Κυριακή 13 Ιουνίου 2021

Epidermal growth factor as a potential prognostic and predictive biomarker of response to platinum-based chemotherapy

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by Margot Geens, Sofie Stappers, Heleen Konings, Benedicte Y. De Winter, Pol Specenier, Jan P. Van Meerbeeck, Gert A. Verpooten, Steven Abrams, Annelies Janssens, Marc Peeters, Paul Van de Heyning, Olivier M. Vanderveken, Kristien J. Ledeganck

In this study, we investigated serum epidermal growth factor (EGF) in an oncological population of head- and neck and pulmonary neoplasms and whether serum EGF could serve as a prognostic marker of survival and as a predictive marker for treatment response to platinum-based chemotherapy. A total of 59 oncological patients and a control group of age- and sex-matched healthy volunteers were included in this study. Pre-treatment serum EGF from both groups was determined. Patient's and tumour characteristics and mortality were recorded during a 5-year follow up period. Baseline serum EGF significantly differed between the oncological patients and the healthy volunteers (p
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REM-related obstructive sleep apnea and vertigo: A retrospective case-control study

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Via Tinnitus

journal.pone.0252844.g001&size=inline

by Po-Yueh Chen, Tzu-Ying Chen, Pin-Zhir Chao, Wen-Te Liu, Chyi-Huey Bai, Sheng-Teng Tsao, Yi-Chih Lin

Background

In recent population-based case-control studies, sleep apnea was significantly associated with a higher incidence (hazard ratio, 1.71) of vertigo and the risk of tinnitus was found to increase 1.36 times in patients with sleep apnea. The possibility that obstructive sleep apnea (OSA) might affect neurotological consequences was not noticed, until studies using polysomnography (PSG) for these patients.

Objectives

The purpose of this study was to investigate the relationship between vertigo and OSA.

Methods

The collected data among patients from May 1st, 2018 to October 31th, 2018 at Shuang Ho Hospital. Eligibility criteria included an age older than 20 years, a diagnosis of obstructive sleep apnea. The diagnosis of OSA was defined as an oxygen desaturation index of at least 5, was established with the use of polysomnographic examination at hospital. Patients were excluded from the study if they had head injury, brain tumour, headache history and hearing los s. Patients who had vertigo were labeled as Vertigo group. In the other hand, patients who had no dizziness were labeled as control group. 58 patients were in the Vertigo group, and 113 were in the control group.

Results

After PSG examination, 58 patients who had vertigo, were diagnosed OSA (29 males, average age = 57.07 years old, BMI = 26.64, RDI = 24.69, ESS = 8.65), and 24 patients of them (41.3%) were REM-related OSA. Meanwhile, in the control group, 113 patients had OSA (92male, average age = 49.66 years old, BMI = 26.06, RDI = 35.19, ESS = 11.43), and 18 patients of them (15.9%) were REM-related OSA (Table 1). Therefore, patient who had vertigo, would have higher proportion of REM OSA (P Conclusions

The vertigo patients have a higher rate of REM-related OSA, and the acceptance rate to CPAP use is low. Further research is needed to explore novel therapeutic approaches, or combination of currently available non-CPAP therapies, in patients with REM OSA.

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Clinical Validation of the Champagne Algorithm for Evoked Response Source Localization in Magnetoencephalography

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Brain Topogr. 2021 Jun 11. doi: 10.1007/s10548-021-00850-4. Online ahead of print.

ABSTRACT

Magnetoencephalography (MEG) is a robust method for non-invasive functional brain mapping of sensory cortices due to its exceptional spatial and temporal resolution. The clinical standard for MEG source localization of functional landmarks from sensory evoked responses is the equivalent current dipole (ECD) localization algorithm, known to be sensitive to initialization, noise, and manual choice of the number of dipoles. Recently many automated and robust algorithms have been developed, including the Champagne algorithm, an empirical Bayesian algorithm, with powerful abilities for MEG source reconstruction and time course estimation (Wipf et al. 2010; Owen et al. 2012). Here, we evaluate automated Champagne performance in a clinical population of tumor patients where there was minimal failure in localizing sensory evoked responses using the clinical st andard, ECD localization algorithm. MEG data of auditory evoked potentials and somatosensory evoked potentials from 21 brain tumor patients were analyzed using Champagne, and these results were compared with equivalent current dipole (ECD) fit. Across both somatosensory and auditory evoked field localization, we found there was a strong agreement between Champagne and ECD localizations in all cases. Given resolution of 8mm voxel size, peak source localizations from Champagne were below 10mm of ECD peak source localization. The Champagne algorithm provides a robust and automated alternative to manual ECD fits for clinical localization of sensory evoked potentials and can contribute to improved clinical MEG data processing workflows.

PMID:34114168 | DOI:10.1007/s10548-021-00850-4

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Conventional approaches versus laser CO2 surgery in stapes surgery: a multicentre retrospective study

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Eur Arch Otorhinolaryngol. 2021 Jun 11. doi: 10.1007/s00405-021-06926-y. Online ahead of print.

ABSTRACT

PURPOSE: To analyze and compare surgical and audiological outcomes of conventional approaches versus laser CO2 surgery in stapes surgery.

METHODS: 333 patients who underwent stapes surgery were enrolled in the study; the patient population was divided into three groups: group 1: 170 patients treated with conventional stapedotomy with manual microdrill (average age 49.13 years); group 2: 119 patients treated with conventional stapedotomy with electrical microdrill (average age 51.06 years); group 3: 44 patients (average age 50.4 years) who underwent CO2 laser stapedotomy. Intra-operative, postoperative outcomes and audiological results were investigated.

RESULTS: The average surgical time of laser CO2 surgery was longer than for other surgical procedures. No statistical differences emerged in post-operative abnormal taste sensation. There was also no difference in postoperative dizziness. Air-bone gap (ABG) went down from 29.7 ± 10 dB (group 1) and 27.32 ± 9.20 (group 2) to 10 ± 6.9 dB (group 1) and 10.7 ± 6.03 dB (group 2). In group 3 the preoperative ABG was lowered from 28.3 ± 10.1 to 11.8 ± 10.9, with a statistical difference in auditory recovery (p = 0.0001); The group of patients treated with laser CO2 showed a percentage of patients with an ABG closure of between 0 and 10 dB higher than in the group treated with manual microdrills (77.2% vs. 60%, respectively; p = 0.03).

CONCLUSION: Overall surgical results of CO2 laser and conventional stapedotomy are comparable without any significant difference; however, the group treated with CO2 laser appears to have a percentage of patients with an ABG closure 0-10 dB higher than the group treated using the conventional technique.

PMID:34115200 | DOI:10.1007/s00405-021-06926-y

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The pathologic diagnosis of mantle cell lymphoma

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Histol Histopathol. 2021 Jun 11:18351. doi: 10.14670/HH-18-351. Online ahead of print.

ABSTRACT

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma usually characterized by t(11;14) (q13;q32), or CCND1 translocation and Cyclin D1 over expression. A very small subset of MCL may lack the t(11;14) (q13;q32) translocation and Cyclin D1 over expression, but show alternative translocations involving CCND2 and CCND3, and over expression of SOX11. In general, MCL has been considered a very aggressive and incurable lymphoma and patients with MCL usually have a poor prognosis. However, indolent variants, including in situ mantle cell neoplasm and the recently recognized leukemic non-nodal MCL do exist. In recent years, genome-wide molecular genetic studies have revealed a characteristic MCL genetic profile. This review will focus on the pathologic diagnosis of MCL using the traditional morphological and immunophenotypic strategies combined with cytogenetic characteristics and recently identified molecular profile. Morphological subtypes, immunophenotypic variants, recently recognized indolent variants, as well as MCL risk stratification will also be discussed.

PMID:34114641 | DOI:10.14670/HH-18-351

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Comparing prognostic utility between the 8th edition of TNM staging system and the lymph node ratio for oral squamous cell carcinoma

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Abstract

Background

Lymph node metastasis in oral squamous cell carcinoma (OSCC) is associated with poor prognosis. The 8th edition of TNM has implemented new nodal staging criteria. We assess the prognostic utility of the lymph node ratio (LNR) and compare it to that of pN in the TNM 8th edition.

Methods

One hundred and forty-two patients with OSCC were retrospectively studied. Nodal staging was performed using the TMN 8th edition and the prognostic value of the LNR in terms of overall survival (OS) and disease-free survival (DFS) was evaluated.

Results

Fifty-seven patients were eligible for inclusion. The LNR was independently prognostic of OS (p = 0.02). Instead N classification was not significantly predictive of OS (p = 0.10). High LNRs resulted in decreases in OS of approximately 40% within 6 months after surgery.

Conclusions

The LNR identifies patients with poor outcomes better than N classification. The lack of reliable LNR cutoffs compromises its utility in clinical practice.

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Proteomic Characterization of Senescent Laryngeal Adductor and Plantaris Hindlimb Muscles

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Objectives

The goals of this study were to 1) compare global protein expression in muscles of the larynx and hindlimb and 2) investigate differences in protein expression between aged and nonaged muscle using label-free global proteomic profiling methods.

Methods

Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed on thyroarytenoid intrinsic laryngeal muscle and plantaris hindlimb muscle from 10 F344xBN F1 male rats (5 old and 5 young). Protein expression was compared and pathway enrichment analysis performed for each muscle type (larynx and limb) and age group (old and young muscle).

Results

Over 1,000 proteins were identified in common across both muscle types and age groups using LC-MS/MS analysis. Significant age-related differences were seen across 107 proteins in plantaris hindlimb and in 19 proteins in thyroarytenoid laryngeal muscle. Bioinformatic and enrichment analysis demonstrated protein differences between the hindlimb and larynx may relate to immune and stress redox responses and RNA repair.

Conclusion

There are clear differences in protein expressions between the laryngeal and hindlimb skeletal muscles. Initial analysis suggests differences between the two muscle groups may relate to stress responses and repair mechanisms. Age-related changes in the thyroarytenoid appear to be less obvious than in the plantaris. Further in-depth study is needed to elucidate how aging affects protein expression in the laryngeal muscles.

Level of Evidence

NA Laryngoscope, 2021

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A novel mouse model to evaluate neuropeptide Y‐mediated melanocyte pathology

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Abstract

Vitiligo is an autoimmune disease characterized by depigmented patches of skin due to loss of the pigment-producing melanocytes. No cure exists for vitiligo. The available treatments are inefficient for many patients, suggesting that universal treatment approaches may be inappropriate. Deeper understanding of the mechanistic basis for variability in vitiligo etiologies is necessary. Genetic mutations in neuropeptide Y (NPY), a widely distributed protein, are associated with increased NPY expression and increased susceptibility for vitiligo. NPY is also upregulated in the circulation and lesional skin of some vitiligo patients. However, the contributions of NPY to melanocyte pathology are not understood, and presently there are no models with which to investigate this possibility. In this study, we employed NPY-overexpressing mice to explore the role of NPY in melanocyte dysfunction. Our results show that NPY-overexpression induces progressive hair graying (depigmentation) due to p remature depletion of follicular melanocyte stem cells. Additionally, NPY transcripts and protein are elevated in the skin and melanocytes of these mice, respectively, suggesting that these effects may be mediated locally. Together, these results suggest that supraphysiological levels of NPY in the skin can induce melanocyte dysfunction, thus identifying this mouse line as a novel model to study NPY-mediated melanocyte pathology.

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Type 2 diabetes impairs vascular responsiveness to nitric oxide, but not the venoarteriolar reflex or post‐occlusive reactive hyperaemia in forearm skin

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Abstract

The venoarteriolar reflex (VAR) is a local mechanism by which vasoconstriction is mediated in response to venous congestion. This response may minimize tissue overperfusion, preventing capillary damage and edema. Post-occlusive reactive hyperaemia (PORH) is used to appraise microvascular function performed by a brief local arterial occlusion resulting in a subsequent rapid transient vasodilation. In the current study, we hypothesized that type 2 diabetes (T2D) attenuates VAR and PORH responses in forearm skin in vivo. In 11 healthy older adults (Control, 58±8 years) and 13 older adults with controlled T2D (62±10 years), cutaneous blood flow measured by laser-Doppler flowmetry was monitored following a 3-min venous occlusion of 45 mmHg that elicited the VAR, followed by a 3-min recovery period and then a 5-min arterial occlusion of 240 mmHg that induced PORH. Finally, sodium nitroprusside, a nitric oxide donor, was administered to induce maximum vasodilation. VAR and PORH variabl es were similar between groups. By contrast, maximal cutaneous blood flow induced by sodium nitroprusside was lower in the T2D group. Taken together, our observations indicate that T2D impairs vascular smooth muscle responsiveness to nitric oxide, but not VAR and PORH in forearm skin.

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Cellular reprogramming of diabetic foot ulcer fibroblasts triggers pro‐healing miRNA‐mediated epigenetic signature

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Abstract

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes, constitute a major medical challenge with a critical need for development of cell-based therapies. We previously generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts derived from the DFU patients, location-matched skin of diabetic patients and normal healthy donors and re-differentiated them into fibroblasts. To assess the epigenetic microRNA (miR) regulated changes triggered by cellular reprogramming, we performed miRs expression profiling. We found let-7c, miR-26b-5p, −29c-3p, −148a-3p, −196a-5p, −199b-5p and −374a-5p suppressed in iPSC-derived fibroblasts in vitro and in 3D dermis-like self-assembly tissue, whereas their corresponding targets involved in cellular migration were upregulated. Moreover, targets involved in organization of extracellular matrix were induced after fibroblast reprogramming. PLAT gene, the crucial fibrinolysis factor, was upregulated in iPSC-derived fibrobl asts and was confirmed as a direct target of miR-196a-5p. miR-197-3p and miR-331-3p were found upregulated specifically in iPSC-derived diabetic fibroblasts, while their targets CAV1 and CDKN3 were suppressed. CAV1, an important negative regulator of wound healing, was confirmed as a direct miR-197-3p target. Together, our findings demonstrate that iPSC reprogramming is an effective approach for erasing the diabetic non-healing miR-mediated epigenetic signature and promoting a pro-healing cellular phenotype.

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The involvement of translationally controlled tumor protein during lamb rumen epithelium development

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Via histochem

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Acta Histochem. 2021 Jun 8;123(5):151737. doi: 10.1016/j.acthis.2021.151737. Online ahead of print.

ABSTRACT

Early weaning is usually applied to improve the reproductive efficiency of sheep in mutton production, while the development of rumen is of vital importance for sheep weaning age. Translationally controlled tumor protein (TCTP) is a highly conserved protein which participates in multiple tissue and organ development. Thus, we hypothesized that TCTP was involved in shee p rumen development. Histological analyses of sheep rumen epithelium showed that the epithelium formed tough shaped papillae without growing from birth to day 15 of age, after which it rapidly developed to functional epithelia on day 45 of age. We then found TCTP expressed in stratum basale, stratum spinosum and stratum granulosum of rumen epithelium. TCTP protein expression remained at a relative low level from day 0 to day 15 of age, it then significantly increased on day 30 (p < 0.05) and gradually decreased until day 60. Furthermore, to explore the role of TCTP in sheep rumen and its regulation, we found the ratio of Ki67 positive cell in stratum basale cells followed the similar pattern as the expression of TCTP. We also found the ratio of acetate:propionate in rumen fluid decreased from day 30 to day 60 of age (p < 0.05). To conclude, our data indicated that TCTP participated in rumen papillae growth by promoting rumen stratum basale cell proliferation.

PMID:34116359 | DOI:10.1016/j.acthis.2021.151737

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