Artificial human sera: a breakthrough?

Abstract

It is not common that a Brief Communication is chosen for an Editorial; however, the work presented by Offermann et al. (1) deserves to be commented. Obviously the in vitro diagnosis of allergic sensitisation is based on the determination of soluble allergen-specific IgE in serum (2). Although the correlation between sIgE and allergic sensitization might be disturbed by the presence of clinically irrelevant cross-reactive carbohydrate determinants (3), in most cases allergen-specific IgE in serum can be correlated with the symptomatic (4).

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Cannabis sativa allergy: looking through the fog

Abstract

IgE-mediated Cannabis (C. sativa, marihuana) allergy seems to be on the rise. Both active and passive exposure to cannabis allergens may trigger a C. sativa sensitization and/or allergy. The clinical presentation of a C. sativa allergy varies from mild to life-threatening reactions and often seems to depend on the route of exposure. In addition, sensitization to cannabis allergens can result in various cross-allergies, mostly for plant foods. This clinical entity, designated as the "cannabis-fruit/vegetable syndrome" might also imply cross-reactivity with tobacco, natural latex and plant-food derived alcoholic beverages. Hitherto, these cross-allergies are predominantly reported in Europe and appear mainly to rely upon cross-reactivity between non-specific lipid transfer proteins (ns-LTPs) or thaumatin-like proteins (TLPs) present in C. sativa and their homologues, ubiquitously distributed throughout plant kingdom. At present, diagnosis of cannabis-related allergies predominantly rests upon a thorough history completed with skin testing using native extracts from crushed buds and leaves. However, quantification of specific IgE (sIgE) antibodies and basophil activation tests (BAT) can also be helpful to establish correct diagnosis. In the absence of a cure, treatment comprises absolute avoidance measures. Whether avoidance of further use will halt the extension of related cross-allergies remains uncertain.

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3D physiological model of the aortic valve incorporating small coronary arteries

Summary

The diseases of the coronary arteries and the aortic root are still the leading causes of mortality and morbidity worldwide. In this study, a 3D global fluid-structure interaction of the aortic root with inclusion of anatomically inspired small coronary arteries using the finite element method is presented. This innovative model allows to study the impact and interaction of root biomechanics on coronary hemodynamics and brings a new understandings to small coronary vessels hemodynamics. For the first time, the velocity profiles and shear stresses are reported in distal coronary arteries as a result of the aortic flow conditions in a global fluid-structure interaction model.

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Comparative study of chlorhexidine dressings versus simple gauze dressings in midline laparotomy wound

2016-09-03T07-00-50Z
Source: International Journal of Research in Medical Sciences
Jignesh A. Gandhi, Pravin H. Shinde, Alpana A. Awasthi, Rohan Digarse, Amit P. Kawle.
Background: Wound infections are the most common complication of surgery that adds significantly to the morbidity of the patient and the cost of the treatment. Most of the surgical site infections are preventable. Dressing is an active element of wound management, designed to control infection and promote healing. This study was done to compare clinical efficacy of normal gauze dressings versus chlorhexidine dressings in midline laparotomy wounds. Methods: Patients with midline laparotomy incision were randomized to receive either gauze or chlorhexidine dressings. Bacterial colonization, post- operative fever, frequency of infection, change of dressings, hospital stay and postoperative pain were assessed at the start of treatment and at weekly intervals until full healing occurred. Results: A total of 128 patients were enrolled in the study and divided into 2 groups viz chlorhexidine group (Group A) and Simple gauze group (Group B) with 64 patients each. Wound cultures, change of antibiotics, post-operative soakage, median hospital stay duration, postoperative pain, post- operative wound infection, and follow up visits for wound healing were compared between two groups A and B and statistical significance established. Conclusions: The analysis of wound culture, fever incidence and frequency of infection on Chlorhexidine dressings showed decreasing trends compared to traditional dressings.


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Advancing Implementation Research and Practice in Behavioral Health Systems

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Outcome after Interruption or Preservation of Internal Iliac Artery Flow During Endovascular Repair of Abdominal Aorto-iliac Aneurysms

Publication date: Available online 2 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): G.N. Kouvelos, A. Katsargyris, G.A. Antoniou, K. Oikonomou, E.L.G. Verhoeven
AimThe aim was to conduct a systematic review of the literature investigating outcomes after interruption or preservation of the internal iliac artery (IIA) during endovascular aneurysm repair (EVAR).MethodsA systematic review was undertaken using the MEDLINE and EMBASE databases to identify studies reporting IIA management during EVAR. The search identified 57 articles: 30 reported on IIA interruption (1468 patients) and 27 on IIA preservation (816 patients).ResultsThe pooled 30 day buttock claudication (BC) rate was 29.2% (95% CI 24.2–34.7). Patients undergoing bilateral IIA interruption had a higher incidence of BC than patients with unilateral IIA interruption (36.5% vs. 27.2%, OR 1.7, 95% CI 1.11–2.6, p = .01). During a median follow up of 17 months, the pooled rate of persistent BC was 20.5% (95% CI 15.7–26.2). Of the patients, 93.9% underwent an endovascular revascularization procedure for IIA preservation. Most patients (87.6%) had an iliac branched device, and technical success was 96.2%. Within 30 days of EVAR, 4.3% of internal iliac branches occluded. During a median follow up of 15 months, the pooled occlusion rate at the site of IIA revascularization was 8.8% (95% CI 6.8–11.3). In patients treated with an iliac-branched device, 5.2% of internal iliac branches and 1.7% of external iliac arteries occluded. The pooled BC rate on the side of the IIA revascularization during follow up was 4.1% (95% CI 2.9–5.9). Pooled rates of late device related endoleak type I or III and secondary procedures on the side of the previous IIA revascularization were 4.6% (95% CI 3.2–6.5) and 7.8% (95% CI 5.7–10.7) respectively.ConclusionUnilateral or bilateral IIA occlusion during EVAR seems to carry a substantial risk of significant ischemic complications in nearly one quarter of patients. Bilateral IIA occlusion was related to a significantly higher rate of BC. IIA preservation techniques represent a significant improvement in the treatment of aorto-iliac aneurysms and have been associated with high technical success and low morbidity.



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Commentary on ‘Fluid-Structure Interaction Simulations of Aortic Dissection With Bench Validation’

Publication date: Available online 3 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): J.P. Archie




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Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study.

Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study.

Int J Audiol. 2016 Sep 2;:1-20

Authors: Rönnberg J, Lunner T, Ng EH, Lidestam B, Zekveld AA, Sörqvist P, Lyxell B, Träff U, Yumba W, Classon E, Hällgren M, Larsby B, Signoret C, Pichora-Fuller MK, Rudner M, Danielsson H, Stenfelt S

Abstract
OBJECTIVE: The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model.
STUDY SAMPLE: Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL.
DESIGN: LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables.
RESULTS: The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R(2) = 0.40).
CONCLUSIONS: All LEVEL 2 factors are important theoretically as well as for clinical assessment.

PMID: 27589015 [PubMed - as supplied by publisher]

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Cathepsin L coexists with Cytotoxic T-lymphocyte Antigen-2 alpha in distinct regions of the mouse brain.

Cathepsin L coexists with Cytotoxic T-lymphocyte Antigen-2 alpha in distinct regions of the mouse brain.

Acta Histochem. 2016 Aug 29;

Authors: Luziga C, Nga BT, Mbassa G, Yamamoto Y

Abstract
Cathepsins B and L are two prominent members of cystein proteases with broad substrate specificity and are known to be involved in the process of intra- and extra-cellular protein degradation and turnover. The propeptide region of cathepsin L is identical to Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) discovered in mouse activated T-cells and mast cells. CTLA-2α exhibits selective inhibitory activities against papain and cathepsin L. We previously demonstrated the distribution pattern of the CTLA-2α protein in mouse brain by immunohistochemistry, describing that it is preferentially localized within nerve fibre bundles than neuronal cell bodies. In the present study we report colocalization of cathepsin L and CTLA-2α by double labeling immunofluorescence analysis in the mouse brain. In the telencephalon, immunoreactivity was identified in cerebral cortex and subcortical structures, hippocampus and amygdala. Within the diencephalon intense colocalization was detected in stria medullaris of thalamus, mammillothalamic tract, medial habenular nucleus and choroid plexus. Colocalization signals in the mesencephalon were strong in the hypothalamus within supramammillary nucleus and lateroanterior hypothalamic nucleus while in the cerebellum was in the deep white matter, granule cell layer and Purkinje neurons but moderately in stellate, and basket cells of cerebellar cortex. The distribution pattern indicates that the fine equilibrium between synthesis and secretion of cathespin L and CTLA-2α is part of the brain processes to maintain normal growth and development. The functional implication of cathespin L coexistence with CTLA-2α in relation to learning, memory and disease mechanisms is discussed.

PMID: 27586811 [PubMed - as supplied by publisher]

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Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study.

Hearing impairment, cognition and speech understanding: exploratory factor analyses of a comprehensive test battery for a group of hearing aid users, the n200 study.

Int J Audiol. 2016 Sep 2;:1-20

Authors: Rönnberg J, Lunner T, Ng EH, Lidestam B, Zekveld AA, Sörqvist P, Lyxell B, Träff U, Yumba W, Classon E, Hällgren M, Larsby B, Signoret C, Pichora-Fuller MK, Rudner M, Danielsson H, Stenfelt S

Abstract
OBJECTIVE: The aims of the current n200 study were to assess the structural relations between three classes of test variables (i.e. HEARING, COGNITION and aided speech-in-noise OUTCOMES) and to describe the theoretical implications of these relations for the Ease of Language Understanding (ELU) model.
STUDY SAMPLE: Participants were 200 hard-of-hearing hearing-aid users, with a mean age of 60.8 years. Forty-three percent were females and the mean hearing threshold in the better ear was 37.4 dB HL.
DESIGN: LEVEL1 factor analyses extracted one factor per test and/or cognitive function based on a priori conceptualizations. The more abstract LEVEL 2 factor analyses were performed separately for the three classes of test variables.
RESULTS: The HEARING test variables resulted in two LEVEL 2 factors, which we labelled SENSITIVITY and TEMPORAL FINE STRUCTURE; the COGNITIVE variables in one COGNITION factor only, and OUTCOMES in two factors, NO CONTEXT and CONTEXT. COGNITION predicted the NO CONTEXT factor to a stronger extent than the CONTEXT outcome factor. TEMPORAL FINE STRUCTURE and SENSITIVITY were associated with COGNITION and all three contributed significantly and independently to especially the NO CONTEXT outcome scores (R(2) = 0.40).
CONCLUSIONS: All LEVEL 2 factors are important theoretically as well as for clinical assessment.

PMID: 27589015 [PubMed - as supplied by publisher]

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Postoperative changes in sacropelvic junction in short-segment angular kyphosis versus Scheuermann kyphosis

Abstract

Purpose

To comparatively evaluate the biomechanical alterations those occur in the sagittal plane of sacropelvic junction in angular kyphosis (AK) and Scheuermann kyphosis (SK) patients after surgery.

Methods

The spine radiographs of 52 patients operated for short-segment AK (n = 20) or SK (n = 32) were studied. Main outcome measures were sacral slope, pelvic incidence, pelvic tilt, lumbar lordosis, and thoracic kyphosis angles.

Results

In AK group, local and thoracic kyphosis angles, as well as lumbar lordosis angle, showed statistically significant reduction with surgery. Thoracic kyphosis and lumbar lordosis angles were reduced significantly in SK group. Postoperatively, there were significant differences between groups in lumbar lordosis, pelvic tilt angle, and sacral slope (p = 0.021, p = 0.001, and p = 0.027, respectively). Thoracic kyphosis angle and sacral slope were increased, and there was a remarkable correlation between thoracic kyphosis and lumbar lordosis values in the AK group.

Conclusions

The results of this study suggest that a significant sacropelvic improvement can be achieved by balanced sagittal vertical axis and T1 spinopelvic leading to a good sagittal alignment of spine in patients with AK and SK. Changes seen in morphological parameters after surgery may be closely related with baseline biomechanics and structure of the spine and pelvis. Therefore, further clinical and scientific trials are necessary both to elucidate the biomechanics, their clinical implications, and to develop new techniques and models for spine and pelvis surgery.

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Incidence of cancer in adolescent idiopathic scoliosis patients treated 25 years previously

Abstract

Purpose

To report the incidence of cancer in a cohort of adolescent idiopathic scoliosis (AIS) patients treated 25 years previously.

Methods

215 consecutive AIS patients treated between 1983 and 1990 were identified and requested to return for clinical and radiographic examination. The incidence of cancer was determined through chart review and follow-up interviews. Using the original radiographic log file that included patient position, mAs, kV and the total number of X-rays taken, a radiation physicist calculated the total radiation dose during treatment and follow-up adjusted for BMI and sex.

Results

From the original cohort of 215 consecutive AIS patients, radiation information was available in 211 of the patients, and medical charts were available in 209 AIS patients. 170 (83 %) of the 205 AIS patients participated in the follow-up study with questionnaires. The calculated mean total radiation exposure was 0.8–1.4 mSV per examination and 2.4–5.6 mSv/year. An average of 16 radiographs were taken during the treatment period. Nine AIS patients developed cancer, mostly breast (3) and endometrial (4). The AIS patients had a relative risk of 4.8 (CI 2.3–5.8, p < 0.000) for developing cancer compared to the normal Danish population.

Conclusions

The overall cancer rate in this AIS cohort was 4.3 % which is five times higher than compared to the age-matched Danish population, and endometrial and breast cancer was most frequent. The radiation dose applied to the patients in this study, is comparable to modern equipment. This is to our knowledge the first study to report increased rates of endometrial cancers in a cohort of AIS patients, and future attention is needed to reduce the radiation dose distributed to the AIS patients both pre-operatively and during surgery.

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High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells

Abstract

Purpose

Recent evidences indicates that hydroxytyrosol, one of the main olive oil phenols, possess antitumor effects because of its pro-oxidant properties and the capacity to inhibit proliferation and to promote apoptosis in several tumor cell lines, although most of the results were obtained for breast and digestive systems cancers.

Methods

In this study, we evaluated the activities of hydroxytyrosol against papillary (TPC-1, FB-2) and follicular (WRO) thyroid cancer cell lines.

Results

Cellular viability revealed that high doses of hydroxytyrosol reduced cancer cells viability concomitantly with a reduction of cyclin D1 expression and an up-regulation of cell cycle key modulator p21 levels. In the same experimental conditions, Annexin V–PI staining and DNA laddering revealed that hydroxytyrosol exerts proapoptotic effects on papillary and follicular cancer cells. Furthermore, by Western blot analysis, we observed that hydroxytyrosol treatment reduced thyroid cancer cells viability by promoting apoptotic cell death via intrinsic pathway.

Conclusions

Collectively, our results demonstrated for the first time that in thyroid cancer cells hydroxytyrosol promoted apoptosis at higher doses with respect to other cancer cells lines. Therefore, further studies will reveal the mechanisms by which thyroid cancer cells are more resistant to the proapoptotic effect exerted by hydroxytyrosol as well as the potential application as novel target therapeutic in thyroid cancer.

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Improving safety of fluoropyrimidine chemotherapy by individualizing treatment based on dihydropyrimidine dehydrogenase activity - Ready for clinical practice?

Related Articles

Improving safety of fluoropyrimidine chemotherapy by individualizing treatment based on dihydropyrimidine dehydrogenase activity - Ready for clinical practice?

Cancer Treat Rev. 2016 Aug 13;50:23-34

Authors: Meulendijks D, Cats A, Beijnen JH, Schellens JH

Abstract
Fluoropyrimidines remain the cornerstone of treatment for different types of cancer, and are used by an estimated two million patients annually. The toxicity associated with fluoropyrimidine therapy is substantial, however, and affects around 30% of the patients, with 0.5-1% suffering fatal toxicity. Activity of the main 5-fluorouracil (5-FU) metabolic enzyme, dihydropyrimidine dehydrogenase (DPD), is the key determinant of 5-FU pharmacology, and accounts for around 80% of 5-FU catabolism. There is a consistent relationship between DPD activity and 5-FU exposure on the one hand, and risk of severe and potentially lethal fluoropyrimidine-associated toxicity on the other hand. Therefore, there is a sound rationale for individualizing treatment with fluoropyrimidines based on DPD status in order to improve patient safety. The field of individualized treatment with fluoropyrimidines is now rapidly developing. The main strategies that are available, are based on genotyping of the gene encoding DPD (DPYD) and measuring of pretreatment DPD phenotype. Clinical validity of additional approaches, including genotyping of MIR27A has also recently been demonstrated. Here, we critically review the evidence on clinical validity and utility of strategies available to clinicians to identify patients at risk of developing severe and potentially fatal toxicity as a result of DPD deficiency. We evaluate the advantages and limitations of these methods when used in clinical practice, and discuss for which strategies clinical implementation is currently justified based on the available evidence and, in addition, which additional data will be required before implementing other, as yet less developed strategies.

PMID: 27589829 [PubMed - as supplied by publisher]

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Salubrinal Suppresses IL-17-Induced Upregulation of MMP-13 and Extracellular Matrix Degradation Through the NF-kB Pathway in Human Nucleus Pulposus Cells

Abstract

Matrix metalloproteinase 13 (MMP-13) plays an important role in the process of pro-inflammatory cytokine-induced intervertebral disc degeneration (IDD). This study examined the effect of IL-17 on the regulation of MMP-13 and the extracellular matrix (ECM) in the intervertebral disc (IVD). We then examined whether salubrinal, a known inhibitor of eIF2α dephosphorylation, inhibited the IL-17-induced changes mentioned above. Furthermore, we demonstrated a potential therapeutic role for salubrinal in alleviating the chronic inflammatory-dependent degenerative state commonly observed in IDD. After inflammatory distress with IL-17, RT-PCR and western blot were employed to investigate the expression of MMP-13, collagen type II (COL2A1), collagen type I (COL1A1), and aggrecan (ACAN) in nucleus pulpous (NP) tissue. Activation of the NF-kB pathway was measured by western blot and immunocytochemistry following IL-17 treatment. We also examine the level of eIF2α phosphorylation after IL-17 treatment with or without salubrinal. Then, we investigated interactions of the NF-kB pathway to eIF2α phosphorylation. Moreover, we employed salubrinal and a specific inhibitor of NF-kB (BAY11-7082) to evaluate their effects on IL-17-driven regulation of MMP-13 and the ECM, as well as on the activation of NF-kB. The results showed that IL-17 increased the production of MMP-13 and decreased expression of COL2A1 and ACAN via the NF-kB pathway. Either IL-17 or salubrinal increased the level of eIF2α phosphorylation, but the effects of BAY11-7082 on the level of p-eIF2α were not detectable. BAY11-7082 and salubrinal significantly suppressed IL-17-driven intervertebral disc degeneration. Furthermore, salubrinal produced stronger effects than BAY11-7082. These results imply the potential involvement of IL-17 in IDD through activation of NF-kB signaling, which successively upregulated the expression of MMP-13 and led to the degradation of the ECM. Furthermore, salubrinal can inhibit this process through inhibition of NF-kB activation that is not directly linked to eIF2α phosphorylation, suggesting a potential therapeutic role in IDD.

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Mammaglobin and DOG-1 expression in polymorphous low-grade adenocarcinoma: an appraisal of its origin and morphology

Background

Polymorphous low-grade adenocarcinoma (PLGA) remains a diagnostic challenge for most pathologists due to its large spectrum of histological patterns. In this study, the expression of two new markers recently described for salivary gland tumors was studied in PLGA.

Methods

The morphology of 33 cases of PLGA was carefully evaluated using hematoxylin-and-eosin-stained sections and confirmed by immunohistochemistry for cytokeratin 7, vimentin, and S-100. Periodic acid–Schiff with diastase digestion was also used. The expression of mammaglobin and DOG-1 was carried out using the EnVision System. Mammaglobin was assessed according to the percentage of positively stained tumor cells, while DOG-1 was evaluated according to its presence and site. For MCM-2 and Ki-67, markers of proliferation, the labeling index of cell nuclei positivity was evaluated using total cell number. The ETV6-NTRK3 fusion was examined by fluorescence in situ hybridization analysis.

Results

The histological patterns of the tumor were classified as lobular or non-lobular. For the non-lobular pattern, tubular, cribriform, glomeruliform, trabecular, and papillary patterns were observed. Mammaglobin was present in all PLGA cases, and its expression was stronger (P = 0.01) in the lobular than in the non-lobular pattern. The expression of DOG-1 was present in the apical portion and cytoplasm of the cells. Proliferation markers were low for all cases independent of histological pattern.

Conclusions

Polymorphous low-grade adenocarcinoma has been confirmed to originate from the intercalated duct and to feature high expression of mammaglobin in its lobular pattern resembling that of mammary secretory analogue carcinoma, except for the ETV6 gene rearrangement.

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Non-cannibalistic tumor cells of oral squamous cell carcinoma can express phagocytic markers

Abstract

Background

CD68 and lysozyme expression in cannibalistic tumor cells of oral squamous cell carcinoma (OSCC) is well established. Transformation of cancer cells into cannibalistic cells is a process involving sequential events. Initial event could be genetic expression of proteins that is required for execution of cannibalism. Hence, it is quite possible that some non-cannibalistic tumor cells can also show expression of cannibalistic markers (CD68 and lysozyme).

Methodology

Formalin fixed tissue of 30 OSCC with cellular cannibalism (CC) (positive control), 30 OSCC without CC and 17 normal oral epithelium specimens (negative control) were subjected to immunohistochemical analysis for CD68 and lysozyme expression.

Results

OSCC with CC showed CD68 and lysozyme expression in 30 (100%) cases each [CD68: (weak: 21 (70%), strong: 9 (30%); lysozyme: (weak: 24 (80%), strong: 6 (20%)]. In OSCC without CC, CD68 positive tumor cells were present in 13 (43.33%) cases [(weak: 10 (33.33%); strong: 3 (10%)] and lysozyme expression was present in 13 (43.33%) cases [(weak: 12 (40%); strong: 1 (3.33%)]. Control group showed negative expression for CD68 and lysozyme in the oral epithelium. The CD68 and lysozyme expression in OSCC without CC, OSCC with CC and control group showed statistically significant differences (p < 0.001). Significant correlation was also observed between CD68 and lysozyme expression and different grades of OSCC.

Conclusion

CD68 and lysozyme expression in non-cannibalistic tumor cells of OSCC can be related to CC.

This article is protected by copyright. All rights reserved.

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Decrease in Middle Ear Resonance Frequency During Pregnancy.

Related Articles

Decrease in Middle Ear Resonance Frequency During Pregnancy.

Audiol Res. 2016 Apr 20;6(1):147

Authors: Dag EK, Gulumser C, Erbek S

Abstract
Many physiological changes occur during pregnancy. The aim of the study was to reveal whether there is a change in middle ear resonance frequency during pregnancy. A prospective case-control study was designed at a tertiary referral center. The study included 46 pregnant women at the third trimester (27-40 weeks) and 43 nonpregnant voluntary women. All the study subjects underwent pure-tone audiometry and multifrequency tympanometry. Pure-tone hearing levels at frequencies of 250 to 8000 Hz and resonance frequency values were compared between pregnant and nonpregnant women. Impact of age, side of the tested ear, and weight gained in pregnancy on resonance frequency were evaluated. Air conduction threshold values at frequencies of 250 Hz and 500 Hz were significantly higher in pregnant women than in the control group (P<0.001). Middle ear resonance frequency values of both ears in pregnant women were found to be significantly lower than those in control group (P<0.001). There was no statistically significant relation of middle ear resonance frequency values to age or side of the tested ear in both groups (P>0.05). A negative correlation between weight gained in pregnancy and middle ear resonance frequency values was determined for the left ear (correlation coefficient for left ears: -0.348, P=0.018). The results of this study suggest that resonance frequency may be decreased during the pregnancy. More comprehensive studies in which many pregnant women followed regularly before and after pregnancy are needed to have more certain links.

PMID: 27588163 [PubMed]

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Evaluation of Speech-Perception Training for Hearing Aid Users: A Multisite Study in Progress.

Related Articles

Evaluation of Speech-Perception Training for Hearing Aid Users: A Multisite Study in Progress.

Semin Hear. 2015 Nov;36(4):273-83

Authors: Miller JD, Watson CS, Dubno JR, Leek MR

Abstract
Following an overview of theoretical issues in speech-perception training and of previous efforts to enhance hearing aid use through training, a multisite study, designed to evaluate the efficacy of two types of computerized speech-perception training for adults who use hearing aids, is described. One training method focuses on the identification of 109 syllable constituents (45 onsets, 28 nuclei, and 36 codas) in quiet and in noise, and on the perception of words in sentences presented in various levels of noise. In a second type of training, participants listen to 6- to 7-minute narratives in noise and are asked several questions about each narrative. Two groups of listeners are trained, each using one of these types of training, performed in a laboratory setting. The training for both groups is preceded and followed by a series of speech-perception tests. Subjects listen in a sound field while wearing their hearing aids at their usual settings. The training continues over 15 to 20 visits, with subjects completing at least 30 hours of focused training with one of the two methods. The two types of training are described in detail, together with a summary of other perceptual and cognitive measures obtained from all participants.

PMID: 27587914 [PubMed]

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Auditory Training: Consideration of Peripheral, Central-Auditory, and Cognitive Processes.

Related Articles

Auditory Training: Consideration of Peripheral, Central-Auditory, and Cognitive Processes.

Semin Hear. 2015 Nov;36(4):197-8

Authors: Preminger JE

PMID: 27587908 [PubMed]

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Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema.

Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema.

J Dermatolog Treat. 2016 Sep 2;:1-19

Authors: Jin H, Kim JM, Kim GW, Mun JH, Song M, Kim HS, Ko HC, Kim MB, Kim BS

Abstract
BACKGROUND: The limited efficacy of topical tacrolimus may result from insufficient frequency of application or amount applied in eczema patients.
OBJECTIVE: To investigate the frequency of application and amount of use of topical tacrolimus in patients with various types of eczema.
METHODS: The frequency of application and the applied amount of topical tacrolimus were assessed over 2 weeks.
RESULTS: A total of 200 eczema patients completed this study. The average number of applications per day was 1.75 ± 0.53, despite instructions to apply the topical tacrolimus twice daily. With respect to the frequency of application, 147 (73.5%) and 122 (61.0%) of patients followed the prescription in the first and second weeks, respectively. The average amount applied per 2% of total body surface area was 0.54 ± 0.52 g. Only 53 (26.5%) patients applied between 80% and 120% of expected amount of topical tacrolimus.
LIMITATIONS: The frequency of application was self-reported, possibly resulting in limited accuracy.
CONCLUSION: Korean patients with eczema tend to apply topical tacrolimus less frequently and in inappropriate amounts. Clear instructions regarding both the frequency and amount of application are needed to improve the therapeutic outcome with treatment with topical tacrolimus.

PMID: 27588441 [PubMed - as supplied by publisher]

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Proposal for magnetic resonance imaging-guided salvage radiotherapy for prostate cancer.

Related Articles

Proposal for magnetic resonance imaging-guided salvage radiotherapy for prostate cancer.

Acta Oncol. 2016 Sep 1;:1-6

Authors: Dirix P, van Walle L, Deckers F, Van Mieghem F, Buelens G, Meijnders P, Huget P, Van Laere S

Abstract
BACKGROUND: A subset of patients experience a biochemical recurrence following radical prostatectomy. Radiotherapy can salvage those patients, provided that all disease is encompassed within the target volume. We hypothesized that this can be achieved more adequately with magnetic resonance imaging (MRI)-guided treatment planning.
MATERIAL AND METHODS: From January 2009 to April 2014, 183 patients were referred to our department for salvage radiotherapy (SRT). According to protocol, patients received a planning computed tomography (CT) as well as an MRI in treatment position. All MRI scans were retrospectively reviewed by an experienced uro-radiologist.
RESULTS: Median prostate-specific antigen (PSA) value at time of referral was 0.3 ng/ml (range 0.02-4.7 ng/ml). MRI did not show any suspected macroscopic disease in 137 patients (75%). In 46 (25%) patients, MRI did indicate a pelvic recurrence. The mean PSA level was significantly higher in patients with a suspected recurrence on MRI (0.4 vs. 1.4 ng/ml, p < .001) on a Student's t-test. The mean follow-up was 33 months (range 5-69 months). Biochemical disease-free survival (bDFS) was significantly worse in patients with suspected disease on MRI [hazard ratio (HR) 2.9, p < .0001]. bDFS was significantly worse in the subgroup where the macroscopic recurrences on MRI received a lower radiation dose (HR 3.4, p = .01).
CONCLUSION: MRI detects loco-regional disease in a substantial subset of patients with a biochemical recurrence after prostatectomy, especially in a PSA above 0.5 μg/l. Lack of MRI-based dose escalation on these macroscopic recurrences could explain some of the biochemical progression observed after SRT.

PMID: 27587084 [PubMed - as supplied by publisher]

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Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study

Abstract

Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan–gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan–gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan–gelatin scaffolds. Implantation of both the gelatin and chitosan–gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin–chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects.

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Specific Features of Progression of the Parasitic Invasion, caused by Opisthorchis felineus , in Golden Hamsters

The influence of Opisthorchis felineus invasion on the development of pathological changes in the hepatobiliary system was studied in 120 golden hamsters in a long-term experiment (42 weeks) after single infection per os in the dose of 50 metacercariae per animal. The animals were sacrificed on weeks 4, 8, 12, 16, 28 and 42. Chronic experimental infestation with O. felineus triggered a cascade of morphogenetic processes in both extrahepatic and intrahepatic biliary systems. At the early stages of the experiment, polyps and strictures of bile ducts were formed in the lobar bile ducts; in portal tracts, hyperplasia and adenomatous transformation of the newly formed epithelial structures were observed. At the later stages, third-degree biliary intraepithelial neoplasia developed in the lobar bile ducts; in the intrahepatic bile ducts, increased epitheliocyte hyperplasia and invasive growth of cell cords were observed, that impaired tissue architectonics. Progressing cell atypia can be classified as cholangiocellular cancer.

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Preparation of Articular Cartilage Specimens for Scanning Electron Microscopy

We developed and adapted a technology for preparation of articular cartilage specimens for scanning electron microscopy. The method includes prefixation processing, fixation, washing, and dehydration of articular cartilage specimens with subsequent treatment in camphene and air-drying. The technological result consists in prevention of deformation of the articular cartilage structures. The method is simpler and cheaper than the known technologies.

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Biocompatibility of Experimental Polymeric Tracheal Matrices

Biocompatibility of a new tracheal matrix is studied. The new matrix is based on polymeric ultra-fiber material colonized by mesenchymal multipotent stromal cells. The experiments demonstrate cytoconductivity of the synthetic matrices and no signs of their degradation within 2 months after their implantation to recipient mice. These data suggest further studies of the synthetic tracheal matrices on large laboratory animals.

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Effect of Linagliptin on Structural Changes in the Kidney in Experimental Type 2 Diabetes Mellitus

Effect of the dipeptidyl peptidase-4 inhibitor linagliptin on structural manifestations of diabetic nephropathy was studied in BKS.Cg-Dock7m+/+Leprdb/J mice (experimental model of type 2 diabetes mellitus). Linagliptin (10 mg/kg per day) or vehicle was administered by gavage over 8 weeks. Mesangial expansion, thickening of the basement membrane in glomerular capillaries and proximal tubules, and retraction of cytopodia were less pronounced in mice receiving linagliptin. The protective effect of linagliptin on the kidney structure was not associated with its hypoglycemic action.

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Changes in Sympathetic Innervation of Rat Caudal Artery in Experimental Myocardial Infarction. Effect of Semax Peptide

Activation of the sympathetic nervous system aggravates the course of myocardial infarction. Semax peptide moderated the degree of this activation and prevented the increase in the density of sympathetic endings in rat caudal artery in 28 days after ischemia or ischemia/reperfusion. The peptide reduced the density of α-adrenoreceptors in the caudal artery of rats with myocardial infarction. Semax produced no effect on β-adrenoreceptors in both experimental models. The experiments on isolated segments of the caudal artery revealed reduced vascular responsiveness to electrical stimulation and norepinephrine infusion in rats treated with Semax after ischemia/reperfusion injury.

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Expression of Molecular Markers of Angiogenesis, Lymphangiogenesis, and Proliferation Depending on the Stage of Skin Melanoma

The expression of molecular markers characterizing activity of the tumor process and metastases (proliferation marker Ki-67, angiogenesis marker CD34, and lymphangiogenesis markers podoplanin and LYVE-1) was assessed by immunohictochemical method in the primary tumor specimens collected during surgery for cutaneous melanoma (40 patients). Proliferative activity of the tumor tissue and volume density of peritumoral blood and lymph vessels increased with increasing tumor malignancy, which could indicate the risk of metastases.

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Response of Inflammatory Mediators, Extracellular Matrix Proteins and Stem and Progenitor Cells to Emphysema

Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45^–CD31⁺CD34⁺) and epithelial (CD45^–CD117⁺CD49f⁺) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue. Emphysematous changes in the lungs were accompanied by infiltration of the alveolar septa with macrophages and lymphocytes, increase in the serum and lung concentrations of transforming growth factor-β, IL-1β, IL-2, IL-5, IL-10, and IL-13, and lung concentration of IL-17. In the lungs, inflammation was associated with marked increase in the number of multipotent mesenchymal stromal cells CD90⁺CD73⁺CD106⁺CD44⁺) and Clara cells (CD45^–CD34^–CD31^–Sca1⁺) and overexpression of extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, fibronectin) and Clara cells protein. On the other hand, elastase reduced the number of angiogenic precursor cells (CD45^–CD117⁺Flk1⁺).

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Intravital Computer Morphometry on Protozoa: A Method for Monitoring of the Morphofunctional Disorders in Cells Exposed in the Cell Phone Communication Electromagnetic Field

Morphofunctional disorders in unicellular aquatic protozoa – Spirostomum ambiguum infusorians after 30-, 60-, and 360-min exposure in electromagnetic field at a radiation frequency of 1 GHz and energy flow density of 50 μW/cm² were analyzed by intravital computer morphometry. Significant disorders in morphometric values correlated with low mobility of the protozoa. The results suggested the use of intravital computer morphometry on the protozoa for early diagnosis of radiation-induced effects of the mobile communication electromagnetic field, for example, low mobility of spermatozoa.

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Dynamics of Structural Parameters and Accumulation of Collagen Fibrils in Rat Lung after Inhalations of Surfactant-BL at Various Terms of Bleomycin-Induced Alveolitis

Rats were subjected to surfactant-BL inhalations at the early and late phases of bleomycininduced alveolitis. In both regimens, the drug reduced the severity of inflammation. In the acute phase of alveolitis, the therapeutic effect of inhalation was accompanied by activation of the synthesis of fine lose collagen fibrils. In the late phase of alveolitis, inhalation of surfactant-BL thickened the fibrils and diminished their population in alveolar walls.

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Pro-Cognitive Effects of Non-Peptide Analogues of Soluble Amyloid Peptide Precursor Fragment sAPP

We studied pro-cognitive effect of two heterocyclic low-molecular-weight compounds that serve as non-peptide analogues of soluble fragment of amyloid peptide precursor (sAPP). Intracerebroventricular and systemic administration of peptide mimetics P2 and P5 improved weak memory on the model of passive avoidance in chicks and in the object location task in mice. Both compounds were effective if administered close to the moment of training or 4 h after it. The time windows and dose range for the pro-cognitive effects of the mimetics were similar to those observed in previous studies with sAPP peptide fragments.

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Inflammatory Pattern of the Bronchial Mucosa in Patients with Asthma with Airway Hyperresponsiveness to Hypoosmotic Stimulus

Positive reaction of the bronchi to distilled water inhalation in asthmatics is associated with significant stimulation of the respiratory epithelium desquamation against the background of increased content of eosinophilic and neutrophilic leukocytes in induced sputum, predomination of eosinophil and neutrophil cytolysis, and lower activity of myeloperoxidase in leukocyte granules (in comparison with the parameter in patients with a negative response to bronchostimulation). Enhanced cytolysis and destruction of leukocytes and high myeloperoxidase concentration in the extracellular space are essential for the development of bronchial hyperresponsiveness to hypoosmotic stimulus in asthma.

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Effect of Bioregulators Isolated from Rat Liver and Blood Serum on the State of Murine Liver in Roller Organotypic Culture after CCl 4 -Induced Fibrosis

We studied the protective effect of bioregulators isolated from the liver and blood serum of mammals under conditions of manifest fibrosis. Fibrosis was induced by CCl₄ administration for 30 days and then, the liver was cultured in a roller organotypic culture for 30 days in the presence of bioregulators. Hepatoprotective effect of bioregulators was evaluated on histological sections of the liver at different terms of culturing. Experiments with roller organotypic culture of the liver isolated from animals with in vivo CCl₄-induced fibrosis demonstrated the protective effect of bioregulator of the liver origin, while bioregulator isolated from the blood was ineffective.

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Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension

Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.

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Effect of Prolyl-Glycyl-Proline (PGP) and Its Acetylated Form (N-AcPGP) on Calcium Level in the Cytoplasm of Rat Peritoneal Mast Cells

Tripeptide glycyl-prolyl-proline (PGP), a regulatory peptide of the glyproline family, possesses a pronounced anti-inflammatory effect primarily due to its ability to prevent secretion of the proinflammatory mediator histamine by rat peritoneal mast cells. Activation of mast cell with synacthen (ACTH1-24) and substance 48/80 leads to an increase in intracellular calcium concentration. Pretreatment of mast cells with PGP prevented calcium entry into the cytoplasm from both intercellular space and intracellular stores. Acetylated peptide (N-AcPGP) produced a similar effect on histamine release and intracellular calcium content in mast cells activated with synacthen. These findings indicate that both forms of the peptide can stabilize mast cells and prevent intracellular calcium increase.

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Development and Differentiation of Mesenchymal Bone Marrow Cells in Porous Permeable Titanium Nickelide Implants In Vitro and In Vivo

We studied the structure of porous permeable titanium nickelide used as the scaffold. In vitro population of the porous scaffold with multipotent mesenchymal stem bone marrow cells on days 7, 14, 21, and 28 was analyzed by scanning electron microscopy. Stage-by-stage histogenesis of the tissues formed from the bone marrow cells in the titanium nickelide scaffold in vivo is described in detail. Using mesenchymal stem cells, we demonstrated that porous permeable titanium nickelide scaffolds are unique incubators for cell cultures applicable for tissue engineering.

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Interaction of Lymphocytes with Mesenchymal Stem Cells

We studied the interaction of neural stem cells and dental pulp-derived mesenchymal stem cells with lymphocytes from autologous and heterologous donors. Flow cytometry analysis with the use of CFSE-labeled lymphocytes demonstrated an increase in the content of proliferating CD8, CD16 and CD56 cells, but not CD4 cells in cultures of HLA-DR-negative mesenchymal stromal cells from the dental pulp co-cultured with lymphocytes. In neural cultures expressing HLA-DR, all subpopulations of T cells and NK cells were activated. No differences between the autologous and heterologous cultures were revealed.

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Expression of Early Activation Marker CD69 on Peripheral Blood Lymphocytes from Pregnant Women after First Trimester Alloimmunization

We studied the expression of an early activation marker CD69 in peripheral blood lymphocytes of pregnant women with a history of recurrent pregnancy loss after immunization with paternal lymphocytes. Spontaneous and phytohemagglutinin-stimulated expression of CD69 on the surface of T cells and NK cells isolated from the peripheral blood was analyzed. On gestation week 5-6, the number of T cells expressing CD69 spontaneously and after stimulation was significantly higher in women with miscarriage than in woman with prolonged pregnancy. However, the number of cells with CD56⁺ phenotype expressing CD69 did not differ in these groups. No differences were found in the number of cells of all subpopulations expressing CD69 after stimulation on gestation week 12 in woman with full-term current pregnancy and in woman with physiological pregnancy.

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Angiogenic Effects of Dimeric Dipeptide Mimetic of Loop 4 of Nerve Growth Factor

Angiogenic action of compound GK-2, a dimeric dipeptide mimetic of loop 4 of nerve growth factor (NGF), was studied in in vitro and in vivo experiments. Experiments on human endothelial cell culture HUVEC showed that compound GK-2 significantly (p<0.05) stimulated the initial stage of angiogenesis, and its angiogenic activity was not inferior to the reference neurotrophin NGF. In experiments with hindlimb ischemia modeled in rats, GK-2 (1 mg/kg intraperitoneally for 14 days) significantly increased the total length of capillary vessels (p<0.003) and the number of vessels per 1 mm2 ischemic tissue (p<0.001) in comparison with the control. Our findings indicate that under experimental conditions compound GK-2 exhibits not only angiogenic, but also anti-ischemic activity.

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Pharmacological Correction of Alcohol Motivation Depends on the Phenotype of the Response to Emotional Stress

The specific features of alcohol behavior were studied in MR and MNRA rats that exhibit an opposite reaction to emotional stress. We evaluated the effect of a dipeptide anxiolytic GB-115 (N-phenyl-hexanoyl-glycyl-L-tryptophan amide, neuropeptide cholecystokinin-4 analogue with antagonistic activity) on alcohol motivation in rats, which was formed over 12 months. High-emotionality MR rats were more sensitive to the anxiolytic effect of ethanol in the conflict situation test than low-emotionality MNRA rats. MNRA rats consumed a greater amount of ethanol under a free-choice condition with 15% ethanol solution and water (as in comparison with MR rats). However, the behavior of MR rats was transformed due to a significant increase in alcohol motivation from the 5th month of long-term free access to ethanol. An anxiolytic GB-115 (0.025 mg/kg intraperitoneally for 14 days) with selective activity in high-emotionality rats was shown to reduce significantly the average daily consumption and alcohol-deprivation effect in MR rats, but did not modulate ethanol addiction in MNRA rats.

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Internalization of Vectored Liposomes in a Culture of Poorly Differentiated Tumor Cells

Internalization of liposomal nanocontainers conjugated with monoclonal antibodies to VEGF, VEGFR2 (KDR), and proteins overproduced in the tumor tissue was studied in vitro on cultures of poorly differentiated tumor cells. Comparative analysis of accumulation of vectored liposomes in the tumor cells was performed by evaluating co-localization of labeled containers and cell organelles by laser scanning confocal microscopy. We observed nearly 2 times more active penetration and accumulation of liposomes vectored with antibodies in the tumor cells in comparison with non-vectored liposomes. Selective clathrin-dependent penetration of vectored liposomes into tumor cells was demonstrated by using pharmacological agents inhibiting endocytosis.

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Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

Esophageal Acidification During Nocturnal Acid-breakthrough with Ilaprazole Versus Omeprazole in Gastroesophageal Reflux Disease.

J Neurogastroenterol Motil. 2016 Sep 1;

Authors: Karyampudi A, Ghoshal UC, Singh R, Verma A, Misra A, Saraswat VA

Abstract
Background/Aims: Though nocturnal acid-breakthrough (NAB) is common in gastroesophageal reflux disease (GERD) patients, its clinical importance results from esophageal acidification, which has been shown to be uncommon. Ilaprazole, a long-acting proton pump inhibitor, may cause NAB infrequently. Accordingly, we studied prospectively, (1) frequency and degree of esophageal acidification during NAB, and (2) frequency and severity of NAB while on ilaprazole versus omeprazole.
Methods: Fifty-eight consecutive patients with GERD on once daily ilaprazole, 10 mg (n = 28) or omeprazole, 20 mg (n = 30) for > one month underwent 24-hour impedance-pH monitoring prospectively. NAB was defined as intra-gastric pH < 4 for > one hour during night and esophageal acidification as pH < 4 for any duration. Nocturnal symptoms (heartburn, regurgitation, and chest pain) were also recorded.
Results: Of 58 patients (age 35.5 [inter-quartile range 26.5-46.0] years, 38 (65.5%) male), 42 (72.4%) had NAB. Though patients with NAB had lower nocturnal intra-gastric pH than without (2.8 [1.9- 4.1] vs 5.7 [4.6-6.8], P < 0.001), frequency and duration of nocturnal esophageal acidification (17/42 vs 4/16, P = 0.36 and 0.0 [0.0-1.0] vs 0.0 [0.0-0.3] minutes, P = 0.26, respectively) and symptoms were comparable (13/42 vs 6/16, P = 0.75). Though ilaprazole was associated with less NABs (1 [range 1-2, n = 19] vs 1 [range 1-3, n = 23], P = 0.01) than omeprazole, frequency, duration, and mean intra-gastric pH during NAB were comparable (19/28 vs 23/30, P = 0.56; 117 [0-315] vs 159 [69-287] minutes, P = 0.5; 1.02 [0.7-1.4] vs 1.04 [0.44-1.3], P = 0.62, respectively).
Conclusions: Though NAB was common while on proton pump inhibitor, esophageal acidification was uncommon. Frequency and severity of NAB were comparable among patients on ilaprazole and omeprazole except for lesser number of NABs.

PMID: 27585842 [PubMed - as supplied by publisher]

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Pylephlebitis: Through These Portals Pass Bad Bugs

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Role of Iron and Copper in the Pathogenesis of Parkinson’s Disease

Abstract

Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system. Abnormalities in iron (Fe) and copper (Cu) metabolism have been reported to produce oxidative stress which is one of the major cause in pathogenesis of PD. In the present study 35 PD patients and 33 controls of Northern Indian population were included and serum levels of Fe, Cu and ceruloplasmin (Cp) were measured. Serum Fe (p < 0.01) and Cu (p < 0.01) levels were found to be significantly decreased in PD, whereas there was no significant change in Cp levels in PD patients as compared to controls. These results suggest the existence of a defect in iron which over the time, may hasten the entry of iron into the brain and decrease iron in the extracellular compartment in PD patients.

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Incidence rate for breast cancer in Japanese in Japan and in the United States from the Cancer Incidence in Five Continents.

Incidence rate for breast cancer in Japanese in Japan and in the United States from the Cancer Incidence in Five Continents.

Jpn J Clin Oncol. 2016 Sep;46(9):883

Authors: Katanoda K, Hori M

PMID: 27585802 [PubMed - in process]

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Grid-Independent Descriptors (GRIND) analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2.

Grid-Independent Descriptors (GRIND) analysis and SAR Guided Molecular Docking Studies to Probe Selectivity Profiles of Inhibitors of Multidrug Resistance Transporters ABCB1 and ABCG2.

Curr Cancer Drug Targets. 2016 Aug 31;

Authors: Shafi T, Jabeen I

Abstract
ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are major determinant of pharmacokinetic, safety and efficacy profiles of drugs thereby effluxing a broad range of endogenous substances across the plasma membrane. Overexpression of these transporters in various tumors is also implicated in the development of multidrug resistance (MDR) and thus, hampers the success of cancer chemotherapy. Modulators of these efflux transporters in combination with chemotherapeutics could be a promising concept to increase the effective intracellular concentration of anticancer drugs. However, broad and overlapped specificity for substrates and modulators of ABCB1 and ABCG2, merely induce toxicity and unwanted drug-drug interactions and thus, lead to late-stage failure of drugs. Therefore, it is of great importance to identify specific 3D structural requirements for selective inhibition of ABCB1 and ABCG2 transport function. Towards this goal, GRID Independent Molecular Descriptor (GRIND) models of selective inhibitors of both transporters have been developed, using their most probable binding conformations obtained from molecular docking protocol. Our results demonstrated a dominant role of molecular shape and different H-bonding patterns in drug-ABCB1/ABCG2 selective interactions. Moreover, distinct distances of different pharmacophoric features from steric hot spots of the molecules provided a strong basis of selectivity for both transporters. Additionally, our results suggested the presence of two H-bond donors at a distance of 8.4-8.8 A° in selective modulators of ABCG2.

PMID: 27585695 [PubMed - as supplied by publisher]

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Three-dimensional cone-beam CT sialography in non tumor salivary pathologies: Procedure and results.

Three-dimensional cone-beam CT sialography in non tumor salivary pathologies: Procedure and results.

Dentomaxillofac Radiol. 2016 Sep 2;:20150431

Authors: Bertin H, Bonnet R, Delemazure AS, Mourrain-Langlois E, Mercier J, Corre P

Abstract
OBJECTIVE: Non-tumor salivary diseases are common. Imaging studies are essential for their diagnosis and before undergoing an endoscopic or surgical treatment. In this study we aimed at presenting our procedure and results obtained with three dimensional cone-beam CT (3D-CBCT) sialography for non-tumor salivary gland diseases.
METHODS: Patients with parotid or submandibular salivary symptoms were examined by 3D-CBCT sialography. They received an intraductal injection of 0.5mL of water-soluble contrast medium maintained in the gland, followed by the examination in a NewTom wide-field CBCT device. Images were processed with multiplanar and three-dimensional reconstructions.
RESULTS: A ductal exploration could be performed until the fourth divisions. The main lesions found were stones, stenosis, dilatations and "dead tree" appearance of the ductal system. No side effects of the catheterization or the iodin contrast was reported, nor tissue damages related to the contrast keeping technique.
CONCLUSION: 3D-CBCT sialography seems to represent a reliable non invasive diagnostic tool for the ductal salivary diseases. More studies are needed to assess the value of 3D-CBCT sialography compared to conventional imaging.

PMID: 27588734 [PubMed - as supplied by publisher]

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Exploring Current Sensory Enhancement Practices Within Videofluoroscopic Swallow Study (VFSS) Clinics.

Exploring Current Sensory Enhancement Practices Within Videofluoroscopic Swallow Study (VFSS) Clinics.

Dysphagia. 2016 Sep 1;

Authors: Turkington L, Nund RL, Ward EC, Farrell A

Abstract
Whilst some research evidence supports the potential benefits of sensory enhancement strategies (SES) in dysphagia management, there is limited understanding of how SES are used in clinical services and the influencing drivers involved in selection during instrumental assessment. SES include modification of temperature, flavour, texture, chemesthetic qualities and bolus size of food/fluid. This study aimed to explore the use of SES within Australian Videofluoroscopic Swallow Study (VFSS) clinics providing adult services, via a qualitative methodology. Maximum variation sampling was used to select a cross section of speech-language pathologists (SLPs) with a range of experience working within 16 VFSS clinics across metropolitan and regional settings to participate in semi-structured, focus group or individual teleconference interviews. Content analysis of interview transcripts was conducted, with four themes emerging as influencing drivers of SES use, including: Patient factors influence SES use; Clinician factors influence SES use; Trials of SES require planning and organisation, and; Organisational barriers impact on SES use. These four themes were all connected through a single integrative theme: Extensive variations of SES procedures exist across clinical settings. Findings indicate that achieving alignment of clinical purpose and implementation of practices amongst VFSS clinicians will be complex given current diversity in SES use. Organisational issues and clinician training need to be addressed, and more research is needed to provide a stronger evidence base to inform clinical practice in this emerging area of dysphagia management.

PMID: 27586878 [PubMed - as supplied by publisher]

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