Δευτέρα 20 Σεπτεμβρίου 2021

Intratumor Epigenetic Heterogeneity-A Panel Gene Methylation Study in Thyroid Cancer

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Front Genet. 2021 Sep 3;12:714071. doi: 10.3389/fgene.2021.714071. eCollection 2021.

ABSTRACT

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy, and the incidence is increasing very fast. Surgical resection and radioactive iodine ablation are major therapeutic methods, however, around 10% of differentiated thyroid cancer and all anaplastic thyroid carcinoma (ATC) are failed. Comprehensive understanding the molecular mechanisms may provide new therapeutic strat egies for thyroid cancer. Even though genetic heterogeneity is rigorously studied in various cancers, epigenetic heterogeneity in human cancer remains unclear.

METHODS: A total of 405 surgical resected thyroid cancer samples were employed (three spatially isolated specimens were obtained from different regions of the same tumor). Twenty-four genes were selected for methylation screening, and frequently methylated genes in thyroid cancer were used for further validation. Methylation specific PCR (MSP) approach was employed to detect the gene promoter region methylation.

RESULTS: Five genes (AP2, CDH1, DACT2, HIN1, and RASSF1A) are found frequently methylated (>30%) in thyroid cancer. The five genes panel is used for further epigenetic heterogeneity analysis. AP2 methylation is associated with gender (P < 0.05), DACT2 methylation is associated with age, gender and tumor size (all P < 0.05), HIN1 methyl ation is associated to tumor size (P < 0.05) and extra-thyroidal extension (P < 0.01). RASSF1A methylation is associated with lymph node metastasis (P < 0.01). For heterogeneity analysis, AP2 methylation heterogeneity is associated with tumor size (P < 0.01), CDH1 methylation heterogeneity is associated with lymph node metastasis (P < 0.05), DACT2 methylation heterogeneity is associated with tumor size (P < 0.01), HIN1 methylation heterogeneity is associated with tumor size and extra-thyroidal extension (all P < 0.01). The multivariable analysis suggested that the risk of lymph node metastasis is 2.5 times in CDH1 heterogeneous methylation group (OR = 2.512, 95% CI 1.135, 5.557, P = 0.023). The risk of extra-thyroidal extension is almost 3 times in HIN1 heterogeneous methylation group (OR = 2.607, 95% CI 1.138, 5.971, P = 0.023).

CONCLUSION: Five of twenty-four genes were found frequently methylated in human thyroid cancer. Based on 5 genes panel analysis, epigenetic heterogeneity is an universal event. Epigenetic heterogeneity is associated with cancer development and progression.

PMID:34539742 | PMC:PMC8446600 | DOI:10.3389/fgene.2021.714071

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Bilateral vocal cord paralysis caused by accidental button battery ingestion in children: A case report and literature review

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Ear Nose Throat J. 2021 Sep 19:1455613211043678. doi: 10.1177/01455613211043678. Online ahead of print.

ABSTRACT

Button battery ingestion in pediatric populations is a common occurrence with severe sequelae. Multiple case reports have established the occurrence of death, fistula formation, mucosal erosion, esophageal perforation, and bleeding post-ingestion of button batteries. However, there is a gap in the literature on the occurrence of bilateral vocal cord paralysis post -lithium battery ingestion. We present a case in which a 12-month-old male developed bilateral vocal cord paralysis following ingestion of a button battery. We compare our case to eleven other reports that exist in the literature based on age, sex, time until removal, clinical presentation, day upon which vocal cord paralysis developed, anatomic location, and post-operative course. We conclude that bilateral vocal cord paralysis is a time-sensitive complication which requires prompt diagnosis. Any child with stridor following button battery ingestion should undergo consultation with pediatric otolaryngology immediately. In addition, long-term follow-up is necessary to evaluate return of normal vocal cord function.

PMID:34541933 | DOI:10.1177/01455613211043678

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Effects of acrylonitrile on apoptosis of rat cerebral nerve cells

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Int J Clin Exp Pathol. 2021 Aug 15;14(8):908-914. eCollection 2021.

ABSTRACT

The brain, especially the hippocampus, is sensitive to damage caused by anoxic chemicals. In this study, we established a rat model of acrylonitrile poisoning with administration by gavage, aiming to determine the influence of acrylonitrile on rat cerebral nerve cells. Transmission electron microscopy observation and TdT-mediated dUTP nick-end labelling (TUNEL) staining were used to explore preliminarily the apoptotic changes of cerebral nerve cells. The pathogenesis revealed by transmission electron microscopy indicated that apoptosis in the control group was more serious than that of the exposure groups. The results of TUNEL staining showed the apoptotic rate was significantly higher in the control group than that of other exposure groups. All the results indicated that acrylonitrile can inhibit the apoptosis of rat cerebral nerve cells, which is closely rel ated to its animal carcinogenicity.

PMID:34527134 | PMC:PMC8414433

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Adenoid cystic carcinoma. An indolent but aggressive tumour. Part B: treatment and prognosis

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):296-307. doi: 10.14639/0392-100X-N1729.

NO ABSTRACT

PMID:34533533 | DOI:10.14639/0392-100X-N1729

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How to predict the outcome of septorhinoplasty? A normative study of ROE and FROI-17 scores

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):327-335. doi: 10.14639/0392-100X-N1291.

ABSTRACT

OBJECTIVE: Normative values of patient-reported outcome instruments are needed to identify good candidates for rhinoplasty. Rhinoplasty Outcome Evaluation (ROE) and Functional Rhinoplasty Outcome Inventory-17 (FROI-17) are disease-specific questionnaires that evaluate quality of life in patients undergoing rhinoplasty.

METHODS: The reference cohort contained 1,000 participants, selected from a non-probability panel. Normative ROE and FROI-17 scores from this reference cohort were compared with ROE and FROI-17 scores from a patient cohort before (n = 104) and 6 (n = 55) and 12 months (n = 32) after septorhinoplasty.

RESULTS: Mean FROI-17 scores (± SD) were: overall score, 20.8 ± 17; nasal symptoms, 16.8 ± 7; general symptoms, 24.8 ± 22; and self-confidence, 16.4 ± 21. The ROE total score was 73.1 ± 16. Normative values differed significantly from the preoperative ROE and FROI-17 scores of septorhinoplasty patients (p < 0.01). Except for the FROI-17 general score at 12 months postoperatively (p = 0.004), there were no significant differences between normative ROE/FROI-17 and septorhinoplasty scores postoperatively, indicating that they returned to normalcy.

CONCLUSIONS: Normative scores for ROE and FROI-17 provide a reference point from which to identify patients who are most likely to benefit from rhinoplasty.

PMID:34533536 | DOI:10.14639/0392-100X-N1291

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Development of a questionnaire to investigate socio-cultural differences in the perception of smell, taste and flavour

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):336-347. doi: 10.14639/0392-100X-N0766.

ABSTRACT

OBJECTIVES: Clinical experience and daily life indicate that the importance of smell, taste and flavour is variable among individuals. Therefore, the aim of this research was to develop a questionnaire to investigate the importance attributed to smell, taste and flavour and socio-cultural differences among individuals.

METHODS: Cross-cultural adaptation of the questionnaire was executed by two professional translators and one bilingual investigator and pre-tested on a pilot group of 25 subjects with normal smell and taste abilities. The final version of the questionnaire was sent by e-mail to 850 healthy subjects. The Google form consisted of three parts: "The importance of olfaction" developed by Croy et al. in 2010, "The importance of taste and flavour" developed by our team and a section to collect demographic data. The questions were classified into "association", "application", "consequence" and "aggravation". Statistical differences were assessed using t-test with p ≤ 0.05. Correlations were calculated using Spearman's test. Internal consistency was assessed using the Cronbach's Alpha, while test-retest reliability was analysed by calculating the Intraclass Correlation Coefficients (ICC2k).

RESULTS: The questionnaire received a non-response rate of 10.7%. Calculation of Cronbach's alpha showed good internal reliabi lity (a = 0.87). Test-retest evaluation was satisfactory for all subscales, with an overall ICC2k = 0.84 (CI 0.79-0.89). Statistical analysis showed that smell, taste and flavour appeared to be more important for women when compared to men (p < 0.001). No statistical differences were seen between individuals with various educational background (p > 0.05), and the importance of smell (r = 0.16; p < 0.01), taste and flavour (r = 0.08; p < 0.05) did not decline with age.

CONCLUSIONS: The development of this original test provides an overview into the importance of smell, taste and flavour among individuals. Although further research is needed, it can help in the evaluation and investigation of aspects that influence people to seek medical attention in the presence of sensory alterations.

PMID:34533537 | DOI:10.14639/0392-100X-N0766

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Sound frequency spectra of snore in relation to the site of obstruction among snorers

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):348-355. doi: 10.14639/0392-100X-N1202.

ABSTRACT

OBJECTIVE: This study aimed to describe the sound frequency of snoring in relation to the site of upper airway vibration among snorers.

METHODS: 383 snores from 40 participants who complained of snoring were digitally recorded during natural and induced sleep using a level III polysomnography monitor with a built-in microphone. During drug-induced sleep endoscopy (DISE), the rea l-time site of upper airway obstruction was assessed, and the sound frequency of snoring was recorded synchronously.

RESULTS: The mean peak of snoring frequency for unilevel palatal, oropharynx and epiglottis obstruction were 522.5, 482.4 and 300.0 Hz, respectively. Most participants showed multilevel obstruction at the palate and oropharynx, in which the mean for bi-peak snoring frequency were 402.90 Hz and 1086.96 Hz, respectively. Severity of OSA was significantly associated with multilevel obstruction.

CONCLUSIONS: There was a significant association between the snoring sound frequency and site of unilevel obstruction. Palatal or oropharyngeal obstruction produced sound at mid-frequency range, while the epiglottis produced a low frequency range. Multilevel obstruction documented a bi-peak snoring frequency.

PMID:34533538 | DOI:10.14639/0392-100X-N1202

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Nasal autoinflation devices for middle ear disease in cleft palate children: are they effective?

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Acta Otorhinolaryngol Ital. 2021 Aug;41(4):364-370. doi: 10.14639/0392-100X-N1277.

ABSTRACT

OBJECTIVE: Cleft lip palate (CLP) and cleft palate (CP) patients have a higher incidence of otitis media with effusion (OME) and conductive hearing problems. This article aims to evaluate the effectiveness of a 6-month course of self-administered autoinflation therapy in paediatric CP/CLP patients in terms of conductive hearing loss (CHL) and OME prevalence.

METHODS: Fifty-one p atients with surgically corrected CP/CLP and diagnosis of OME received indication to 6-months autoinflation therapy with an Otovent® device. Clinical evaluation, tympanogram and pure tone audiometry were carried out at the time of prescription (T0), at the end of treatment (T1) and at 6-month follow-up (T2). Patients were divided in 2 groups based on therapeutic compliance (29 compliant children, group A, vs 22 non-compliant children, group B).

RESULTS: Case series showed better audiological results and tympanometries at both time points (p < 0.001). Group A showed better outcomes at tympanograms and at each frequency, but were statistically significant only in terms of CHL at 250 and 1000 Hz frequencies at T1 (respectively 0.024 and 0.012).

CONCLUSIONS: Nasal autoinflation therapy accelerates improvement of OME and hearing thresholds at short-/mid-term, leading to an earlier improved hearing performance.

PMID:34533540 | DOI:10.14639/0392-100X-N1277

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Socio-economic determinants of prenatal anaemia in rural communities of South-West Nigeria: a preliminary report

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Am J Blood Res. 2021 Aug 15;11(4):410-416. eCollection 2021.

ABSTRACT

BACKGROUND: Anaemia is common worldwide and pregnant women are one of the most vulnerable group. Although, anaemia in the general population including pregnant women is multi-factorial in aetiology, the most frequent cause in pregnancy worldwide is iron deficiency. In Nigeria, an estimated prevalence of anaemia among pregnant women ranges from 35-75%. Anaemia in pregnancy (AIP) is associated with significant perinatal and maternal morbidity and mortality including premature birth and low birth weight.

AIM: The aim of this study was to determine the prevalence, demographic and socio-economic determinants of anaemia in pregnancy in a rural community of South-West Nigeria.

MATERIALS AND METHODS: One-hundred and fifty consenting pregnant women aged 18-42 years in the three trimesters were recruited from four primary health centres of Ikene Local Government of Ogun State of Nigeria after ethical approval was obtained from the Ethics Unit of the Medical officer of Health of the Local Government. Pre-tested interviewer-administered questionnaire was used to collect data on socio-demographic information and 24-hour dietary recall. Using a finger prick, the haemoglobin concentration of each respondent was determined with a haemoglobinometer (DG-300HB manufactured by DouBle, China). Data was analyzed using the Statistical Package for Social Sciences (SPSS) version 20.

RESULTS: All the respondents belonged to low socio-economic class. The mean haemoglobin (Hb) concentration obtained in this study was 10.22±1.60 g/dL with a range of 6-14.8 g/dL. Using WHO cut-off Hb concentration of 11 g/dL, the prevalence of anaemia in this study was 67.3%. The frequency of anaemia increased with increase in age group. P=0.010. About 21.4% of those with adequate dietary iron intake were anaemic when compared with 72.1% (98 of 136) of those with i nadequate dietary iron intake who were anaemic. AOR-0.090; 95% CI- 0.018-0.457; P=0.004.

CONCLUSION: Increasing age, low socio-economic status, poor health education and low dietary iron intake were the predominant socio-economic determinants of prenatal anaemia in the population studied. Efforts must be intensified to alleviate poverty in rural areas and give health education on iron-rich foods to girls and women of children-bearing age in the rural communities.

PMID:34540350 | PMC:PMC8446826

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A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels

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Am J Blood Res. 2021 Aug 15;11(4):399-404. eCollection 2021.

ABSTRACT

INTRODUCTION: PCSK9 inhibitors (PCSK9i) are often used in statin-intolerant patients, aiming to reduce low-density lipoprotein cholesterol (LDL-C). Along with the growing experience with their use, there is a lack of evidence regarding the safety, tolerability, and clinical utility of PCSK9i in patients with markedly elevated creatine phosphokinase (CPK) levels.

METHODS: We screened a comprehensive HMO database for patients treated with PCSK9i (Jan 2016-Dec 2019), in whom elevated CPK levels (>1,000 U/L) were documented prior to the initiation of therapy. Treatment plans, adherence, and the levels of CPK and LDL-C were analyzed.

RESULTS: Of the 1,600 patients initiating treatment with PCSK9i, 26 had prior CPK values >1,000 U/L [median (IQR): 3,687 (1,876-8,344) U/L]. All 26 patients were previously treated with statins, which presumably resulted in adverse effects (myalgia in 24, and rhabdomyolysis in 5 patients) therefore mandating their discontinuation. Concomitant secondary factors for CPK elevation were present in 11 patients, and included renal failure, rheumatoid disorders, hypothyroidism, intensive exercise, proteinuria and genetic muscular disease. Of the 26 patients treated with PCSK9i, alirocumab was administered to 12 patients, and evolocumab to 14. Following the initiation of treatment with either drug, 24 patients (92%) demonstrated a reduction in CPK of >50%, and in 12 (46%) CPK levels have returned to normal values. With regard to treatment goals, 17 patients (65%) have achieved an LDL-C level of <70 mg/dL, and 12 (46%) have reached a level of <55 mg/dL. No serious adverse reactions were documented, and only 2 patients discontinued the treatment (not due to muscle symptoms or CPK elevation).

CONCLUSIONS: PCSK9i constitute a safe, tolerable, and effective treatment for hyperlipidemia in patients wi th markedly elevated CPK. While statin intolerance is a major cause for CPK elevation, concomitant etiologies for increased CPK values were rather common.

PMID:34540348 | PMC:PMC8446829

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