Αρχειοθήκη ιστολογίου

Σάββατο 2 Ιουλίου 2016

Umbilical reconstruction with the bow tie flap

Abstract

The umbilicus can be absent in congenital malformations that are associated to umbilical agenesia such as bladder exstrophy, gastroschisis or omphalocele or it can be excised during surgical procedures such as umbilical herniorrhaphy, abdominoplasty and laparotomy. We report a new technique for umbilical reconstruction, using a "bow tie"-shaped flap, partially made of scar tissue. We treated three female patients with absent umbilicus as a consequence of congenital malformations or previous surgical treatments. This method provided a good conical shape to the neoumbilicus with adequate depth and a wide external ring. Follow-up at 2 years showed that a satisfactory shape was maintained. Previously described techniques for neoumbilicoplasty were unsatisfying or seemed too complex in our hands. The reported technique is easy and simple, with good, stable and natural aesthetic results, and it can be effectively used for umbilical reconstruction in all primary or secondary cases of umbilical absence.

Level of evidence: Level V, therapeutic study.



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Versatility of lateral arm flap for hand reconstruction—a clinical experience

Abstract

Background

The lateral arm free flap (LAFF) has several advantages in hand reconstruction due to multiple factors. We aimed to show the versatility of LAFF in treating hand defects.

Methods

A retrospective analysis of all LAAF for hand reconstruction carried out at our institutions between August 2006 and August 2012 was undertaken. Clinical records were reviewed with respect to patients' age and gender, size and location of defect, type and size of flaps, and complications.

Results

Twenty-four hand defects were reconstructed using LAFF. These included 15 cutaneous flaps, 8 fascial flaps, and 1 osteocutaneous flap. All flaps survived well except for one case that developed arterial insufficiency and required anastomotic revision. Primary closure of the donor site was possible in all patients. No complications occurred during the healing procedure.

Conclusions

The free lateral arm flap is a versatile and reliable option for defect coverage at the hand for small- and medium-size defects. It can be raised as a cutaneous, fascial, or osteocutaneous flap. Several advantages favor the use of lateral arm flap in hand reconstruction. These include preservation of major arm blood vessels, its constant vascular anatomy, long pedicle, and low donor site morbidity.

Level of Evidence: Level IV, therapeutic study.



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Pleurodesis with Thulium Cyber Laser versus talc poudrage: a comparative experimental study

Abstract

Sclerosing fluids to achieve pleurodesis could be hardly replaced for bed-side procedures, but other devices may be successfully applied during thoracoscopy. Thulium Cyber Laser was experimented for this purpose and compared to talc poudrage. Twenty pigs underwent operative videothoracoscopy (VATS). Ten models were subjected to double-port VATS and parietal pleura photoevaporation using Thulium Cyber Laser™ (TCL) 150 W 2010 nm on the posterior third of three ribs; the pleural surface was homogeneously treated inside the target perimeter. The remaining ten pigs underwent uniportal thoracoscopy; talc poudrage was performed using the current clinical practice dosage (1 g/18 kg) with accurate talc powder spread over the whole pleural surface. All models were followed up for 60 days. Pleurodesis firmness was graded on a three-tier scale (none-moderate-firm) and site-matching topographical expectancy was evaluated. TCL produced pleurodesis in all models: 7/10 were firm and 3/10 moderate. Talc poudrage pleurodesis was firm in 4/10 and moderate in 6/10. Pleural adhesions were found exclusively in the treated area after laser treatment, while talc created a wide spectrum of effects, most commonly anarchic jagged adhesions obliterating less than 50 % of the pleural cavity (7/10), mostly declivous. The pathologist found more aggressive inflammation (sometimes severe) in the talc group. Expected localized pleurodesis was always registered in laser group (10/10), while talc poudrage was found poorly effective if consistent pleurodesis is expected in an apico-dorsal position (2/10). Laser pleurodesis appears more homogeneous, qualitatively not inferior, and topographically more predictable than talc pleurodesis. Parietal photoevaporation seems effective and the localized pleurodesis is reproducible.



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MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

Abstract

Background

MicroRNA-506 (miR-506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR-506 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR-506 in PDAC.

Methods

Using miRNA in situ hybridization, we examined the expression of miR-506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated miR-506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR-506 expression and the clinicopathologic characteristics of PDAC patients.

Results

miR-506 expression was higher in PDAC than in matched normal pancreatic ductal cells (P < 0.001). On the other hand, the combined group of well and moderately differentiated PDACs showed higher levels of miR-506 than the poorly differentiated ones (P = 0.023). Moreover, miR-506 expression was negatively associated with pathologic T category (P = 0.004) and lymph node metastasis (P = 0.033), suggesting that miR-506 might inhibit the progression of PDAC.

Conclusions

Our results suggest that miR-506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house-keeping, tumor-suppressing miRNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.



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Relapse of both small cell lung cancer and Lambert–Eaton myasthenic syndrome after a 13-year disease-free survival period

Abstract

Lambert–Eaton myasthenic syndrome (LEMS) is a paraneoplastic syndrome and only 3% of small cell lung carcinoma (SCLC) patients have LEMS. Moreover, the recurrence of SCLC after a disease-free survival (DFS) of more than 10 years is rare. We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period. A 69-year-old man was diagnosed with LEMS and SCLC (cT0N2M0, stage IIIA) 13 years ago. Chemoradiotherapy was performed and a complete response was achieved. With anticancer treatment, the LEMS symptoms was alleviated. At the age of 82 years, gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC. Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.



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A New Technique for Correction of Tethered and Depressed Scars: Layered Dermal Support

Abstract

Background

Many methods have been used for correcting tethered and depressed scars, but most of these methods have had unsatisfying results and ended up with recurrence. The aim of this study is to present a new surgical technique that overcomes these problems.

Materials and Methods

Twenty-two depressed scars were corrected using the layered dermal support technique. With this technique, the depressed part of the scar is deepithelialized and used in a layered fashion to support the skin flaps.

Results

All of the patients were evaluated 1 year postoperatively. There was no recurrence of tethering or depression.

Conclusion

The layered dermal support technique is a relatively quick procedure that uses only basic plastic surgery principles. It offers a good solution for the correction of tethered and depressed scars without recurrence.

Level of evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.



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Monitoring What is Real: the Effects of Modality and Action on Accuracy and Type of Reality Monitoring Error

Publication date: Available online 2 July 2016
Source:Cortex
Author(s): Jane R. Garrison, Rebecca Bond, Emma Gibbard, Marcia K. Johnson, Jon S. Simons
Reality monitoring refers to processes involved in distinguishing internally generated information from information presented in the external world, an activity thought to be based, in part, on assessment of activated features such as the amount and type of cognitive operations and perceptual content. Impairment in reality monitoring has been implicated in symptoms of mental illness and associated more widely with the occurrence of anomalous perceptions as well as false memories and beliefs. In the present experiment, the cognitive mechanisms of reality monitoring were probed in healthy individuals using a task that investigated the effects of stimulus modality (auditory vs. visual) and the type of action undertaken during encoding (thought vs. speech) on subsequent source memory. There was reduced source accuracy for auditory stimuli compared with visual, and when encoding was accompanied by thought as opposed to speech, and a greater rate of externalization than internalization errors that was stable across factors. Interpreted within the source monitoring framework (Johnson, Hashtroudi, & Lindsay, 1993), the results are consistent with the greater prevalence of clinically observed auditory than visual reality discrimination failures. The significance of these findings is discussed in light of theories of hallucinations, delusions and confabulation.



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Aortic valve aneurysm associated with infective endocarditis: case report and review of literature

Abstract

Although there are several mitral valve aneurysm reports, studies on aortic valve aneurysm are extremely rare. This paper describes an uncommon case of a large saccular aortic valve aneurysm associated with infective endocarditis. A 37-year-old man was hospitalized in our hospital with fever and dyspnea. Echocardiography found severe aortic regurgitation and aortic valve aneurysm of the non-coronary cusp going in and out of the left ventricular chamber. Blood cultures grew Streptococcus viridance. Therefore, the patient underwent aortic valve replacement. During the operation, we observed a 30 × 20 mm ruptured aneurysm that arose from the non-coronary cusp. The aortic valve containing the aneurysm was resected and replaced with a mechanical heart valve. Histopathological examination of the aortic valve aneurysm showed active inflammatory changes. Infective endocarditis was considered to be the cause of this aortic valve aneurysm.



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Prognostic significance of p53 expression in patients with esophageal cancer: a meta-analysis

Abstract

Background

The prognostic value of p53 protein expression in esophageal cancer has been evaluated, but the results remain inconclusive and no consensus has yet been achieved. This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in esophageal cancer.

Methods

Publications that assessed the clinical or prognostic significance of p53 expression in esophageal cancer and were published before July 1, 2015 were identified by searching the PubMed and EMBASE databases. A meta-analysis was performed to clarify the association between p53 expression and the clinical outcomes.

Results

A total of 36 publications met the criteria and included 4577 cases. Analysis of these data showed that p53 expression in esophageal cancer was significantly associated with poorer 5-year survival (RR = 1.30, 95 % CI: 1.11–1.51, P = 0.0008). Subgroup analyses according to histological type, continent of the patients, and cut-off value revealed the similar results. The results also indicated that p53 expression was highly associated with advanced TNM stages (I/II vs. III/IV, OR = 0.74, 95 % CI: 0.55–0.99, P = 0.04), lymph node metastasis (OR = 0.77, 95 % CI: 0.66–0.90, P = 0.001), and distant metastasis (OR = 0.46, 95 % CI: 0.26–0.80, P = 0.006). However, p53 expression in the included studies was not significantly associated with tumor size (≤ 5 cm vs. > 5 cm, OR = 1.13, 95 % CI: 0.92–1.40, P = 0.24), tumor location (upper + middle vs. lower, OR = 0.91, 95 % CI: 0.70–1.17, P = 0.45), grade of differentiation (well + moderate vs. poor, OR = 1.10, 95 % CI: 0.90–1.34, P = 0.35), and the depth of invasion (T1/T2 vs. T3/T4, OR = 0.86, 95 % CI: 0.71–1.03, P = 0.09).

Conclusions

This meta-analysis showed that p53 expression may be a useful biomarker for predicting poorer prognosis in patients with esophageal cancer.



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Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice

Abstract

Every year 170,000 patients are diagnosed with brain metastases (BMs) in the United States. Traditionally, adjuvant whole brain radiotherapy (AWBRT) has been offered following local therapy with neurosurgery (NSx) and/or stereotactic radiosurgery (SRS) to BMs. The aim is to increase intracranial control, thereby decreasing symptoms from intracranial progression and a neurological death. There is a rapidly evolving change in the radiation treatment of BMs happening around the world. AWBRT is now being passed over in favour of repeat scanning at regular intervals and more local therapies as more BMs appear radiologically, BMs that may never become symptomatic. This change has happened after the American Society for Radiation Oncology (ASTRO) in Item 5 of its "Choosing Wisely 2014" list recommended: "Don't routinely add adjuvant whole brain radiation therapy to SRS for limited brain metastases". The guidelines are supposed to be based on the highest evidence to hand at the time. This article debates that the randomised controlled trials (RCTs) published prior to this recommendation consistently showed AWBRT significantly increases intracranial control, and avoids a neurological death, what it is meant to do. It also points out that, despite the enormity of the problem, only 774 patients in total had been randomised over more than three decades. These trials were heterogeneous in many respects. This data can, at best, be regarded as preliminary. In particular, there are no single histology AWBRT trials yet completed. A phase two trial investigating hippocampal avoiding AWBRT (HAWBRT) showed significantly less NCF decline compared to historical controls. We now need more randomised data to confirm the benefit of adjuvant HAWBRT. However, the ASTRO Guideline has particularly impacted accrual to trials investigating this, especially the international ANZMTG 01.07 WBRTMel trial. This is an RCT investigating AWBRT following local treatment in patients with one to three BMs from melanoma. WBRTMel has accrued 196 of a required 220 to date but accrual has slowed. HAWBRT may now never be tested in a randomised setting. Encouraging more data in AWBRT is the wiser choice.



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Clinical parameters for predicting radiation-induced liver disease after intrahepatic reirradiation for hepatocellular carcinoma

Abstract

Background

Few data are available on the tolerance of reirradiation in patients with hepatocellular carcinoma (HCC). This study determined the clinical parameters contributing to the development of radiation-induced liver disease (RILD).

Methods

We included 36 patients with HCC who received 2 courses of radiotherapy (RT) to the liver. Using α/β = 15 for tumor and α/β =8 for normal liver tissue for biologically equivalent doses in 2 Gy fractions, mean cumulative to the hepatic tumor and normal liver were 87.7 Gy15 and 31.1 Gy8, respectively. Hepatic toxicities were classified according to the Common Terminology Criteria for Adverse Events, Version 4.0. Clinical data, including liver function test results, radiological study findings, and RT parameters before and after both courses of RT were retrieved for analysis. Using multivariate analysis, logistic regression was used to identify the predictors of RILD, and Cox regression was performed to explore the prognostic factors for overall survival (OS).

Results

Thirteen patients (36 %) developed RILD after reirradiation. Nine of them died because of progressive liver failure without evidence of tumor progression and were categorized to have lethal RILD. A pretreatment Child–Turcotte–Pugh (CTP) score ≥6 was the only predictor of RILD [odds ratio (OR): 15.83, p = 0.001] and lethal RILD [OR: 72.56, p = 0.005]. In addition, a CTP score ≥6 and the presence of portal vein tumor thrombosis before reirradiation were 2 prognostic factors for OS.

Conclusion

Despite a limited sample size, residual liver function using a preirradiation CTP score ≥6 is a clinical parameter associated with an increased risk of RILD in patients requiring hepatic reirradiation.



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The pathophysiological role of bacterial biofilms in chronic sinusitis

Abstract

Chronic rhinosinusitis (CRS) is a very common disorder that remains poorly understood from a pathogenic standpoint. Recent research on the pathogenesis of CRS has been focused on the potential role of biofilms in this chronic infection. The aim of this study was to assess the sinuses' microflora and biofilm formation on the sino-nasal mucosa in patients with CRS. Paranasal sinus mucosa specimens were harvested at the time of functional endoscopic sinus surgery (FESS). Classical microbiology techniques for the isolation and identification of sinus mucosa microbial flora were used. Scanning electron microscopy (SEM) was used to detect biofilm on the surface of mucosa. A microtiter plate assay for in vitro biofilm formation was employed, divided into three aliquots. One part was assessed for bacterial presence, utilizing an API manual system and the Vitek® 2 Compact system. The two remaining aliquots were tested by in vitro conventional microbiological assay with the use of the Infinite M200 (Tecan) microtiter plate reader, and also by scanning electron microscopy (SEM). A microbiological examination of mucosal specimens had taken during FESS operation revealed the presence of various types of bacteria in 29 out of 30 tested samples. Out of 62 different strains isolated from patients with CRS, 23 strains of coagulase-negative Staphylococcus epidermidis and 6 strains of Escherichia coli were the most frequently isolated microorganisms, accounting for 37.1 and 9.7 %, respectively. Among the 62 isolated strains, 58 were used to assess biofilm formation. From the total of 58 isolates, 8.6 % were strong biofilm producers, 20.7 % were moderate, and 70.7 % of isolates were considered to be non- or weak biofilm producers. SEM of the 30 nasal concha mucosal samples taken from patients with CRS revealed biofilm in 23 specimens. A marked destruction of the epithelium was observed, with variation in degrees of severity, from disarrayed cilia to complete absence of cilia. The vast majority of nasal concha mucosal samples of patients affected by chronic sinusitis presented with biofilm formation. Our study showed that 76.7 % of patients having FESS for CRS had evidence of biofilms on SEM micrographs. Although certain detection methods could lead to various discrepancies in the amount of biofilm produced, the consistent demonstration of biofilms in patients with CRS suggests that this convoluted three-dimensional structures might play a significant role in either the pathogenesis or persistence of chronic rhinosinusitis.



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Jan Olofsson, a man of great achievements



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Nomenclature proposal to describe vocal fold motion impairment

Abstract

The terms used to describe vocal fold motion impairment are confusing and not standardized. This results in a failure to communicate accurately and to major limitations of interpreting research studies involving vocal fold impairment. We propose standard nomenclature for reporting vocal fold impairment. Overarching terms of vocal fold immobility and hypomobility are rigorously defined. This includes assessment techniques and inclusion and exclusion criteria for determining vocal fold immobility and hypomobility. In addition, criteria for use of the following terms have been outlined in detail: vocal fold paralysis, vocal fold paresis, vocal fold immobility/hypomobility associated with mechanical impairment of the crico-arytenoid joint and vocal fold immobility/hypomobility related to laryngeal malignant disease. This represents the first rigorously defined vocal fold motion impairment nomenclature system. This provides detailed definitions to the terms vocal fold paralysis and vocal fold paresis.



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Reply to the comment on: ‘Evaluation of resident’s training for endoscopic sinus surgery using a sheep’s head’



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Two-stage autotransplantation of human submandibular gland: a novel approach to treat postradiogenic xerostomia

Abstract

Xerostomia is a persistent side effect of radiotherapy (RT), which severely reduces the quality of life of the patients affected. Besides drug treatment and new irradiation strategies, surgical procedures aim for tissue protection of the submandibular gland. Using a new surgical approach, the submandibular gland was autotransplanted in 6 patients to the patient's forearm for the period of RT and reimplanted into the floor of the mouth 2–3 months after completion of RT. Saxon's test was performed during different time points to evaluate patient's saliva production. Furthermore patients had to answer EORTC QLQ-HN35 questionnaire and visual analog scale. Following this two-stage autotransplantation, xerostomia in the patients was markedly reduced due to improved saliva production of the reimplanted gland. Whether this promising novel approach is a reliable treatment option for RT patients in general should be evaluated in further studies.



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Erratum to: Open questions and novel concepts in oral cancer surgery



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Cross-cultural adaptation and validation of the Nijmegen Cochlear Implant Questionnaire into Italian

Abstract

The NCIQ is a quantifiable self-assessment health-related quality of life instrument specific for cochlear implant users. The aim of this study was to culturally adapt the NCIQ into Italian (I-NCIQ). A prospective instrument validation study was conducted. Cross-cultural adaptation and validation were accomplished. Cronbach α was used to test internal consistency in 51 CI users and in a control group composed by 38 post-lingual deaf adult on a waiting list for a CI. ICC test was used for test–retest reliability analysis. Kruskal–Wallis test with Mann–Whitney post hoc were used to compare the I-NCIQ scores in CI users before and after the cochlear implantation and in control patients. I-NCIQ scores obtained in CI users were compared with the results of Italian version of disyllabic testing without lip-reading and without masking. Good internal consistency and good test–retest reliability were found. I-NCIQ scores obtained in the 51 CI users after implantation were consistently higher than those obtained before implantation and in the control group. Moreover, no differences were found in the results of I-NCIQ obtained in the group of 51 CI users before implantation and in the group of control patients on post hoc Mann–Whitney analysis. Positive correlations between I-NCIQ scores and the results of disyllabic testing without lip-reading and without masking were found. The I-NCIQ is a reliable, valid, self-administered questionnaire for the measurement of QOL in CI users; its application is recommended.



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Trends in the 15D health-related quality of life over the first year following diagnosis of head and neck cancer

Abstract

Management of head and neck cancer influences both physical and mental wellbeing. Measuring the health-related quality of life (HRQoL) is important, as various treatment modalities are associated with significant morbidity and mortality. In this prospective cohort study, we tested the feasibility of the generic 15D HRQoL instrument in 214 head and neck cancer patients managed with surgery, definitive (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at baseline and three times after treatment onset during 1 year, and compared with that of general population standardized for age and sex. At baseline, the patients' mean 15D score was significantly worse compared with general population. Overall HRQoL was at lowest at 3 months after treatment onset, it gradually improved towards 12 months but never reached baseline levels. The dimensions "vitality", "distress", "depression" and "sexual activity" showed marked deterioration at 3 months after the treatment onset, but improved gradually during 12 months. The 15D instrument seems useful for evaluation of HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing improved gradually after 3 months, but they seldom reached baseline levels. The support for patients at the time of diagnosis, during treatment, and recovery is emphasized.



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Training model for endoscopic sinus surgery using lamb’s head



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Childhood otitis media is associated with dizziness in adulthood: the HUNT cohort study

Abstract

The objective of the study was to examine the association between otitis media in childhood and dizziness in adulthood. Longitudinal, population-based cohort study of 21,962 adults (aged 20–59 years, mean 40) who completed a health questionnaire in the Nord-Trøndelag Hearing Loss Study was conducted. At 7, 10 and 13 years of age, the same individuals underwent screening audiometry in a longitudinal school hearing investigation. Children found with hearing loss underwent an ear, nose and throat specialist examination. Adults diagnosed with childhood chronic suppurative otitis media (n = 102) and childhood hearing loss after recurrent acute otitis media (n = 590) were significantly more likely to have increased risk of reported dizziness when compared to adults with normal hearing as children at the school investigation and also a negative history of recurrent otitis media (n = 21,270), p < 0.05. After adjusting for adult age, sex and socio-economic status, the odds ratios were 2.1 [95 % confidence interval (CI): 1.4–3.3] and 1.3 (95 % CI: 1.0–1.5), respectively. This longitudinal cohort study suggests that childhood chronic suppurative otitis media and childhood hearing loss after recurrent acute otitis media are associated with increased risk of dizziness in adulthood. This might reflect a permanent effect of inflammatory mediators or toxins on the vestibular system. The new finding stresses the importance of treatment and prevention of these otitis media conditions.



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The effect of the transducers on paediatric thresholds estimated with auditory steady-state responses

Abstract

The objective of this study was to investigate the usefulness of auditory steady-state responses (ASSRs) for estimating hearing thresholds in young children, compared with behavioural thresholds. The second objective was to investigate ASSR thresholds obtained with insert earphones versus supra-aural headphones to determine which transducer produces ASSR thresholds most similar to behavioural thresholds measured with supra-aural headphones. This retrospective study included 29 participants (58 ears): 12 children (24 ears) in the insert group and 17 children (34 ears) in the supra-aural group. No general anaesthesia was used. For both groups, there was a strong correlation between behavioural and ASSR thresholds, with a stronger correlation for the insert group. When behavioural thresholds are difficult to obtain, ASSR may be a useful objective measure that can be combined with other audiometric procedures to estimate hearing thresholds and to determine appropriate auditory rehabilitation approaches.



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Variability of the mental representation of the cochlear anatomy during cochlear implantation

Abstract

The aim of this study was to assess the mental representation of the insertion axis of surgeons with different degrees of experience, and reproducibility of the insertion axis in repeated measures. A mastoidectomy and a posterior tympanotomy were prepared in five different artificial temporal bones. A cone-beam CT was performed for each temporal bone and the data were registered on a magnetic navigation system. In these five temporal bones, 16 surgeons (3 experts; >50 cochlear implant surgery/year; 7 fellows with few cochlear implant experience, and 6 residents) were asked to determine the optimal insertion axis according to their mental representation. Compared to a planned ideal axis, the insertion axis was better determined by the experts with higher accuracy (axial: 7° ± 1.5°, coronal: 6° ± 1.5°) than fellows (axial: 14° ± 1.7°, coronal: 13° ± 1.7°; p < 0.05), or residents (axial: 15° ± 1.5°; p < 0.001, coronal: 17° ± 1.9°; p < 0.001). This study suggests that mental representation of the cochlea is experience-dependent. A high variation of the insertion axis to the scala tympani can be observed due to the complexity of the temporal bone anatomy and lack of landmarks to determine scala tympani orientation. Navigation systems can be used to evaluate and improve mental representation of the insertion axis to the scala tympani for cochlear implant surgery.



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Bilateral use of active middle ear implants: speech discrimination results in noise

Abstract

Binaural sound reception has advantages over unilateral perception, including better localization and sound quality as well as speech and tone reception in both quiet and noisy environments. Up to now, most active middle ear implant (AMEI) users have been unilaterally implanted, but patient demand for an implant on the other side is increasing. Ten bilaterally-AMEI implanted native German-speaking adults were included in the study. The Oldenburg sentence test was used to measure speech reception thresholds in noise. The subject's signal-to-noise ratio (SNR) at a speech reception score of 50 % was calculated for different noise conditions. SRT was measured as a function of noise condition (nc) and listening condition (lc)—for example, SRT (lc, nc), with nc from S0N0, S0N-90, or S0N90 and lc from left, right or both. For each noise condition, the squelch effect and the binaural summation effect were calculated. Patients in this study demonstrated improvement with bilateral AMEIs compared to right or left AMEI only in all three tested listening conditions. Statistical significance was found in the S0N0 condition to favor usage of bilateral AMI versus either the right or left side only. The benefits of binaural hearing are well known, also in normal-hearing individuals. In the future every bilateral implantation should be a part of the clinical routine. Bilateral implantation can help to reduce problems in background noise and restore directional hearing.



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Influence of allelic v ariations of hypoxia-related and DNA repair genes on patient outcome and toxicity in head and neck cancer treated with radiotherapy plus cetuximab

Abstract

Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1β, VHL, FIH-1, XRCC1, and XRCC5). The results were then correlated with time to progression (TTP), overall survival (OS), and toxicity (epithelitis, mucositis, and folliculitis). The median TTP and OS were better in patients with severe vs mild mucositis (17 vs 7 months, p = 0.03; and 26 vs 12 months, p = 0.016, respectively) and folliculitis (10 vs 7 months, p = 0.01, and 26 vs 10 months, p < 0.001, respectively). Patients with the HIF-1α CT/TT genotype had better OS than those with the wild-type HIF-1α CC genotype (28 vs 13 months, p = 0.035). Patients with the XRCC5 GG/AA genotype had longer TTP than patients with the XRCC5 AG genotype (11 vs 7 months, p = 0.035). Severe skin toxicity and SNPs of HIF- and XRCC5 were associated with different outcomes among patients treated with radiotherapy plus cetuximab.



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Clinical impact of malnutrition on complication rate and length of stay in elective ENT patients: a prospective cohort study

Abstract

Malnutrition is considered as an independent risk factor for morbidity, mortality and a prolonged hospital stay for in-hospital patients. While most available data on the impact of malnutrition on health-related and financial implications refer to gastroenterologic or abdominal surgery patients, little is known about the impact of malnutrition on Ear Nose Throat (ENT)/head and neck surgery patients. The objective of this study was to investigate the impact of malnutrition on morbidity and length of hospital stay in an elective ENT/head and neck surgery patient cohort. The study was performed as a single-center, prospective cohort study at a tertiary referral centre. Nutritional risk at admission was assessed using the NRS-2002 screening tool. Multivariate regression models were used to determine independent risk factors for complications and a prolonged hospitalization. Three hundred fifty one participants were included in the study. A malignant disease was found in 62 participants (17.7 %). 62 patients (17.7 %) were at a moderate to severe risk of malnutrition. A bad general health condition and complications during hospital stay could be identified as independent risk factors for a prolonged hospitalization. Patients with a malignant tumor showed a more than fourfold higher risk of developing at least one complication. Malnutrition, however, was not statistically associated with a higher complication rate or a prolonged hospital stay. Our data suggests that malnutrition does not seem to play such an important role as a risk factor for complications and a prolonged hospital stay in ENT patients as it does in other disciplines like abdominal surgery or gastroenterology.



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Oncological Patient Anxiety in Imaging Studies: the PET/CT Example

Abstract

The purpose of this study was to investigate the subjective perception of anxiety pre- and post-procedure, and explore the relationship between demographic, clinical variables and cancer patients' anxiety during a positron emission tomography/computed tomography (PET/CT) scan. Two hundred and thirty-two oncological out patients, with clinical indication for performing an 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scan and attending a nuclear medicine (NM) department, participated in the study. Patients' anxiety and subjective experience of PET/CT were examined using two self-report questionnaires. The pre-procedure questionnaire focused on demographic information, level of knowledge regarding the scan and subjective perception of anxiety before the procedure. The post-procedure questionnaire included the subjective perception anxiety after the procedure, information adequacy and satisfaction with the NM department. The self-reported data indicate that patients were anxious during PET/CT. Furthermore, our data revealed a significant difference between the anxiety pre-procedure and post-procedure (z = −3909, p < 0.05), in which the anxiety pre-procedure has significantly higher values. No significant correlation was found between anxiety and age of the patients, education levels, adequacy of information or satisfaction with the NM Department. Perception of anxiety post-procedure differs between gender (U = 5641, p = 0.033). In conclusion, PET/CT generated anxiety levels in oncological patients, especially before the procedure. Although patients seemed to be satisfied with information delivered by staff and with the NM Department, attention has to be focused on effective interventions strategies that help patients to reduce anxiety.



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Insulin, insulin receptors, and cancer

Abstract

Insulin is a major regulator of cell metabolism but, in addition, is also a growth factor. Insulin effects in target cells are mediated by the insulin receptor (IR), a transmembrane protein with enzymatic (tyrosine kinase) activity. The insulin receptor, however, is represented by a heterogeneous family of proteins, including two different IR isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate IGF-1 receptor. These different receptors may bind insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many cancer cells require insulin for optimal in vitro growth. Recent data indicate that: (1) insulin stimulates growth mainly via its own receptor and not the IGF-1 receptor; (2) in many cancer cells, the IR is overexpressed and the A isoform, which has a predominant mitogenic effect, is more represented than the B isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to insulin. For this reason, all conditions of hyperinsulinemia, both endogenous (prediabetes, metabolic syndrome, obesity, type 2 diabetes before pancreas exhaustion and polycystic ovary syndrome) and exogenous (type 1 diabetes) will increase the risk of cancer. Cancer-related mortality is also increased in patients exposed to hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with hyperinsulinemia and their therapies does not allow a precise evaluation of the cancer-promoting effect of hyperinsulinemia, but its detrimental effect on cancer incidence and mortality is well documented.



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Effects of two dominance manipulations on the stress response: Cognitive and embodied influences

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Publication date: Available online 2 July 2016
Source:Biological Psychology
Author(s): Christian Eric Deuter, Hartmut Schächinger, Daniel Best, Roland Neumann
In response to stress, physiological and mental resources are allocated towards those systems that are needed for rapid responding in terms of fight or flight. On the other hand, long term regenerative processes such as growth, digestion and reproduction are attenuated. Levels of the sex steroid testosterone are reduced in participants that suffer from chronic stress. However, beyond its role for reproductive functions, testosterone plays an important role in the regulation of social status and dominance, testosterone levels increase during competition or when the social status is challenged. The Trier Social Stress Test (TSST), a laboratory stressor with a substantial social-evaluative component, can provoke an increase in salivary testosterone levels. Still, so far the reported findings regarding acute stress effects on testosterone are equivocal, possibly due to moderating effects. In this study we experimentally manipulated social dominance in 56 healthy participants (28m) by two independent manipulations (body posture and cognitive role taking) and subjected them to the TSST. We analyzed salivary testosterone and cortisol levels as dependent measures for the endocrine stress response. The role taking manipulation interacted with the testosterone response: we found the strongest increase when participants had to put themselves in a dominant (vs. submissive) role. Our results suggest that transient changes in testosterone levels during stress reflect a response to status threat that is affected by social dominance.



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Neural response to modulating the probability that actions of self or other result in auditory tones: A parametric fMRI study into causal ambiguity

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Publication date: Available online 2 July 2016
Source:Biological Psychology
Author(s): Christophe E. de Bézenac, Vanessa Sluming, Andre Gouws, Rhiannon Corcoran
In normal circumstances we can easily distinguish between changes to the external world brought about by our own actions from those with external causes. However, in certain contexts our sense of ownership and agency over acts is not so clear. Neuroimaging studies have implicated a number of regions in the sense of agency, some of which have been shown to vary continuously with action-outcome discordance. However, little is known about dynamic, ambiguous contexts characterised by a lack of information for self-other differentiation, yet such ambiguous states are important in relation to symptoms and levels of consciousness that characterise certain mental health conditions. With a block-design fMRI paradigm, we investigated neural responses to changes in the probability that a participant's irregular finger taps over 12sec would result in auditory tones as opposed to tones generated by 'another's finger taps'. The main findings were that misattribution increased in ambiguous conditions where the probability of a tone belonging to self and other was equal. Task-sensitive brain regions, previously identified in self-agency, motor cognition, and ambiguity processing, showed a quadratic response to our self-to-other manipulation, with particular sensitivity to self-control. Task performance (low error and bias) was related to attenuated response in ambiguous conditions while increased response in regions associated with the default mode network was associated with greater overall error and bias towards other. These findings suggest that causal ambiguity as it occurs over time is a prominent feature in sense of agency, one that may eventually contribute to a more comprehensive understanding of positive symptoms of psychosis.



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Early averted gaze processing in the right Fusiform Gyrus: An EEG source imaging study

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Publication date: Available online 2 July 2016
Source:Biological Psychology
Author(s): Cristina Berchio, Tonia A. Rihs, Camille Piguet, Alexandre G. Dayer, Jean-Michel Aubry, Christoph M. Michel
Humans are able to categorize face properties with impressively short latencies. Nevertheless, the latency at which gaze recognition occurs is still a matter of debate. Through spatio-temporal analysis of high-density event-related potentials (ERP), we investigated the brain activity underlying the ability to spontaneously and quickly process gaze. We presented neutral faces with direct and averted gaze in a matching picture paradigm, where subjects had to detect repetition of identical faces and gaze was implicitly manipulated.The results indicate that faces with averted gaze were better discriminated than faces with direct gaze, and evoked stronger P100 amplitudes localized to the right fusiform gyrus. In contrast, direct gaze induced stronger activation in the orbital frontal gyrus at this latency. Later in time, at the beginning of the N170 component, direct gaze induced changes in scalp topography with a stronger activation in the right medial temporal gyrus. The location of these differential activations of direct vs. averted gaze further support the view that faces with averted gaze are perceived as less rewarding than faces with direct gaze. We additionally found differential ERP responses between repeated and novel faces as early as 50ms, thereby replicating earlier studies of very fast detection of mnestic aspects of stimuli. Together, these results suggest an early dissociation between implicit gaze detection and explicit identity processing.



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Helping from the heart: Voluntary upregulation of heart rate variability predicts altruistic behavior

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Publication date: Available online 2 July 2016
Source:Biological Psychology
Author(s): Boris Bornemann, Bethany E. Kok, Anne Böckler, Tania Singer
Our various daily activities continually require regulation of our internal state. These regulatory processes covary with changes in High Frequency Heart Rate Variability (HF-HRV), a marker of parasympathetic activity. Specifically, incidental increases in HF-HRV accompany positive social engagement behavior and prosocial action. Little is known about deliberate regulation of HF-HRV and the role of voluntary parasympathetic regulation in prosocial behavior. Here, we present a novel biofeedback task that measures the ability to deliberately increase HF-HRV. In two large samples, we find that a) participants are able to voluntarily upregulate HF-HRV, and b) variation in this ability predicts individual differences in altruistic prosocial behavior, but not non-altruistic forms of prosociality, assessed through 14 different measures. Our findings suggest that self-induction of parasympathetic states is involved in altruistic action. The biofeedback task may provide a measure of deliberate parasympathetic regulation, with implications for the study of attention, emotion, and social behavior.



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Neural correlates of mindful self-awareness in mindfulness meditators and meditation-naïve subjects revisited

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Publication date: Available online 1 July 2016
Source:Biological Psychology
Author(s): J. Lutz, A.B. Brühl, H. Scheerer, L. Jäncke, U. Herwig
Mindful self-awareness is central to mindfulness meditation and plays a key role in its salutary effects. It has been related to decreased activation in cortical midline structures (CMS) and amygdala, and increased activation in somatosensory regions. However, findings in untrained individuals are contradictory, and scarce in experienced meditators.Using fMRI, we investigated experienced mindfulness meditators (LTM, n=21, average 4652 practice-hours) and matched meditation-naïve participants (MNP, n=19) during short periods of mindful self-awareness (FEEL) and self-referential thinking (THINK).We report somatosensory activations and decreases in CMS during FEEL for both groups, but significantly stronger decreases in prefrontal CMS in LTM. LTM further showed decreases in language-related and amygdala regions, but the latter was not significantly different between groups. Overall, higher activations in amygdala and mid-line regions during FEEL were related to levels of depressiveness.Neural patterns of mindful self-awareness emerge already in MNP but more pronounced in LTM. Specifically, meditation training might reduce self-reference and verbalization during mindful awareness. We further corroborate the suggested link between mindfulness and healthy self-related functions on the neural level. Longitudinal studies need to corroborate these findings.



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Systematic review of the use of granulocyte–macrophage colony-stimulating factor in patients with advanced melanoma

Abstract

Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte–macrophage colony-stimulating factor (GM-CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have been mixed, and while GM-CSF has the potential to promote anti-tumor responses, some preclinical data suggest that GM-CSF may sometimes promote tumor growth. GM-CSF has not been approved as a melanoma treatment. We undertook a systematic literature review of studies of GM-CSF in patients with advanced melanoma (stage IIIB–IV). Of the 503 articles identified, 26 studies met the eligibility criteria. Most studies investigated the use of GM-CSF in combination with another treatment, such as peptide vaccines or chemotherapy, or as an adjuvant to surgery. Some clinical benefit was reported in patients who received GM-CSF as an adjuvant to surgery, or in combination with other treatments. In general, outcomes for patients receiving peptide vaccines were not improved with the addition of GM-CSF. GM-CSF may be a valuable therapeutic adjuvant; however, further studies are needed, particularly head-to-head comparisons, to confirm the optimal dosing regimen and clinical effectiveness in patients with advanced melanoma.



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Dental treatments, tooth extractions, and osteonecrosis of the jaw in Japanese patients with rheumatoid arthritis: results from the IORRA cohort study

Abstract

This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients ≥65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA.



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Cancer treatment-related cardiac toxicity: prevention, assessment and management

Abstract

Cancer therapies, especially anthracyclines and monoclonal antibodies, have been linked with increased rates of cardiotoxicity. The development of some cardiac side effects happens over several months, and changes in ejection fraction can be detected long before permanent damage or disability occurs. Advanced heart failure could be averted with better and earlier detection. Methodologies for early detection of cardiac changes include stress echocardiograms, cardiac velocity measurements, radionuclide imaging, cardiac MRI and several potential biomarkers. Many agents have been described for prophylaxis of cardiac events precipitated by cancer therapy. Prophylactic use of beta-blockers and ACE inhibitors may be considered for use with trastuzumab in breast cancer as tolerated. Recovery of cardiac function is possible early after the injury from a cancer therapy. Late complications for coronary artery disease, hypertension and arrhythmia are underappreciated. Treatments for severe cancer therapy-related cardiac complications follow the existing paradigms for congestive heart failure and coronary artery disease, although outcomes for cancer patients differ from outcomes for non-cancer patients.



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Phthalate pollution in an Amazonian rainforest

Abstract

Phthalates are ubiquitous contaminants and endocrine-disrupting chemicals that can become trapped in the cuticles of insects, including ants which were recognized as good bioindicators for such pollution. Because phthalates have been noted in developed countries and because they also have been found in the Arctic, a region isolated from direct anthropogenic influence, we hypothesized that they are widespread. So, we looked for their presence on the cuticle of ants gathered from isolated areas of the Amazonian rainforest and along an anthropogenic gradient of pollution (rainforest vs. road sides vs. cities in French Guiana). Phthalate pollution (mainly di(2-ethylhexyl) phthalate (DEHP)) was higher on ants gathered in cities and along road sides than on those collected in the pristine rainforest, indicating that it follows a human-mediated gradient of disturbance related to the use of plastics and many other products that contain phthalates in urban zones. Their presence varied with the ant species; the cuticle of Solenopsis saevissima traps higher amount of phthalates than that of compared species. However, the presence of phthalates in isolated areas of pristine rainforests suggests that they are associated both with atmospheric particles and in gaseous form and are transported over long distances by wind, resulting in a worldwide diffusion. These findings suggest that there is no such thing as a "pristine" zone.



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The role of coping strategies on health-related quality of life in adults with anorectal malformations

Abstract

Purpose

Coping strategies have been acknowledged as crucial for the well-being and for health-related quality of life (HRQoL). The main aim of the present study is to determine whether different types of coping strategies predict HRQoL in patients born with ARM, above and beyond the variance explained by fecal and urinary continence.

Methods

71 adult patients from the Italian Parents' and Patients' Organization for Anorectal Malformations (AIMAR) participated in the study. Participants completed measures of fecal and urinary continence of the Hirschsprung Disease/Anorectal Malformation Quality of Life (HAQL) (Hanneman et al. in Dis Col Rect 44:1650–1660, 2001), the Short Form Health Survey (SF-36) (Apolone and Mosconi in J Clin Epidemiol 51:1025–1036, 1998), and the Brief Coping Orientation to Problems Experienced (COPE) Inventory (Carver in Int J Behav Med 4:92–100, 1997), which measures different coping strategies: maladaptive, problem-focused and emotion-focused.

Results

Hierarchical regression analyses showed that fecal continence (β = 0.53, p < 0.01) and urinary continence significantly predict (β = 0.23, p < 0.05) Physical HRQoL. Fecal continence (β = 0.36, p < 0.01) and maladaptive coping strategies significantly predict (β = −0.27, p < 0.05) Mental HRQoL.

Conclusion

Besides considering the importance of fecal and urinary continence for Physical HRQoL, these findings indicate that maladaptive coping strategies are associated with worse Mental HRQoL. Interventions aimed at enhancing the patients' HRQoL should target coping strategies by reducing denial, behavioral disengagement, substance abuse, and self-blame.



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A minimally invasive micro sampler for quantitative sampling with an ultrahigh-aspect-ratio microneedle and a PDMS actuator

Abstract

This study describes a novel micro sampler consisting of an ultrahigh-aspect-ratio microneedle and a PDMS actuator. The microneedle was fabricated by a new method which introduced reshaped photoresist technology to form a flow channel inside. The microneedle includes two parts: shaft and pedestal. In this study, the shaft length is 1500 μm with a 45° taper angle on the tip and pedestal is 1000 μm. Besides, the shaft and pedestal are connected by an arc connection structure with a length of 600 μm. The microneedles have sufficient mechanical strength to insert into skin with a wide safety margin which was proved by mechanics tests. Moreover, a PDMS actuator with a chamber inside was designed and fabricated in this study. The chamber, acting as a reservoir in sampling process as well as providing power, was optimized by finite element analysis (FEA) to decrease dead volume and improve sampling precision. The micro sampler just needs finger press to activate the sampling process as well as used for quantitative micro injection to some extent. And a volume of 31.5 ± 0.8 μl blood was successfully sampled from the ear artery of a rabbit. This micro sampler is suitable for micro sampling for diagnose or therapy in biomedical field.



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Genomic Landscape of poorly Differentiated and Anaplastic Thyroid Carcinoma

Abstract

Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are aggressive thyroid tumors associated with a high mortality rate of 38–57 % and almost 100 % respectively. Several recent studies utilizing next generation sequencing techniques have shed lights on the molecular pathogenesis of these tumors, providing evidence to support a stepwise tumoral progression from well-differentiated to poorly differentiated, and finally to anaplastic thyroid carcinomas. While BRAF V600E and RAS mutations remain the main drivers in aggressive thyroid carcinoma, PDTC and ATC gains additional mutations, e.g., TERT promoter mutation, TP53 mutation, as well as frequent alterations in PIK3CA-PTEN-AKT-mTOR pathway, SWI-SNF complex, histomethyltransferases, and mismatch repair genes. RAS-mutated PDTCs are commonly associated with a histologic phenotype defined by Turin proposal, high frequency of distant metastasis, high thyroid differentiation score, and a RAS-like gene expression profile, whereas BRAF-mutated PDTCs are usually defined solely by the Memorial Sloan Kettering Cancer Center (MSKCC) criteria with a propensity for nodal metastasis and are less differentiated with a BRAF-like expression signature. Such demarcation is largely lost in ATC which is characterized by genomic complexity, heavy mutation burden, and profound undifferentiation. Additionally, several molecular events, e.g., EIF1AX mutation, mutation burden, and chromosome 1q gain in PDTCs, as well as EIF1AX mutation, chromosome 13q loss, and 20q gains in ATCs, may serve as adverse prognostic markers predicting poor clinical outcome.



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Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

Abstract

Purpose

We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis.

Methods

Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan–Meier estimates and Cox regression analyses.

Results

XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02).

Conclusions

Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.



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Flagellin based biomimetic coatings: from cell-repellent surfaces to highly adhesive coatings

Publication date: Available online 2 July 2016
Source:Acta Biomaterialia
Author(s): Boglarka Kovacs, Daniel Patko, Inna Szekacs, Norbert Orgovan, Sandor Kurunczi, Attila Sulyok, Nguyen Quoc Khanh, Balazs Toth, Ferenc Vonderviszt, Robert Horvath
Biomimetic coatings with cell-adhesion-regulating functionalities are intensively researched today. For example, cell-based biosensing for drug development, biomedical implants, and tissue engineering require that the surface adhesion of living cells is well controlled. Recently, we have shown that the bacterial flagellar protein, flagellin, adsorbs through its terminal segments to hydrophobic surfaces, forming an oriented monolayer and exposing its variable D3 domain to the solution. Here, we hypothesized that this nanostructured layer is highly cell-repellent since it mimics the surface of the flagellar filaments. Moreover, we proposed flagellin as a carrier molecule to display the cell-adhesive RGD (Arg-Gly-Asp) peptide sequence and induce cell adhesion on the coated surface. The D3 domain of flagellin was replaced with one or more RGD motifs linked by various oligopeptides modulating flexibility and accessibility of the inserted segment. The obtained flagellin variants were applied to create surface coatings inducing cell adhesion and spreading to different levels, while wild-type flagellin was shown to form a surface layer with strong anti-adhesive properties. As reference surfaces synthetic polymers were applied which have anti-adhesive (PLL-g-PEG poly(L-lysine)-graft-poly(ethylene glycol)) or adhesion inducing properties (RGD-functionalized PLL-g-PEG).Quantitative adhesion data was obtained by employing optical biochips and microscopy. Therefore, cell-adhesion-regulating coatings can be simply formed on hydrophobic surfaces by using the developed flagellin-based constructs. The developed novel RGD-displaying flagellin variants can be easily obtained by bacterial production and can serve as alternatives to create cell-adhesion-regulating biomimetic coatings.Statement of SignificanceIn the present work, we show for the first time that- an oriented and dense monolayer of flagellin molecules mimics the surface of the bacterial flagellar filament. Consequently, the fabricated layer is completely cell repellent.- By genetically modifying flagellin, we incorporate cell adhesion regulating functionalities into this anti-adhesive coating.- We can easily tune the adhesion of living cells from completely cell repellent to highly adhesive.

Graphical abstract

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The role of the human cerebellum in performance monitoring

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Publication date: October 2016
Source:Current Opinion in Neurobiology, Volume 40
Author(s): Jutta Peterburs, John E Desmond
While the cerebellum has traditionally been thought of as mainly involved in motor functions, evidence has been accumulating for cerebellar contributions also to non-motor, cognitive functions. The notion of a cerebellar internal model underlying prediction and processing of sensory events and coordination and fine-tuning of appropriate responses has put the cerebellum right at the interface of motor behavior and cognition. Along these lines, the cerebellum may critically contribute to performance monitoring, a set of cognitive and affective functions underlying adaptive behavior. This review presents and integrates evidence from recent neuroimaging and clinical studies for a cerebellar role in performance monitoring with focus on sensory prediction, error and conflict processing, response inhibition, and feedback learning. Together with evidence for involvement in articulatory monitoring during working memory, these findings suggest monitoring as the cerebellum's overarching function.



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Insulin, insulin receptors, and cancer

Abstract

Insulin is a major regulator of cell metabolism but, in addition, is also a growth factor. Insulin effects in target cells are mediated by the insulin receptor (IR), a transmembrane protein with enzymatic (tyrosine kinase) activity. The insulin receptor, however, is represented by a heterogeneous family of proteins, including two different IR isoforms and also hybrid receptors resulting from the IR hemireceptor combination with a hemireceptor of the cognate IGF-1 receptor. These different receptors may bind insulin and its analogs with different affinity and produce different biologic effects. Since many years, it is known that many cancer cells require insulin for optimal in vitro growth. Recent data indicate that: (1) insulin stimulates growth mainly via its own receptor and not the IGF-1 receptor; (2) in many cancer cells, the IR is overexpressed and the A isoform, which has a predominant mitogenic effect, is more represented than the B isoform. These characteristics provide a selective growth advantage to malignant cells when exposed to insulin. For this reason, all conditions of hyperinsulinemia, both endogenous (prediabetes, metabolic syndrome, obesity, type 2 diabetes before pancreas exhaustion and polycystic ovary syndrome) and exogenous (type 1 diabetes) will increase the risk of cancer. Cancer-related mortality is also increased in patients exposed to hyperinsulinemia but other factors, related to the different diseases, may also contribute. The complexity of the diseases associated with hyperinsulinemia and their therapies does not allow a precise evaluation of the cancer-promoting effect of hyperinsulinemia, but its detrimental effect on cancer incidence and mortality is well documented.



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Erratum to: Transvaginal hybrid NOTES cholecystectomy—results of a randomized clinical trial after 6 months



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Primary adrenal leiomyosarcoma with lymph node metastasis: a case report

Abstract

Background

Leiomyosarcomas typically originate in smooth muscle cell. Leiomyosarcoma potentially arising from the adrenal gland is an extremely rare mesenchymal tumors associated with delayed diagnosis and poor prognosis.

Case presentation

A 34-year-old man visited our department complaining of right hypochondriac pain. Computed tomography demonstrated a solid mass measuring 5.2 cm in diameter above the right kidney, corresponding to the right adrenal gland, and a lymph node mass, which appeared to have invaded the IVC wall. Right adrenalectomy and lymphadenectomy were performed. A microscopic examination revealed primary adrenal leiomyosarcoma with lymph node metastasis. No adjuvant therapy was performed, and the patient remains recurrence-free at 10 months postoperatively.

Conclusions

We experienced a very rare case of primary adrenal leiomyosarcoma.

Aggressive surgical resection including vascular reconstruction may be associated with improved survival.



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Combined effects of age and polymorphisms in Notch3 in the pathogenesis of cerebral infarction disease

Abstract

Cerebral infarction disease is a severe hypoxic ischemic tissue necrosis in the brain, often leading to long-term functional disability and residual impairments. The Notch signaling pathway plays key roles in proliferation and survival of the stem/progenitor cells of the central and peripheral nervous systems. Notch3 is an important member of the pathway, but the relationships between the genetic abnormalities and cerebral infarction disease still remain unclear. The aim of this work was to evaluate variations in Notch3 gene for their possible associations with the cerebral infarction disease. We sequenced the Notch3 gene for 260 patients with cerebral infarction disease, 300 normal controls with old ages and 300 normal controls with younger ages, and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Six variations, including rs1044116, rs1044009, rs1044006, rs10408676, rs1043996 and rs16980398 within or near the Notch3 gene, were found. The genetic heterozygosity of rs1044116, rs1044009, rs1044006, and rs1043996 was very high, whereas that of rs10408676 and rs16980398 was very low. Statistical analyses showed that rs1044009 and rs1044006 were associated with the risk of cerebral infarction disease in the Chinese Han agedness population. The SNPs rs1044009 and rs1044006 in the Notch3 gene were associated with the risk of cerebral infarction diseases in the Chinese Han agedness population.



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Pharmacological evidences for cytotoxic and antitumor properties of Boswellic acids from Boswellia serrata

Publication date: 15 September 2016
Source:Journal of Ethnopharmacology, Volume 191
Author(s): Mohammad Ahmed Khan, Ruhi Ali, Rabea Parveen, Abul Kalam Najmi, Sayeed Ahmad
Ethnopharmacological relevanceIncreasing research on traditional herbal medicines and their phytoconstituents has recognized their usefulness in complementary as adjuvant to chemotherapy in various types of cancers. The oleo-gum resin of Boswellia serrata tree is one such folk medicine, which has been traditionally used for religious, cosmetic as well as medical purposes since ages. The oleo-gum resin of the plant has been used in traditional medicine to treat variety of conditions including inflammatory diseases like arthritis, asthma, chronic pain, bowel conditions and many other diseases. This review presents an overview of scientific studies on cytotoxic and antitumor properties of B. serrata and its constituents.Materials and methodsLiterature search was carried out for activities of B. serrata and various isolated boswellic acids such as β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid reported in various cancer types in vitro as well as in vivo.ResultsThe triterpenoidal fraction of B. serrata (containing boswellic acids) is responsible for the cytotoxic and antitumor properties. Among the screened compounds, 3-O-acetyl-11-keto-β-boswellic acid has been found to be most promising cytotoxic molecule. The cytotoxic and antitumor effects are mainly due to induction of apoptosis through caspase activation, increased Bax expression, NF-κB down regulation and induction of poly (ADP)-ribose polymerase (PARP) cleavage.ConclusionsBoswellic acids appear to be promising candidates for anticancer drug development in future. However, further in vivo studies are needed. Studies in combination with clinically used anticancer drugs and QSAR studies on individual boswellic acid also need to be carried out.

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Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrhea via attenuating uterus contraction

Publication date: 15 September 2016
Source:Journal of Ethnopharmacology, Volume 191
Author(s): Lan Sun, Lina Liu, Shaobo Zong, Zhengzhong Wang, Jun Zhou, Zhiliang Xu, Gang Ding, Wei Xiao, Junping Kou
Ethnopharmacological relevanceGuizhi Fuling formula, a well-known Chinese herbal formula recorded in the Eastern Han Dynasty, is composed of Cinnamomum cassia (L.) J.Presl (Cassia bark), Poria cocos (Schw.) Wolf (Poria), Paeonia suffruticosa andrews (Moutan Cortex), Paeonia lactiflora Pall (Herbaceous peony), and Amygdalus persica L.(Persicae Semen). It has clinical efficacy of activating blood circulation to dissipate blood stasis and is commonly used for the treatment of primary dysmenorrhea. However, its therapeutic mechanism has not been clearly elucidated. The aim of this study is to reveal molecular mechanisms of action using in vivo and in vitro experimental models.Material and methodsThe ICR mouse uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment. Mice were given GZFLC (0.54, 1.08g/kg) by gavage. The levels of NO, PGF2α and Ca2+ in uterine tissue were determined according to instructions. Cyclooxygenase-2 (COX-2) and oxytocin receptor (OTR) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of GZFLC on spontaneous uterine contraction, and uterine contraction induced by oxytocin, PGF2α was observed. Myometrial cells were exposed to oxytocin (5U/L) to induce calcium release, and the effect of GZFLC and its components (PL, PGG, CA) on intracellular Ca2+ was analyzed with fluorometry imaging.ResultsIn vivo study demonstrated that GZFLC significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 55%. It also decreased the levels of NO, PGF2α and Ca2+ in oxytocin-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and OTR expressions in uterine tissue of dysmenorrhea mice were significantly reduced. GZFLC inhibited spontaneous uterus contractions in a dose-dependent manner, and the IC50 value was 0.99mg/ml. The IC50 values of GZFLC on PGF2α, oxytocin-induced contractions were 1.45mg/ml, 3.53mg/ml, respectively. Further in vitro studies indicated that GZFLC and its components (PL, PGG, CA) could restrain intracellular calcium levels in favour of uteri relaxation.ConclusionsBoth in vivo and in vitro results indicated that GZFLC possessed a significant spasmolytic effect on uterine tetanic contraction. The present study provides in vivo and in vitro experimental evidence to support the use of GZFLC for the clinical treatment of primary dysmenorrheal (PD).

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Subcutaneous trigeminal nerve field stimulation for refractory trigeminal pain: a cohort analysis

Abstract

Background

Neurosurgical pain management of drug-resistant trigeminal neuralgia (TN) is highly challenging. Microvascular decompression is a first-line neurosurgical approach for classical TN with neurovascular conflict, but can show clinical relapse despite proper decompression. Second-line destructive techniques like radiofrequency thermocoagulation have become reluctantly used due to their potential for irreversible side effects. Subcutaneous peripheral nerve field stimulation (sPNFS) is a minimally invasive neuromodulatory technique which has been shown to be effective for chronic localised pain conditions. Reports on sPNFS for the treatment of trigeminal pain (sTNFS) are still sparse and primarily focused on pain intensity as outcome measure. Detailed data on the impact of sTNFS on attack frequency are currently not available.

Methods

Patients were classified according to the International Headache Society classification (ICHD-3-beta). Three patients had classical TN without (n = 3) and another three TN with concomitant persistent facial pain (n = 3). Two patients suffered from post-herpetic trigeminal neuropathy (n = 2). All eight patients underwent a trial stimulation of at least 7 days with subcutaneous leads in the affected trigeminal area connected to an external neurostimulator. Of those, six patients received permanent implantation of a neurostimulator. During the follow-up (6–29 months, mean 15.2), VAS-scores, attack frequencies, oral drug intake, complications and side effects were documented.

Results

Seven out of eight patients responded to sTNFS (i.e. ≥50 % pain reduction) during the test trial. The pain intensity (according to VAS) was reduced by 83 ± 16 % (mean ± SD) and the number of attacks decreased by 73 ± 26 % (mean ± SD). Five out of six patients were able to reduce or stop pain medication. One patient developed device infection. Two patients developed stimulation-related side effects which could be resolved by reprogramming.

Conclusions

Treatment by sTNFS is a beneficial option for patients with refractory trigeminal pain. Prospective randomised trials are required to systematically evaluate efficacy rates and safety of this low-invasive neurosurgical technique.



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