Ectopic location of the ampula of Vater within the pyloric channel

The ampulla of Vater is commonly located in the posteromedial wall of the second portion of the duodenum. At times, the ampulla of Vater may be found at uncommon sites such as the third and fourth portions of the duodenum, the duodenal bulb and the stomach. We found the ampulla of Vater in the pyloric channel in a 44 year old patient who had undergone surgery for acute cholecystitis. An intra-operative T-tube cholangiography revealed distal narrowing. The major papilla was not found during endoscopic retrograde cholangiopancreatography [ERCP] and a more accurate T-tube cholangiography revealed that the common bile duct opened in the distal stomach, probably in the pylorus. Finally the ampulla opening was located in the pylorus by methylene blue injection through the T-tube at endoscopy. This rather unusual location of the ampulla of Vater has implications for gastroenterologists performing ERCP

[Photocatalytic degradation of phenol in aqueous solutions by Fe[III]-doped TiO2/UV process]

Phenol and phenolic compounds are widely used in industry and daily liFe, and are of high interest due to stability in the environment, dissolution ability in water and health problems. In this regard, phenol removal from water is of high importance. The purpose of this study was to investigate the efficiency of photodegradation process for removal of phenol from aqueous system by use of Fe-doped TiO[2] nanoparticles prepared by sol-gel method. Phenol concentrations of 5, 10, 50 and 100 mg/L were prepared and exposed to UV and Fe-doped TiO[2], separately and simultaneously. Also the effect of initial phenol concentration, Fe-doped TiO[2] loading and pH were studied. Various doses of photocatalist investigated for Fe- doped TiO[2] were 0.25, 0.5 and 1 g/L. pH was studied at three ranges, acidic [pH=3], neutral [pH=7] and alkaline [pH=11]. Maximum degradation was obtained at acidic pH, 0.5 g/L of Fe-doped TiO[2] for all of phenol concentrations. With increasing initial concentration of phenol, photocatalytic degradation decreased. In comparison with Fe-doped TiO[2]/UV process, efficiency of UV radiation alone was low in phenol degradation [% 64.5 at 100 mg/l of phenol concentration]. Also the amount of phenol adsorbed on the Fe-doped TiO[2] was negligible at dark conditions. Results of this study showed that Fe[III]- doped TiO[2] nanoparticles had an important effect on photocatalytic degradation of high initial phenol concentration when Fe[III]-doped TiO[2]/ UV process applied

[Investigating the efficiency of UV/H[2]O[2] process for removal of linear alkylbenzene sulfonate [LAS] in aqueous solutions]

Surfactants are one of the largest pollutants which exist in urban and industrial wastewaters. Large quantities of surfactants have entered to the environment since last decade due to increased use of synthetic detergent in industrial and home consumptions.In this study, the efficiency of UV/H[2]O[2] process in removal of linear alkylbenzane sulfonate [LAS] from aqueous solutions was investigated. In this study methylene blue active substane[MBAS]method and spectrometery were used to determine anion and residual surfactant respectively. In this study important variables were H[2]O[2] concentration, initial concentration of surfactant, pH and duration of UV radiation. The effect of UV/H[2]O[2] process on the degradation of LAS was analyzed statistically by using Multiple Linear Regression test. The resulted showed that after 20 minute, ultraviolet radiation solely removed 38.44 percent of Anionic detergent, Hydrogen peroxide showed no significant removal of detergent solution in the time course study. The efficiency of UV/H[2]O[2] process in 10, 20 and 30 minute were to 86.2, 90 and 96.5%, respectively. The results showed that the efficiency of ultraviolet radiation and hydrogen peroxide process in anionic detergent was not significant thoogh it was considerable in combination process [UV/H[2]O[2]]

Optimization of operational parameters for decolorization and degradation of c l reactive blue 29 by ozone

Because conventional wastewater treatment of effluent containing anthraquinone dye causes notable environmental problems, it is important to find effective alternative methods for dye removal. This study evaluated the efficacy of ozonation for dye removal and Chemical Oxygen Demand reduction and identified optimal operational conditions for parameters such as pH, contact time and concentration of C.I. Reactive Blue 29 dye in a semi-batch reactor. Values of pH between 3 and 11 and contact times between 15 and 120 minutes were investigated. Dye concentrations were based on the American Dye Manufacture Institute standards and ranged from 1000 to 5000. Although results showed that Chemical Oxygen Demand removal by ozone alone was not very efficient [58%], ozonation proved to be an efficient method for decolorizing Reactive Blue 29 [96%]. pH was found to significantly influence the effectiveness of Chemical Oxygen Demand removal, and optimal pH conditions [95% confidence interval] were between 9 and 11. For decolorization, pH adjustment was not necessary. Degradation and decolorization of dye were found to be strongly influenced by the contact time, optimal conditions [95% confidence interval] for degradation and decolorization were 60 and 30 minutes, respectively. The optimal dye concentration was 1000 American Dye Manufacture Institute

Effect of fenton process [H[2]O[2] / Fe[2+]] on removal of linear alkylbenzene sulfonate using central composite

This study investigates the degradation of Linear Alkylbenzene Sulfonate [LAS] in aqueous solution using Fenton's process in a batch reactor [at pH = 3 and 25 Degree C]. Experiments were carried out to survey the effects of the amounts of ferrous sulfate [FeSO[4].7H[2]O] and hydrogen peroxide [H[2]O[2]] on the LAS and COD removal. Central composite design and response surface methods were used to optimize the Fenton oxidation process through examination of three independent operating variables namely oxidant dose [H[2]O[2]], catalyst dose [Fe[+2]] and reaction time., hydrogen peroxide dose ranging from 150 to 750 mg /L and Fe[+2] concentration in the range of 10 -130 mg /L were selected to be examined at different reaction times between 20 and 80 minutes. Models were developed and results shows that the oxidation capacities of H[2]O[2] /Fe[+2] were highly dependent on the concentration of H[2]O[2] and Fe[+2]. Satisfactory decay rates of LAS to lock up biodegradable concentration level were obtained, and in the case for oxidation of 200 mg /L LAS, the optimum values were achieved at 600 and 130 mg/L for H[2]O[2] and Fe[+2], respectively

Photocatalytic degradation of linear alkyl benzene solfunate from aqueous solution by TIO[2] nanoparticles

The possibility of linear alkyl benzene solfunate [LAS] photocatalytic degradation through application of TIO[2] nanoparticles was investigated. 10[mg/L] of LAS has been affected by either UV or TIO[2] and simultaneous use of both of them in separated experiments. Moreover, the effect of initial concentrations of LAS and TIO[2], pH, present various anions and different UV power was studied to determine the optimal operating conditions for LAS degradation in water. The amount of mineralization of LAS was reported by measuring the primary and final COD of the solution that was irradiated under optimized conditions. Maximum degradation was obtained at acidic pH, 50 mg/L of TIO[2] and 30 minute irradiation time. It was also shown that 99.5% of LAS was degraded in optimal conditions. Kinetic analysis indicated that photo catalytic degradation rates of LAS can be approximated by pseudo-first order model. Measuring the initial and final COD of illuminated solution under optimized conditions, indicated that almost complete mineralization of LAS was occurred. Based on the results, UV/TIO[2] process may be effectively applied in LAS removal in low concentrations but this process is not economically efficient in high concentrations

Removal of Trichloroethylene from water by adsorption on to multiwall carbon nanotubes

Groundwater recourses may be contaminated with trichloroethylene [TCE] which is used in electronic, electric, dry cleaning and other similar industries and often treated by air stripping, which TCE in its vapor form is stripped from groundwater by air and is emitted into the atmosphere without any additional treatments. Carbon nanotubes are expected to play an important role in sensing, pollution treatment and separation techniques. In this study adsorption of trichloroethylene on multiwall carbon nanotubes has been investigated. The effect of contact time, pH, initial concentration of trichloroethylene and temperature on its adsorption were investigated. Adsorption isotherms and related constants were also determined. Results showed that contact times to reach equilibrium changed from 30 min [for 150 microg/L initial concentration] to 10 min [for 600 microg/L concentrations] at 25 [degree sign]C; the equilibrium times in 40[degree sign] C were 40 min and 15 min, respectively. Multi-wall carbon nanotubes showed to act as a good adsorbent for TCE in a wide range of pH=[3-9]. For pH>9, adsorption decreased due to ionization of oxygen-containing groups. Adsorption test results revealed that TCE adsorption on the studied adsorbents could be better described by Freundlich isotherm

Comparing different brands of omeprazole with pantozole in GERD patients

Gastro-esophageal reflux disease [GERD], a chronic and relapsing condition with increasing prevalence, can affect quality of life very drastically [1, 2, 3, 4, 5, 6, 7] therefore different studies have been done to compare the effectiveness of each drug in comparison to the others and to determine the priority of each one to others regarding the efficacy and fewer side effects [15]. In this study we aimed to make a comparison between Pantoprazol and different brands of omeprazol regarding their efficacy and meanwhile determine if different brands of omeprazole can have various effects on different cases. In this clinical trial One-hundred GERD patients were studied to compare the effects of pantozole and three different brands of omeprazole regarding their efficacy in treating GERD symptoms. Among all cases 64.3% were female and mean age was 37.1 years [min: 16, max: 76, standard deviation: 15.0]. 15.1%, 36.0%, 29.1% and 12.8% had BMI less than 20, 20-25, 25-30 and more than 30 consecutively. Both follow ups were successful in 73.5% while 14.2% had just one successful follow up and 12.2% were excluded from the study because they had no successful follow up after first visit. 25.5% were treated with A, 24.5% with B, 25.5% with C and 24.5% with D. Although the response rate in different drug groups showed various results, the differences were not statistically significant [all P values> 0.05]. Sex and BMI category of patients had no significant effect on response rate between patients [all P values> 0.05]. According to our data, Pantozole, Exiprazole, Dr Abidi's Omeprazole and Losec have similar efficacy for control of GERD symptoms among Iranian patients with GERD

Effect of hydrophilic and hydrophobic organic matter on amoxicillin and cephalexin residuals rejection from water by nanofiltration

Antibiotics such as amoxicillin and cephalexin are a group of pharmaceutical compounds in human medicine practice that have been entered in water bodies. Presence of these compounds in the environment has raised concerns regarding the toxicity to aquatic organisms and the emergence of strains of antibiotic-resistant bacteria. Removal of these substances before entering the aquatic environment as well as water reuse plant is very important. The objective of this investigation was to evaluate the impact of hydrophilic and hydrophobic fractions of Natural Organic Matter [NOM] on the removal efficiency of cephalexin and amoxicillin, by using two different commercially available composite NF membranes [TFC-SR2 and TFC-SR3]. In addition, the effect of NOM fractions on retention mechanism and permeates flux behavior was studied. Amoxicillin and cephalexin were used as models of antibiotics; alginate and humic acid were used as models of hydrophilic and hydrophobic fractions of NOM, respectively. It was observed that the rejection and permeate flux of amoxicillin and cephalexin were influenced by the membrane characteristics and properties of NOM. The results showed that as the alginate proportion was increased, the rejection improved. The permeate flux decreased with increasing alginate ratio. It was observed that the rejections of amoxicillin and cephalexin in TFC-SR2 were >97.3% and >95.8% in all experiments, respectively. In TFC-SR3, the rejection percentage were [95.9%-100%] and [86.1%-96.3%], respectively. Alginate and humic acid had synergistic effect on flux decline. In other words, increasing alginate concentration increased the rate and extent of flux reduction

Optimization of reactive blue 19 decolorization by ganoderma SP. using response surface methodology

Synthetic dyes are extensively used in different industries. Dyes have adverse impacts such as visual effects, chemical oxygen demand, toxicity, mutagenicity and carcinogenicity characteristics. White rot fungi, due to extracellular enzyme system, are capable to degrade dyes and various xenobiotics. The aim of this study was to optimize decolorization of reactive blue 19 [RB19] dye using Ganoderma sp. fungus. Response Surface Methodology [RSM] was used to study the effect of independent variables, namely glycerol concentration [15, 20 and 25 g/L], temperature [27, 30 and 33 °C] and pH [5.5, 6.0 and 6.5] on color removal efficiency in aqueous solution. From RSM-generated model, the optimum conditions for RB19 decolorization were identified to be at temperature of 27°C, glycerol concentration of 19.14 mg/L and pH=6.3. At the optimum conditions, predicted decolorization was 95.3 percent. The confirmatory experiments were conducted and confirmed the results by 94.89% color removal. Thus, this statistical approach enabled to improve reactive blue 19 decolorization process by Ganoderma sp. up to 1.27 times higher than non-optimized conditions

Influence of bioaugmentation in biodegradation of PAHs-contaminated soil in bio-slurry phase reactor

Polycyclic Aromatic Hydrocarbons [PAHS] are important pollutants which have toxic, carcinogenic and mutagenic properties and are considered as a serious hazard to human health and environment. Bioremediation of PAHs contaminated soil was studied in the soil slurry phase bioreactor. For enhancement of biodegradation, bioaugmentation [which is the process of adding microorganisms with the potential of pollution biodegradation to the bio-slurry reactor] was applied. Phenanthrene [C[14]H[10]], a three-benzene ring PAHs, was added in concentration of 100mg/kg soil. Two isolated species and consortium of bacteria were inoculated to the medium in density of 7_10[7] CFU/mL. The analysis of variance [ANOVA] was used for finding of optimum levels of type of bacterial culture and presence effect of endogenous factors. The base of the bacteria was petroleum-contaminated soil from around Tehran petroleum Refinery. Control reactor [killed bacteria] showed 5% loss of phenanthrene and biodegradation in the non-augmented reactor [endogenous microorganisms] in a slurry bioreactor was about 17%. In the case of bioaugmentation with Pseudomonas.spp, Pseudomonas aeruginosa and consortium, phenanthrene degradation efficiency were 87.8%, 85.5% and 92.8%, respectively, presenting the positive effect of biodegradation in consortium augmented compared to the isolated one. Colony forming units [CFUs] variation showed good conformity and agreement with the performance of the reactors with respect to phenanthrene degradation. Hence, the results of this experiment show that bioaugmentation may be considered as an effective method to enhance the bioremediation in removal of PAHs from contaminated soils

Methyl tert-butyl ether adsorption on surfactant modified natural zeolites

Surfactant-modified clinoptilolite-rich tuff was used for the removal of methyl tert-butyl ether [MTBE] from aqueous solutions. Clinoptilolite zeolite from Miyaneh region of Iran was treated with sodium chloride and then modified with hexadecyltrimethylammonium chloride [HDTMA-Cl] and n-Cetylpyridinium bromide [CPB] to be used in different experimental conditions. The ability of raw or Non-Modified Zeolite [NMZ] and Surfactant-Modified Zeolites [SMZ] to remove MTBE from aqueous solutions was investigated as a function of contact time, pH and concentrations of adsorbent and adsorbate, by using a batch technique in aqueous system. The removal of MTBE from aqueous solutions by modified zeolites seemed to be more effective than non-modified samples. Also, HDTMA-modified zeolite had more effective performance than CPB-modified zeolite. The adsorption efficiency of MTBE onto SMZ[S] was found to increase by contact time and adsorbent concentrations, and by decreasing of pH and adsorbate concentrations. Empirical adsorption models of Langmuir and Freundlich were applied for the experimental data. Results showed that Langmuir isotherm was more suitable for this process. The experimental data fitted very well with the pseudo-second-order kinetic model. It was overally found that Surfactant-Modified Zeolites is an effective adsorbent for removal of methyl tert-butyl ether from contaminated solutions

Digestive and liver disease statistics in Iran

Gastrointestinal and liver diseases [GILD] are among the most common causes of morbidity in Iran and constitute a substantial proportion of mortality which imposes enormous economic consequences. Our purpose is to collect information and report current statistics on physician visits, hospitalizations, and deaths due to common GILD in Iran. Data on the leading causes of death were obtained from the Iranian Ministry of Health, Office of Health Statistics. A total of 213,322 deaths were reported from March 2003 to February 2004 [excluding mortality from the Bam earthquake] which equaled 4.4 deaths per 1000 population. Of these, 36,575 were due to accidents. Causes of death were reported on the basis of the 10th revision of the International Classification of Diseases [ICD-10; 1992]. The leading causes of hospitalization were obtained from the database of the GILD ward in Shariati Hospital, one of the largest and best known gastroenterology referral hospitals in Iran. Similarly, leading causes of out-patient referrals were identified from a large multi-physician outpatient clinic in Tehran. The five leading gastrointestinal causes of death in order of frequency were: gastric cancer, hepatobiliary cancer, liver cirrhosis, esophageal cancer, and colorectal cancer. The five leading causes of hospitalization in the GILD ward of Shariati Hospital were: liver cirrhosis, hepatitis, peptic ulcer disease, cholycystitis and cholangitis, and colorectal cancer. The most common outpatient diagnosis was gastroesophageal reflux disease followed by irritable bowel syndrome [IBS], duodenal ulcer [DU], non-ulcer dyspepsia, and chronic hepatitis B [HBV]. Gastrointestinal and liver malignancy along with chronic liver disease constitute the main GILD reasons for hospitalization and deaths in Iran. Gastroesophageal reflux disease, IBS, and chronic HBV are the most common GILD outpatient diagnoses

Treatment of non-alcoholic fatty liver disease [NAFLD]: a systematic review

No treatment has been proven to be effective in nonalcoholic fatty liver disease [NAFLD] and/or steatohepatitis [NASH]. Numerous studies have addressed this issue. However conclusive recommendations cannot be drawn solely from the currently available studies. Hence we performed this systematic review to determine which of the available therapeutic modalities are supported by adequate evidence in terms of decreasing the adverse clinical outcomes of interest. A specific strategy was utilized to perform a computerized literature search in MEDLINE; of which, a total of 375 studies were retrieved. According to current literature, modifying the potential risk factors such as obesity, hyperlipidemia, and poor diabetic control in all patients is considered the treatment of choice. Certain treatments can be recommended under special circumstances and some medications, although used clinically, are not supported by adequate evidence to be recommended for the treatment of NAFLD/NASH

Fate of atrazine in the agricultural soil of corn fields in Fars Province of Iran

Atrazine, a herbicide widely used in corn production, is frequently detected as pesticide in water resources. In this research, four agricultural fields with a long history of atrazine application in Shiraz and its vicinity in Fars province of Iran, have been studied to determine the fate of atrazine through the passage of time. These four farms were cultivated under a crop rotation [corn-wheat] during the past 10 years. Samples were collected from four soil profiles of 0-10, 10-20, 20-40, and 40-60 cm soil depth at different times. The time intervals for soil sampling started before atrazine application and continued until no atrazine was detected. According to the general linear model, there was no significant difference between atrazine residual concentrations and the soil moisture and depth [p?0.05]. But, significant difference between atrazine residual concentrations and the sampling regions was observed [p<0.001]. Based on the data, atrazine leaching and dissipation rate in different soil profiles in the four sampling regions were high and significant. Therefore, there is a high risk of atrazine pollution in groundwater resources of the region

Efficiency of domestic reverse osmosis in removal of trihalomethanes from drinking water

The reaction of disinfectants with natural organic matters existing in water lead to the formation of Disinfection By-Products. Potentially hazardous and carcinogenic characteristics of trihalomethanes [THMs] are recognized. Thus removal of THMs or its precursors are necessary for human health. The aim of this study was to study the efficiency of domestic reverse osmosis [RO] in removal of trihalomethanes from drinking water. A pilot scale of RO system with Polyamide membrane as Spiral-Wound, Tape wrapping module was used. Feed solution was made by using of pure chloroform. The samples containing chloroform were analyzed using a gas chromatograph equipped with a flame ionization detector. By increasing the flow, the removal rate of chloroform decreased and with declining removal of EC, the removal of chloroform declined too. In this research, at the worst condition, the efficiency of the pilot scale reverse osmosis reached to 80% removal of chloroform

Removal of methyl tert-butyl ether [MTBE] from contaminated water by photocatalytic process

Methyl tert-butyl ether [MTBE] has been commercially used as an octane enhancer to replace tetraethyl lead in gasoline since 1979. The high mobility, water solubility, and resistance to natural attenuation associated with MTBE may result in contamination of ground and surface waters. In this investigation the degradation of aqueous MTBE at relatively high concentrations was studied by UV-vis/TiO2/O2 photocatalytic process. The effect of important operational parameters such as pH, oxygen flow, catalyst loading, and irradiation time were also studied. Concentration of MTBE and intermediates such as tert-butyl formate [TBF] and tert-butyl alcohol [TBA] were measured using a gas chromatograph equipped with flam ionization detector and combined with headspace sampler. The time required for complete degradation increased from 15 to 150 min, when the initial concentration was increased from 10 to 500 mg/L. The first order rate constant for degradation of MTBE from the hydroxyl radical was estimated to be 0.266 to 0.033 min[-1] as the concentration increased from 10 to 500 mg/L. Study on the overall mineralization monitored by total organic carbon [TOC] analysis showed that in the initial concentration of 100 mg/L MTBE, complete mineralization was obtained after 110 mm under UV-vis/TiO2/O2 photocatalytic process. The data presented in this paper clearly indicate that UV/TiO2/O2 advanced oxidation process provides an efficient treatment alternative for the remediation of MTBE contaminated water

Nanofiltration process on dye removal from simulated textile wastewater

Dyestuffs removal from industrial wastewater requires special advanced technologies, since dyes are usually difficult to remove by biological methods. In this study nanofiltration process was used for removal of different dyestuffs from solutions. The rate of dye removal by spiral wound nanofiltration membrane in film thin composite MWCO=90 Dalton, was evaluated for four classes of dyes acidic, disperse, reactive and direct in red and blue dyes medium. Dye absorbance was measured by spectrophotometric method [2120 Standard Method 1998]. Effects of feed concentration, pressure and total dissolved solids concentration were also studied. Results showed that increasing dye concentration lead to higher color removal up to 98% and at different pressures for acidic and reactive blue were up to 99.7%. Different types of dyes had no effect on dye removal and permeate flux. During 2 h. of the operation time, permeate flux decline was increased. Permeate fluxes for different types of red dyes were from 16.6 to 12.6 [L/m[2]/h.] and for blue dyes were from 16.6 to 10.45 [L/m[2]/h.]. Presence of sodium chloride in dye solutions increased dye rejections nearby 100%. Chemical oxygen demand removal efficiencies for reactive blue, disperse blue, direct and disperse red dyes were also approximately 100%

Prevalence and risk factors of gastroesophageal reflux disease in Tabriz, Iran

Gastroesophageal reflux disease [GERD] is one of the most common gastrointestinal problems in the west while different reports indicate an increase in the prevalence in Iran. The aim of this study was to estimate the prevalence and clinical spectrum of GERD in staff of a referral hospital and evaluate the risk factors. This cross-sectional study using a modified Mayo clinic questionnaire was performed on staff of Imam Hospital, Tabriz, Iran on a pilot of 50 subjects, and a randomly selected group consisted of 522 subjects in the year 2005. GERD symptoms were defined as at least weekly heartburn and/or acid regurgitation during the past year. Response rate was 95%. Mean age of responders was 40.02 +/- 10.72 yr. The prevalence of recurrent heartburn and/or acid regurgitation experienced at least weekly and monthly was 26.8% and 34.1%, respectively. They were not related to age and gender. The severity of symptoms was mainly reported of a mild to moderate degree. 45% of the cases reported at least one of the atypical symptoms. There was no relation between marriage status and prevalence of GERD. On the other hand, GERD was less common among cases with no family history of upper gastrointestinal disease. The prevalence of frequent GERD was more common among medical staff. Increased BMI [but no recent weight gain or lose] was associated with higher prevalence of GERD symptoms only in women. Interestingly 33% of our population had a history of using antacid or PPIs which was more among cases with frequent GERD symptoms. This study revealed a high prevalence of frequent GERD symptoms in a selected population of Tabriz. Atypical symptoms should be considered in this area

[Correlation of null Btk expression and gene noncoding mutations in XLA patients]

X-linked agammaglobulinemia [XLA] is a primary immunodeficiency disorder characterized by recurrent bacterial infections, profound lack of serum antibodies and reduced circulating B lymphocytes. Mutations in Bruton's tyrosine kinase gene [BTK] result in XLA. It is shown that absence of Btk protein expression may be accompanied by no mutations in coding regions in some cases, instead alterations in conserved regulatory domains of promoter and the first intron of BTK gene maybe occurred The aim of this study was evaluation of Btk expression and mutation analysis in coding and regulatory regions of the gene. In this study, eleven XLA patients were enrolled. Btk expression was analyzed by western immunoblotting method. Mutation analysis was carried out in eight patients. In three cases, PCR of the regulatory regions was performed with designed primers, followed by sequencing. According to western blot, normal Btk expression in three patients and null expression in eight others was observed. Mutation analysis showed two novel BTK mutations in two patients [1038-1040 delAGG and IVS8-2delA]. No coding or regulatory region mutations were found in three cases with null Btk expression. Based on these results, three cases with null expression and had no coding or regulatory region mutations are interesting. It is possible that some rare regulatory defects may have been occurred, other than conventional sites. This must be taken into account for future investgations