In vitro toxicological assessment of flumethrin's effects on MCF-7 breast cancer cells.

Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells.

Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic ß cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients' own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward â€‹the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.

Evidence of acrylamide- and glycidamide-induced oxidative stress and apoptosis in Leydig and Sertoli cells.

Acrylamide (AA) is a common chemical, produced during food processing and widely used in various industries and laboratory processes. Thus, AA causes a significant risk for human and animal health. Recently published studies have suggested that reproductive toxicity of AA and glycidamide (GA) was mainly due to the oxidative stress which can lead to cell apoptosis. The present experiment was conducted to investigate the effect of oxidative stress on the apoptosis of mouse Leydig (TM3) and Sertoli (TM4) cells induced by AA and its metabolite GA. TM3 and TM4 cells were exposed to AA (10 µM and 1 mM) and GA (1 µM and 0.5 mM) for 24 h. Following the exposure time, the Leydig and Sertoli cells were evaluated for measurement of cell viability, lactate dehydrogenase activity, lipid peroxidation and hydrogen peroxide levels, apoptosis/necrosis rate, and mRNA expression levels of apoptotic genes (caspase3, Bcl-2, Bax, and p53). The present study showed that AA and GA exposure caused decrease in cell viability and increase in excessive oxidative stress and apoptosis in both cell types. In conclusion, our in vitro results demonstrate that oxidative stress probably plays a major role in AA- and GA-induced apoptosis of Leydig and Sertoli cells.

Effect of preoperative biliary drainage on bacterial flora in bile of patients with periampullary cancer.

BACKGROUND: Patients with obstructive jaundice due to periampullary tumours may undergo preoperative biliary drainage (PBD). The effect of PBD on the microbiome of the biliary system and on postoperative outcome remains unclear. METHODS: A single-centre retrospective study of patients with obstructive jaundice due to periampullary cancer, treated between July 2007 and July 2015, was undertaken. Intraoperative bile samples were obtained for microbiological analysis after transection of the common bile duct. Postoperative complications were registered. RESULTS: Of 290 patients treated, intraoperative bile samples were present for 172 patients (59·3 per cent) who had PBD and 118 (40·7 per cent) who did not. Contamination of bile was increased significantly in patients who underwent stenting (97·1 per cent versus 18·6 per cent in those without stenting; P < 0·001). PBD resulted in a shift in the biliary microbiome from Escherichia coli in non-stented patients (45 per cent versus 19·2 per cent in stented patients; P = 0·009) towards increased contamination with Enterococcus faecalis (9 versus 37·7 per cent respectively; P = 0·008) and Enterobacter cloacae (0 versus 20·4 per cent; P = 0·033). This shift was associated with a high incidence of bacterial resistance against ampicillin-sulbactam (63·6 per cent versus 18 per cent in patients with no PBD; P < 0·001), piperacillin-tazobactam (30·1 versus 0 per cent respectively; P = 0·003), ciprofloxacin (28·5 versus 5 per cent; P = 0·047) and imipenem (26·6 versus 0 per cent; P = 0·011). The rate of wound infection was higher in patients with a positive bile culture (21·0 per cent versus 6 per cent in patients with sterile bile; P = 0·002). Regression analysis revealed the presence of Enterococcus faecium (odds ratio 2·83, 95 per cent c.i. 1·17 to 6·84; P = 0·021) and Citrobacter species (odds ratio 5·09, 1·65 to 15·71; P = 0·005) as independent risk factors for postoperative wound infection. CONCLUSION: There are fundamental differences in the biliary microbiome of patients with periampullary cancer who undergo PBD and those who do not. PBD induces a shift of the biliary microbiome towards a more aggressive and resistant spectrum, which requires a differentiated perioperative antibiotic treatment strategy.

Second to fourth digit ratio, sex differences and antropometric measuments: their relationship in children.

BACKGROUND: The aim of this study was to determine the effect of socio-demographic factors and anthropometric measurements on 2/4 digit ratio in the school aged children. METHODS: This cross-sectional study was completed in primary and secondary schools in the city center of Canakkale, Turkey. The students were seated at a table by the responsible doctor, and were asked to extend the palm of the right and left hand in the schools. Using a Vernier Caliper the 2/4 fingers were measured from the palm twice, and the results were noted together with socio-demographic information. Weight, length, waist and hip measurements were taken while students were behind a folding screen. RESULTS: A total of 1860 students from 5-14 years were included in the study. The right hand 2/4 digit ratio was 0.9765±0.035 and the left hand ratio was 0.9716±0.036 for girls. For the boys the ratios were 0.9688±0.035 for right hand and 0.9653±0.033 for left hand. The digit ratios of girls were significantly higher than boys and the right hand ratio was even greater. The 2/4 digit measurements of both hands of students were positively correlated with each other. In regression model left hand 2/4 ratio is dependent hip circumference, monthly income and gender as adjusted r2 0.051. The right hand 2/4 ratio was dependent gender, monthly income, hip circumference and birthweight as adjusted r2 0.041. CONCLUSIONS: The 2/4 digit ratio of school-aged in Turkish children differed based on gender. Digit ratios depend on the hip circumference, gender (girls have higher ratio), birthweight, gestation week and monthly income. Further research, especially the effect of monthly income, is needed.

Knowledge, attitude and behavior of mothers related to acute respiratory infections.

BACKGROUND: The aim of this paper was to evaluate the level of knowledge and general attitude to acute respiratory diseases and behavior of antibiotic usage and related factors. METHODS: The study included 122 mothers of children between 2 and 16 years of age who applied the complaint of respiratory infections and experienced the respiratory infections previous year, to policlinics between January and May 2012. A survey form was used to evaluate the sociodemographic properties of the mothers, and the level of knowledge, attitude and behavior of mothers to childhood acute respiratory infections, fever and antibiotic use. RESULTS: Of the children, 58.1% applied with cough, and 40.9% applied with fever to the doctor. Before attendance 28.6% of mothers had used antibiotics and 27.8% antipyretics. The rate use of not prescribed antibiotics was 12.3%. Before medical evaluation of children, the use of a variety of traditional and alternative medical methods was at the high rate of 57.4%. The average attitude scores of mothers about the antibiotics use for acute respiratory infections fell into the category of being against antibiotic use and income level toward antibiotic use and a correlation between duration of mother's education against antibiotic use. CONCLUSIONS: We found that the level of knowledge of parents about medications used by their children was insufficient and there is a high percentage of non-prescription use of antibiotics. In low income and low education level of parents the use of antibiotics increased. Health workers must correctly inform parents about symptoms, course and medication. The effects of health education in the management of common diseases must be evaluated with studies.

Strategies to improve the outcome in locally advanced pancreatic cancer.

Pancreatic cancer is associated with the worst prognosis of all gastrointestinal malignancies. The major reasons for the dismal outcome are late diagnosis due to unspecific symptoms and aggressive tumor biology. Although highly effective chemotherapeutic options have emerged within the last decade, radical resection offers the only chance of cure. Only 10-20% of patients are resectable at presentation, and 30-40% present with borderline resectable or locally advanced/unresectable tumors. Even if resectable, the 5-year-survival rate after complete resections remains unsatisfactory, with less than 25%. This article gives an overview on current therapy standards as well as on new approaches especially for locally advanced tumors and outlines the importance of ongoing research to improve prognosis.

Testicular development of male mice offsprings exposed to acrylamide and alcohol during the gestation and lactation period.

Acrylamide (Ac) in the foods and alcohol (Al) in the drinks are unavoidable. Several previous studies demonstrated that these substances which are taken into the body via diet may cause adverse effects in the cells. However, there is no study about how Ac and Al may affect the male reproductive system of the offspring when consumed by the mother during pregnancy and lactation. For this purpose, sexual development in male mice was evaluated after intake of 14 mg/kg Ac and 2 g/kg Al from gestation day 6 to postnatal day (PND) 21. The weight of the offspring was reduced at birth and PND 21 for those exposed to Ac and/or Al. The gonadosomatic index of male offsprings was reduced except for the Ac-treated lactation group. Both substances induced multinuclear giant cells, degenerative cells, atrophic tubules, and maturation-arrested tubules, while decreased Leydig, Sertoli, and spermatogenic cell numbers. Lipid peroxidation level and superoxide dismutase enzyme activity increased in both Al-treated and Ac and Al-treated groups. There was only reduction in the catalase activity during the gestation and lactation periods. These findings suggest that consumption of Ac together with Al may induce impairments on testicular spermatogenesis in male offsprings.

Are insulin resistance and serum resistin levels increased in women with idiopathic hirsutism?

OBJECTIVE: To investigate the insulin resistance and serum resistin levels in women with idiopathic hirsutism compared to controls and women with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Three groups of women including 23 women with idiopathic hirsutism, 28 women with PCOS and 28 non-hirsute women serving as controls were included into the study. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), serum fasting insulin and resistin levels were compared between the groups. RESULTS: There were no statistically significant differences regarding the age, BMI and waist circumferences between the groups. Mean and median fasting blood glucose, fasting insulin, HOMA-IR, serum resistin levels were statistically similar between the groups (p = 0.966, p = 0.378, p = 0.409 and p = 0.784, respectively). There were no correlations between the resistin, HOMA-IR, fasting insulin levels and BMI in any of the three groups. CONCLUSIONS: Insulin resistance and serum resistin levels do not appear to be increased in women with idiopathic hirsutism compared to controls at similar BMI's and waist circumferences.

Sexual dysfunction in Turkish women with dyspareunia and its impact on the quality of life.

PURPOSE OF INVESTIGATION: The authors aimed to determine the prevalence of female sexual dysfunction (FSD) among Turkish dyspareunic women and to establish the associated factors with FSD. Furthermore, they aimed to investigate if dyspareunia and possible associated sexual complaints were related to impaired quality of life (QoL). MATERIALS AND METHODS: The study included 154 women admitted to the present gynecology department at a tertiary center in the west region of Turkey, 67 of which suffered from dyspareunia. The remaining 87 sexually healthy women were included in the control group. FSD was assessed with 19-item validated female sexual function index (FSFI). QoL was assessed using short form 36 (SF-36). The chi-squared test and t-test were used for analysing the group differences. Pearson's correlation test was used to determine the effect of the variables of FSFI on the SF-36. Multivariance analysis and logistic regression was used to determine independent risk factors for FSD and to estimate odds ratio (OR) with 95% confidence interval (CI). RESULTS: The incidence of FSD in dyspareunic group and control group was 86.57% and 36.8%, respectively (p < 0.001). Dyspareunic women had lower scores with regards to sexual desire, arousal, lubrication, orgasm, satisfaction, and pain domains at significant level (p < 0.001). Education level, time period after the last delivery, duration of marriage, parity, and dyspareunia were significantly related to FSD. However, dyspareunia was an independent risk factor for FSD (OR 11.49; 95% CI 4.95-26.67). Regarding the impact on the QoL, dyspareunic women had lower scores with regards to the physical role, social function, bodily pain, and vitality domains. CONCLUSION: The present results show that dyspareunia has a major impact on women's sexual function and QoL. Clinicians have an important role for encouraging women to report their sexual complaints. Identifying dyspareunia and treating FSD may positively affect women's sexual function and overall QoL.

Can sludge dewatering reactivate microorganisms in mesophilically digested anaerobic sludge? Case of belt filter versus centrifuge.

The anaerobic digestion process that successfully reduces the organic content of sludge is one of the most common alternatives to meet pathogen reduction requirements for particular classes of biosolids. However, recently it was reported that, much higher densities of indicator bacteria were measured in dewatered cake samples compared to samples collected after anaerobic digestion. Additionally, this increase was commonly observed after centrifugation but not after belt filter dewatering. Several hypotheses were tested to explain this occurrence; however, much of the attention was given to the reactivation of the indicator bacteria which might enter a viable but non-culturable state (VBNC) during digestion. The objective of this research is to examine sludge samples from 5 different full-scale treatment plants in order to observe the effect of dewatering processes on the reactivation potential of indicator bacteria. The bacterial enumerations were performed by both Standard Culturing Methods (SCM) and quantitative polymerase chain (qPCR) on samples collected after digestion and dewatering. Results obtained by SCM indicated that in two investigated treatment plants operating belt filter dewatering, an average 0.6 log decrease was observed after the dewatering process. However, 0.7-1.4 log increases were observed immediately after centrifuge dewatering for the other three treatment plants. On the other hand, qPCR results gave 0.1-1.9 log higher numbers compared to SCM. Comparative evaluation of results obtained by two analytical methods for five treatment plants indicates that the differences observed might be originating from both reactivation of VBNC bacteria and amplification of DNA from dead cells found in the sludge.

Comparison of 3'-deoxy-3'-[¹8F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours.

PURPOSE: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET) and [(18)F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery. METHODS: A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images. RESULTS: Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT (n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV(max) 1.1-6.5; mean FDG SUV(max) 7.9, range 3.3-17.8; p < 0.001). CONCLUSION: For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined.

AZGP1 is a tumor suppressor in pancreatic cancer inducing mesenchymal-to-epithelial transdifferentiation by inhibiting TGF-ß-mediated ERK signaling.

Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-ß (TGF-ß) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation. In vitro, ZAG silencing strikingly increased invasiveness of pancreatic cancer cells accompanied by the induction of a mesenchymal phenotype. Expression analysis of a set of EMT markers showed an increase in the expression of mesenchymal markers (vimentin (VIM) and integrin-α5) and a concomitant reduction in the expression of epithelial markers (cadherin 1 (CDH1), desmoplakin and keratin-19). Blockade of endogenous TGF-ß signaling inhibited these morphological changes and the downregulation of CDH1, as elicited by ZAG silencing. In a ZAG-negative cell line, human recombinant ZAG (rZAG) specifically inhibited exogenous TGF-ß-mediated tumor cell invasion and VIM expression. Furthermore, rZAG blocked TGF-ß-mediated ERK2 phosphorylation. PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals. Thus, epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype.

Tumor microenvironment and progression of pancreatic cancer.

Pancreatic ductal adenocarcinoma is characterized by « tumor desmoplasia ¼, a remarkable increase in connective tissue that penetrates and envelopes the neoplasm. It is becoming clear that this desmoplastic microenvironment of pancreatic cancer--which is forming approximately eighty percent of the tumor mass--is not a passive scaffold for the tumor cells but an active player in carcinogenesis. Several chemotherapeutic agents and novel molecular targeted therapies against epithelial tumor cells--although showing antitumor activity in cell culture and mouse experiments--have failed to show significant effects in the clinic. Thus, targeting pancreatic tumor cells alone seems unlikely to improve the dismal prognosis of pancreatic cancer. It has recently been shown that the activated stroma of pancreatic cancer is an independent prognostic marker with an impact on patient survival as much as the lymph node status of the cancer. Several primarily benign conditions associated with expansion of stromal and inflammatory components, such as chronic pancreatitis or hereditary pancreatitis are believed to increase the risk of pancreatic cancer. Similar observations have been made in other cancer types such as chronic hepatitis-liver cancer, Barrett dyplasia-esophageal cancer, and inflammatory bowel disease-colon cancer. The common denominator of all these conditions is; chronic inflammation leads to increased incidence of cancer. In this review the impact of the activated stroma on pancreatic carcinogenesis is discussed.

Ex vivo chemosensitivity testing and gene expression profiling predict response towards adjuvant gemcitabine treatment in pancreatic cancer.

Efficacy of chemotherapy for pancreatic cancer may be improved by tailoring it to individual chemosensitivity profiles. Identification of nonresponders before initiation of treatment may help to avoid side effects. In this study, primary pancreatic cancer cells were isolated from 18 patients undergoing pancreaticoduodenectomy for pancreatic cancer. Eight commonly used pancreatic cancer cell lines were used as controls. Ex vivo chemosensitivity for gemcitabine, 5-fluorouracil, mitomycin-C, cisplatinum, oxaliplatinum, paclitaxel and a combination of gemcitabine with oxaliplatinum or mitomycin-C was determined using a cellular ATP-based tumour chemosensitivity assay (ATP-TCA). Quantitative real-time-polymerase chain reaction was performed to determine RNA expression levels of genes implicated in chemoresistance. Chemosensitivity towards cytotoxic agents was highly variable in primary pancreatic cancer cells and pancreatic cancer cell lines. ATP-TCA results for gemcitabine correlated to the tissue expression of human equilibrative nucleoside transporter-1 (hENT1). Time to relapse in patients with gemcitabine-sensitive tumours was significantly higher than in patients with chemoresistant pancreatic cancers (P=0.01; 71 vs 269 days). Furthermore, time to relapse in gemcitabine-treated patients was related to hENT1 expression (P=0.0067). Thus, chemosensitivity testing using ATP-TCA in pancreatic cancer is feasible and correlated with time to relapse in gemcitabine-treated patients. This suggests that ATP-TCA testing could be used as a decision-making tool in the adjuvant treatment of pancreatic cancer.

Facilitation of facial prosthesis placement with tattoo markers: a clinical report.

Proper repeatable alignment of an adhesive-retained auricular prosthesis may be a difficult challenge. Usually anatomical undercuts, tissue remnants, and scars are used as references to secure a facial prosthesis and provide retention and stability. Repeated application may be hindered when none of these references is present. This clinical report describes a method of using tattoo marks as references to repeatably align the facial prosthesis of a patient with a skin flap reconstruction.

Portable stimulator design aimed at differentiating facial nerves from normal tissues.

Facial nerves are very prone to risk of being cut away in the facial surgeries. In order to differentiate the normal tissues from the nerves during the surgeries, facial stimulator is very essential. These stimulators are particularly useful in triggering action potentials in the facial muscle tissue. In the case of any damage to these nerves, paralysis is unavoidable. Second use of the stimulator would be to diagnose how severe the facial problems are. Third use, which is a noninvasive application, is the employment of facial stimulator to treat and diagnose facial problems that arose from temperature differences, cuts or strain. The stimulation is achieved through DC voltage pulses that conform to user-specified amplitude, pulse duration and pulse intervals. These variables are set according to the age, sex, and physiological conditions of the patient. Peripheral Interface Controller is used to derive different pulse patterns. The current specifications of our stimulator are a range of 0.1-20 V pulse amplitude, 0.1-2 msec pulse duration, and 0.05-1 sec pulse interval. The main benefits of our stimulator are its graphic display that shows the form of pulse, its compact size, and operation on a battery power supply and adaptability to convert to other stimulation applications.