Caspian Journal of Internal Medicine
Year:2019 | Volume:10 | Issue:4|Papers Count:18

Background: Polycystic ovary syndrome (PCOS) is the most popular endocrine disorder in reproductive age with unknown etiology and many comorbidities. This systematic review focused on the effectiveness of calcium and vitamin D (Ca/ Vit. D) supplementation on metabolic factors, menstrual cycles, and follicular responses in PCOS patients. Methods: Relevant studies were identified from the following electronic databases including Pub Med, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library, issue Oct. 2018, Evidence Based Medicine Reviews (EBMR), Google Scholar, EMBASE, as well as Farsi databases including Magiran and SID from 2000 to 2018. Out of 449 articles, six clinical trials met the inclusion criteria. Results: Out of six studies included in the study, only three studies had sufficient data for meta-analysis. Overall, studies showed that prescribing Ca/ Vit. D supplementation with metformin improved menstrual regularity and follicular maturation and significant decreases in serum insulin levels, homeostasis model of assessment-insulin resistance (HOMA-IR) and fasting blood sugar (FBS) and also significant rises on quantitative insulin sensitivity check index (QUICKI) at two studies. Hirsutism and level of testosterone decreased significantly after adding Ca/ Vit. D to metformin in two different studies. Based on two different trials, co-supplementation of Ca/ Vit. D had a significant impact to decrease serum triglycerides and VLDL-cholesterol levels as well as levels of cholesterol and LDL. Conclusion: It is possible that calcium and vitamin D supplementation improve menstrual disturbances and metabolic factors in PCOS in a long-term period, but further trials are still needed to confirm these findings.

Integrons are a segment of dsDNA that play a major role in bacterial adaptation and evolution. These genetic determinants are known by the presence of three necessary apparatuses: an integrase (intI gene), Pc (a promoter) and attI (a recombination site). These elements are able to acquire gene cassettes, which can carry antibiotic resistance factors, via site-specific recombination mechanism. The most common types of resistance integrons are class I (Tn402 derivatives), followed by class II and III. In recent years, the role of integrons as an important factor in the transmission and spread of resistance factors has been considered. Therefore, the ongoing threats posed by integrons require an understanding of their origins and evolutionary history. This review examines the functions and activities of integrons. It shows how antibiotics use selected particular integrons from the environmental pool, so that integrons carrying resistance genes are now present in the majority of Gram-negative pathogens.

Background: The relationship between vitamin D and asthma is still under investigation. We aimed to evaluate the association between serum vitamin D levels and clinical characteristics of asthma, and the impact of vitamin D deficiency on the clinical manifestations, as them being the issues of debate. Methods: Patients who were admitted to the outpatient clinics of Chest Diseases Department of Akdeniz University Hospital between January 2014 and December 2014, have been diagnosed as asthma according to the GINA 2014 guidelines were included in this study. Subjects with COPD, bronchiectasis, pneumonia or tuberculosis were excluded. Asthma exacerbation was defined, according to the GINA guidelines, as episodes of progressive shortness of breath, cough, wheezing or chest tightness accompanied by PFT abnormalities such as decreased PEF or FEV1. Results: A total of 158 patients with mean age of 48. 8 years were included in the study. Twenty-seven (17. 08%) of the patients demonstrated sufficient vitamin D serum levels (i. e. ≥ 30 ng/mL), while the remaining 131 (82. 92%) patients had vitamin D insufficiency (i. e. <30 ng/mL). When these two patient groups (vitamin D sufficient vs. insufficient) were compared with each other, the patients showing sufficient levels of vitamin D were found to reveal significantly higher FEV1 (L) and FVC (L) values. When the patients were grouped into 4 categories with regard to their serum vitamin D measurements, hospitalization numbers were found to significantly increase with decreasing vitamin D levels. Conclusion: Vitamin D deficiency was significantly associated with poorer pulmonary functions and higher hospitalization numbers.

Background: In the elderly population joint swelling, effusion and pain indicate local synovitis and the presence of inflammation. At present, no serum marker has been shown linking to knee synovitis in KOA. With regard to serum high sensitive C-reactive protein (hsCRP) as a measure of inflammation, this study aimed to determine the association of systemic inflammation with local synovitis, as well as with pain and muscle strength in KOA. Methods: The study population was selected consecutively among patients with KOA presented to Ayatollah Rouhani Hospital Rheumatology Clinic with knee joint synovitis. The diagnosis of KOA was confirmed according to the American College of Rheumatology diagnostic criteria. Data regarding radiographic, demographic and biochemical characteristics were provided and IL-17, IL-10, TGF-ß and hsCRP in serum and synovial fluid (SF) were measured in all patients. Stepwse linear regression models were used to determine the correlation between SF-hsCRP as a measure of local inflammation with other systemic or local markers of inflammation. Results: A total of 40 patients (women 65%) with mean age 65. 6+8. 9 (49-86) years, mean BMI 27. 7+3. 7 (22-38) kg/m2, were analyzed. SF-hsCRP was positively correlated with serum hsCRP as well as serum and SF cytokines. Knee pain was positively associated with BMI and radiographic severity and negatively with quadriceps muscle strength (QMS) (r=-0. 350, p=0. 029). In stepwise linear regression analysis the SF-hsCRP was positively correlated with serum hs-CRP (r=0. 769, p=0. 001), SF-IL-17 (r=0. 428, p=0. 001) and negatvely with serum IL-10 (r=-0. 316, p=0. 002). Conclusion: These findings indicate that systemic markers of inflammation such as serum hsCRP, and IL-17 are associated with local inflamation in KOA.

Background: To evaluate the association between pre/post-procedural high sensitive Creactive protein (hs-CRP) level and hs-CRP difference, and the risk of major adverse cardiovascular events (MACE) or new diffusion-weighted MRI lesions after carotid angioplasty and stenting (CAS). Methods: In this study, conducted in 2016 in Shiraz (Iran), patients who underwent diagnostic angiography and CAS were recruited. CAS was performed with distal embolic protection device on patients with both standard and high risk of endarterectomy. Pre/postprocedural hs-CRP, and hs-CRP difference were determined by immunoenzymometric assay method. Results: A total of 50 patients with diagnostic angiography and 60 patients with CAS were enrolled. No death, myocardial infarction, ischemic or hemorrhagic stroke, and need to revascularization occurred during the 30-days of the post-procedural period. Accordingly, the statistical evaluation in associating MACE and hs-CRP levels was impossible. Angioplasty was associated with higher frequency of elevated post-procedural hs-CRP in comparison to angiography (P=0. 003). The higher age, symptomatic lesions, negative history of hypertension, and hs-CRP difference had significant association with the presence of new DWI lesions in univariate analysis (all P<0. 05). Angioplasty of left carotid bulb and post-procedural hs-CRP levels was very close to the level of significance (P=0. 06). But only left sided lesions had positive association (P=0. 037) and hypertension had negative association (P=0. 037) in multivariate regression analysis. There were significant association between post-procedural hs-CRP level (P=0. 02) and hs-CRP difference (P=0. 003), and the number of new lesions; and the hs-CRP difference and the accumulated lesion surface area (P=0. 009). Conclusion: Post-procedural hs-CRP and hs-CRP difference may predict embolic complications of CAS.

Background: Identifying the incidence of cancer helps in planning and prioritizing resources for its screening, prevention, treatment and diagnosis. This study aimed at investigating a 25-year trend in gastrointestinal cancer in northern Iran during 1991-2016. Methods: This research was a trend analysis. The study population was one thousand five hundred and thirty-five cancer patients referring to Shahid Rajai Hospital in Babolsar, northern Iran, as the only center for radiotherapy in the North of Iran, during 1991-2016. SPSS version 22 was used for entering data and t-test, ᵡ 2 and ANOVA were used for analyzing data in the significant level of ≤ 0. 05. Results: The highest incidence of stomach cancer was 111 (35%) in 2011 and the lowest incidence was 44 (16. 3%) in 1996, The highest frequency of esophageal cancer was reported 137(56. 1%) cases in 1991 and the lowest frequency was 78 (26. 3%) cases in 2016, while the highest incidence of colorectal cancer was 109 (36. 7%) cases in 2016 and its lowest frequency was 32 (16. 3%) in 1996. There was also a significant difference in the frequency of gastrointestinal cancers in different studied years (p <0. 001). Conclusion: The trends in the incidence of stomach and colorectal cancers in northern Iran were increasing while esophageal cancer was decreasing.

Background: Among the inflammatory factors, high-sensitivity C-reactive protein (hsCRP) is one of the strongest predictors of cardiovascular disease. This study aimed to evaluate the relationship of serum hs-CRP level with shift work among reproductive age women. Methods: This cross-sectional study was conducted from September 2017 to May 2018 in three cities in Mazandaran Province, North of Iran. Through purposive sampling, 350 women (172 shift workers and 178 day workers) were recruited. The guideline recommended by the American Heart Association and the Centers for Disease Control and Prevention was used to interpret the result of hs-CRP measurement as the following: less than 1 µ g/ml: low CVD risk; 1– 3 µ g/ml: moderate CVD risk; and more than 3 µ g/ml: high CVD risk. The data were analyzed using the independent-sample t and the chi-square tests as well as the logistic regression analysis. Results: 11. 1% of participants had a serum hs-CRP level of more than 3 µ g/ml. This rate among shift workers was significantly greater than day workers (15. 6% vs. 7. 0%; p=0. 012). After adjusting the effects of potential confounders shift work significantly increased the odds of serum hs-CRP level of more than 3 µ g/ml by 2. 45 times (OR=2. 45, 95% CI: 1. 01– 5. 93, p=0. 047). Conclusion: Shift work is a significant predictor of high serum hs-CRP level probably due to its association with sleep problems and occupational stress. Improving the knowledge of female shift workers about the importance of quality sleep can reduce their CVD risk and improve their health.

Background: To determine the expression of cancer stem cell marker Leucine-rich repeatcontaining G-protein coupled receptor 5 (Lgr5) in colorectal carcinoma samples compared to normal adjacent tissue and any possible association with clinicopathological findings. Methods: This study was performed on forty samples of cancerous colorectal tissues (case group) and their adjacent normal mucosa (control group) in Imam Khomeini Hospital (Sari, Mazandaran, Iran). Expression of Lgr5 in tissue sections was done by immunohistochemistry. Statistical analysis was carried out using SPSS software. Results: Forty colorectal cancer patients including 21 males (57. 8± 11. 6 years) and 19 females (58. 4± 12. 77 years) were enrolled. Lgr5 was overexpressed in tumoral samples than normal adjacent tissues (77. 5% vs 27. 5%, p<0. 001). Also, no association was found between primary tumor, regional lymph nodes, invasion, histological type, grade, distant metastasis and IHC results. Patients with low Lgr5 expression had a better survival rate than patients with high expression but this was not statistically significant (p=0. 121). Conclusion: The higher immunoreactivity of Lgr5 in colorectal cancer tissues may indicate its role as a cancer stem cell marker in tumor carcinogenesis and patient’ s survival however; Lgr5 is not associated with pathological prognostic variables.

Background: Bladder cancer ranks ninth in world-wide cancer incidence and is 2. 5-4 times more common in men, and painless gross hematuria is its typical clinical symptom. Cystoscopy is used to evaluate the cause of hematuria in bladder while the use and reliability of ultrasonography is questionable for this purpose. Therefore, the aim of this study was to compare abdominal ultrasonography and rigid cystoscopy in the diagnosis of bladder tumors in Babol Shahid Beheshti Hospital. Methods: In this cross-sectional study, 60 patients who were candidate for cystoscopy referred to Babol Shahid Beheshti Hospital in Iran in 2017-2018. In this study, rigid cystoscope was used to view the bladder after doing sonography. The numbers, demographic information (age, gender and residence) and clinical characteristics (indication of cystoscopy, history of chronic disease, sonographic and cystoscopic results) of patients were recorded in the checklist. Results: The mean age of patients (37 (61. 7%)=males) was 58. 65± 14. 26 (19-85) years and 48 (80%) of them were >50 years old. The sensitivity and specificity of sonography was 71. 43 (95% CI: 29. 4, 96. 33) and 96. 23% (95% CI: 87. 02, 99. 54) in detecting bladder tumors, respectively. The negative predictive and positive predictive values in sonography were 96. 23 (95% CI: 88. 76, 98. 8) and 71. 43% (95% CI: 37. 25, 91. 33) respectively. Conclusion: The results of this study indicate that since sonography has high negative predictive values in evaluating hematuria; therefore it can be replaced with rigid cystoscopy for patients with lower risk of malignancy.

Background: To determine whether it is possible to predict intravenous thrombolytic therapy (IVT) outcome after 3 months in acute ischemic stroke patients who are candidate to receive recombinant tissue plasminogen activator (rt-PA), before rt-PA administration based on their risk factors and some available laboratory results. Methods: We enrolled 118 ischemic stroke patients who were treated with standard dose of Alteplase in our hospital. Baseline characteristics, door-to-needle time (DTN), onset-totreatment time (OTT), the National Institute Health Stroke Scale (NIHSS), systolic and diastolic blood pressure on admission, history of diabetes, hypertension, dyslipidemia, coronary artery disease (CAD), previous ischemic stroke, atrial fibrillation (AF), laboratory results were retrospectively collected. The modified Rankin Scale (mRS) was recorded after 3 months of admission and patients were divided into good (mRS 2) and poor (mRS>2) outcome groups. Chi-square test and t-test were used for categorical and continuous variables, respectively. Predictors for outcome after 3 months were studied by multivariable logistic regression. Results: Good outcome was seen in 60 (51%) patients and poor outcome was seen in 58 (49%) patients. Significant predictors for outcome at 3 months according to multivariable regression analysis were NIHSS score (odds ratio [OR], 0. 61; 95% confidence interval [CI], 0. 498-0. 750; p<0. 001), SBP (OR, 0. 95; 95% CI, 0. 925-0. 991; P=0. 01), AF (OR, 0. 09; 95% CI, 0. 013-0. 708; P=0. 02), CAD (OR, 17. 08; 95% CI, 0. 013-0. 708; p=0. 003). Conclusion: Higher NIHSS score, higher SBP on admission, AF and history of CAD could be the independent predictors of outcome after IVT in acute ischemic stroke patients.

Background: Short-wave diathermy (SWD) is an electrotherapeutic modality used in the conservative treatment of knee osteoarthritis (KOA). Electromagnetic radiation delivered in continuous (cSWD) or pulse (pSWD) mode provides a deep heating effect on tissues. There is no consensus on outcomes of treatment with cSWD versus pSWD in KOA. The aim of this study was to compare the effects of cSWD versus pSWD on pain, functionality and walking distance in KOA. Methods: 34 female patients aged 49-65 with KOA were randomized into two groups. A total of 27 patients completed the study. One group (n=11) was treated with cSWD, the other (n=16) with pSWD for three weeks. Patients were assessed before, after and at one month post therapy. Outcome measures included visual analogue scale (VAS) for knee pain, Western Ontario and Mcmaster University Osteoarthritis Index (WOMAC) and a sixminute walking test (6MWT). Results: Based on the minimal clinically important improvement (MCII), there was a reduction in VAS and WOMAC scores in both cSWD and pSWD groups post treatment (-37. 3mm, 31. 2mm respectively for VAS and 26%, 23% respectively for WOMAC) and at one month post treatment. There was no difference in pre and post treatment VAS for pain, WOMAC or 6MWT scores between the two groups. There was a small post treatment effect size on between-group 6MWT scores (Cohen’ s d: 0. 238). Conclusion: Both treatment options appear to be efficacious in reducing pain and improving functionality in KOA. There was no between-group difference. A larger study must be conducted to consolidate these findings.

Background: Cancer is still the most common cause of morbidity in the world. Chitosan, a commonly used natural polymer, is consisted of different molecular weight with different biological activities. The purpose of this study was to determine cytotoxicity effect of high molecular weight (HMWC) and low molecular weight of chitosan (LMWC) on three cancerous cell lines MCF-7, HeLa and Saos-2 with different histological origin. Methods: The anticancer property of two types of chitosan on three cancerous cell lines and human fibroblast as normal cell line, was evaluated by cytotoxic activity including their apoptosis induction properties. Chitosan solutions 2% (w/v) were prepared. The cells were treated by different concentration of chitosan and viability was determined by MTT assay after 24, 48 and 72 h. Also the mode of cell death-apoptosis vs necrosis, was determined by Annexin V staining assay and analyzed by flow cytometry. Results: While both types of chitosan were effective in inhibiting cell proliferation of three cancerous cell lines, fibroblast cells showed somehow more compatibility with chitosan. Despite of a significant decrease in all 3 cell lines viability, up to 90%, but we didn't see a concentration dependent difference between both types of chitosan (HMWC and LMWC) in their cytotoxic effects. Flow cytometry analysis showed necrosis more observable with MCF7 while the apoptosis pattern of death was more in Saos-2 and HeLa. Also, higher viability with both types of chitosan was seen in fibroblast as normal cells. Conclusion: While chitosan is compatible with normal diploid fibroblast cells, it shows anticancerous effect against 3 cancerous cell lines. Furthermore, it seems that the molecular weight of chitosan does not affect its anticancerous property.

Background: Previous studies showed that one of the complications of rheumatoid arthritis disease was auditory disorder. The goal of the present study was to compare the auditory status in patients with rheumatoid arthritis and healthy individuals. Methods: In the present case-control study, 30 normal persons and 60 persons with rheumatoid arthritis with mean age of 46. 72 and standard deviation of 6. 76 of both genders were appraised using pure tone audiometry, tympanometry and speech audiometry. The mean disease duration in patients with rheumatoid arthritis was 12. 51± 6. 09 years. Results: The frequency of hearing loss in rheumatoid arthritis group was significantly more than the control group (p=0. 001). All patients had sensorineural hearing loss. Only in 5% of rheumatoid arthritis group, abnormal tympanometry (as type) was reported. Speech discrimination score analysis showed significant difference between the patients with rheumatoid arthritis and controls. In terms of hearing threshold level, the mean hearing threshold level (in 2000, 4000 and 8000 Hz frequencies) of the patients with rheumatoid arthritis was significantly higher than control group in both ears (p<0. 05). A positive significant correlation was found among mean hearing threshold level in 4000 and 8000 Hz frequencies and rheumatoid arthritis duration in both ears. Conclusion: The frequency of hearing loss and the average hearing threshold in RA patients were higher than healthy individuals. The most common type hearing loss is sensorineural.

Background: Spermatogenesis is a necessary process in fertility and reproductive capacity of humans. In view of the relative high prevalence of spermatogenesis disorders in men and the failure of treatments provided in conventional medicine, new therapeutic approaches are being considered. This study will be designed to investigate the effect of Ceratonia siliqua (Carob) syrup and vitamin E on sperm parameters, oxidative stress index and reproductive hormones in infertile men. Methods: This randomized controlled trial protocol will be set in Babol Uuniversity of Medical Sciences. The proposed sample size is 60 men with oligozoospermia and teratospermia with 30 men in the experimental group taking Carob syrup while 30 men in the comparison group receiving vitamin E. The primary outcome measure is the change in semen parameters and secondary outcome measures including change in endocrine parameters and stress oxidative markers. This research was registered in the website of Iranian Registry of Clinical Trials as IRCT20171209037794N1identification number Conclusion: If the beneficial effect of this herb can be confirmed, it will provide a costeffective method for helping infertile men and provide evidence-based references for the treatment of male infertility in future.

Background: Metal phosphides are widely used as a rodenticide and insecticide and poisoning with these substances has a very high mortality. The aim of this study was to evaluate the butyrylcholinesterase (BuCh) level in poisoning with metal phosphides. Methods: In this case series study, 60 poisoned patients with zinc phosphide (ZnP) and aluminum phosphide (ALP) who was admitted to poisoning ward in Hamadan, Iran, enrolled in the study and BuCh level was measured. The sex, age, amount of ingestion, time of consumption, signs and symptoms, ECG and arterial blood gas (ABG) changes and clinical outcomes were evaluated. Results: Most (58. 3%) patients were males, the mean age was 32. 76± 17. 65 years. The average amount of ingestion was 7. 5± 4. 6 and 2. 5± 2. 96 gr for ZnP and ALP, respectively. Most signs and symptoms were hypotension (97%), nausea and vomiting (82%) and abdominal pain (32%). The average amount of BuCh level in all patients was 5163. 25± 2158. 31 U/L, that's while in ZnP and ALP poisoned patients was 5608± 1577 U/L and 4721. 46± 2562U/L respectively. The most dysrhythmia (26. 7%) was sinus tachycardia. Acidosis was seen in 33. 3% of patients. 14 patients died after hospital admission, which caused a 23. 3% fatality rate. Conclusion: Our results showed that, there was no significant change in BuCh level in poisoned patients with phosphide compounds.

Background: Selective serotonin reuptake inhibitors (SSRIs) and serotoninnorepinephrine reuptake inhibitors (SNRIs) are prescribed widely for the treatment of depression, anxiety disorders and other psychiatric disorders. Although antidepressants are considered as a safety drug category but unexpected cardiovascular events have been reported as the most serious complications. The aim of this study was to introduce a case presentation on bradycardia due to the drug interference of venlafaxine and cyclosporine. Case presentation: The patient was a 38-year old woman diagnosed with systemic lupus erythematosus 5 years ago, who was admitted to a general educational hospital in northern Iran due to intensified rheumatologic symptoms and complaining about abdominal pain. Cyclosporine tab were administered to the patient, 50 mg twice daily. Two weeks after the administration of cyclosporine, the level of blood cyclosporine was checked. The patient became bradycardic after starting a single dose of venlafaxine (heart rate 52 ppm). Cardiac assessment showed no reason for bradycardia and it subsided after a drop of venlafaxine. Conclusion: As a result of the potential adverse drug interactions between cyclosporine and antidepressants such as venlafaxine, physicians should be aware of the possibility of bradycardia in the simultaneous prescription of these drugs in cases.

Background: Schwannoma is a peripheral nerve sheath tumor originating from schwann cells. It is the most common neurogenic tumor of the posterior mediastinum. Pleural effusion is a rare presentation of benign schwannoma and it is mainly related to malignant tumors. Histologically, schwannoma as well as solitary fibrous tumor should be considered as a differential diagnosis of spindle cell lesions. Case presentation: Here, we report a case of an asymptomatic 61-year-old female misdiagnosed as solitary fibrous tumor of posterior mediastinum which was revealed to have blood stained pleural effusion during the video-assisted thoracic surgery. Eventually pathological study and 1. Department of Surgery, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran 2. Student Research Committee, Babol University of Medical Sciences, Babol, Iran 3. Department of Pathology, Ayatollah Rouhani Hospital, Babol University of Medical Sciences, Babol, Iran * Correspondence: Ramin Nosrati, Ganjafrouz Av. Ayatollah Rouhani Hospital, Babol, Mazandaran, Iran E-mail: raminosrati@yahoo. com Tel: 0098 1132199592 Fax: 0098 1132190181 Received: 10 Nov 2018 Revised: 19 Jan 2019 Accepted: 13 Feb 2019 immunohistochemistry profile of the tumor was reported as benign schwannoma. Conclusion: This report indicates that benign schwannoma can be accompanied by bloody pleural effusion and it also emphasizes the role of immunohistochemistry in the diagnosis of biopsy specimen of spindle cell lesions.

Background: Parvimonas micra is a gram-positive anaerobe and a part of the normal commensal flora of the gastrointestinal tract. Factors predisposing to anaerobic bacteremia include malignant neoplasms, periodontal disease, immune deficiencies, chronic renal insufficiency, decubitus ulcers and perforated abdominal viscus. Cases of Parvimonas bacteremia in a patient with esophageal carcinoma and in a patient following ERCP procedure have been reported but to our best knowledge no case has been reported yet in which a patient had colonic carcinoma. Case presentation: We present a rare case of a 94-year-old male who presented with chief complaint of fever and constipation. Complete blood count revealed normal white blood cell count anemia. Urinalysis came out to be unremarkable for any evidence of infection. Two blood cultures grew Parvimonas micra and Gamella morbillorum and patient was later switched to ampicillin-sulbactam as per blood culture susceptibility results. Echocardiogram came negative for any evidence of infective endocarditis. CT abdomen/pelvis showed soft tissue mass in the ascending colon just superior to the ileocecal valve (fig. 1, 2). Colonoscopy showed non-obstructing eccentric mass (fig. 3). Biopsy of the mass revealed moderately differentiated adenocarcinoma. Because of lack of distant metastasis, surgical resection of the mass as definitive curative treatment was done. Conclusion: Immune deficiency is a risk factor for anaerobic bacteremia. Apart from immediately starting the patient on antibiotics, a thorough search for malignancy may be considered when a patient presents with anaerobic bacteremia, especially, when the source of infection is not known. Identifying malignancy in earliest stages may improve treatment outcome.