Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

Background@#The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. @*Methods@#We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. @*Results@#There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). @*Conclusions@#The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

Background@#The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. @*Methods@#We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform. @*Results@#There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217). @*Conclusions@#The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

Studies on metals and pesticide content in some Ayurvedic formulations containing Bacopa monnieri L / 中西医结合学报

<p><b>OBJECTIVE</b>Ayurvedic formulations are preferred over other formulations as well as commercialized on broad level to treat various ailments. The World Health Organization has established certain guidelines for quality control of heavy metals and pesticide residues. Bacopa monnieri, a popular herb with immunomodulator and memory-enhancing properties is the chief constituent of several Ayurvedic formulations, which include Brahmi Vati (BV), Brahmi Ghrita (BG) and Saraswat Churna (SC), etc. In view of the World Health Organization guidelines, two products of each formulation from six different manufacturers were purchased from Ayurvedic Pharmacy, Bulanala-Varanasi, India for testing heavy metal and pesticide residue.</p><p><b>METHODS</b>In the present study, all the formulations--BV, BG and SC--were selected for estimation of four heavy metals namely lead (Pb), cadmium (Cd), chromium (Cr) and nickel (Ni) by a plasma emission spectrophotometer. Organochlorine pesticidal residues were estimated for dichlorodiphenyl trichloroethane, isomers of hexachlorocyclohexane (HCH) and α-endosulfan, etc. in total 12 samples of test formulations containing Bacopa monnieri L. using gas chromatography technique.</p><p><b>RESULTS</b>Out of 12 samples, Pb, Cd, Cr and Ni were present in all samples but below the permissible limit. Although atrazine, aldrin, dialdrin were in below detection limit, but other pesticides were detected in some samples as oxamyl, hexachlorocyclohexanes (α-HCH, β-HCH and γ-HCH), dichlorodiphenyl trichloroethane and dichlorodiphenyl dichloroethylene.</p><p><b>CONCLUSION</b>The presence of heavy metals in the formulations was low to cause toxicity. However evaluation of heavy metals and pesticide residue in every batch is necessary.</p>

Palisaded encapsulated neuroma: a unique presentation

Palisaded encapsulatee neuroma [PEN] is a genign intraneural neuroma presenting as a solitary, sessile, immobile, asymptomatic, skin-coloured papule or nodule, commonly affecting the butterfly area of the face of a middle-aged person. It is not associated with neurofibromatosis or multiple endocrine neoplasia. We hereby report a unique case presenting with a firm, nodular growth over the posteromedial aspect of right knee which progressively increased in size over one year. On the basis of histopathologic findings, diagnosis of palisaded encapsulated neuroma was made. It is imperative to diagnose it histopathologically, because it is more commonly middiagnosed clinically with schwannoma and neurofibroma

In-house preparation and characterization of an Ayurvedic bhasma: Praval bhasma / 中西医结合学报

<p><b>OBJECTIVE</b>To prepare the Praval bhasma (PB) and to perform its characterization.</p><p><b>METHODS</b>The preparation was performed strictly as per method prescribed in Ayurvedic formulary of India followed by preliminary tests including Nischandratva, Rekhapurnatvam, Varitaramtavm, Nisvadutvam and Amla pariksha. The physicochemical characterization was done with the use of instrumental techniques such as Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X ray diffraction (XRD), and energy dispersive X-ray (EDAX).</p><p><b>RESULTS</b>The FTIR bands appearing in final product spectra showed a significant shift in infrared vibration frequency as well as intensity when compared with the raw material, which was indicative of formulation of bhasma. The XRD analysis revealed that raw material contained CaCO3 whereas in case of final product of bhasma, CaO was identified. SEM analysis revealed the difference in particles size of bhasma (10-15 μm) and raw material (100-150 μm). The EDAX analysis showed presence of different concentration of carbon in both the samples.</p><p><b>CONCLUSION</b>It may be concluded that modern analytical techniques may be involved to evaluate the quality aspects of PB. The findings of the present research work may be helpful for further formulation and standardization of PB in routine analysis.</p>

Protective effect of ferulic acid on ionizing radiation induced damage in bovine serum albumin

Ionizing radiation causes deleterious effects on living system mainly due to oxidative damages of macromolecules and protein is the major target due to its abundance. The aim of this study was to investigate the effects of ionizing radiation induced changes in the molecular properties of bovine serum albumin [BSA]; its secondary and tertiary structures, degradation, cross linking and radioprotective role of ferulic acid, a natural antioxidant on these radiation induced changes. This study was carried out to investigate the gamma radiation induced oxidative, structural damage of BSA and radioprotective efficacy of ferulic acid through SDS-PAGE, DTNB assay, DNPH assay, FOX assay methods. Hydroxyl radical scavenging capacity of ferulic acid was estimated using 2-deoxy ribose assay. Further, radiation induced changes in the anisotropy and excitation state lifetimes of BSA were examined. SDS -PAGE data suggested that the loss of protein was linearly dependent on the radiation dose. Gamma-irradiation of BSA caused the formation of protein carbonyls, hydroperoxides and loss of thiols. Ferulic acid protected the radiation induced loss of protein as well as reduced various oxidative damages. Ferulic acid protected the protein from radiation induced damages in a concentration dependent manner. The results provide insight into radiation induced molecular changes in the protein. Ferulic acid protected the BSA from oxidative modification caused by radiation suggesting that ferulic acid possesses strong antiradical properties. Ferulic acid is known to protect DNA, the prime target of radiation and further its ability to protect protein suggesting its ability to protect different biomolecules and therefore can be a good candidate for development radioprotector

Isolation, characterization and therapeutic potential assessment of bacteriophages virulent to Staphylococcus aureus associated with goat mastitis

In the present study, the therapeutic potential of bacteriophages virulent to Staphylococcus aureus associated with goat mastitis were isolated, identified and assessed. Staphylococcus aureus [host or indicator bacterium] was isolated from a goat suffering from clinical mastitis. Based on cultural, morphological, biochemical tests and amplification of S. aureus specific thermonuclease gene in PCR, the identity of the organism was confirmed as S. aureus. Bacteriophages were isolated from soil and faecal samples [n=42] collected from different parts of the Mathura district in Uttar Pradesh [India], and their identity was confirmed by amplification of the bacteriophage-specific endolysin gene fragment in PCR. The thermal tolerance study revealed that all phage isolates were stable at 30 and 40°C with 100% lytic efficacy and their activities reduced to 62-80% at 50°C declining sharply at 60°C with less than 5% efficacy. Likewise, at pH = 6.5 and 7.5, the survivability of all isolates was 100% which reduced to 70-79% and 84-91% at pH = 5.5 and 8.5, respectively. All isolates were stable up to 3 months at 37°C, and for 16 months at 4°C but the stability of their respective endolysins only lasted for 12-23 days at 37°C and 6 months at 4°C. Three of the bacteriophage isolates, S. aureus phage/CIRG/1, S. aureus phage/CIRG/4 and S. aureus phage/CIRG/5 exhibited lytic activity against over 80% of the staphylococcal isolates. The results of the present study provide insight for the use of lytic bacteriophages for therapeutic interventions against multi-drug-resistant S. aureus inducing mastitis in goats

observational study of the risk factors and incidence of invasive fungal infections in ICU patients

The fungal infections have become a persistent health problem, still always remain under reported. A change in species distribution has been observed now a days with the emergence of many non-albicans candida species. Our study aimed at evaluating the incidence of invasive Candidiasis [Candida albicans and non-albicans] and to assess the risk factors and predictors of mortality in seriously ill patients. This prospective, observational study was conducted at Division of Intensive Care Unit, Institute of Medical Science, BHU, Varanasi [India], during the period of 2009 to 2011. Patients with >8 out of 16 risk factors, e.g. prolonged antibiotic use, IV cannulation, steroid use etc, Candida scores [CS] > 2, Age >12 years and ICU stay >2 days were included in the study. Those with Candida scores > 3 were prophylactically given fluconazole. A case report performa was completed for each patient, including demographic characteristics, dates of hospital and ICU admission and of discharge, vital sign status at discharge, previous treatment with antibiotics or immunosuppressive agents, presence of risk factors. Patients were followed till discharge from the ICU or death. Candida was isolated from blood in 53/206 patients. The P-value calculated in five risk groups, e.g. diabetics, patients receiving TPN, neutropenic patients, HIV and malignancy was significant [P<0.05]. For all other risk factors P-value was >0.05. Over half of the Candida isolates recovered from blood were non-albicans species. The overall mortality in candidaemia patients was 37/53 [69.81%]. Mortality was low with Candida tropicalis [57.7%] but number of patient was high among candida species. Multiple risk factors were found to be associated with invasive fungal infection in critically ill patients. In the ICU population studied, candidemia was due to non-albicans spp. The importance of Candida scores on predicting mortality was also observed

Lymphangioma circumscriptum of buttock mimicking lupus vulgaris and responding with anti-tubercular chemotherapy

Lymphangioma circumscriptum [LC] is a form of lymphangioma involving skin and subcutaneous tissue. Circumscriptum as its name suggests, is a well-circumscribed small lesion but it has a rare extensive variety also. LC may resemble other entities such as metastatic carcinoma of skin, lymphangiectasis, syringocystadenoma papilliferum, lupus vulgaris, actinomycosis etc. It is a difficult condition to treat. Different modalities of treatment such as surgical excision, laser, sclerotherapy, radiofrequency coagulation are used to treat this condition. We report here clinical presentation mimicking lupus vulgaris and responding with anti-tubercular [ATT] chemotherapy

An HIV1/2 point of care test on sputum for screening TB/HIV co-infection in Central India - Will it work?

OBJECTIVE@#To determine whether the OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA) in sputum is a valid tool for HIV surveillance among TB patients.@*METHODS@#A cross sectional study was carried out on sputa of patients diagnosed with tuberculosis. Sputa were tested for antibodies to HIV using OraQuick® HIV-1/2 Assay (OraSure Technologies, Inc., Bethlehem, PA, USA). The results were compared with results of serum ELISA.@*RESULTS@#Compared to serum ELISA, the OraQuick® HIV-1/2 Assay in sputum specimens reported 90% sensitivity (9/10) and 100% specificity (307/307), with a positive predictive value of 100% (95%CI: 66.37%-100.00%) and a negative predictive value of 99.68% (95%CI: 98.20%-99.99%).@*CONCLUSIONS@#This testing method may provide a useful strategy for conducting HIV surveillance in possible co-infected TB patients at peripheral centres. Since there is no investment on infrastructure, it may be possible for paramedical health professionals to carry out the test, particularly in areas with low HIV endemicity.

Fact-finding Survey of Nosocomial Infection Control in Hospitals in Kathmandu, Nepal—A Basis for Improvement

The purpose of this study was to investigate the actual conditions of nosocomial infection control in Kathmandu City, Nepal as a basis for the possible contribution to its improvement. The survey was conducted at 17 hospitals and the methods included a questionnaire, site visits and interviews. Nine hospitals had manuals on nosocomial infection control, and seven had an infection control committee (ICC). The number of hospitals that met the required amount of personal protective equipment preparation was as follows: gowns (13), gloves (13), surgical masks (12). Six hospitals had carried out in-service training over the past one year, but seven hospitals responded that no staff had been trained. Eight hospitals were conducting surveillance based on the results of bacteriological testing. The major problems included inadequate management of ICC, insufficient training opportunities for hospital staff, and lack of essential equipment. Moreover, increasing bacterial resistance to antibiotics was recognized as a growing issue. In comparison with the results conducted in 2003 targeting five governmental hospitals, a steady improvement was observed, but further improvements are needed in terms of the provision of high quality medical care. Particularly, dissemination of appropriate manuals, enhancement of basic techniques, and strengthening of the infection control system should be given priority.

Effect of Iron Deficiency Anemia on Hemoglobin A1c Levels

BACKGROUND: Iron deficiency anemia is the most common form of anemia in India. Hemoglobin A1c (HbA1c) is used in diabetic patients as an index of glycemic control reflecting glucose levels of the previous 3 months. Like blood sugar levels, HbA1c levels are also affected by the presence of variant hemoglobins, hemolytic anemias, nutritional anemias, uremia, pregnancy, and acute blood loss. However, reports on the effects of iron deficiency anemia on HbA1c levels are inconsistent. We conducted a study to analyze the effects of iron deficiency anemia on HbA1c levels and to assess whether treatment of iron deficiency anemia affects HbA1c levels. METHODS: Fifty patients confirmed to have iron deficiency anemia were enrolled in this study. HbA1c and absolute HbA1c levels were measured both at baseline and at 2 months after treatment, and these values were compared with those in the control population. RESULTS: The mean baseline HbA1c level in anemic patients (4.6%) was significantly lower than that in the control group (5.5%, p<0.05). A significant increase was observed in the patients' absolute HbA1c levels at 2 months after treatment (0.29 g/dL vs. 0.73 g/dL, p<0.01). There was a significant difference between the baseline values of patients and controls (0.29 g/dL vs. 0.74 g/dL, p<0.01). CONCLUSIONS: In contrast to the observations of previous studies, ours showed that HbA1c levels and absolute HbA1c levels increased with treatment of iron deficiency anemia. This could be attributable to nutritional deficiency and/or certain unknown variables. Further studies are warranted.

Protective effect of ischemia postconditioning on reperfusion injury in patients with ST-segment elevation acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of ischemia postconditioning during the first minutes of reperfusion for the myocardial reperfusion injury in ST-segment elevation acute myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>STEMI patients undergoing emergency PCI in affiliated hospital of Beihua University between October 2006 and January 2009 were randomly divided into two groups: the control group (n = 34) without any intervention after PTCA, and the postconditioning group (n = 30) with ischemia postconditioning within first minutes of reflow by 3 episodes of 30-second inflation and 30-second deflation with the angioplasty balloon. Reperfusion arrhythmias, CK and CKMB, corrected TIMI frame count (CTFC), wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) by echocardiography were compared between the two groups. MI areas were evaluated with the ECG-54 criteria/32 system and myocardial blush grade (MBG) was measured.</p><p><b>RESULTS</b>The incidence of reperfusion arrhythmias-frequent ventricular premature (26.7% vs. 52.9%) and short array ventricular tachycardia beat (23.3% vs. 58.8%) as well as values of peaks CK [(1162 ± 548) U/L vs. (1732 ± 480) U/L, P < 0.01], CKMB [(165 ± 70) U/L vs. (280 ± 99) U/L, P < 0.01], CTFC (22.23 ± 3.81 vs. 26.97 ± 3.42), WMSI (1.27 ± 0.52 vs. 1.82 ± 0.83), and infarction areas determined by ECG methods (10.60% ± 4.97% vs.14.65% ± 6.88%, all P < 0.05) were all significantly lower in the postconditioning group than in control group while LVEF (0.55 ± 0.08 vs. 0.47 ± 0.10) and MBG (2.27 ± 0.64 vs. 1.47 ± 0.61, all P < 0.05) were significantly higher in the postconditioning group than in control group.</p><p><b>CONCLUSIONS</b>Ischemia postconditioning can significantly reduce myocardial reperfusion injury in patients with STEMI.</p>

Evaluation and analysis of traffic noise along bus rapid transit system corridor

Due to increasing motorization, construction of flyovers and growth in transport network, the noise level has exceeded the prescribed limits in many Indian cities. The health implications of high noise levels are being identified as hypertension, sleeplessness, mental stress, etc. Due to this adverse effect of noise level, it is essential to assess the impact of traffic noise on residents and road users. This research is an effort to quantify and analyze the traffic noise emissions along bus rapid transit corridor in Delhi. Field measurements were carried out to understand and assess various aspects of the impact of bus rapid transit system corridor on land use and social lives of residents and road users. The present analysis presents the comparison between observed and predicted noise level at selected corridors and also describes the mitigatory measures to overcome such type of traffic noise pollution through design of noise barrier along the road and motivate people towards the use of public transport system

Simultaneous determination of multi drug components theophylline, etofylline, guaiphenesine and ambroxol hydrochloride by validated RP-HPLC method in liquid dosage form

The RP-HPLC [reverse phase high performance liquid chromatography] method was developed and validated for simultaneous determination of Multi drug components i.e., Theophylline, Etofylline, Guaiphenesine and Ambroxol Hydrochloride in a liquid dosage form. Chromatographic separation of the four drugs was performed on a Hypersil Phenyl BDS [25cmX4.6mm, 5um]. The mobile phase constituted of triethylamine pH 3.0 buffer: methanol [85:15] v/v was delivered at the flow rate 1.5 mL/min. Detection was performed at 235 nm. The peak purity of Theophylline, Etofylline, Guaiphenesine and Ambroxol Hydrochloride were 0.99970, 0.99979, 0.99986 and 0.99949 respectively. Calibration curves were linear with correlation coefficient between 0.99995 to 0.99997 over a concentration range of 5 to 37 micro g/mL for Theophylline, 19 to 140 micro g/mL for Etofylline, 20 to 149 micro g/mL for Guaiphenesine and 6 to 45 micro g/mL for Ambroxol hydrochloride. The relative standard deviation [RSD] was found < 2.0%. The percentage recovery was found between th e range of 98.6% and 100.5% at three different levels. Robustness and ruggedness were performed and result found within the RSD of 2%. All the parameters of validation were found in the acceptance range of ICH guideline

Phytochemical and pharmacological studies on bryonopsis laciniosa naud, roots

The quantitative ash values and extractive values were determined for the roots of Bryonopsis laciniosa Naud [family - Cucurbitaceae]. The roots were extracted successively with various organic solvents and the subsequent fluorescence analysis was carried out. The extracts were subjected to qualitative phytochemical analysis and presence of steroids and saponins was found. One steroidal compound was isolated from the ethanolic extract by column chromatography. The gross behavioural and toxicity studies of the ethanolic extract revealed marked analgesia at the tested dose levels of 1000, 2000 and 3000 mg/kg body weight, but no mortality was observed at the end of 72 hours. The ethanolic extract was screened for anti-inflammatory and analgesic activities in two different dose levels of 200 and 400 mg/kg by carrageenan-induced paw oedema method in rats and writhing test in mice respectively. The extract showed significant anti-inflammatory and analgesic activities at both the dose levels tested. However, the degree of activity observed with the extract in the dose of 400 mg/kg revealed a higher value, which confirms the dose dependent nature of the extract. Present findings suggest that the roots of Bryonopsis laciniosa Naud are endowed with potential anti-inflammatory and analgesic activities

Phytochemical and microbiological studies on mahonia leschenaultii takeda

The stem bark, stem wood, root bark and root wood of Mahonia leschenaultii Takeda [Family -Berberidaceae] were extracted successively with various organic solvents and the subsequent fluorescence analysis was carried out. The quantitative ash values and extractive values were determined. Berberine was isolated and characterized. The quantitative estimation of berberine in the various extracts was carried out by High performance thin layer chromatography method. The antibacterial and antifungal activity of methanolic extracts were carried out by agar diffusion and serial dilution method. The methanolic extracts showed prominent activity against Staphylococcus aureus in comparison to other strains

Phytochemical and microbiology studies on Berberis tinctoria lesch

The stem bark, stem wood, root bark and root wood of Berbetis tinctoria Lesch. were extracted successively with various organic solvents and the subsequent fluorescence analysis was carried out. The quantitative ash values and extractive values were determined. Berberine was isolated and characterized. The quantitative estimation of berberine in the various extracts was carried out by HPTLC technique. The antibacterial and antifungal activities of methanolic extracts were carried out by cylinder-plate and serial dilution method. The methanolic extracts showed prominent activity against Staphylococcus aureus in comparison to control [Ampicillin trihydrate]

Microsatellite instability and its correlation with clinicopathological features in a series of thyroid tumors prevalent in iodine deficient areas

Thyroid tumors display diverse spectrum of histopathological groups with geographic variation in its prevalence. Influence of iodine deficiency (a major causative factor) in its etiology, prevalence, or aggressiveness is debatable which reflects the existence of various genetic events in pathogenesis. The present study was undertaken to study the role of Microsatellite instability (MSI) or LOH (loss of heterozygosity), an indicator of defective mismatch repair system as a genetic change and to explore it as a prognostic marker in thyroid tumors. Tumor tissues from total thyroidectomy surgical specimens and blood (matched control) of 36 patients from iodine deficient areas (10 benign; 26 malignant) were obtained after their consent. Urinary iodine analysis was done by alkali ash method for which 10 ml of urine was collected from 18 patients before surgery. Genomic DNA, isolated from tumor tissue and blood was amplified by polymerase chain reaction (PCR) using mono and dinucleotide markers - BAT-26, BAT-40, TGF(RII, IGFIIR, hMSH3, BAX, D2S123, D9S283, D9S851 and D18S58. PCR products were analysed on 8% denaturing polyacrylamide gel followed by autoradiography. Of total, 66.6% of tumors [70% (7/10) benign and 65.4% malignant cases (17/26)] showed MSI/LOH. Strong association of MSI/LOH with low iodine (P=0.01) and with AMES risk groups i.e. age (P=0.02), tumor size (P=0.04) and metastases (P=0.002) in thyroid tumors was observed. This may help in predicting the biological behaviour and strengthening the hypothesis that iodine deficiency has influence on MSI in thyroid tumors. Our results further substantiate the risk group classification and help in deciding the treatment modality in particular patient.