while additional leaching increased basal respiration and metabolic quotient. It was concluded that a combination of drying and crushing the residue, amending it with gypsum and organic manure followed by extensive leaching results in the formation of a medium that supports plant growth.
https://ift.tt/2MoWEDl
The health economics of cholera: A systematic review
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Amber Hsiao, Angela H. Hall, Vittal Mogasale, Wilm Quentin
BackgroundVibrio cholera is a major contributor of diarrheal illness that causes significant morbidity and mortality globally. While there is literature on the health economics of diarrheal illnesses more generally, few studies have quantified the cost-of-illness and cost-effectiveness of cholera-specific prevention and control interventions. The present systematic review provides a comprehensive overview of the literature specific to cholera as it pertains to key health economic measures.MethodsA systematic review was performed with no date restrictions up through February 2017 in PubMed, Econlit, Embase, Web of Science, and Cochrane Review to identify relevant health economics of cholera literature. After removing duplicates, a total of 1993 studies were screened and coded independently by two reviewers, resulting in 22 relevant studies. Data on population, methods, and results (cost-of-illness and cost-effectiveness of vaccination) were compared by country/region. All costs were adjusted to 2017 USD for comparability.ResultsCosts per cholera case were found to be rather low: <$100 per case in most settings, even when costs incurred by patients/families and lost productivity are considered. When wider socioeconomic costs are included, estimated costs are >$1000/case. There is adequate evidence to support the economic value of vaccination for the prevention and control of cholera when vaccination is targeted at high-incidence populations and/or areas with high case fatality rates due to cholera. When herd immunity is considered, vaccination also becomes a cost-effective option for the general population and is comparable in cost-effectiveness to other routine immunizations.ConclusionsCholera vaccination is a viable short-to-medium term option, especially as the upfront costs of building water, sanitation, and hygiene (WASH) infrastructure are considerably higher for countries that face a significant burden of cholera. While WASH may be the more cost-effective solution in the long-term when implemented properly, cholera vaccination can still be a feasible, cost-effective strategy.
https://ift.tt/2tIPIJA
Breaking the inertia in coverage: Mainstreaming under-utilized immunization strategies in the Middle East and North Africa region
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Nahad Sadr-Azodi, Denise DeRoeck, Kamel Senouci
Vaccination coverage rates have stagnated in the past several years in many middle-income countries (MICs), especially in the UNICEF Middle East and North Africa region, with political and economic turmoil as contributing factors. This paper reviews country experiences with three under-utilized strategies aimed at increasing vaccination coverage and reducing disparities between socio-economic and geographic groups in MICs. These strategies include: (1) identifying and accounting for displaced, mobile and neglected populations; (2) assessing and addressing missed opportunities for vaccination, including by expanding immunization into the second year of life and beyond; and (3) engaging effectively with the private/nongovernmental health providers in the coordination, provision and reporting of immunization services. The examples focus primarily on quality data collection, analysis, use and reporting aspects of the strategies. While data are limited, there is evidence from MICs that each of these strategies can have a positive impact on vaccination coverage, especially among marginalized populations.
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Chiral triazole fungicide tebuconazole: enantioselective bioaccumulation, bioactivity, acute toxicity, and dissipation in soils
Abstract
Enantioselectivity in environmental behavior and toxic effect of chiral pesticides has been received much attention. In this study, enantioselective bioactivity towards target organism Botrytis cinerea, acute toxicity and bioaccumulation in Eisenia fetida, and degradation in five kinds of soil under laboratory conditions regarding triazole fungicide tebuconazole were investigated. The results showed that fungicidal activity to Botrytis cinerea of R-(−)-tebuconazole was 44 times higher than S-(+)-tebuconazole with an order of R-(−)-tebuconazole > rac-tebuconazole > S-(+)-tebuconazole. No significant difference was found in acute toxicity of rac-, R-, and S-tebuconazole to E. fetida with 48-h EC50 of 10.78, 10.48, and 10.84 μg/cm2, respectively. Dissipation of tebuconazole in the five tested soils varied upon soil characteristics with half-life ranging from 32.2 to 216.6 days. Enantioselective and rapid dissipation of tebuconazole were observed in soils Hainan and Huajiachi, compared to the other soils. Enantioselective accumulation of tebuconazole in E. fetida was found with a preferential of S-(+)-tebuconazole although no significant difference in acute toxicity to E. fetida between rac-tebuconazole and enantiomers. The results indicated that S-(+)-tebuconazole with less fungicidal activity may be more likely to be accumulated in earthworm E. fetida. This research is helpful to better evaluate the environmental and ecological risk of tebuconazole on enantiomeric level.
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The influence of the intestinal microbiome on vaccine responses
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Petra Zimmermann, Nigel Curtis
There is substantial variation between individuals in the immune response to vaccinations. The intestinal microbiome plays a crucial rule in the development and regulation of the immune system and therefore its composition might affect how individuals respond to vaccinations. In this review, we summarise studies that investigated the influence of the intestinal microbiome on humoral and cellular vaccine responses.To date, only four studies (three in infants and one in adults) have investigated the influence of the intestinal microbiome on vaccine responses. All found an association between the intestinal microbiome and vaccine responses. Despite the heterogeneity in study designs (including different vaccines, schedules, timing of collection of stool and blood samples, analysis methods and reporting of results on different taxonomic levels), findings across studies were consistent: a higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses.Further, well-designed, adequately powered studies using whole-genome sequencing (to include the influence of viruses, fungi and parasites) are needed to investigate in more detail the influence of the intestinal microbiome on vaccine responses. This will help identify strategies to improve vaccine efficacy and duration of protection, particularly in infancy when the intestinal microbiome is more amenable to external influences and plays an important role in the development of the immune system.
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Editorial Board/Aims and Scope
Source:Vaccine, Volume 36, Issue 30
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Burden of clinical infections due to S. pneumoniae during Hajj: A systematic review
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Amani S. Alqahtani, Mohamed Tashani, Iman Ridda, Amgad Gamil, Robert Booy, Harunor Rashid
The burden of pneumococcal disease at Hajj has not been precisely evaluated through a systematic review. To this end we have conducted a systematic review on the burden of clinical infections due to Streptococcus pneumoniae among Hajj pilgrims.Major electronic databases including OVID Medline, Web of Science, OVID Embase, Social Sciences Citation Index, Google Scholar and relevant websites (e.g., online Saudi Epidemiology Bulletin) were searched by using MeSH terms and text words containing but not limited to 'Hajj', pneumonia and S. pneumoniae. This was buttressed by hand searching of reference lists of identified studies.Of 21 full text papers reviewed, nine articles were included in this review. Seven studies reported the burden of pneumococcal pneumonia and the other two reported the burden of invasive pneumococcal diseases including meningitis and sepsis. The proportion of pneumonia that was pneumococcal ranged from 1% to 54% of bacteriologically confirmed pneumonias. The pneumococcus accounted for 2/3rd of bacteriologically diagnosed meningitis cases, and 1/3rd of confirmed cases of sepsis. Case fatality rate of pneumococcal pneumonia was recorded in only two studies: 33.3% and 50%. Only one study provided data on antimicrobial susceptibility of S. pneumoniae isolates, reporting 33.3% to be penicillin resistant. None of the included studies provided data on serotype distribution of S. pneumoniae.This systematic review highlights the significance of pneumococcal disease during Hajj, and demonstrates paucity of data on its burden particularly on disease-causing serotype.
https://ift.tt/2tCEJRQ
Correlations of indoleamine 2,3-dioxygenase, interferon-λ3, and anti-HBs antibodies in hemodialysis patients
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Alicja E. Grzegorzewska, Hanna Winnicka, Wojciech Warchoł, Adrianna Mostowska, Paweł P. Jagodziński
BackgroundIndoleamine 2,3-dioxygenase (IDO) contributes to maintaining immune homeostasis. Polymorphisms (SNPs) of the IDO encoding gene (IDO1) influence the IDO activity. Interferon (IFN)-λ3 induces IDO expression. We aimed to investigate whether IDO1 variants are associated with anti-HBs production in response to HBV vaccination or infection, interact with IFN-λ3 associated variants of IFNL4, and influence survival of hemodialysis (HD) patients. We also tested circulating IDO concerning IDO1 SNPs and plasma IFN-λ3 and anti-HBs levels.MethodsThe study included HD patients who had established status concerning responsiveness to HBV vaccination (n = 1022) or were exposed to HBV (n = 315). Ability to generate anti-HBs was diagnosed if anti-HBs after vaccination or infection exceeded 10 IU/L. Genotyping of IDO1 (rs3739319 A < G, rs9657182 C < T), IFNL4 rs8099917 G < T and IFNL4 rs12979860 C > T polymorphisms was carried out by high-resolution melting curve analysis. Circulating IDO and IFN-λ3 were measured with ELISA in 57 subjects. Survival probability was analyzed using the Kaplan-Meier method.ResultsIDO1 SNPs did not correlate with the ability to produce anti-HBs after vaccination or infection. Anti-HBs titers, including a frequency of anti-HBs ≥ 1000 IU/l, also did not associate with IDO1 SNPs, but there was an epistatic interaction between rs9657182, rs8099917, and rs12979860 concerning anti-HBs titers (P = 0.028). Significant associations between IDO1 SNPs and circulating IDO were not demonstrated. Anti-HBs titers negatively correlated with plasma IDO (r = −0.358, P = 0.006), and positively with circulating IFN-λ3 (r = 0.498, P = 0.00008). IDO and IFN-λ3 did not correlate. Patients possessing the rs9657182 TT genotype showed higher infection-related mortality, also in multivariate analysis (HR 2.073, 1.221–3.518, P = 0.007).ConclusionsIDO1 rs9657182, IFNL4 rs8099917, and IFNL4 rs12979860 show epistatic interaction concerning anti-HBs titers. Overreacting immune responses to HBsAg occur in patients with lower IDO but simultaneously higher IFN-λ3 levels. The rs9657182 TT genotype associates with infection-related mortality of HD patients.
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Control of mycobacteriosis in zebrafish (Danio rerio) mucosally vaccinated with heat-inactivated Mycobacterium bovis
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): María Angeles Risalde, Vladimir López, Marinela Contreras, Lourdes Mateos-Hernández, Christian Gortázar, José de la Fuente
BackgroundMycobacterial infections greatly affect human and animal health worldwide, and vaccines are effective, sustainable and economic interventions for the prevention and control of these infectious diseases. Recent results support the use of zebrafish as a model for studying the pathophysiology of mycobacterial infection and for the development of novel interventions for tuberculosis (TB) control. Recently, we showed that oral immunization with the heat-inactivated M. bovis vaccine (M. bovis IV) protect wild boar against TB, and suggested that this vaccine may controls mycobacterial infection in other species.MethodsIn this study we evaluated the effect of M. bovis IV on the control of mycobacteriosis in zebrafish mucosally vaccinated by immersion and challenged intraperitoneally with Mycobacterium marinum.ResultsThe results showed that the M. bovis IV administered by immersion protected zebrafish against mycobacteriosis caused by M. marinum by reduction in mycobacterial infection, the number of mycobacteria per granuloma and the number of granulomas per fish. An IgM antibody response against M. bovis antigens was developed in vaccinated fish. Evidences suggested that the protective mechanism elicited by mucosal vaccination with M. bovis IV in zebrafish was based on the activation of the innate immune response through the C3 pathway.ConclusionsThese results support the use of the M. bovis IV administered by immersion for the control of mycobacteriosis in fish.
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Adenovirus based HPV L2 vaccine induces broad cross-reactive humoral immune responses
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Marija Vujadinovic, Selina Khan, Koen Oosterhuis, Taco G. Uil, Kerstin Wunderlich, Sarra Damman, Satish Boedhoe, Annemiek Verwilligen, Jonathan Knibbe, Jan Serroyen, Hanneke Schuitemaker, Roland Zahn, Gert Scheper, Jerome Custers, Jort Vellinga
Oncogenic high-risk human papillomavirus (HPV) infections cause a substantial number of genital and non-genital cancers worldwide. Approximately 70% of all cervical cancers are caused by the high-risk HPV16 and 18 types. The remaining 30% can be attributed to twelve other high-risk HPV-types. Highly efficacious 2-valent, 4-valent and 9-valent L1 protein based prophylactic HPV vaccines are available however with limited cross-protection. To further increase the coverage, development of a multivalent cross-protective HPV vaccine is currently focused on the conserved N-terminus of HPV's L2 protein. We have developed a vaccine candidate based on the rare human adenovirus type 35 (HAdV35) vector that displays a concatemer of L2 protein epitopes from four different HPV-types via protein IX (pIX). A mix of two heterologous HAdV35 pIX-L2 display vectors present highly conserved linear epitopes of nine HPV-types. Each HAdV35 pIX-L2 display vector exhibits a good manufacturability profile. HAdV35 pIX-L2 display vaccine vectors were immunogenic and induced neutralizing antibodies against HPV-types included in the vaccine and cross-neutralizing antibodies against distant a HPV-type not included in the vaccine in mice. The HAdV35 pIX-L2 display vectors offer an opportunity for a multivalent HAdV-based prophylactic HPV vaccine.
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Enhancement of Ag85B DNA vaccine immunogenicity against tuberculosis by dissolving microneedles in mice
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Qinying Yan, Zhigang Cheng, Houming Liu, Wanshui Shan, Zhide Cheng, Xuyong Dai, Yun Xue, Fan Chen
Tuberculosis (TB) remains a major global public health problem. New immunization methods against TB are urgently needed. Plasmid DNA with a microneedle patch is a potentially attractive strategy to improve the immune effect. A DNA vaccine encoding the secreted protein Ag85B of Mycobacterium tuberculosis was immunized in the skin using microneedles, which can improve protective immunity compared to conventional intramuscular (IM) injection. There is no significant difference between microneedle patch (MNP) and IM immunization when the immunizing dose is low (4.2 μg). However, the results for detecting humoral immunity showed MNP immunization could better provoke an antibody response than IM when the dose is high (12.6 μg). A similar result was observed in cellular immune responses by measuring the cytokines in splenocytes. The effective protection of MNP can also be demonstrated by counting bacteria and analyzing the survival rate. This study indicated that DNA vaccination in the skin using dissolving microneedles may provide a new strategy against TB.
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Evaluation of carbopol as an adjuvant on the effectiveness of progressive atrophic rhinitis vaccine
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Jiansong Zhang, Meifen Wang, Nini Zhou, Yijuan Shen, Yufeng Li
The Gram-negative pathogen toxigenic P. multocida causes progressive atrophic rhinitis (PAR) in swine throughout the world. Although some vaccines are being developed against PAR, their efficacy has not been evaluated using carbopol. In our study, a mixture of killed B. bronchiseptica and P. multocida bacteria, combined with recombinant proteins containing the C- and N-termini of PMT, was emulsified using two different adjuvants (ISA-15A and carbopol 971). The efficacy of these two vaccines was evaluated in a mouse model. Balb/C mice were immunized twice at a 14-day interval. Two weeks after the secondary immunization, blood samples were collected and the mice were challenged with toxigenic P. multocida. Thirty-five days later, the mice were euthanized, blood and tissue samples were collected. Compared with mice inoculated with vaccine emulsified with ISA-15A, higher titers of SN (1:64) and significantly increased levels of TNF-α, IL-6 and IL-17A were observed in mice inoculated with vaccine emulsified with the carbopol 971P. Especially, mice immunized with vaccine emulsified with the carbopol 971P had no detectable pathological changes in snouts or organs after challenge. The results demonstrated that carbopol adjuvanted vaccine provides good protection against PAR and P. multocida infection which can induce robust humoral and cell-mediated responses. We conclude that the carbopol adjuvanted vaccine is a good candidate for PAR prevention.
https://ift.tt/2lBFXJx
A novel serological assay for influenza based on DiD fluorescence dequenching that is free from observer bias and potentially automatable – A proof of concept study
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Alexander I. Makarkov, Aakash R. Patel, Valentine Bainov, Brian J. Ward
BackgroundSerum hemagglutination inhibition (HAI) and microneutralization (MN) antibodies are often used as a correlate of protection for influenza. However, these manual assays are labor-intensive and difficult to standardize due to variability in biologic reagents used and subjective interpretation of the results.MethodsSera with known HAI and MN titers were used to assess a novel test based on the inhibition of fluorescence 'dequenching'. Whole influenza virions (A/California/07/2009 (H1N1), A/Hong Kong/4801/2014 (H3N2) and B/Brisbane/60/2008) labelled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate (DiD) were exposed to serial dilutions of serum and mixed with turkey red blood cells followed by acidification of the media (pH 5.0–5.5). The H1N1 and B/Brisbane strains were high hemagglutinating while the H3N2 strain had low hemagglutinating activity. In some experiments, labelled virions were subjected to repetitive freeze-thaw cycles prior to use in the assay.ResultsIn the absence of detectable HAI/MN antibodies, there were consistent and substantial increases from baseline DiD fluorescence upon acidification. Sera with known high titer HAI/MN antibodies reduced or completely prevented DiD dequenching at low dilutions with progressive increases in fluorescence at higher dilutions, which permitted a reproducible assignment of an antibody 'titer' based on baseline and acidified DiD fluorescence values. The 'titers' measured by the DiD dequenching assay were highly correlated with HAI/MN results for the H1N1 and B strains (Spearman's correlation coefficients (rs) 0.874 to 0.946, p < 10−7 to 10−35). Correlations with HAI/MN titres for the low-hemagglutinating H3N2 strain tested were lower but remained statistically significant (rs 0.547–0.551, p < 0.004). Freeze-thawing of the DiD pre-stained virus stocks had no significant impact on the results of the assay.ConclusionsThe DiD dequenching assay may be a labour-saving and more objective alternative to the classic serologies. This novel assay could theoretically be standardized across laboratories using pre-stained virions and has the potential to be fully automated.
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Comparative analysis of adaptive immune responses following experimental infections of cattle with bovine viral diarrhoea virus-1 and an Asiatic atypical ruminant pestivirus
Publication date: 16 July 2018
Source:Vaccine, Volume 36, Issue 30
Author(s): Victor Riitho, Magdalena Larska, Rebecca Strong, S. Anna La Rocca, Nicolas Locker, Stefan Alenius, Falko Steinbach, Lihong Liu, Åse Uttenthal, Simon P. Graham
Atypical ruminant pestiviruses are closely related to the two bovine viral diarrhoea virus (BVDV) species, BVDV-1 and BVDV-2. While there is evidence of cross-protective immune responses between BVDV-1 and BVDV-2, despite antigenic differences, there is little information on the antigenic cross-reactivity with atypical ruminant pestiviruses. The aim of this study was therefore to assess the specificity of antibody and T cell responses induced by experimental infection of calves with BVDV-1 strain Ho916, Th/04_KhonKaen (TKK), an Asiatic atypical ruminant pestivirus, or co-infection with both viruses. Homologous virus neutralization was observed in sera from both single virus infected and co-infected groups, while cross-neutralization was only observed in the TKK infected group. T cell IFN-γ responses to both viruses were observed in the TKK infected animals, whereas Ho916 infected calves responded better to homologous virus. Specifically, IFN-γ responses to viral non-structural protein, NS3, were observed in all infected groups while responses to viral glycoprotein, E2, were virus-specific. Broader antigen-specific cytokine responses were observed with similar trends between inoculation groups and virus species. The limited T cell and antibody immune reactivity of Ho916 inoculated animals to TKK suggests that animals vaccinated with current BVDV-1-based vaccines may not be protected against atypical ruminant pestiviruses.
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