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ஐ.எஸ்.எஸ்.என்: 1747-0862

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தொகுதி 11, பிரச்சினை 3 (2017)

ஆய்வுக் கட்டுரை

Identification of Thr241Met Polymorphisms of the XRCC3 Gene in People with Gastric Cancer in the Amazon Region, Brazil

Lobato LL, Da Silva Cabra l S, Vanzeler TL, Do Nascimento RE, Picanço OM and Do Nascimento Rodrigues AS

XRCC3 Thr241Met polymorphism has been associated with cancer susceptibility. Studies have shown a relationship between Thr241Met polymorphism and gastric cancer. The present study was aimed at examining the presence of XRCC3 Thr241Met polymorphism in patients diagnosed with gastric cancer in the city of Macapá. We analyzed 150 DNA samples, of which 100 comprised the control group and 50 were case patients. Our findings revealed that 76% of case samples had the Thr/Met genotype (OR (CI 95% 54.29 (18.84-156.38) p ≤ 0.0001) whereas in the control group, the same genotype represented 7%. Also, most gastric cancer patients with XRCC3 241Met polymorphism were heterozygotes. Given the small sample size in this study, a larger number of patients will be analyzed.

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Consecutive Rhinovirus Infection of Epithelial Cells Alters Chrono- Inflammatory Expression Network

Weckmann M, Becker T, Pech M, Koch CE, Oster H and Kopp MV

Introduction: Asthma exacerbations are associated with viral upper respiratory tract infections, and rhinovirus (RV) is the major cause of these virus-associated exacerbation. Circadian clocks regulate physiological rhythms via transcriptional networks. These networks contain several feedback mechanisms inducing complex tissue specific patterns of gene activation and repression that help to maintain and regulate important biological processes. For example, the neutrophil inflammation of the lung is gated by epithelial circadian oscillators. We hypothesized that recurrent, human rhinovirus infection (HRVI) of in in vitro cultured cells alter the circadian-gated inflammatory networks and imprint a methylation pattern similar to the network found in asthmatic patients.

Results: We measured the methylation of clock and inflammatory genes in the BEAS2-B cell line after 1, 3 or 5 consecutive rhinovirus infections. Hierarchical clustering of methylation levels identified distinct clusters of numbers of infection (NOI: 1,3 and 5) for clock and inflammatory genes in BEAS2-B cells. Furthermore, a linear regression model of the methylation level was used to identify significantly increased or decreased loci (p<0.01). In non-infected cells, clear clusters of RNA expression of circadian clock genes CRY1, PER2, PER3, CLOCK were found to be negatively associated with interleukin 8 (IL-8) expression. After HRVI a partial reversal is observed and the expression of the CLOCK gene is positively correlated to IL-8 expression Similarly, in asthmatic patients, a strong positive correlation between CLOCK and IL-8 was found.

Conclusion: This study provides first insights in how repeated viral infections (e.g. HRVI exacerbations in asthma) may introduce persistent changes to circadian-gated inflammatory networks involved in governing neutrophil recruitment. This could offer novel diagnostic strategies to identify and define certain asthmatic endotypes and lead to novel therapeutic approaches based on circadian rhythm stabilization.

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Design of Plasmalemma and Nucleolemma Specific Quantum Dots Stem Cell Labeling

Wang L, Li Z, Xu MM, Sun MT, Zhou X, Ma J, Isaacs WB and Xu X

To date, there are no efficient treatments for most of human congenital, developmental, or degenerative diseases because functional cells failed to regenerate new cells following damages to original cells. Stem Cell (SC) based therapeutic approach holds tremendous promise for treating these abnormalities by replacing the damaged cells. This approach has sparked unprecedented attention in this field. However, SC researchers should adopt more robust techniques that incorporate marker genes that render stem cells visible using fluorescence and conventional microscopy. We design a unique approach to label embryonic and adult stem cells, the peptide-mediated quantum dots (QDs) SCs labeling with plasmalemma and nucleolemma specific fusion peptides. Therefore, the targeted SCs will be distinguishable by the new markers to report grafted cells from endogenous cardiomyocytes and to display the trans-differentiation from the SCs. The fluorescence strength of nanocrystal QDs will surmount the interference of the false signals originating from auto-fluorescence of cardiac tissues with their features for anti-bleaching of nonorganic dye.

மினி விமர்சனம்

Saliva Biomarkers: The Unsung Hero of Diagnostics

Mishra A

With the advancement in technology, compositional analysis of saliva for diagnosis of various medical conditions has attracted the researchers over the last decade. Monitoring the salivary biomarkers help in early detection of diseases and increase the rate of success of the treatment. Sampling of saliva is safe, simple, cost effective and does not demand an expertise for collection. Therefore, saliva can be an important diagnostic armamentarium for mass screening for a specific disease or in remote areas. However, despite of various research, there are no definite guidelines regarding sensitivity and specificity of salivary diagnostic tools. Health care professionals must go hand in hand with government agencies to develop more research so that a general acceptance can be developed like that of traditional blood/urine analysis.

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Donepezil for Lewy Body Constipation: A Six-Month Follow-up

Lepkowsky CM

In a previous case study, four patients at different stages of Parkinson’s disease (PD) and Neurocognitive Disorder with Lewy Bodies (NCDLB) disease progression were treated with Donepezil, with the intention of mitigating Lewy body impairment of the cholinergic pathways in the myenteric plexus, increasing bowel motility, and reducing the symptom of constipation. In all four cases, the use of Donepezil was associated with significant reduction of the symptom of constipation. There was no exacerbation or instigation of other symptoms. The symptom status of the four patients was reviewed six months later. In none of the patients has there been exacerbation of the symptom of constipation, nor emergence of new symptoms. The findings suggest that Donepezil might have long-term efficacy for reducing constipation in patients with PD and NCDLB. Further research is recommended using larger numbers of subjects matched for diagnosis, age, gender, and other variables.

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The Prevalance of Sensori-Neural Hearing Loss and Ototoxicity in Acute Myeloid Leukemia Patients

Shanmugam R, Raman R, Zakaria MZ and Chang KM

Objective: The aim of this study is to investigate the prevalence of sensori-neural hearing loss and ototoxicity in acute myeloid leukemia (AML) patients.

Study design: This is a prospective non-randomized study.

Methods: 14 patients with the diagnosis of acute myeloid leukemia were treated with Daunorubicin and Cytarabine (ARA-C). Pure Tone Audiometry (PTA) was performed prior to induction chemotherapy and immediately after completion of induction protocol. Primary outcome was the prevalence of sensori-neural hearing loss. Secondary outcome was correlation of age, sex, absolute neutrophil counts, total white counts, platelet counts and creatinine levels in the study population.

Results: Fourteen patients participated in this study (n=14). Ten patients had normal hearing prior to preinduction treatment. Four patients had pre-existing hearing loss prior to treatment. Post induction treatment, ten patients had normal hearing. However, from these ten patients, one had pre-existing hearing loss which improved. Two patients, whom had normal hearing and pre-existing hearing loss pre-induction treatment respectively, expired. Two patients who had pre-existing hearing loss had the same level of hearing post induction. The prevalence of sensori-neural hearing loss in this study is 71.4%. From our observation, there is no evidence of ototoxicity from induction therapy of Daunorubicin and Cytarabine (ARA-C) in our study population (p=0.001). Induction treatment with Daunorubicin and Cytarabine (ARA-C) shows statistically significant reduction in Absolute Neutrophils Counts (p=0.013), Total White Counts (p=0.001), Haemoglobin Counts (p=0.036) and Creatinine levels (p=0.017) in our study population. Even though Platelet counts showed reduction, this was not supported statistically (p=0.258).

Conclusion: Induction treatment with Daunorubicin and Cytarabine (ARA-C) are safe chemotherapy agents to be administered during the induction phase in treatment of Acute Myeloid Leukemia with no evidence of sensorineural hearing loss. Further study is required to monitor the long-term effects of these drugs during consolidation, remission or relapse phases of treatment and if possible during stem cell transplant treatment.

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Genesis of Personalized Medicine: Relevance of Ayurveda in the Present Millennium

Chakraborty S and Chakraborty R

Deciphering human genome has ushered modern bio-medical science towards a future hope of revitalizing current symptomatic or prophylactic treatment methods into personalized and predictive medicine depending upon an individual’s genetic makeup. Genetic variations related to a person’s response towards drugs, differential susceptibility to disease and reciprocity of phenotypic attributes related to environment, ethno-racial origin and diseases to genotypes have not been meticulously apprehended yet. Ayurveda, an age-old health science resonated unequivocally with ancient system of classifying a person on the basis of “Prakriti” or unchangeable constitution type might be an advantageous inclination towards personalized medicine, bearing testable molecular and genetic correlates. Several genomic and metabolomic studies augmented the possibilities of yet undisclosed molecular and genetic basis of Ayurveda, which could further be integrated or complemented to current medical diagnosis and treatment. Further deep dive into the extremes of utilizable science and technology of this holistic practice remained quintessential for better enlightenment of future bio-medical science to fight all fiends of ailments.

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Understanding the Biology Behind the EGFR to Improve NSCLC Patients’ Treatment

Verlicchi A and Addeo A

Epidermal growth factor receptor (EGFR) is a member of the EGFR tyrosine kinase family, which consists of EGFR (erbB1/Her1), Her2/neu (erbB2), Her3 (erbB3) and Her4 (erbB4). HER receptors are ubiquitously expressed in various cell types, under homeostatic conditions, receptor activation is tightly regulated by the availability of ligands, which collectively form the EGF family.

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Value of 18F-FDG Accumulation in Mediastinal and Hilar Lymph Nodes on 18F-FDG PET/CT: Relation to Recurrence of Cardiac Sarcoidosis

Maruoka Y, Baba S, Isoda T, Kitamura Y, Nagao M, Ide T, Hiasa K, Sasaki M and Honda H

Purpose: 18F-fluorodeoxyglucose (18F-FDG) accumulation in the left ventricular (LV) wall detects active myocardial inflammatory lesions in cardiac sarcoidosis (CS), but the significance of 18F-FDG accumulation in mediastinal and hilar lymph nodes (LNs) remains unclear. We investigated the association between CS recurrence and 18F-FDG accumulation in the mediastinal and hilar LNs, using positron emission tomography/computed tomography (PET/CT).

Materials and Methods: We retrospectively analyzed the records of 68 patients diagnosed with CS, who underwent 18F-FDG PET/CT before beginning treatment. The minimum follow-up period was 24 months. Patients were assigned to the recurrence (n=18) or no recurrence group (n=50) based on follow-up examinations. The 18FFDG PET/CT maximum standardized uptake value (SUVmax) was measured in the LV wall, right ventricular (RV) wall, and mediastinal and hilar LNs. The association of CS recurrence was analyzed using Cox proportional hazards models. Recurrence-free survival (RFS) curves were made using the Kaplan-Meier method.

Results: In univariate analysis, sex, BNP, LVEF, and the SUVmax in the LV wall, RV wall, and mediastinal and hilar LNs were significant risk factors for CS recurrence. In multivariate analysis, only the SUVmax in the mediastinal and hilar LNs was a significant risk factor for CS recurrence. RFS rates were significantly higher in patients with an SUVmax<4.1 vs. ≥ 4.1 (log-rank value=36.0, p<0.01).

Conclusion: The mediastinal and hilar LN SUVmax was an independent risk factor for CS recurrence after treatment. 18F-FDG accumulation in mediastinal and hilar LNs on 18F-FDG PET before treatment may be a useful biomarker to predict CS recurrence.

வழக்கு அறிக்கை

Osteomas in a Patient with Familial Adenomatous Polyposis

Almeida FT, Leite AF, Acevedo AC and Guerra ENS

This case report aimed to characterize dento-osseous anomalies in Familial Adenomatous Polyposis (FAP) in a Brazilian patient. Furthermore, FAP was investigate for possible causative. This case report showed the importance of dento-osseous knowledge related to FAP. Early dento-osseous anomalies diagnosis revealed the need to followup FAP family members from childhood and was essential for subsequent clinical or genetic FAP diagnosis. The authors think that this work is important as it provides highlights about the role of the dentist in the early diagnosis of FAP, a disease that predisposes colorectal cancer.

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Association of Heme Oxygenase-1 (Number of GT Repeats) with The Methemoglobin Levels in Recessive Congenital Methemoglobinemia in Indian Population

Das S, Chiddarwar A, Warang P and Kedar P

Heme oxygenase-1 (HO-1) is important in the defense against oxidative stress. Length polymorphisms in this GT repeat region correlate with levels of HO-1 expression and associates with several diseases. The aim of this study was to test for possible association of HO-1 (number of GT repeats) with methemoglobin levels in recessive congenital methemoglobinemia in Indian population. Genotyping of DNA isolated from whole blood of 25 RCM patients due to NADH cytochrome b5 reductase deficiency and 50 healthy controls was performed. Fragment size analysis by sequencing was used for genotype/allele definition by ABI 3130 genetic analyzer and size of PCR product was determined by Gene Mapper software. Significance of findings was tested using χ(2) test. The HO-1 (number of GT repeats) polymorphisms was significantly associated with RCM. Results of genotyping analysis indicated that a genotype carrying short alleles (<24 (GT)n repeats was preferentially associated with RCM patients than in control (P<0.001). The short allele (<24 GT repeats) genotype were present in 82% of the methemoglobinemia patients group and long allele (≥31 GT repeats) observed in the normal control group. This study is supporting the association of HO-1 (number of GT repeats) polymorphism and RCM. . Allele and genotype frequencies for HO-1 polymorphisms show significant association with disease severity. This data could also be valuable to the clinicians, mainly hematologists, when attempting a definitive diagnosis for the cause of methemoglobinemia that will help clinical decisions for treatment.

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Recurrent Bilateral Orbital Infiltration as Primary Manifestation of Rosai Dorfman Disease

Pustina B, Salihu N, Rroji A, Kaloshi G and Petrela M

Rosai Dorfman disease also known as histiocytosis with massive lymphadenopathy is a very rare idiopathic disease. It is characterized by over production and accumulation of non-Langerhans sinus histiocyte most often in lymph nodes, but may occur in other areas leading to organ damage. Based on the research it can be caused by an infectious agent, immunodeficiency or autoimmunity and genetic causes. Extranodal manifestation is uncommon; however extranodal sites include liver, kidney, respiratory organs, orbit and eyeball. We present a case report of a 44-year-old female with recurrent bilateral orbital infiltration as first location of Rosai Dorfman disease.

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Prenatal Diagnosis of an Extralobar Infradiaphragmatic Pulmonary Sequestration: A Case Report and Review of the Literature

Lv B, Jiang B and Wang X

Pulmonary sequestrations (PSs) are masses of non-functioning pulmonary tissue. Most PSs are situated in thoracic cavity; very rarely PSs are located below the diaphragm, particularly in the left suprarenal area. A 33-yearold primigravida underwent ultrasound scan at 24+2 weeks of gestation. Ultrasonography showed a hyperechogenic mass situated below the diaphragm. Color Doppler Flow Imaging (CDFI) showed the supplying vessels within the mass originated in the abdominal aorta. The fetus was preliminarily diagnosed with infradiaphragmatic PS. The patient opted to terminate the pregnancy. She underwent odinopoeia to deliver a male fetus who underwent postmortern examination confirmed prenatally diagnosed abnormalities.

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The Adjustment Effects of Confounding Factors on Radiation Risk Estimates: Findings from A Japanese Epidemiological Study on Low-Dose Radiation Effects (J-EPISODE)

Kudo S, Ishida J, Yoshimoto K, Ohshima S, Furuta H and Kasagi F

Purpose: To investigate the degree of any decreasing effects for excess relative risk (ERR) of radiation exposure caused by adjusting for smoking and years of education.

Methods: In this cohort study, we assembled a cohort of 41,742 males who responded to a lifestyle questionnaire survey performed in 2003, were registered in the Radiation Dose Registry as Japanese nuclear workers by the end of March 1999. There were a total of 215,000 person-years, while the number of deaths for all cancers excluding leukemia was 978. Poisson regression was used to quantify ERR per Sv and a comparison of ERRs was performed before adjustment for smoking or years of education and after those adjustments.

Findings: For all cancers excluding leukemia, the ERR/Sv was 0.78 (90%CI: -0.65, 2.20). However, it decreased to 0.31 (-1.03, 1.65) when adjusted for smoking and to 0.42 (-0.94, 1.79) when adjusted for years of education. When adjusting for both smoking and years of education, it decreased to 0.08 (-1.22, 1.39).

Conclusion: Our results demonstrate the importance of collecting lifestyle data and adjusting for them when estimating radiation risk.

கட்டுரையை பரிசீலி

Circulating MicroRNAs in Colorectal Cancer

Huang Q, Ge B, Hu M, Zhou J and Bai X

Colorectal cancer (CRC) poses a serious threat to the health of global populations. Screening for the early detection of CRC is important to improve patient survival. Circulating microRNAs (miRNAs, miRs), as nucleic acid markers, play variety of important roles in early screening, diagnosis, TNM stage and prognosis of CRC. In this review, an overview covers recent researches on the roles of circulating miRNAs and their variety potential values correlated with CRC. Studies on the detectable marker values of circulating miRNAs for CRC will help making a global consensus of procedures and standardized protocols to make their clinical transformation more reliable.

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