A novel missense mutation (c.1006C>T) of SPG20 gene associated with Troyer syndrome

The number of gene mutations involved in the hereditary spastic paraplegias is rapidly growing due to the expansion of the frontiers of genomic research by next-generation DNA sequencing platforms. Nevertheless, a comprehensive genetic diagnosis method remains yet unavailable for these diseases. In the current research, an 8-year-old boy with short stature and developmental delay impairment, from a nonconsanguineous family, was referred to our genetic lab. Firstly, based on the physician recommendation, the patient was evaluated by tandem mass spectrometry (MS/MS) for the quantitative examination of amino acids, and then the patient was genetically investigated by karyotype analysis and whole-exome sequencing (WES) technique. Subsequently, targeted Sanger sequencing was applied to confirm the presence of the candidate variant in all the members of the family and screening the other patients for Troyer syndrome. Analysis of inherited metabolic disorders by tandem MS/MS showed the state of all the family members as normal and also karyotyping indicated no chromosomal aberration in the patient. Further investigation by WES technique indicated a homozygous missense variant in the SPG20 gene, c.1006C[T. Targeted sequencing result of the mutation confirmed homozygote state for the affected case and a heterozygote genotype for his parents. The mutation was classified as pathogenic. Detection of novel variants especially pathogenic variant in the SPG20 gene was associated with Troyer syndrome, which encodes a multifunctional protein termed Spartin, assist in improving genotype–phenotype correlation of genetic variants and may facilitate initial diagnosis of Troyer syndrome

Accuracy of the dose delivery in prostate cancer patients-using an electronic portal imaging device [EPID]

Background: To correct patient positioning errors [setup errors] during prostate cancer treatment using EPID and fiducial gold markers, to improve the accuracy of the dose delivery in these patients

Materials and Methods: Fifteen patients with localized prostate carcinoma after implantation of fiducial gold markers in their prostate gland underwent the five-field IMRT planning technique. The plan was prepared in accordance with ICRU 50 guidance [PTV to receive 95-107% dose]. The software program reconstructed the three-dimensional position of the markers from the different Beams Eye Views [BEV]. The discrepancies of the seeds' positions [prostate surrogate] between plan and daily images were calculated three dimensionally. Then, necessary corrections were applied to match the prostate fiducial markers in the portal image with the BEV image in the planned one by moving the couch in the X, Y and Z directions

Results: Data from 15 patients and 469 fractions of radiotherapy were analyzed in this study. Two sets of data were available from EPID software before and after 3D set-up corrections. The mean of the population displacement in Left /Right [L/R], Anterior/Posterior [A/P] and Crania/Caudal [C/C] directions were 0.5, -1.0 and 2.4mm before, and -0.1, -0.5 and 0.9mm after corrections, respectively. The systematic and random errors for the measured populations in the three mentioned directions were 2.4, 2.7 and 2mm and 6.4, 5.9 and 6.1mm before corrections, and 1.1, 2.4 and 1.4mm and 3.8, 3.9 and 3.6mm after corrections, correspondingly

Conclusion: This study provides further evidence that using gold markers in the prostate improves dose delivery to the prostate. Also, it has been demonstrated that the EPID can be a powerful tool in the reduction of treatment setup errors and the quality assurance and verification of complex treatments

[Carrier frequency of alpha thalassemia mutations among newborns in northern Iran]

Background and Objective: Alpha Thalassemia is one of the most prevalent hemaglobinophaties worldwide. Alpha thalasseima patients may represent wide spectrum of symptoms ranging from asymptomatic to severe life threatening anemia. This study was done to assess the carrier frequency of alpha globin gene mutations among newborns in north of Iran

Methods: In this descriptive study, 412 cord blood samples of neonate from Amir Mazandari hospitali were randomly selected during 2012. Genomic DNA was extracted using phenol-chloroform method. Multiplex Gap- PCR and PCR-RFLP methods were applied in order to detect three common gene deletions, one triplication and one point mutation

Results: Total allelic frequency of investigated mutations was 0.0825. The -alpha3.7 deletion with allelic frequency of 0.0485 was the most prevalent mutation among 412 neonates. Allelic frequencies of -alpha4.2, alphaalphaalphaanti3.7 triplication and alpha-5nt mutations were 0.0206, 0.0109 and 0.0024; respectively and -Med double gene deletion was not detected

Conclusion: Most mutated cases had single gene deletion that is asymptomatic while -Med double gene deletion was not detected among the neonates. Therefore, there is low probability of a child birth with Hb H disorder in the region

[Detection of common mutations causing drug resistance to mycobacterium tuberculosis strains among patients with tuberculosis using line probe assay method]

Drug resistance to tuberculosis and especially multiple drug resistance tuberculosis [MDR-TB] variants are a serious problem in tuberculosis patients and make difficulties in controlling the disease. This study was coducted for detection of common mutations causing drug resistance of mycobacterium tuberculosis strains among tuberculosis patients using line probe assay method. In this descriptive study, fifty four sputum samples of tuberculosis patients were randomly selected in health centers of Mazandaran, northern Iran during 2012. After culturing of sputum samples on Lowenstein-Jensen medium, genomic DNA was extracted from colonies using CTAB method. Molecular analysis of mutations causing resistance to five different antibiotics including Isiniazide, Rifampin, Sterptomycine, Amicasin / Canamycine, Kinolon were performed using long probe assay [LPA] method. Out of 54 sputum samples, three [5.5%], three [5.5%], four [7.4%] were resistance to Kinolon, Amicasin / Canamycine and Sterptomycine, respectively. Mutation in KATG was seen in 2 samples resistant to Isiniazide. Mutation in rpoB 516 was seen in 3 samples resistant to Rifampin. Four samples [7.4%] were resistant to the two anti-tuberculosis antibiotics, while three samples were resistant to Sterptomycine and Kinolon and one sample was resistant to Rifampin and Canamycine. 7.4% of sputum samples were resistant to the two anti- tuberculosis antibiotics. Line probe assay is a rapid and suitable method for detecting tuberculosis drug resistance

Beta globin gene haplotypes associated with hemoglobin D-Punjab in northern Iran

Background and Objective: Hemoglobin D-Punjab is one of the variant of hemoglobin caused by a mutation on position 121 of beta globin gene which is frequent in India, PakistanandIran. Heterozygote form of this variant is mainly asymptomatic while in combination with hemoglobin S, severe form of anemia occure. This study was carried out to determine the beta globin gene haplotypes associated with hemoglobin D-Punjab in Northern Iran. Methods: This descriptive study was carried out on families of 18 individuals whom were carriers of hemoglobin D-Punjab in Sari in Northern Iran. Genomic DNA was extracted from peripheral blood samples using Phenol-chloroform st and ard protocol. In order to identify different haplotypes associated with hemoglobin D-Punjab, PCR-RFLP method and family linkage analysis were used. Results: In 17 subjects hemoglobin D-Punjab was linked to [+ - - - - + +] haplotype and in one case association with [- + + - + + +] haplotype was observed. Conclusion: The hemoglobin D-Punjab alleles have mainly unicentric origin and [- + + - + + +] rare haplotype may have different genetic origin or is created as a result of gene recombination

Optimization of clinical target volume delineation using magnetic resonance spectroscopic imaging [MRSI] in 3D conformal radiotherapy of prostate cancer

For the purpose of individual clinical target volume assessment in radiotherapy of prostate cancer, MRSI was used as a molecular imaging modality with MRI and CT images. The images of 20 prostate cancer patients were used in this study. The MR and MRSI images were registered with CT ones using non-rigid registration technique. The CT based planning [BP], CT/MRI BP and CT/MRSI BP was performed for each patient. For plan evaluation, Dose Volume Histograms [DVHs] data were used. A paired sample T-test was used for the analysis of the obtained data. The percentage of variation of CTVMRI to CTVCT and PTVMRI to PTVCT were 12.83% and 8.97%, respectively. CTVMRSI and PTVMRSI were 21% and 27.41% more than their corresponding values of CT volumes. The mean percentage of variation in rectum volume that received 60% of the prescribe dose [V60R] in MRSI/CT BP relative to CT BP was 14.66%. The use of MRSI in detecting of prostate adenocarcinoma could provide some decisive information to determine optimum volume and safe margin for target definition to improve adaptive radiotherapy in prostate cancer

[Prevalence of alloimmunization in major beta thalassemia in northern Iran [2010]]

Repeated blood transfusion is the major treatment for patients with major thalassemia. However due to antigen encounters, it may initiate body reactions, including alloantibodies against red blood cell antigens. This study was done to determine the Prevalence of alloimmunization in major beta thalassemia patients in northern Iran. This descriptive - analytic study was carried out on 218 thalassemic patients [100 males and 118 females] with average age of 22.5 +/- 7 years in northern Iran during 2010. Each sample was tested for the presence of Alloantibodies including C, Cw, Lea, E, Lua, Leb, K, Jkb, N, P1, D, Jka, M, S, Xga, e, Fya, s, c, Fyb, k, Kpa, Jsb, Lub and Coa. Eighty eight cases [40.4%; 95% CI: 33.9-46.9] were positive for the presence of alloantibodies. Alloantibodies against C, Cw, Lea red blood cell surface antigens were the most prevalent [40%]. No significant correlation was found between emergence of alloantibody with the age of initial, frequency and duration of blood transfusion. Alloimmunization is a common observation in thalassemic patients and should be prevented by transfusing compatible blood

Effect of uniform magnetic field on dose distribution in the breast radiotherapy

To reduce the dose to normal tissues surrounding the treated breast, a uniform magnetic field was used within a humanoid phantom in breast radiotherapy. Monte Carlo simulations were performed with GEANT4, irradiating humanoid phantoms in a magnetic field. To reconstruct phantoms, computed tomography [CT] data slices of four patients were used for the Monte Carlo simulations. All of them had left breast cancer either or not mastectomy. In the simulations, the planning and methods of chest wall irradiation were similar to the actual clinical planning. Utilizing magnetic field will help to produce uniform dose distribution to the breast with a sharp dose-volume histogram [DVH] curve for the planning target volume [PTV], however, for the ipsilateral lung and chest wall skin the mean dose was reduced by a mean of 16% and 12% at 1.5 T, and 9% and 7% at 3 T, respectively. The magnetic field was shown to restrict the lateral spread of secondary electrons to the contralateral organs, resulting in significient dose reductions to the contralateral breast [CB] and contralateral chest wall skin [CCWS] by a mean [range] of 28% [21-37%] and 58% [44-75%] at 1.5 T, and 48% [32-81] and 66% [54-73%] at 3 T, respectively. The simulations established that the magnetic field can reduce the dose to the internal and contralateral tissues and increase it to the PTV with sharper edge DVH curve

Monte Carlo study on beam hardening effect of physical wedges

Physical wedges are still widely used as beam modifiers in external beam radiotherapy. However the presence of them in the beam trace may cause beam hardening which may not be considered in many treatment planning systems. The aim of this study is to investigate the beam hardening effect generated by physical wedges via different beam quality indexes as photon spectrum, half value layer, mean energy and tissue-phantom ratio. The effect of physical wedges on the photon beam quality of a 6-18MV Varian 2100C/D accelerator was studied with the BEAMnrc Monte Carlo code. Good agreements were obtained between measured and calculated depth doses and beam profiles for open and wedged photon beams at both energies. It was noticed that for 6 MV photon beams, physical wedges have more significant effects on beam quality than for 18 MV. Also it was obtained that at 18 MV photon beam as the wedge angle increased, the effect of wedge on beam quality becomes reversed and beam softening occurred. According to these results, it is recommended that beam hardening and softening of physical wedges should be considered in treatment planning systems in order to increase the accuracy in dose delivery

Dosimetric characterization of a high dose rate 192I source for brachytherapy application using Monte Carlo simulation and benchmarking with thermoluminescent dosimetry

The purpose of this project was to derive the brachytherapy dosimetric functions described by American Association of Physicists in Medicine [AAPM] TG-43 U1 based on high dose rate [192]I sources. The method utilized included both simulation of the designed Polymethyl methacrylate [PMMA] phantom using the Monte Carlo of MCNP4C and benchmarking of the simulation with thermoluminescent [TL] dosimeters. The obtained results for the radial dose function and anisotropy function showed nominal errors of less than 3% between TL measurements and the MCNP4C results. It may be concluded that due to small observed errors and the large uncertainty associated with the high dose gradients near the source point the simulation results can be used for dose estimation

[Molecular evaluation of hemoglobin D mutations in Mazandaran province, Iran]

Hemoglobinopathies are among the most prevalent genetic disorders worldwide, and occur as a result of mutations in the gene involved in synthesizing hemoglobin chains. By now more than 1000 defects in hemoglobin chains are discovered. Hemoglobin D [Hb D] is one of these disorders, identified by a single nucleotide mutation on codon 121 of beta globin chain. This study was carried out to evaluate Hb D mutations through molecular methods in Mazandaran province of Iran. This descriptive laboratory study was done on 70 patients with an electrophoresis band in hemoglobin-S zone in Mazandaran province of Iran during 2010-11. Capillary zone electrophoresis was done to find out Hb D in 51 patients. Subsequently, PCR-RFLP was performed to evaluate the samples at molecular level. Molecular investigation revealed all cases are carriers of hemoglobin D-Punjab. Two patients were shown to be homozygote carriers of the abnormal gene. This study showed all Hb D affected patients were carriers of Hb D Punjab

Urbanization and non-communicable risk factors in the capital city of 6 big provinces of Iran

The prevalence of non-communicable diseases such as hypertension and diabetes including obesity has increased over the past few years in Iran. The increase in these diseases has been associated with increased urbanization and lifestyle changes. The burden of non-communicable diseases [NCD] is increasing in low and middle-income countries. The aim of this report is to address the threat of NCDs in the capital city of 6 big provinces of Iran. A community based cross sectional study was carried out between March 2010 to January 2011 in 6 provinces' capital cities [Isfahan, Karaj, Mashad, Shiraz, Tabriz, and Tehran]. Participants were men and women of 30 years and older who had been screened through the National Diabetes Prevention and Control Program. BMI, blood pressure, fasting blood glucose and lipids were measured. 439406 cases [60% female and 40% male] were studied. The prevalence of pre-diabetes [13%], diabetes [13%], hypercholesterolemia [14%], hypertension [11%], overweight [27%] and obesity [20%] was higher than expected. Only 35% of participants were healthy. This study reveals a high prevalence of NCDs in urban living population in those capital cities. It also shows that increasing urbanization may be an important threat to public health regarding NCDs especially in developing countries. It is crucial to implement a comprehensive NCD program [across the life time] in the health system with a strong collaboration with all stakeholders [governmental and non-governmental sector, academic, research centers and scientific associations] in the community [Multisectoral Approaches]

Megavoltage dose enhancement of gold nanoparticles for different geometric set-ups: Measurements and Monte Carlo simulation

Gold nanoparticles [GNPs] have been shown as a good radiosensitizer. In combination with radiotherapy, several studies with orthovoltage X-rays have shown considerable dose enhancement effects. This paper reports the dose enhancement factor [DEF] due to GNPs in 18 megavoltage [MV] beams. Different geometrical 50-nm GNPs configurations at a concentration of 5 mg/ml were used by both experimental and Monte Carlo [MC] simulation in a deep-seated tumor-like insertion within a phantom. Using MCNP repeated structure capability; a large number of gold nanospheres with a semi-random distribution were applied to simulate this phantom based study. Thermoluminescence dosimetries were used to verify the process of irradiation and MC simulation. Under geometries with different probable combinations of water and GNPs distribution in the tumor, the percentage depth dose and DEF were calculated. Incorporation of GNPs into the radiation field in our set-ups showed a 12% DEF. We show that the method of nanoparticles, distribution, and orientation can effectively change the DEF value

distinct autosomal recessive ocular anomaly in Chaharborj, Islamic Republic of Iran

In Chaharborj, a village in north-eastern of the Islamic Republic of Iran, a high prevalence of congenital blindness [1.1%] has been reported. The clinical findings have not been fully described. We therefore assessed the clinical aspects of this condition in a case series of 20 congenially blind patients and 24 of their parents. All patients had been blind since birth. There was anterior segment dysgenesis and retinal non-attachment in all patients. There were no systemic anomalies. Histopathologically, there was iridocorneal adhesion, normal angle structure and retinal dysplasia. No significant difference was found in the frequency of different HLA class I alleles compared with the general population. The anomaly causing congenital blindness in these patients has components of both anterior and posterior segment dysgenesis. It appears to be a distinct entity with an autosomal recessive pattern of inheritance

[Evaluation of the efficacy and correlation between blood glucose measured using glucometers and enzymatic laboratory methods]

Diabetes Mellitus [DM] is the most common chronic metabolic disease, with many complications including renal failure, blindness and non-traumatic amputation, so it is important to monitor and regulate blood glucose. Considering how easy home blood glucose monitoring is, we decided to evaluate the performance of two available glucometers for detection of blood glucose compared with standard laboratory methods. In this analytical study, we compared the capillary blood glucose levels of 60 volunteers with mean age of 32.8 +/- 9.6 years in Tabriz Mehr Laboratory as determined by test strips [two different Glucometers] with venous blood glucose levels' measurements by the enzymatic method [the standard laboratory kit]. Data were analyzed using one way-ANOVA test, T-test, Pearson correlation and Bland and Altman plot. The mean differences of No: 1 and No: 2 Glucometers with enzymatic laboratory method were 20.78 +/- 11.61 and 4.5 +/- 3.76mg/dl respectively. The one way ANOVA test indicated significant differences between three methods [p<0.05]. Further Duncan's test revealed significant differences between two devices [p=0.001] and device No.1 and laboratory method [p=0.001]; however, the differences between device No.2 and laboratory method were not statistically significant [p=0.83]. According to the results, calibrating the devices with laboratory instruments in order to make major clinical decisions is recommended

[Oxidative stress-related parameters and antioxidant status in non-alcoholic fatty liver disease patients]

Non-alcoholic fatty liver disease [NAFLD] is a denomination that encompasses clinical and pathological spectrums, ranging from simple steatosis to Non-alcoholic steatohepatitis [NASH], fibrosis and cirrhosis. Considering the importance of obesity as a risk factor of this disease and oxidative stress, as an effective factor in pathogenesis, coupled with inflamation and its progression to non-alcoholic steatohepatitis, this study was conducted to investigate the rate of overweight and obesity and oxidative stress status in patients with nonalcoholic fatty liver disease. In this case-control study, 50 NAFLD patients and 48 healthy controls were enrolled. Antropometric measurements were taken, according to standard protocol. Serum hepatic enzymes, lipid profile and total antioxidant capacity [TAG] were determined by the auto analyzer and Serum malondialdehyde [MDA] was measured by the feluorimetry method. Data was analyzed by SPSS [version 11.5], and statistical tests such as T-test and Chi-square were used. Correlations were performed using Pearson's correlation coefficient. Mean BMI was significantly higher in NAFLD patients, compared to controls. There was no significant difference between the two groups in relation to mean serum levels of MDA [p=0.1]. In contrast, the mean serum levels of TAC was significantly lower in patients than in controls [p=0.02]. Based on this study, combating overweight and obesity seems to be a preventive strategy for healthy people, thereby forestalling the progression of this disease. Furthermore, considering the lower level of TAC in NAFLD patients, the use of antioxidant-rich foods and supplements can be therapeutically valuable

Monte Carlo estimation of electron contamination in a 18 MV clinical photon beam

The electron contamination may reduce or even diminish the skin sparing property of the megavoltage beam. The detailed characteristics of contaminant electrons are presented for different field sizes and cases. The Monte Carlo code, MCNPX, has been used to simulate 18 MV photon beam from a Varian Linac-2300 accelerator. All dose measurements were carried out using a PTW-MP2 scanner with an ionization chamber [0.6 CC] at the water phantom. The maximum electron contaminant dose at the surface ranged from 6.1% for 5 x 5 cm[2]to 38.8% for 40 x 40 cm[2] and at the depth of maximum dose was 0.9% up to 5.77% for the 5 x 5 cm[2] to the 40 x 40 cm[2] field sizes, respectively. The additional contaminant electron dose at the surface for the field with tray increased 2.3% for 10 x 10 cm[2], 7.3% for 20 x 20 cm[2], and 21.4% for 40 x 40 cm[2] field size comparing to the standard field without any accessories. This increase for field with tray and shaping block was 5.3% and 13.3% for 10 x 10 and 20 x 20 cm[2], respectively, while, the electron contamination decreased for the fields with wedge, i.e. 2.2% for the 10 x 10 cm[2] field. The results have provided more comprehensive knowledge of the high-energy clinical beams and may be useful to develop the accurate treatment planning systems capable of taking the electron contamination in to account

Comparing the results of 3D treatment planning and practical dosimetry in craniospinal radiotherapy using Rando phantom

Craniospinal radiotherapy faces technical challenges which are due to the sensitivity of the location in which the gross tumor is, and to organs at risk around planning target volume. Using modern treatment planning systems causes a reduction in the complexities of the treatment techniques. The most effective method to assess the dosimetric accuracy and the validity of the software used for treatment planning is to investigate the radiotherapy and treatment planning by means of a anthropomorphic Rando phantom which was used here for treatment planning and practical dosimetry for craniospinal radiotherapy. Studying the absorbed dose by the organs at risk was the secondary objective discussed in this paper. Treatment planning in craniospinal radiotherapy was done using CorePlan 3D treatment planning software. Radiotherapy was administered on a anthropomorphic Rando phantom and practical dosimetry was done using GR-200 TLDs. Varian Clinac 2100C/D was used for radiotherapy. The absorbed dose by regions of interest was separately calculated for treatment planning and radiotherapy. Except the conjunction areas of the cranial and spinal radiation fields, the difference among the results was not more than 5%. Full comparison of the results for each part has been presented. The comparison the results of practical dosimetry and treatment planning software supports the validity of CorePlan treatment planning system. Also analysis of the absorbed dose through organs at risk showed that the absorbed dose by organs at risk have an acceptable value with respect to tolerance dose of these organs. The only unacceptable result was related to thyroid

role of rheumatoid factor and anti-cyclic citrullinated peptide antibody in diagnosis of rheumatoid arthritis

Rheumatoid Factor [RF] occurs in 70- 90% of patients with established rheumatoid arthritis [RA]. Anti-cyclic Citrullinated peptide antibody [Anti-CCP] detection may be used to confirm the diagnosis of RA in patients with uncharacterized chronic inflammatory arthritis. This study is an attempt to evaluate the role of RF and anti-CCP in the diagnosis and prognosis of rheumatoid arthritis. Blood samples were obtained from 55 patients with established RA and 55 healthy controls. Anti-CCP and RF were measured by ELISA and nephelometry. The patient's demographics, disease duration, DMARDs usage, ESR and radiographic abnormalities were recorded. Fifty five RA patients and 55 healthy age and sex matched controls were enrolled. Odd ratio [OR] was 87.42 [C 1=11.2-680.1] for RF and 27.48 [6/08-124/09] for Anti- CCP. Five patients had used more than 3 DMARDs; all of them were RF positive and 4 were also anti-CCP positive. Eleven patients had erosions in their radiographs; 10 of them were seropositive for RF and 9 positive for anti-CCP. Our study suggests that despite lack of specificity, RF continues to be a central part of the definition of RA due to favorable sensitivity profile and the combined use of RF. Also, anti-CCP is a more powerful diag-nostic and prognostic tool