The Impact of DNA Methylation on IL6 mRNA Levels in Hematinic Deficiency and Atopy-Associated Recurrent Aphthous Stomatitis Patients

Objective. To investigate the DNA methylation using pyrosequencing and its effects on the upregulation of IL6 mRNA in patients with recurrent aphthous stomatitis (RAS) in connection with hematinic deficiency and atopy. Material and Methods. This cross-sectional study was conducted at Dr. Hasan Sadikin Hospital, Bandung, from January–March 2019 and was approved by the Health Research Ethics Committee of Universitas Padjadjaran (Ethics No. 990/UN6.KEP/EC/2018). Furthermore, the subjects had RAS ulcers with a history of at least twice a year along with atopy and dietary imbalance with no history of recurrent intraoral herpes or any systemic diseases. This study was performed on 23 RAS patients and 21 healthy subjects, and the sampling was carried out consecutively. The blood samples were collected from all the subjects, and then, the DNA and RNA were extracted from the peripheral blood mononuclear cells (PBMCs). Consequently, the bisulfite-modified DNA was used to confirm the methylation status of the IL6 gene promoter through the pyrosequencing method. The methylation levels of the IL6 promoter were assessed by a reverse transcriptase-polymerase chain reaction technique. The gene expression of RAS and the control group was analyzed by the 2−ΔΔCT method. The statistical analysis using the Mann–Whitney U test was conducted to evaluate IL6 mRNA levels and DNA methylation with p value <0.05 considered to be statistically significant. Result. The IL6 mRNA levels were approximately 1.88-fold in RAS patients, and there was a significant relationship between the expression of the IL6 gene and the increased risk of RAS p < 0.001 . It was reported that four out of six sites in the cytosine phosphate guanine (CpG) island IL6 promoter had a lower degree of methylation, and two other sites in patients with RAS had greater methylation compared with control, but not statistically significant. Conclusion. This study showed the upregulation of IL6 mRNA levels in RAS patients compared to control. DNA methylation in the present study is at sites 566–658, whereas the location of the IL6 promoter is at sites 1–1684. Thus, it would be necessary conducting some research at other CpG sites of IL6 promoter islands to determine the status of DNA methylation.

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LncRNA NEAT1 is upregulated in recurrent aphthous stomatitis (RAS) and has predictive values

BMC Oral Health ◽

10.1186/s12903-021-01909-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yaolun Han ◽

Lu Wang ◽

Qingfu Li ◽

Hongli Chen ◽

Xin Ma

Keyword(s):

Plasma Levels ◽

Inflammatory Responses ◽

Recurrent Aphthous Stomatitis ◽

Aphthous Stomatitis ◽

Control Group ◽

Predictive Values ◽

Tnf Α ◽

History Of ◽

Lncrna Neat1 ◽

Proinflammatory Factors

Abstract Background LncRNA NEAT1 promotes inflammatory responses, which contribute to recurrent aphthous stomatitis (RAS). This study focused on the involvement of NEAT1 in RAS. Methods RT-qPCR and ELISA were performed to determine the expression of NEAT1 and proinflammatory factors (IL-2, IL-1β, and TNF-α) in plasma from patients with a history of RAS and showing symptom (n = 80, S-RAS group), people with a history of RAS but showing no symptom (n = 80, NS-RAS group), and controls without a history of RAS (n = 80, Control group). Correlation analysis was performed with Pearson’s correlation coefficient. S-RAS group received treatmen,t and plasma levels of NEAT1 and proinflammatory factors were compared before and after treatment. S-RAS group was followed up for 12 months, and the recurrence was recorded. Results Plasma NEAT1, IL-2, IL-1β, and TNF-α levels were the highest in the S-RAS group, followed in turn by NS-RAS and control groups. NEAT1 was positively and significantly correlated with IL-2, IL-1β, and TNF-α across S-RAS and NS-RAS samples, but not control samples. After treatment, plasma levels of NEAT1, IL-2, IL-1β, and TNF-α decreased significantly. Moreover, a higher recurrence rate was observed during the follow-up in patients with high plasma NEAT1 levels. Conclusion NEAT1 is upregulated in RAS and correlated with multiple proinflammatory factors. Moreover, NEAT1 has predictive values for RAS.

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The Rapeutic Effect of Proaftol in Treatment of Recurrent Aphthous Stomatitis

PRILOZI ◽

10.1515/prilozi-2015-0024 ◽

2014 ◽

Vol 35 (3) ◽

pp. 195-202

Author(s):

Aneta Atanasovska Stojanovska ◽

Mirjana Popovska ◽

Ilijana Muratovska ◽

Kristina Mitic ◽

Emilija Stefanovska ◽

...

Keyword(s):

Lesion Size ◽

Recurrent Aphthous Stomatitis ◽

Aphthous Stomatitis ◽

Controlled Study ◽

Unknown Etiology ◽

Control Group ◽

Subjective Feeling ◽

Double Blind ◽

Two Parameters ◽

The Impact

AbstractRecurrent aphthous stomatitis (RAS) is a quite frequent, painful, ulcerative disease that affects the lining of the oral cavity and has an unknown etiology. The aim of this article is to examine the impact of the medication proaftol on epithelization speed and severity of pain in patients with RAS. In this randomized, double-blind, placebo-controlled study respondents were divided into two groups where one group was treated with proaftol spray and the other with a placebo. Aphthae considered for treatment had a diameter of 5-6 mm. The participants were given instruction on the use of the spray, two sprayings on the place of the aphtae 3-4 times a day. We examined two parameters in the symptomatology of RAS-lesion size (mm) and pain intensity (noted on four subjective levels: 0-no pain, 1-discomfort, 2-moderate pain, 3-severe pain). These parameters were noted on the baseline, the third, the fifth and the eighth days of examination.Results: A significant faster reduction of the dimension of aphthous ulcers in patients treated with proaftol 3rd day p < 0.001, 5th day p < 0.0006, 8th day full epithelization in the control group. The magnitude of pain in the experimental compared with the control group on 3rd, 5th and 8th day was also significantly reduced: p < 0.0001, p < 0.007, p < 0.007 respectively.Conclusion: The use of proaftol positively influences the rate of epithelization and reduction of subjective feeling of pain in patients with RAS. The action of propolis should be the goal of studies with a larger number of subjects.

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Neurodevelopment in Children Exposed to Zika Virus: What Are the Consequences for Children Who Do Not Present with Microcephaly at Birth?

Viruses ◽

10.3390/v13081427 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1427

Author(s):

Paula Sobral da Silva ◽

Sophie Eickmann ◽

Ricardo Ximenes ◽

Celina Martelli ◽

Elizabeth Brickley ◽

...

Keyword(s):

Neurological Examination ◽

Zika Virus ◽

Control Group ◽

P Value ◽

Zikv Infection ◽

Clinical Neurological Examination ◽

Cognitive Delay ◽

Increased Risk ◽

Neurodevelopmental Impairment ◽

The Impact

The relation of Zika virus (ZIKV) with microcephaly is well established. However, knowledge is lacking on later developmental outcomes in children with evidence of maternal ZIKV infection during pregnancy born without microcephaly. The objective of this analysis is to investigate the impact of prenatal exposure to ZIKV on neuropsychomotor development in children without microcephaly. We evaluated 274 children including 235 ZIKV exposed and 39 controls using the Bayley-III Scales of Infant and Toddler Development (BSIDIII) and neurological examination. We observed a difference in cognition with a borderline p-value (p = 0.052): 9.4% of exposed children and none of the unexposed control group had mild to moderate delays. The prevalence of delays in the language and motor domains did not differ significantly between ZIKV-exposed and unexposed children (language: 12.3% versus 12.8%; motor: 4.7% versus 2.6%). Notably, neurological examination results were predictive of neurodevelopmental delays in the BSIDIII assessments for exposed children: 46.7% of children with abnormalities on clinical neurological examination presented with delay in contrast to 17.8% among exposed children without apparent neurological abnormalities (p = 0.001). Overall, our findings suggest that relative to their unexposed peers, ZIKV-exposed children without microcephaly are not at considerably increased risk of neurodevelopmental impairment in the first 42 months of life, although a small group of children demonstrated higher frequencies of cognitive delay. It is important to highlight that in the group of exposed children, an abnormal neuroclinical examination may be a predictor of developmental delay. The article contributes to practical guidance and advances our knowledge about congenital Zika.

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Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I

Acta Neurochirurgica ◽

10.1007/s00701-021-04780-9 ◽

2021 ◽

Author(s):

Annamaria Biczok ◽

Philipp Karschnia ◽

Raffaela Vitalini ◽

Markus Lenski ◽

Tobias Greve ◽

...

Keyword(s):

Medical History ◽

Tumor Recurrence ◽

Clinical History ◽

Study Endpoint ◽

Past Medical History ◽

Who Grade ◽

Increased Risk ◽

History Of ◽

Meningioma Recurrence ◽

The Impact

Abstract Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

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Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

Ethnicity & Disease ◽

10.18865/ed.26.4.513 ◽

2016 ◽

Vol 26 (4) ◽

pp. 513 ◽

Cited By ~ 2

Author(s):

Kathleen A. Griffith ◽

Seon Yoon Chung ◽

Shijun Zhu ◽

Alice S. Ryan

Keyword(s):

Breast Cancer ◽

Insulin Resistance ◽

Black Women ◽

White Women ◽

Cancer Recurrence ◽

Control Group ◽

Study Objective ◽

Increased Risk ◽

Tnf Α ◽

History Of

Objective: After chemotherapy for breast cancer, Black women gain more weight and have an increased mortality rate compared with White women. Our study objective was to compare biomarkers associated with obesity in Black women with and without a history of breast cancer.Design: Case-controlSetting: Academic/federal institutionParticipants: Black women with a history of breast cancer (cases) and age-matched controls.Methods: We compared insulin resistance, inflammation, and lipids in overweight and obese Black women with a history of breast cancer (n=19), age similar controls (n=25), and older controls (n=32). Groups did not differ on mean body mass index (BMI), which was 35.4 kg/m2, 36.0 kg/m2, and 33.0 kg/m2, respectively.Main Outcome Measures: Insulin resistance (HOMA-IR); inflammation (TNF-α, IL-1b, IL-6, IL-8, CRP); lipids (cholesterol, triglycerides).Results: Cases had 1.6 and 1.38 times higher HOMA-IR values compared with age similar and older controls, respectively (P≤.001 for both). TNF-α and IL-1b were significantly higher in cases compared with both control groups (P<.001 for both). IL-6 was also higher in cases compared with age-similar controls (P=.007), and IL-8 was lower in cases compared with older controls (P<.05). Lipids did not differ between cases and either control group.Conclusions: Black women with breast cancer were significantly more insulin resistant with increased inflammation compared not only with age similar controls but with women who were, on average, a decade older. These biomarkers of insulin resistance and inflammation may be associated with increased risk of breast cancer recurrence and require ongoing evaluation, especially given the relatively abnormal findings compared with the controls in this underserved group. Ethn Dis. 2016;26(4):513-520; doi:10.18865/ed.26.4.513

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Shingles Immunity and Health Functioning in the Elderly:Tai Chi Chihas a Behavioral Treatment

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/neh048 ◽

2004 ◽

Vol 1 (3) ◽

pp. 223-232 ◽

Cited By ~ 30

Author(s):

Michael Irwin ◽

Jennifer Pike ◽

Michael Oxman

Keyword(s):

Older Adults ◽

Behavioral Treatment ◽

Tai Chi ◽

Relaxation Response ◽

Control Group ◽

Varicella Zoster ◽

Specific Immunity ◽

Health Functioning ◽

Increased Risk ◽

The Impact

Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in older adults is associated with declines in VZV-responder cell frequency (VZV-RCF), an immunological marker of shingles risk. In this review, we discuss recent findings that administration of a relaxation response-based intervention,tai chi chih(TCC), results in improvements in health functioning and immunity to VZV in older adults as compared with a control group. TCC is a slow moving meditation consisting of 20 separate standardized movements which can be readily used in elderly and medically compromised individuals. TCC offers standardized training and practice schedules, lending an important advantage over prior relaxation response-based therapies. Focus on older adults at increased risk for HZ and assay of VZV-specific immunity have implications for understanding the impact of behavioral factors and a behavioral intervention on a clinically relevant end-point and on the response of the immune system to infectious pathogens.

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MOLECULAR GENETIC STUDY OF THE IMPACT OF SNP C677T OF THE GENE MTHFR IN THE DEVELOPMENT OF CONGENITAL ISOLATED CLEFT LIP AND PALATE

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2018-25-5-104-110 ◽

2018 ◽

Vol 25 (5) ◽

pp. 104-110

Author(s):

V. S. Uchaeva ◽

Yu. A. Vasiliev ◽

A. S. Gracheva ◽

O. V. Gulenko ◽

I. G. Udina

Keyword(s):

Genetic Study ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Control Group ◽

Population Genetic Study ◽

Molecular Genetic Study ◽

Increased Risk ◽

Significant Difference ◽

Congenital Cleft ◽

The Impact

Aim. This research was designed to conduct an associative population genetic study for the consideration of the impact of SNP C677T of the gene MTHFR in the congenital maxillofacial developmental anomalies (CMDA): congenital cleft lip (CCL), congenital cleft palate (CCP), congenital cleft lip and palate (CCLP) in the Krasnodar territory. The aim of the study is to establish the associations between SNP C677T of the gene MTHFR and the development of congenital cleft lip and/ or palate.Materials and methods. In this research, the peculiarities of distribution of SNP C667T of the gene MTHFR in children with congenital cleft lip and/or palate (n=223) and their mothers (n=78) in comparison with the control group (n=124) were studied in the Krasnodar territory. The genetic demographic questionnaires were gathered for children with CMDA, the information about diagnosis was obtained from the medical records. The biological samples, including blood or scrapings of oral mucosa, were collected from children with the pathology and their mothers. The DNA was extracted from the samples by the standard method. The study of the peculiarities of distribution of alleles of SNP C677T of the gene MTHFR was performed by PCR-PFLP with endonuclease Hinf I or by tetra-primer ARMS-PCR method in children with CCL, CCP, CCLP, their mothers and the control group. Statistical processing of the obtained data was performed by the algorithms of the “Statistica” program.Results. While comparing the profiles of frequencies of SNP C677T in children with CCL, CCP and CCLP with the control group, there were identified no significant differences in the frequency of this SNP and no peculiarities of genotypes distribution. There was identified a significant difference in the peculiarities of genotypes distribution with the control group (G=19,5232, d.f.=1, p<0,001) as well as united genotypes (С/C и С/T) in accordance to T/T (G=10,4657, d.f.=1; p<0,001) and united genotypes (C/T и T/T) in accordance to C/C (G=15,1896, d.f.=1, p<0,001) for the mothers of children with CCL, CCP and CCLP.Conclusion. As a result of the study, we established the association of SNP C677T of the MTHFR gene with the development of congenital cleft lip and/or palate: mothers’ T/T genotype is associated with the increased risk of giving birth to a child with CCL, CCP and CCLP (in comparison with mothers with C/C+C/T genotype): odds ratio [OR]=16,63, 95% CI: 3,86-71,71; p=0,0003 and also for mothers with genotypes (C/T+T/T) in comparison with mothers with genotypes C/C: OR=3,22, CI:1,71-6,08; p=0,0002. The amount of risk is not significant in children with CMDA for T/T genotype. So it is possible to make a conclusion about the impact of C677T of the gene MTHFR in the development of CCL, CCP and CCLP only in mother’s genotype.

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RECURRENT APHTHOUS STOMATITIS RELATED TO PSYCHOLOGICAL STRESS, FOOD ALLERGY AND GERD

ODONTO Dental Journal ◽

10.30659/odj.6.0.45-51 ◽

2019 ◽

Vol 6 ◽

pp. 45

Author(s):

Rina Kartika Sari ◽

Diah Savitri Ernawati ◽

Bagus Soebadi

Keyword(s):

Food Allergy ◽

Psychological Stress ◽

Oral Mucosa ◽

Recurrent Aphthous Stomatitis ◽

Predisposing Factors ◽

Aphthous Stomatitis ◽

Cow Milk ◽

Esophageal Mucosa ◽

History Of ◽

Multiple Ulcers

Background: Recurrent Aphthous Stomatitis (RAS) is inflammation in oral mucosa characterized by recurrent single or multiple ulcers that usually affected in non keratinized mucosa. Etiology RAS is unknown but psychological stress, allergy, and gastrointestinal disease can be predisposing factors Case Management: A 23rd years old complained recurrent oral ulcer with free ulcer period for 3-5 days. The patient had a history of food allergy, GERD and psychological stress. Intraoral examination showed recurrent multiple ulcers in variation site of the mouth. DASS 42 screening showed high stress and high anxiety. Skin Prick Test showed positive allergy to kapok, beef, chicken, cow milk, white egg, duck egg, shrimp, cob fish, milkfish, chocolate, and peanut. Ulcers treated with nonsteroid antiinflammation Aloe Vera gel and stress management by reading assignment method.Discussion: Psychological stress altered the immune system so oral mucosa prone to inflammation, and make the history of GERD getting worse. Stress causes cortisol secretion that changes the imbalance of proinflammatory and antiinflammatory cytokines. Oral mucosa becomes more susceptible to hypersensitivity. In addition, stress decreased oral and esophageal mucosa resistance to GERDConclusion: RAS triggered by psychological stress, allergy, and GERD. Treatment of RAS is by elimination predisposing factors to prevent recurrence.

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Call for Emergency Room Guidelines to Identify Hyperthyroid Patients Prior to Contrast Imaging

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1885 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A922-A923

Author(s):

Sandhya Bassin ◽

Louis F Amorosa

Keyword(s):

Atrial Fibrillation ◽

Emergency Room ◽

Definitive Treatment ◽

Graves Disease ◽

Contrast Imaging ◽

Iodinated Contrast ◽

Increased Risk ◽

History Of ◽

The Impact ◽

Hyperthyroid Patients

Abstract Background: Thyrotoxicosis can be mistaken for conditions such as atrial fibrillation and pulmonary embolism (PE) given the nonspecific symptoms of fatigue, palpitations, and dyspnea. Patients often undergo further imaging on presentation to the emergency room (ER), many of which use iodine for contrast. This can put patients at increased risk for iodine induced hyperthyroidism and delay definitive treatment in patients with Graves’ disease, the most common cause of hyperthyroidism. Clinical Case: A 53-year-old male with history of hyperthyroidism, atrial fibrillation, and prior PE presented with palpitations to the ER. He developed worsening dyspnea on exertion and palpitations over the last three days. He was unable to afford his medications, including methimazole, for the last nine months. In the ER he was in atrial fibrillation with rapid ventricular response. Due to concern for PE, he underwent a CTA with contrast, which was negative. His physical exam was notable for a diffusely enlarged goiter. His labs showed low TSH <0.01 (norm 0.35-5.50mIU/L) and high free T4 >7.77 (norm 0.9-1.8ng/dL). TSH stimulating antibodies were elevated at 1.9 (norm <1.3 TSI index), consistent with Graves’ hyperthyroidism. Endocrinology was then consulted for severe thyrotoxicosis, initially treating the patient with PTU and propranolol. The patient was transitioned to methimazole and continued propranolol on discharge. Since he was given contrast, plan was for repeat thyroid uptake scan and iodine ablation in 3 months. However, patient was not compliant with medications, resulting in readmission for thyrotoxicosis 3 months later. Conclusion: This case highlights the impact of increased use of contrast in imaging in hyperthyroid patients. Hyperthyroid patients are at an increased risk for emboli. However, iodine can cause contrast-induced hyperthyroidism and delay definitive treatment of Graves’ disease. As almost half of thyrotoxic patients receive iodinated contrast prior to an endocrine consultation, endocrinologists should work with emergency physicians to develop a set of guidelines to identify at risk populations for hyperthyroidism (1). We advocate for urgent thyroid testing in patients with new onset atrial fibrillation, a history of Graves’ disease, specific symptoms of Graves’, or those taking thyrotoxic-inducing medications. This will assist in determining if patients should receive a prophylactic dose of anti-thyroid medication prior to iodinated contrast imaging. These guidelines can help prevent contrast induced hyperthyroidism and disruptions in treatment of Graves’ while still imaging patients for other diagnoses on the differential. Reference: (1) Giacomini A, et al. Urgent thyroid-stimulating hormone testing in emergency medicine: A useful tool? J Emerg Med. 2015;49(4):481-487.

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Abstract 18516: Regional Dysfunction of Left Atrial Appendage and its Association with Stroke in Atrial Fibrillation

Circulation ◽

10.1161/circ.130.suppl_2.18516 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Abdullah A Alissa ◽

Yuko Inoue ◽

Jochen Cammin ◽

Qiulin Tang ◽

Elliot Fishman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Left Atrial Appendage ◽

Atrial Appendage ◽

Control Group ◽

Prior History ◽

Area Change ◽

Increased Risk ◽

History Of ◽

Regional Dysfunction

Background: Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF. Methods: Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model. Results: A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score. Conclusions: LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.

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