Never make your home in a place. Make a home for yourself inside your own head. You'll find what you need to furnish it - memory, friends you can trust, love of learning, and other such things. That way it will go with you wherever you journey. Serrattia marcensus & corynebacterium used to ma...
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 13 Δεκεμβρίου 2015
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TWiV 367: Two sides to a Coyne
Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove,
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Interleukin-2 receptor antagonist immunosuppression and consecutive viral management in living-donor liver transplantation for human immunodeficiency virus/hepatitis C-co-infected patients: a report of 2 cases
Abstract
Management of immunosuppression for human immunodeficiency virus/hepatitis C (HIV/HCV) in living-donor liver transplantation (LDLT) has not been established. We performed LDLT for two patients with HIV/HCV-co-infected end-stage liver disease. The immunosuppression protocol consisted of early calcineurin inhibitor-free and interleukin-2 receptor antagonist (IL2Ra) induction and methylprednisolone. Maintenance low-dose tacrolimus was started and anti-retroviral therapy for HIV was re-started 1 week after LDLT. Consecutively, pegylated interferon and ribavirin therapy were successfully added as pre-emptive therapy for HCV. HIV-RNA and HCV-RNA were undetectable on anti-retroviral therapy and HCV treatment at 17 and 8 months after LDLT, respectively, with normal liver function. This study is the first report of early calcineurin inhibitor-free and IL2Ra induction with methylprednisolone immunosuppression in LDLT for HIV/HCV-co-infected patients with a favorable outcome. Consecutive HIV/HCV treatment was well tolerated.
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Vocal Fold Augmentation with Beta Glucan Hydrogel Cross-Linked by γ Irradiation for Enhanced Duration of Effect: In Vivo Animal Study
This study explored a novel strategy to restore the vocal gap by using cross-linked β-glucan hydrogel by γ-irradiation. An aqueous solution of 5 wt% β-glucan was prepared and cross-linked using 60Co γ irradiation. Ten nude mice were injected with 0.8 mL of irradiated β-glucan on the left back and the same volume of nonirradiated β-glucan on the right back for comparison. The mice were sacrificed at 1 and 2 weeks after injection and histological evaluations were performed. Irradiated β-glucan demonstrated a significantly larger volume than nonirradiated β-glucan in the back of nude mice with less inflammatory reaction. After unilateral recurrent laryngeal nerve section in New Zealand White rabbits, irradiated and nonirradiated β-glucan were injected into paralyzed vocal folds. Irradiated β-glucan remained at the paralyzed vocal fold without definite inflammatory signs on endoscopy. High-speed recordings of vocal fold vibration showed decreased vocal gap in irradiated group compared to nonirradiated group. Histologically, the laryngeal epithelium and lamina propria remained intact, without inflammatory cell infiltration. Our newly developed injection material, irradiated β-glucan, showed excellent biocompatibility and remained longer than nonirradiated β-glucan in vivo, suggesting irradiated hydrogels as a new therapeutic approach that may be useful for the long-term treatment of vocal fold palsy.
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Qingyihuaji Formula Inhibits Pancreatic Cancer and Prolongs Survival by Downregulating Hes-1 and Hey-1
The dire prognosis of pancreatic cancer has not markedly improved during past decades. The present study was carried out to explore the effect of Qingyihuaji formula (QYHJ) on inhibiting pancreatic cancer and prolonging survival in related Notch signaling pathway. Proliferation of pancreatic cancer cells (SW1990 and PANC-1) was detected by MTT assay at 24, 48, and 72 h with exposure to various concentrations (0.08–50 mg/mL) of QYHJ water extract. Pancreatic tumor models of nude mice were divided into three groups randomly (control, QYHJ, and gemcitabine). mRNA and protein expression of Notch target genes (Hes-1, Hey-1, Hey-2, and Hey-L) in dissected tumor tissue were detected. Results showed that proliferation of SW1990 cells and PANC-1 cells was inhibited by QYHJ water extract in a dose-dependent and time-dependent manner. QYHJ effectively inhibited tumor growth and prolonged survival time in nude mice. Expression of both Hes-1 and Hey-1 was decreased significantly in QYHJ group, suggesting that Hes-1 and Hey-1 in Notch signaling pathway might be potential targets for QYHJ treatment. This research could help explain the clinical effectiveness of QYHJ and may provide advanced pancreatic cancer patients with a new therapeutic option.
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Trichodysplasia spinulosa: a polyomavirus infection specifically targeting follicular keratinocytes in immunocompromised patients
Abstract
Trichodysplasia spinulosa (TS) is a rare skin disease occurring in immunocompromised patients, caused by a specific polyomavirus. Pathophysiological mechanisms of TS are not yet fully understood. We report evidence of follicular keratinocytes being the primary target of trichodysplasia spinulosa-associated polyomavirus (TSPyV) by PCR and skin biopsy immunostaining in a pædiatric case.
This article is protected by copyright. All rights reserved.
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Prognostic relevance of LDH and serum S-100 levels in Stage IV melanoma with known BRAF mutation status
Abstract
Background
Activating mutations of the BRAF-gene provide an important treatment target in melanoma patients. However, prognostic role of several biochemical markers in relation to the mutation status is not clear yet.
Objectives
Prognostic significance of BRAF mutation in melanoma patients was analyzed and correlated to different additional markers.
Patients and Methods
162 melanoma stage IV patients with known BRAF-mutation status were included. Clinical, histopathological and laboratory information was collected and compared between BRAF-mutant (BRAFm) and wildtype (BRAFwt) melanoma patients at time of first distant metastasis.
Results
88 patients (54.3%) were BRAFm (V600E or K). At first distant metastasis S100B levels in BRAFm patients were more frequently elevated and significantly higher (p = 0.013 resp. p = 0.021). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared to patients with elevated S100B levels (p < 0.001). However, in BRAFm melanoma, elevated S100B levels showed no prognostic influence (p = 0.18). Elevated LDH levels had a significant negative impact on mOS in both BRAFm and BRAFwt groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared to BRAFm patients without BRAFi treatment (p = 0.012). However, no difference in mOS between BRAFm patients without BRAFi treatment and BRAFwt patients was observed.
Conclusions
The analysis confirms the better mOS in BRAFm patients treated with BRAFi. Interestingly, BRAFm patients not treated with BRAFi show similar survival curves as BRAFwt patients. Additionally, elevated LDH is a BRAF-independent prognostic parameter in all patients, whereas S100B has prognostic significance in BRAFwt patients only.
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Photodynamic therapy with 80 mg/g methyl aminolaevulinate for severe facial acne vulgaris: a randomised vehicle-controlled study
Abstract
Background
Severe acne vulgaris has limited therapeutic options.
Objectives
To evaluate photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL, 80 mg/g) as the photosensitiser in severe facial acne
Methods
Double-blind, randomised, vehicle-controlled multicentre trial in 153 patients (12-35 years) with severe facial acne (Investigator Global Assessment [IGA] score 4; 25-75 inflammatory lesions with ≤3 nodules; 20–100 non-inflammatory lesions). Treatment (4 treatments 2 weeks apart) involved incubation with MAL (n=100) or vehicle cream (n=53) 1.5 hours under occlusion, then illumination (635 nm red light, total dose 37 J/cm2). IGA assessment and standardised lesion counts were performed before each treatment and 12 weeks after first treatment. Treatment success was defined as improvement from baseline in IGA by ≥2 grades at 12 weeks. Safety assessments were pain (10 cm visual analogue scale [VAS], immediately after illumination), erythema (four-point rating scale) and adverse events.
Results
At 12 weeks, PDT using 80 mg/g MAL reduced inflammatory lesions versus vehicle PDT (mean change -15.6 vs. -7.8, p=0.006; mean percent change -37.3% vs. –16.2%, p=0.003). Although non-inflammatory lesions did not decrease significantly (mean change –11.8 vs. -10.7, p=0.85; mean percent change -28.6% vs. -24.9%, p=0.72). Treatment success rates were greater with 80 mg/g MAL PDT (44% vs. 26%, p=0.013). Pain was low and manageable by briefly pausing illumination. There was similar pain or erythema with successive treatments.
Conclusions
PDT using topical 80 mg/g MAL and red light may offer promise for severe acne vulgaris.
[ClinicalTrials. gov Identifier NCT01347879; registered May 3, 2011].
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How to Clear Snow Without Getting Hurt
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DNA methylation markers for oral pre-cancer progression: A critical review
Publication date: Available online 12 December 2015
Source:Oral Oncology
Author(s): Krithiga Shridhar, Gagandeep Kaur Walia, Aastha Aggarwal, Smriti Gulati, A.V. Geetha, Dorairaj Prabhakaran, Preet K. Dhillon, Preetha Rajaraman
Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control (n=15), DNA-repair (n=7), cell-cycle-signalling (n=4) and apoptosis (n=3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57–63.6% versus 8–32.1%; p<0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci (TRHDE; ZNF454; KCNAB3). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression.
Graphical abstract
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Survivin, cyclin d1 and p21hras in keratocystic odontogenic tumors before and after decompression
Abstract
Objectives
The aim of this study was to investigate survivin, cyclin D1, and p21hras expression in keratocystic odontogenic tumors before and after decompression, as well as in pericoronal follicles. A potential correlation between the expression levels of these proteins was also investigated.
Materials and methods
We analyzed eighteen keratocystic tumors treated by decompression and subsequent enucleation along with seven pericoronal follicles using immunohistochemistry.
Results
Keratocystic tumors samples, both before and after decompression, were positive for each of the investigated proteins. In pericoronal follicles, survivin exhibited cytoplasmic staining in contrast to nuclear staining in keratocystic tumors. Cyclin D1 expression was negative in pericoronal follicles and p21hras expression was similar in both groups. Survivin showed significantly higher expression after decompression, while cyclin D1 and p21hras remained unchanged (p=0.039, p=0.255, p=0.913, respectively). There was no correlation between these proteins neither before nor after decompression.
Conclusions
Within the limits of the study, we can conclude that following decompression, keratocystic odontogenic tumors preserve distinct immunohistochemical profiles of cyclin D1 and p21hras expression, despite substantial reduction in size of the lesions. Significant increase of survivin expression after decompression might be attributed to higher level of epithelial proliferation caused by this procedure.
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B7-H3 overexpression in oral cancer
Abstract
In a recent study published in Proceedings of the National Academy of Sciences of the United States of America, Chen and collaborators (2015), aiming to discover predictive markers with impact on treatment and survival of patients with oral squamous cell carcinoma (OSCC), described an important role of the transmembrane receptor B7 homolog 3 (B7-H3), also known as CD276 and B7RP-2, in OSCCs. Besides the overexpression of this protein, the results highlight differences in the N-glycan structure of this glycoprotein between normal and tumor cell lines, suggesting a possible mechanism of explanation of its function in both cancer and immune response.
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Fatty acids profile of new promising unconventional plant oils for cosmetic use
Abstract
Objective
Oils have been used in cosmetics since antiquity. With the development of cosmetic formulation and demand for active ingredients of strictly natural origin, there has been an increased interest in the use of unconventional oils obtained from nuts, botanicals, fruit and vegetable seeds. Since there seem to be no comprehensive scientific reports on the cosmetic plant oils available in Poland, the aim of our research was to characterize fatty acids (FA) profile and oxidative quality of selected unconventional plant oils which are used as cosmetics or cosmetic ingredients.
Methods
Oils were purchased from health and beauty retailers in Warsaw (Poland) .FA profile was analysed by gas chromatography with flame-ionization detection. Peroxidability index (PI), content of hydroperoxides (PV) and free fatty acids (AV) were also determined.
Results
Oxidative quality and FA composition varied widely among analyzed oils. Cluster analysis revealed three clusters. Clusters S1 and S3 included only one oil each (perilla and sea buckthorn, respectively). Perilla oil was characterized by relatively small content of both saturated FA (8.5%) and monounsaturated FA (14.2%), and much higher amount of polyunsaturated FA (73.5%), whereas in sea buckthorn these proportions were reversed (saturated FA and monounsaturated FA – 33.5% and 51.0% respectively, and the lowest amount of polyunsaturated FA – 5.2%). In cluster S2 two sub-clusters were identified and the content of linoleic (p = 0.0015), α-linolenic (p = 0.0092) and oleic (p = 0.0015) acids caused this distinction. PI ranged from 8.9 in sea buckthorn oil to 135 in perilla oil. Perilla oil and raspberry seed oil were also characterized by the highest PV (225 ± 14.9 mEq O/kg oil and 232 ± 13.8 mEq O/kg oil, respectively), whereas the lowest PV was in walnut oil (0.82 ± 0.18 mEq O/kg oil) and carrot seed (0.87 ± 0.21 mEq O/kg oil) oils.
Conclusion
FA composition of cosmetic oils in combination with data concerning their oxidative quality are useful in determining their safety and efficacy. It is important to standardize and test the FA content in commercially available oils for cosmetic use.
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Comparison between the effectiveness of expiration and abdominal bracing maneuvers in maintaining spinal stability following sudden trunk loading
Publication date: Available online 12 December 2015
Source:Journal of Electromyography and Kinesiology
Author(s): Hiroshi Ishida, Tadanobu Suehiro, Chiharu Kurozumi, Susumu Watanabe
The purpose of this study was to clarify the effectiveness of expiration and abdominal bracing maneuvers in response to sudden trunk loading in healthy subjects. Fifteen healthy male subjects were anteriorly loaded under different experimental conditions. Tests were conducted at rest and while performing each of the stabilization maneuvers (expiration and abdominal bracing) at 15% of the maximal voluntary isometric contraction of the internal oblique muscle. Subjects had no knowledge of the perturbation timing. An electromyographic biofeedback system was used to control the intensity of internal oblique muscle activation. Muscular pre-activation of three trunk muscles (internal oblique, external oblique, and L3 erector spinae musles) and lumbar acceleration in response to loading were measured. The expiration and abdominal bracing maneuvers promoted torso co-contraction, reduced the magnitude of lumbar acceleration, and increased spinal stability compared to the resting condition. There were no differences between the expiration and abdominal bracing maneuvers in the pre-activation of the three trunk muscles or in lumbar acceleration in response to loading. It appears that both expiration and abdominal bracing maneuvers are effective in increasing spinal stability in response to sudden anterior loading.
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Hearing in School-Aged Children With Trisomy 21 – Results of a Longitudinal Cohort Study in Children Identified at Birth
Abstract
Objectives
To report the prevalence of hearing problems and the hearing sequelae in school-aged children with Trisomy 21 in a longitudinal study.
Design
All children with Trisomy 21 were identified via schools, community-based Child Development Centres, General Practitioners or the Universal Newborn Hearing Screen. Audiological data and otorhinolaryngological problems were prospectively entered in to the Audiological Surveillance Programme database from each visit.
Setting
Retrospective review of the Audiological Surveillance Programme database in the Glasgow area (United Kingdom) of all children reviewed between 2004 and 2012.
Participants
All pre-teenaged children with Trisomy 21 of school age (aged 5 years to 12 years old).
Main Outcome Measures
Hearing thresholds, aetiology of hearing loss and management of hearing loss was determined for the cohort of children.
Results
102 children were included. 54 had normal hearing. 26 had fluctuating otitis media with effusion; 5 had hearing in normal limits, 6 were managed with hearing aids, 14 were managed conservatively and one had ventilation tube insertion. 15 had persistent otitis media with effusion; 4 had ventilation tube insertion and 9 were managed with hearing aids. 7 had mixed hearing loss with 4 required hearing aids.
Conclusions
Otitis media with effusion was the commonest cause of hearing impairment; effusions may fluctuate through the pre-teenaged years thus hearing aids are beneficial. Ventilation tube insertion and bone-conducting hearing aids were useful when ear-level hearing aids were not tolerated. Mixed hearing loss occurred in later years as sensorineural hearing loss developed on a background of otitis media with effusion.
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Complications Associated with the Use of Supraglottic Airway Devices in Perioperative Medicine
Supraglottic airway devices are routinely used for airway maintenance in elective surgical procedures where aspiration is not a significant risk and also as rescue devices in difficult airway management. Some devices now have features mitigating risk of aspiration, such as drain tubes or compartments to manage regurgitated content. Despite this, the use of these device may be associated with various complications including aspiration. This review highlights the types and incidence of these complications. They include regurgitation and aspiration of gastric contents, compression of vascular structures, trauma, and nerve injury. The incidence of such complications is quite low, but as some carry with them a significant degree of morbidity the need to follow manufacturers' advice is underlined. The incidence of gastric content aspiration associated with the devices is estimated to be as low as 0.02% with perioperative regurgitation being significantly higher but underreported. Other serious, but extremely rare, complications include pharyngeal rupture, pneumomediastinum, mediastinitis, or arytenoid dislocation. Mild short-lasting adverse effects of the devices have significantly higher incidence than serious complications and involve postoperative sore throat, dysphagia, pain on swallowing, or hoarseness. Devices may have deleterious effect on cervical mucosa or vasculature depending on their cuff volume and pressure.
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Berberine in Combination with Insulin Has Additive Effects on Titanium Implants Osseointegration in Diabetes Mellitus Rats
This study evaluated the effects of berberine in combination with insulin on early osseointegration of implants in diabetic rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: healthy rats were used as control (HC), and streptozotocin-induced diabetic rats were treated with insulin, berberine, berberine + insulin (IB), or no treatment. Each rat received one machined-surface cp-Ti implant into the right tibia and was given insulin injection and/or gavage feeding with berberine daily for 8 weeks until being sacrificed. Serum levels of alkaline phosphatase (ALP) and bone gamma-carboxyglutamic acid-containing protein (BGP) were analyzed in each group. Peri-implant mineral apposition was marked by fluorochrome double-labeling and osseointegration was histomorphologically examined. The ALP and BGP levels decreased in diabetic rats but were successfully corrected by insulin and berberine combined treatment. Moreover, untreated diabetic rats had less labeled mineral apposition and impaired osseointegration. In contrast, Groups I, B, and IB were observed with increased peri-implant bone formation. The combination treatment of insulin and berberine was more effective than each administrated as a monotherapy. These results suggest that berberine combined with insulin could promote osseointegration in diabetic rats, thereby highlighting its potential application to patients, though further studies are needed.
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Mammary Analogue Secretory Carcinoma of the Parotid Gland: A Third World Country Perspective—A Case Series
Mammary analogue secretory carcinoma (MASC) is a recently described pathological entity in major salivary glands, which was first described by Skálová et al. in 2010. Since then only a limited number of case reports/series have been published describing this tumor with the majority of them discussing the genetic and cytoarchitectural aspect of this tumor. Keeping this in view with the lack of clinical correlation with regard to this tumor, we present our approach to management of two such cases which, according to the best of our knowledge, are the first 2 cases presenting in the South Asian continent. Both patients were diagnosed and managed at Aga Khan University Hospital, Karachi, Pakistan.
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Frequent Flyers: Just a flesh wound
See all of Lenwood Brown's comics.
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Chronic Comorbidities Contribute to the Burden and Costs of Persistent Asthma
Background. We aimed to study the prevalence of chronic comorbidities in asthma patients and the costs of health care use associated with asthma with comorbidities. Material and Methods. We analysed the prevalence of the four most common chronic diseases in asthma patients in 2008–2014 in Finland. Prevalence of coronary artery disease, diabetes and dyslipidaemia, hypertension, epilepsy, inflammatory bowel disease, rheumatic diseases, and severe psychiatric disease was studied by register of the Social Insurance Institution of Finland. The costs of health care services were collected from the registries maintained by the National Institute for Health and Welfare (THL). Results. Prevalence of asthma was 4.6% in 2014. Diabetes was among the four most common comorbidities in all the age groups. The other common comorbidities were hypertension (≥46 years; 12.9–37.6%), severe psychiatric disorders (age groups of 16–59 years; 1.4–3.5%), and ischaemic heart disease (≥60 years; 10–25%). In patients with both asthma and diabetes, the costs of hospitalization were approximately 169% compared with patients with asthma alone. Conclusions. Prevalence of asthma increases by tenfold when aging. The comorbidity diversity and rate are age-dependent. Prevalence of diabetes as comorbidity in asthma has increased. Costs of hospitalizations in asthma approximately double with chronic comorbidities.
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The judicialization of the medical act
Publication date: Available online 13 December 2015
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Roberto Augusto de Carvalho Campos, Rosmari Aparecida Elias Camargo, Luciano Rodrigues Neves
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Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas
Abstract
Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.
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Design and Implementation of Improved Electronic Load Controller for Self-Excited Induction Generator for Rural Electrification
This paper offers an alternative technique, namely, Improved Electronic Load Controller (IELC), which is proposal to improve power quality, maintaining voltage at frequency desired level for rural electrification. The design and development of IELC are considered as microhydroenergy system. The proposed work aims to concentrate on the new schemes for rural electrification with the help of different kinds of hybrid energy systems. The objective of the proposed scheme is to maintain the speed of generation against fluctuating rural demand. The Electronic Load Controller (ELC) is used to connect and disconnect the dump load during the operation of the system, and which absorbs the load when consumer are not in active will enhance the lifestyle of the rural population and improve the living standards. Hydroelectricity is a promising option for electrification of remote villages in India. The conventional methods are not suitable to act as standalone system. Hence, the designing of a proper ELC is essential. The improved electronic load control performance tested with simulation at validated through hardware setup.
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Intraoperative auditory evoked potential recordings are more reliable at signal detection from different sensor sites on the forehead compared to bispectral index
Abstract
Bispectral index (BIS) and auditory evoked potential (AEP) monitoring require the attachment of forehead sensors, posing difficulties when the surgical field involves the forehead. This study analyzed the relationship between BIS values and AEP indices from different sites on the head to establish alternative sensor locations for AEP recording. Thirty patients scheduled for elective surgery under sevoflurane anesthesia were randomly assigned to the forehead, nose or mandible groups (n = 10 patients per group). AEP sensors were placed at the assigned position for each group and BIS sensors were placed on the forehead. BIS value and AEP index were simultaneously recorded from induction until emergence from general anesthesia. Relationships between BIS values and AEP indices were analyzed using a regression method and compared between groups using Pearson's correlation coefficients. Square regression models better expressed the relationships than linear models in all groups. The z-transformed coefficient in the forehead group was the same as the nose group (p = 0.24) and significantly different in the mandible group (p = 0.0046). These findings suggest that AEPs can be accurately recorded from sensors placed on the nose. Nasal AEP might be useful for monitoring electrical activity in the brain during surgeries involving the forehead.
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Discontinuous Galerkin method for two-dimensional bilayer shallow water equations
Abstract
We present a numerical solution of the two-layer shallow water equations in two space dimensions, based on a discontinuous Galerkin finite element method. The continuous equations are discretized and solved locally using the finite element method of an unstructured computational domain using nodal polynomial basis functions of arbitrary order in space. To complete the discretization in space, we choose the numerical flux based on the local Lax–Friedrichs flux which establishes connection between elements. The numerical discretization results in a set of coupled nonlinear equations which can be solved efficiently and locally by integrating them using a Runge–Kutta scheme. The considered discontinuous Galerkin method is fully explicit, stable, highly accurate, and locally conservative finite element method whose approximate solutions are discontinuous across inter-element boundaries; this property renders the method ideally suitable for the hp-adaptivity. Several numerical results are presented to demonstrate the high resolution of the proposed method and to confirm its capability to provide accurate and efficient simulations to solve the two-dimensional bilayer shallow water equations.
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Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells
Publication date: February 2016
Source:Biomedicine & Pharmacotherapy, Volume 77
Author(s): Xinfeng Yu, Ruilian Li, Wenna Shi, Tao Jiang, Yufei Wang, Cong Li, Xianjun Qu
Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER+) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER+ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER+ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER+ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.
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Brain Parenchymal Fraction: A Relatively Simple MRI Measure to Clinically Distinguish ALS Phenotypes
Even though neuroimaging and clinical studies indicate that amyotrophic lateral sclerosis (ALS) manifests with distinct clinical phenotypes, no objective test exists to assess upper motor degeneration in ALS. There is great interest in identifying biomarkers of ALS to allow earlier diagnosis and to recognize disease subtypes. Current quantitative neuroimaging techniques such as T2 relaxometry and diffusion tensor imaging are time-consuming to use in clinical settings due to extensive postprocessing requirements. Therefore, we aimed to study the potential role of brain parenchymal fraction (BPF) as a relatively simple quantitative measure for distinguishing ALS phenotypes. T1-weighted MR images of brain were obtained in 15 neurological controls and 88 ALS patients categorized into 4 distinct clinical phenotypes, upper motor neuron- (UMN-) predominant ALS patients with/without corticospinal tract (CST) hyperintensity on T2/PD-weighted images, classic ALS, and ALS with frontotemporal dementia (ALS-FTD). BPF was calculated using intracranial grey matter, white matter, and cerebrospinal fluid volumes obtained in control and ALS subgroups using SPM8 software. Only ALS-FTD patients had significant reduction in BPF when compared to controls and nondemented ALS patients. Correlation of clinical measures such as disease duration with BPF further supports the view that the BPF could be a potential biomarker for clinical diagnosis of ALS-FTD patients.
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Fucoidan from sea cucumber may improve hepatic inflammatory response and insulin resistance in mice
Publication date: February 2016
Source:International Immunopharmacology, Volume 31
Author(s): Jinhui Wang, Shiwei Hu, Wei Jiang, Wendong Song, Lu Cai, Jingfeng Wang
Nutrition excess-induced inflammation positively contributed to insulin resistance. Fucoidan from sea cucumber can increase glucose translocation in skeletal muscle. However, its effects on inflammation-associated insulin resistance are not understood. We investigated fucoidan from Isostichopus badionotus (Ib-FUC)-alleviated inflammatory response and signaling as well as -improved insulin resistance in the liver of obesity mice. The results showed that Ib-FUC reduced body weight and glucose levels, increased insulin sensitivity, and inhibited serum lipid concentrations. Meanwhile, Hepatic glycogen synthesis was promoted by Ib-FUC via activation of the PI3K/PKB/GSK-3β signaling and regulation of glucose metabolism-related enzymatic activities. Ib-FUC regulated serum inflammatory cytokines and their mRNA expression in the liver. Ib-FUC-induced inactivation of the JNK and IKKβ/NFκB pathways was involved in the activation of insulin signal cascade and inflammatory factor production. These findings suggested that Ib-FUC supplementary-induced alleviation of inflammatory response could be a mechanism responsible for its beneficial effects against hepatic insulin resistance.
Graphical abstract
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Signaling, stress response and apoptosis in pre-diabetes and diabetes: restoring immune balance in mice with alloxan-induced type 1 diabetes mellitus
Publication date: February 2016
Source:International Immunopharmacology, Volume 31
Author(s): Elena G. Novoselova, Olga V. Glushkova, Sergey M. Lunin, Maxim O. Khrenov, Tatyana V. Novoselova, Svetlana B. Parfenyuk, Evgeny E. Fesenko
The aim of this study was to compare immune imbalances in "pre-diabetic" and diabetic mice and to evaluate the efficacy of several agents in improving the immunity of mice with type 1 diabetes. Pre-diabetic and diabetic models generated by a single or double alloxan injection were monitored for plasma glucose and pancreas immunohistochemistry. To study the immunity in pre-diabetic and diabetic Balb/C male mice; the levels of cytokines; synthesis of inducible heat shock proteins HSP72 and HSP90α; activity of the NF-κB, IFR3, SAPK/JNK, and TLR4 pathways; and apoptosis levels in thymuses were measured. Pre-diabetes resulted in a decrease in IL-4, IL-5 and IL-10 in plasma; in diabetic mice, plasma IFN-gamma, IL-6, TNF-alpha, and IL-10 were decreased. The NF-κB alternative pathway activity and TLR4 expression were significantly increased only in pre-diabetic mice, whereas SAPK/JNK activation was observed at both stages of diabetes. Other measured parameters also showed distinct altered patterns in the immunity of pre-diabetic and diabetic mice. Treatment with an inhibitor of NF-κB, thymulin, or a diet with an antioxidant improved or normalized the immune balance in diabetic mice and also notably decreased pancreatic cell damage in pre-diabetic mice.
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Interleukin-17 Could Promote Breast Cancer Progression at Several Stages of the Disease
Metastatic disease accounts for more than 90% of deaths from breast cancer. Yet the factors that trigger metastasis, often years after primary tumor removal, are not understood well. Recently the proinflammatory cytokine interleukin- (IL-) 17 family has been associated with poor prognosis in breast cancer. Here we review current literature on the pathogenic mechanisms driven by IL-17 during breast cancer progression and connect these findings to metastasis. These include (1) direct effects of IL-17 on tumor cells promoting tumor cell survival and invasiveness, (2) regulation of tumor angiogenesis, and (3) interaction with myeloid derived suppressor cells (MDSCs) to inhibit antitumor immune response and collaborate at the distant metastatic site. Furthermore, IL-17 might also be a culprit in bone destruction caused by late stage bone metastasis. Interestingly, in addition to these potential prometastasis functions, there is also evidence for an opposite, antitumor role of IL-17 during cancer therapies. We hypothesize that these contradictory roles may be due to chronic, imbalanced versus acute transient nature of the immune reactions, as well as differences in the cells that interact with IL-17+ cells under different circumstances.
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The Role of the Glucocorticoid Receptor Gene (NR3C1) for the Processing of Aversive Stimuli
Source:Neuroscience Research
Author(s): Katja Kerstin Schneider, Christian Frings, Jobst Meyer, Andrea B. Schote
The glucocorticoid receptor (GR) is a crucial component of the hypothalamus-pituitary-adrenal (HPA-) axis and as such a part of the stress response system. An impairment of the GR not only alters the level of glucocorticoids, but also modulates cognitive functions and the processing of emotional stimuli. We tested the effects of functional polymorphisms of the GR-encoding gene (NR3C1) on the processing of emotional stimuli on a basal level. In a sample of n=182 participants, we found a haplotype (NR3C1-CTGGACA) to modulate the performance in an emotional reaction time task. Compared to non-carriers, participants who carried the haplotype were quicker to react after aversive stimuli had been presented. In contrast, the presence of the haplotype had no effect on the processing of neutral stimuli. We conclude that properties of the glucocorticoid receptor contribute to the processing of emotional stimuli and influence the intensity of their processing even in the absence of acute stressors.
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The curse of motor expertise: use-dependent focal dystonia as a manifestation of maladaptive changes in body representation
Source:Neuroscience Research
Author(s): Shinichi Furuya, Takashi Hanakawa
Focal task-specific dystonia (FTSD) impairs not only motor dexterity, but also somatosensory perception involved in well-trained behavioral tasks. Occupations that carry a risk of developing FTSD include musician, writer, painter, surgeon, and golfer, which are characterized by repetitive and precise motor actions over a prolonged period. Behavioral studies have uncovered various undesirable effects of FTSD on sensorimotor functions, such as a loss of independent movement control, unintended muscular co-activation, awkward limb posture, and impairment of fine discrimination of tactile and proprioceptive sensations. Studies using neuroimaging and noninvasive brain stimulation techniques have related such sensorimotor malfunctions to maladaptive neuroplastic changes in the sensorimotor system, including the primary motor and somatosensory areas, premotor area, cerebellum, and basal ganglia. In this review, we summarize recent empirical findings regarding phenomenological and pathophysiological abnormalities associated with the development of FTSD. We particularly focused on maladaptive alterations of body representations underlying the degradation of fine motor control and somatosensory perception in FTSD patients.
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Interstudy repeatability of self-gated quantitative myocardial perfusion MRI
Purpose
To evaluate the interstudy repeatability of multislice quantitative cardiovascular magnetic resonance myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and extracellular volume (ECV). A unique saturation recovery self-gated acquisition was used for the perfusion scans.
Materials and Methods
An ungated golden angle radial turboFLASH pulse sequence was used to scan 10 subjects on two separate days on a 3T scanner. A single saturation pulse was followed by a set of four slices. Rest and hyperemia scans were acquired during free breathing. The images were reconstructed using an iterative algorithm with spatiotemporal constraints. The ungated images were retrospectively binned (self-gated) into near-systole and near-diastole. Deformable registration was performed to adjust for respiratory and residual cardiac motion, and the data were fit with a Fermi model to estimate the interstudy repeatability of quantitative self-gated MBF and MPR.
Results
The coefficient of variation (CoV) of the territorial MPR using the self-gated near-systole data was 18.6%. The self-gated near-diastole data gave less good CoV of MPR, equal to 46.2%. For MBFs, and using smaller (segmental) regions, the CoVs were 20.1% and 22.7% for the estimation of myocardial blood flow at stress and rest, respectively, using the self-gated near-systole data. The self-gated near-diastole data gave CoV = 48.6% and 44.9% for stress and rest.
Conclusion
The self-gated free-breathing technique for quantification of myocardial blood flow showed good repeatability for near-systole, with results comparable to published studies on interstudy repeatability of quantitative myocardial perfusion MRI using ECG-gating and breath-holds. Self-gated near-diastole data results were less repeatable. J. Magn. Reson. Imaging 2015.
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Vortex-ring mixing as a measure of diastolic function of the human heart: Phantom validation and initial observations in healthy volunteers and patients with heart failure
Purpose
To present and validate a new method for 4D flow quantification of vortex-ring mixing during early, rapid filling of the left ventricle (LV) as a potential index of diastolic dysfunction and heart failure.
Materials and Methods
4D flow mixing measurements were validated using planar laser-induced fluorescence (PLIF) in a phantom setup. Controls (n = 23) and heart failure patients (n = 23) were studied using 4D flow at 1.5T (26 subjects) or 3T (20 subjects) to determine vortex volume (VV) and inflowing volume (VVinflow). The volume mixed into the vortex-ring was quantified as VVmix-in = VV–VVinflow. The mixing ratio was defined as MXR = VVmix-in/VV. Furthermore, we quantified the fraction of the end-systolic volume (ESV) mixed into the vortex-ring (VVmix-in/ESV) and the fraction of the LV volume at diastasis (DV) occupied by the vortex-ring (VV/DV).
Results
PLIF validation of MXR showed fair agreement (R2 = 0.45, mean ± SD 1 ± 6%). MXR was higher in patients compared to controls (28 ± 11% vs. 16 ± 10%, P < 0.001), while VVmix-in/ESV and VV/DV were lower in patients (10 ± 6% vs. 18 ± 12%, P < 0.01 and 25 ± 8% vs. 50 ± 6%, P < 0.0001).
Conclusion
Vortex-ring mixing can be quantified using 4D flow. The differences in mixing parameters observed between controls and patients motivate further investigation as indices of diastolic dysfunction. J. Magn. Reson. Imaging 2015
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Cancer incidence among Asian American populations in the United States, 2009-2011
Abstract
Cancer incidence disparities exist among specific Asian American populations. However, the existing reports exclude data from large metropoles like Chicago, Houston, and New York. Moreover, incidence rates by subgroup have been underestimated due to the exclusion of Asians with unknown subgroup. Cancer incidence data for 2009 to 2011 for eight states accounting for 68% of the Asian American population were analyzed. Race for cases with unknown subgroup was imputed using stratified proportion models by sex, age, cancer site, and geographic regions. Age-standardized incidence rates were calculated for 17 cancer sites for the six largest Asian subgroups. Our analysis comprised 90,709 Asian and 1,327,727 non-Hispanic white cancer cases. Asian Americans had significantly lower overall cancer incidence rates than non-Hispanic whites (336.5 per 100,000 and 541.9 for men, 299.6 and 449.3 for women, respectively). Among specific Asian subgroups, Filipino men (377.4) and Japanese women (342.7) had the highest overall incidence rates while South Asian men (297.7) and Korean women (275.9) had the lowest. In comparison to non-Hispanic whites and other Asian subgroups, significantly higher risks were observed for colorectal cancer among Japanese, stomach cancer among Koreans, nasopharyngeal cancer among Chinese, thyroid cancer among Filipinos, and liver cancer among Vietnamese. South Asians had remarkably low lung cancer risk. Overall, Asian Americans have a lower cancer risk than non-Hispanic whites, except for nasopharyngeal, liver and stomach cancers. The unique portrayal of cancer incidence patterns among specific Asian subgroups in this study provides a new baseline for future cancer surveillance research and health policy. This article is protected by copyright. All rights reserved.
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Menopausal hormone therapy use and risk of primary liver cancer in the Clinical Practice Research Datalink
Abstract
Primary liver cancer occurs less commonly among women than men in almost all countries. This discrepancy has suggested that hormone levels and/or exogenous hormone use could have an effect on risk, although prior studies have reached inconsistent conclusions. Thus, the current study was conducted to examine the relationship between menopausal hormone therapy (MHT) use and development of liver cancer. A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Controls were matched, at a 4-to-1 ratio, to women diagnosed with primary liver cancer between 1988 and 2011. A second match, based on whether the cases and controls had diabetes, was also conducted. Odds ratios (OR) and 95% confidence intervals (95%CI) for associations of MHT with liver cancer were estimated using conditional logistic regression adjusted for known risk factors. In the overall match, 339 women with liver cancer were matched to 1318 controls. MHT use was associated with a significantly lower risk of liver cancer (ORadj=0.58, 95%CI=0.37-0.90) especially among users of estrogen-only MHT (ORadj=0.44, 95%CI=0.22-0.88) and among past users (ORadj=0.53, 95%CI=0.32-0.88). Among the matched cases (n=58) and controls (n=232) with diabetes, the odds ratios were similar to the overall analysis (ORadj=0.57, 95%CI=0.09-3.53), but did not attain statistical significance. In the current study, MHT use, especially estrogen-only MHT use, was associated with a significantly lower risk of liver cancer. These results support the need of further investigation into whether hormonal etiologies can explain the variation in liver cancer incidence between men and women. This article is protected by copyright. All rights reserved.
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Age-specific prevalence of HPV16/18 genotypes in cervical cancer: a systematic review and meta-analysis
Abstract
The prevalence of HPV16/18 in cervical cancer has been reported to decline with age in some papers. However, whether this decline in proportion of cancers positive for HPV16/18 is consistently observed across studies remains to be elucidated. Thus, the aim of our study was to identify papers reporting data on age-specific prevalence of HPV16/18 in cervical cancer and to summarize the results. We employed MEDLINE and Embase for a systematic literature search and thereby identified a total of 644 papers published in the period 1999-2015 of which 15 papers, reporting cross-sectional data, were included for review (11,526 cervical cancers). The prevalence of HPV16/18 in cervical cancer declined significantly with age (ρ =-0.83, p=0.04) from 74.8% (95% CI 67.6 – 80.8) in women aged 30-39 years to 56.8% (95% CI 43.9 – 68.8) in women ≥70 years. As the HPV16/18 positive cancers are prevented in fully vaccinated cohorts, the age-specific epidemiology of cervical cancer is anticipated to change, with a shift in peak incidence rate to older ages. It will be important for integrated vaccination and screening strategies to consider predicted change in the age-specific epidemiology of cervical cancer. This article is protected by copyright. All rights reserved.
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Bacteriology testing of cardiovascular tissues: comparison of transport solution versus tissue testing
Abstract
Bacteriology testing is mandatory for quality control of recovered cardiovascular allografts (CVA). In this paper, two different bacteriology examinations (A tests) performed before tissue antibiotic decontamination were compared: transport solution filtration analysis (A1) and tissue fragment direct incubation (A2). For this purpose, 521 CVA (326 heart and 195 artery tissues) from 280 donors were collected and analyzed by the European Homograft Bank (EHB). Transport solution (A1) tested positive in 43.25 % of hearts and in 48.21 % of arteries, whereas the tissue samples (A2) tested positive in 38.34 % of hearts and 33.85 % of arteries. The main species identified in both A1 and A2 were Staphylococcus spp. in 55 and 26 % of cases, and Propionibacterium spp. in 8 and 19 %, respectively. Mismatches in bacteriology results between both initial tests A1 and A2 were found. 18.40 % of the heart valves were identified as positive by A1 whilst 13.50 % were considered positive by A2. For arteries, 20.51 % of cases were positive in A1 and negative in A2, and just 6.15 % of artery allografts presented contamination in the A2 test but were considered negative for the A1 test. Comparison between each A test with the B and C tests after antibiotic treatment of the allograft was also performed. A total decontamination rate of 70.8 % of initial positive A tests was obtained. Due to the described mismatches and different bacteria identification percentage, utilization of both A tests should be implemented in tissue banks in order to avoid false negatives.
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Towards a Universal Approach Based on Omics Technologies for the Quality Control of Food
In the last decades, food science has greatly developed, turning from the consideration of food as mere source of energy to a growing awareness on its importance for health and particularly in reducing the risk of diseases. Such vision led to an increasing attention towards the origin and quality of raw materials as well as their derived food products. The continuous advance in molecular biology allowed setting up efficient and universal omics tools to unequivocally identify the origin of food items and their traceability. In this review, we considered the application of a genomics approach known as DNA barcoding in characterizing the composition of foodstuffs and its traceability along the food supply chain. Moreover, metabolomics analytical strategies based on Nuclear Magnetic Resonance (NMR) and Mass Spectroscopy (MS) were discussed as they also work well in evaluating food quality. The combination of both approaches allows us to define a sort of molecular labelling of food that is easily understandable by the operators involved in the food sector: producers, distributors, and consumers. Current technologies based on digital information systems such as web platforms and smartphone apps can facilitate the adoption of such molecular labelling.
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Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun—Dexmedetomidine, Clonidine? A Minireview
Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality. Treatment aims at reestablishing circulation within a "central" compartment (i.e., brain, heart, and lung) but fails to reestablish a disorganized microcirculation or an adequate response to noradrenaline, the most widely used vasopressor. Indeed, steroids, nitric oxide synthase inhibitors, or donors have not achieved overwhelming acceptance in the setting of septic shock. Counterintuitively, α2-adrenoceptor agonists were shown to reduce noradrenaline requirements in two cases of human septic shock. This has been replicated in rat and sheep models of sepsis. In addition, some data show that α2-adrenoceptor agonists lead to an improvement in the microcirculation. Evidence-based documentation of the effects of alpha-2 agonists is needed in the setting of human septic shock.
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Effect of use of inhaled epinephrine on intramuscular epinephrine use in patients with idiopathic anaphylaxis and angioedema
Publication date: Available online 12 December 2015
Source:Annals of Allergy, Asthma & Immunology
Author(s): Cosby A. Stone, Jane J. Choi
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Exploratory screening for Fabry’s disease in young adults with cerebrovascular disorders in northern Sardinia
Abstract
Background
The etiologic determinants of stroke in young adults remain a diagnostic challenge in up to one-fourth of cases. Increasing evidences led to consider Fabry's disease (FD) as a possible cause to check up. We aimed at evaluating the prevalence of unrecognized FD in a cohort of patients with juvenile stroke in northern Sardinia.
Methods
For this study, we enrolled 178 patients consecutively admitted to our Neurological Ward for ischemic stroke, transient ischemic attack, intracerebral haemorrhage, neuroradiological evidence of silent infarcts, or white matter lesions possibly related to cerebral vasculopathy at brain MRI, and cerebral venous thrombosis. The qualifying events have to occur between 18 and 55 years of age.
Results
We identified two patients with an α-galactosidase A gene variant, with a prevalence of 0.9 %. According to recent diagnostic criteria, one patient, included for the occurrence of multiple white matter lesions at brain MRI, had a diagnosis of definite FD, the other, included for ischemic stroke, had a diagnosis of uncertain FD.
Conclusions
Our study places in a middle position among studies that found a prevalence of FD up to 4 % and others that did not find any FD patients. Our findings confirm that FD should be considered in the differential diagnosis of patients with juvenile stroke, particularly those with a personal or familial history positive for cerebrovascular events, or evidence of combined cardiologic and/or renal impairment. All types of cerebrovascular disorders should be screened for FD, including patients with white matter lesions possibly related to cerebral vasculopathy at brain MRI.
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The role of IgE recognition in allergic reactions to Amoxicillin and Clavulanic acid
Abstract
Betalactam (BL) antibiotics are the drugs most frequently involved in IgE-mediated reactions. The culprit BL varies according to consumption patterns, with amoxicillin (AX) more prevalent in Southern Europe and penicillin V in Scandinavian countries.
Nowadays, the combination of AX and clavulanic acid (CLV), is the most highly consumed BL containing medicine worldwide. Both BLs, AX and CLV, can independently be involved in reactions, which poses a diagnostic challenge.
In patients with immediate allergic reactions to AX, two patterns of responses have been described, those responding to benzylpenicillin (cross-reactors) and those selective to AX. In addition, selective reactions to CLV account for around 30% of allergic reactions to the combination AX-CLV. These patterns of IgE recognition could be related to differences in the haptenation process, in the immunological response, or in the BL involved in the first sensitization. In this regard, patients with selective responses to CLV are generally younger than those allergic to AX or benzylpenicillin. So far, no evidence of cross reactivity between CLV and other BLs has been reported. This shows the importance of an accurate diagnosis of CLV allergy, since patients with selective reactions to CLV could take other BLs including AX. Diagnosis can be performed in vivo and in vitro, although no immunoassay currently exists. Research regarding the CLV antigenic determinants and protein conjugates is essential to improve diagnosis.
BLs need to covalently bind to a carrier protein to be immunogenic. The antigenic determinant of AX is the amoxicilloyl amide, but CLV leads to unstable structures, many of which are unknown. Moreover, the nature of the BL-protein conjugates plays an important role in IgE recognition. This review aims to summarise current knowledge on the immunochemistry, diagnostic approaches as well as chemical and proteomic studies for both AX and CLV.
This article is protected by copyright. All rights reserved.
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The response to nasal allergen provocation with grass pollen is reduced in patients with chronic rhinosinusitis with nasal polyposis and grass sensitization
Abstract
Background
The majority of grass pollen sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens.
Objective
We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen sensitized CRSwNP patients.
Methods
Twelve grass pollen sensitized CRSwNP patients underwent NAPT with grass pollen and were compared to 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen specific IgE and tryptase were measured in serum and nasal secretions.
Results
NAPT was positive in 6 out of 12 of the grass pollen sensitized CRSwNP patients and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test.
Conclusion And Clinical Relevance
These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared to grass pollen allergic rhinitis patients.
This article is protected by copyright. All rights reserved.
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Relationship between Sputum Clusterin Levels and Childhood Asthma
Abstract
Background
Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated.
Objectives
1) To evaluate sputum clusterin levels in children with asthma compared to a control group. 2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness.
Methods
This study included 170 children aged 5–18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay.
Results
Children with stable asthma had a higher clusterin level than healthy controls (4540 [3872–5651] pg/mL vs. 3857 [1054–4369] pg/mL, P < 0.001). The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma (5094 [4243–6257] pg/mL vs. 4110 [1871–4839] pg/mL, P = 0.0017). Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma (1838 [350–4790] pg/mL vs. 4540 [3871–5651] pg/mL, P < 0.001). Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 second (r = − 0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters.
Conclusions and Clinical Relevance
Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.
This article is protected by copyright. All rights reserved.
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The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations
Abstract
Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.
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Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics
Publication date: March 2016
Source:Archives of Oral Biology, Volume 63
Author(s): Uzma Urooj Malik, Shamshad Zarina, Stephen R. Pennington
BackgroundThe molecular and cellular mechanisms underlying the pathogenesis of oral squamous cell carcinoma (OSCC) are relatively poorly understood and remain a subject of significant importance. However, it is well established that OSCC is associated with a variety of risk factors and notably, the high incidence rates of OSCC found in developing countries are attributable to exposure to different forms of smokeless tobacco. Despite this, the way these factors contribute to the disease pathogenesis and, in particular, the transformation from oral premalignant lesions (OPLs) to primary tumor remains unknown. Recent developments in 'omics' technologies hold promise for deciphering these mechanisms through the discovery of key molecular and cellular regulatory pathways which are involved in disease progression.ObjectiveThe aim of this critical review is to outline, through the current etiological, epidemiological, and molecular understanding of OSCC highlighting the role of key signaling pathways in the disease, and discuss the opportunities offered by recent proteomics strategies to identify potential biomarkers and novel mechanisms for OSCC.Results and conclusionsThe recent consolidation of methods for LC-MS/MS based protein expression analysis mass spectrometry and targeted protein measurement should support the discovery of new drug targets and diagnostic methods. We suggest that such studies will be most effective if they are focused on addressing the key clinical issues in the progression and treatment of this prevalent disease.
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