Prevalence and characteristics of Palestine refugee mothers at risk of postpartum depression in Amman, Jordan: a cross-sectional study.

BACKGROUND: Postpartum depression (PPD) is a major public health concern because it adversely affects maternal health and children's physical and mental development. The prevalence of PPD in Arab countries is higher than the worldwide prevalence. Additionally, refugee women are more likely to develop PPD than women in the general population, but little research of refugee women in Arab countries is available. The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) have provided primary health care to Palestine refugees since 1950 and began the Mental Health and Psychosocial (MHPSS) programme in Jordan in 2017 to enhance the psychosocial and social wellbeing of Palestine refugees. We assessed the prevalence of PPD and examined associated factors among Palestine refugee women living in Amman, Jordan. METHODS: This cross-sectional descriptive study was done between April 21 and May 21, 2018. Eligible participants were Palestine refugee mothers who had given birth 3-16 weeks previously and were attending any of five UNRWA health centres in Amman that were launching the MHPSS programme. Data were gathered in face-to-face structured interviews that included the Edinburgh Postpartum Depression Scale (EPDS) to assess PPD, the Maternal Social Support Scale to assess levels of perceived social support, and a structured questionnaire about sociodemographic, obstetric or paediatric, psychological, and social factors. Participants with scores greater than 12 in the EPDS were classified as having depressive symptoms. Logistic regression was used to identify factors associated with depressive symptoms. The study protocol was approved by the Department of Health, UNRWA Headquarters, Amman, Jordan, and Nagasaki University. Each participant provided written informed consent. FINDINGS: 251 women participated in the study, with a mean age of 27·2 years (range 18-42, SD 5·43). 123 (49%) women were classified as having PPD. Logistic regression showed that factors associated with PPD were perceived low levels of social support (adjusted odds ratio 3·76, 95% CI 1·92-10·93) and experiencing stressful life events (one event 3·92, 1·51-9·91; two events 5·77, 2·33-14·27; and three or more events 14·8, 5·23-41·89). INTERPRETATION: The prevalence of PPD among Palestine refugee women in Amman was higher than that reported in a previous study of the general childbearing population (women aged 18-45 years) in Irbid in Jordan (22%, Mohammad et al. Midwifery 2011; 27: e238-45) but similar to findings in the West Bank (47%, Quandil et al. BMC Pregnancy Childbirth 2016; 16: 375) and in Syrian refugee women in Jordan (49·6%, Mohammad et al. Res Nurs Health 2011; 41: 519-245). Our findings highlight the need to address this disorder in Palestine refugee mothers. Periodical PPD screening, raising awareness about PPD, providing information to husbands and families, and building a support system for mothers could alleviate the risk of PPD. Future studies should examine whether factors of antenatal depression, which were not assessed in this study, correlate with having PPD to clarify the need for early intervention in mothers. FUNDING: Nagasaki University.

Leptin receptor is involved in STAT3 activation in human colorectal adenoma.

The possible role of leptin in colorectal tumors has been investigated in previous studies; however, to date, the conclusions remain under debate. Therefore, we investigated the serum leptin levels in colorectal adenoma patients. In addition, expression of the leptin receptor, and the leptin receptor-mediated signaling pathways were investigated in biopsy specimens collected from human patients with colorectal adenoma. No significant difference in the mean serum leptin level was observed between the colorectal adenoma patients and the control subjects; however, increased expression and activation of the leptin receptor, as indicated by findings such as the phosphorylation of Tyr 1141, was observed in the colorectal adenoma tissues. In addition, activation of the JAK/STAT signaling pathway mediated by the leptin receptor and increased transcriptional regulation of downstream target molecules were observed in colorectal adenomas compared with the non-adenoma tissues. These results indicate STAT3-mediated leptin receptor signaling pathways may be activated in human colorectal adenomas.

Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial.

The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 +/- 6.45 before treatment versus 5.11 +/- 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 +/- 6.65 versus 7.56 +/- 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer.

Metformin suppresses azoxymethane-induced colorectal aberrant crypt foci by activating AMP-activated protein kinase.

Metformin is widely used for the treatment of diabetes mellitus. Adenosine monophosphate-activated protein kinase (AMPK) is known to be activated by metformin and to inhibit the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the protein translational machinery and cell proliferation. We examined the effect of metformin on the suppression of colorectal carcinogenesis in chemical carcinogen-induced models. Seven-wk-old BALB/c mice were intraperitoneally (i.p.) injected with azoxymethane (AOM, 10 mg/kg) and then treated with or without metformin (250 mg/kg/d) for 6 wk (for the investigation of aberrant crypt foci [ACF] formation) or 32 wk (for polyp formation). We next investigated colonic epithelial proliferation using bromodeoxyuridine (BrdU) and the proliferating cell nuclear antigen (PCNA) labeling indices. Furthermore, to examine the indirect effect of metformin, the insulin resistance status and the serum lipid levels were assessed. Treatment with metformin significantly reduced ACF formation. The effect of metformin on colon polyp inhibition was relatively modest. No significant difference in body weight or glucose concentration was observed. The BrdU and PCNA indices decreased in mice treated with metformin. A Western blot analysis revealed that the phosphorylated mTOR, S6 kinase, and S6 protein levels in the colonic mucosa decreased significantly in mice treated with metformin. In conclusion, metformin suppresses colonic epithelial proliferation via the inhibition of the mTOR pathway through the activation of AMPK. As metformin is already used daily as an antidiabetic drug, it might be a safe and promising candidate for the chemoprevention of colorectal cancer.

Endoscopic therapy using an endoscopic variceal ligation for minute cancer of the esophagogastric junction complicated with esophageal varices: a case report.

INTRODUCTION: Standard endoscopic mucosal resection or endoscopic submucosal dissection is a procedure for patients with minute cancers, complicated with esophageal varices that puts them at high risk of bleeding. CASE PRESENTATION: We present the case of a 77-year-old Japanese man with alcoholic cirrhosis who underwent a routine endoscopy examination as a screening procedure for esophageal varices and was incidentally diagnosed as having minute cancer of the esophagogastric junction with esophageal varices. Endoscopic ultrasonography findings suggested that the minute cancer was a non-invasive carcinoma (carcinoma in situ) and a 2 mm in diameter blood vessel, feeding the esophageal varices, pierced the lesion. Following the examination, we carried out endoscopic treatment of the minute cancer and esophageal varices. Endoscopic variceal ligation was performed using a pneumo-activated device (Sumitomo Bakelite, Tokyo, Japan). Two years after the treatment, during the follow-up endoscopic examination on the patient, recurrence of carcinoma was not detected endoscopically or histologically. CONCLUSION: Endoscopic therapy using an endoscopic variceal ligation device for minute cancer of the esophagogastric junction, complicated with esophageal varices, may be an acceptable and easily applicable method.

Serum ferritin is a clinical biomarker in Japanese patients with nonalcoholic steatohepatitis (NASH) independent of HFE gene mutation.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Iron is regarded as a putative element that interacts with oxygen radicals, and high rates of hyperferritinemia and increased hepatic iron stores have been demonstrated in NASH. We investigated serum ferritin concentrations, HFE gene mutations, and insulin resistance in Japanese NASH patients and the diagnostic utility of serum ferritin concentrations as a means of distinguishing NASH. Serum ferritin concentrations were measured in 86 patients with histopathologically verified NAFLD (24 with steatosis and 62 with NASH) and 20 control subjects, they were tested for HFE gene mutations and their insulin resistance was measured. The serum ferritin concentration was significantly higher in the NASH patients than in the patients with simple steatosis (P = 0.006). There was no significant difference between the groups in HFE gene mutation (C282Y, H63D, and S65C), and the serum ferritin level was related with insulin resistance. The area under the ROC curve was 0.732 for distinguishing NASH from simple steatosis (P = 0.005; 95% CI, 0.596-0.856). In conclusion high serum ferritin concentrations are a distinguishing feature of Japanese NASH patients independent of HFE gene mutations.

The continuous real-time 13C-octanoate breath test for patients with nonalcoholic steatohepatitis using the BreathID system.

BACKGROUND/AIMS: Hepatic mitochondrial beta-oxidation is considered to play a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to determine whether there were differences between patients with NASH and healthy controls in a breath test with 13C-octanoate, a medium-chain fatty acid. METHODOLOGY: The subjects were 8 patients (5 men, 3 women, median age 46.5 years) with histologically proven NASH and 6 healthy controls (5 men, 1 women, and median age 27.8 years). The 13C breath test was performed for 4 hours using the BreathID system with a 100 mL of water containing 100 mg 13C-octanoate. RESULTS: There were no significant differences between NASH patients and controls about all breath test parameters. CONCLUSIONS: NASH-mediated changes in breath test parameters after ingestion of 13C-octanoate were not observed in our study. The present study findings suggest the possible preservation of 13C-octanoate metabolism (mitochondrial beta-oxidation) in patients with NASH.

Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease.

BACKGROUND: The association between obesity and the risk of Barrett's esophagus (BE) is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown. METHODS: We conducted a retrospective study in 163 patients with non-alcoholic fatty liver disease (NAFLD) who underwent both endoscopy and abdominal CT at an interval of less than a year at our institution. BE was endoscopically diagnosed based on the Prague C & M Criteria. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT images at the level of the umbilicus. The correlations between the BMI, VAT, and SAT and the risk of BE were examined by univariate and multivariate analyses. RESULTS: Sixty-nine of the 163 study participants (42.3%) were diagnosed to have endoscopic BE, which was classified as short-segment BE (SSBE) in almost all of the cases. There were no significant differences in the age or gender distribution between the groups with and without BE. According to the results of the univariate analysis, VAT was significantly associated with the risk of BE; the BMI tended to be higher in the group with BE than in the group without BE, but this relation did not reach statistical significance. VAT was independently associated with the risk of BE even after adjustment for the BMI. CONCLUSION: In Japanese patients with NAFLD, obesity tended to be associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal visceral adiposity.

Clinical characteristics of patients with gastric perforation following endoscopic submucosal resection for gastric cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the risk factors of perforation during endoscopic submucosal dissection (ESD). METHODOLOGY: ESD was performed using a Flex knife in 64 patients with a total of 67 gastric tumors. Perforation occurred at the sites of a total of 4 lesions (5.9% [4/67]) for which conservative treatment had been effective. We evaluated several possible risk factors for perforation following ESD, such as tumor size, the location of the lesion, the operation time, and other clinical factors. RESULTS: All the perforations occurred in the posterior wall of the gastric upper or middle body. In an analysis adjusted for age and sex, the tumor size (odds ratio (OR), 1.017; 95% confidence interval (CI), 1.004-1.030), the location of the lesion in an upper region (OR, 10.64; 95%CI, 1.160-10.00) and the operation time (OR, 1.017; 95%CI, 1.013-1.295) were significantly associated with the incidence of perforation. All perforations were transient, resolving within 7 days, and did not require surgical treatment. CONCLUSIONS: A large tumor size, the location of the lesion in an upper region, and a long operation time are risk factors for perforation following ESD.

Early effects of intravenous administrations of lansoprazole and famotidine on intragastric pH.

BACKGROUND/AIMS: The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of lansoprazole 30 mg and famotidine 20 mg. METHODOLOGY: Twelve Helicobacter pylori-negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after single intravenous administration of lansoprazole 30 mg or famotidine 20 mg. RESULTS: The average pH during the 4-hour period after administration of famotidine was higher than after lansoprazole (median: 5.15 versus 3.55, respectively; p = 0.0376). During the 4-hour study period, famotidine 20 mg provided a longer duration of pH > 3, 3.5, 4, 5, 6 and 7, compared to lansoprazole 30 mg (median: 73.6% versus 57.0%; p = 0.0414, 66.8% versus 47.8%; p = 0.0281, 60.8% versus 38.8%; p = 0.0150, 55.7% versus 29.7%; p = 0.0281, 45.0% versus 23.1%; p = 0.0414 and 23.9% versus 3.65%; p = 0.0076). CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, an intravenous dose of famotidine 20 mg more rapidly increases intragastric pH than lansoprazole 30 mg.

Identification of Cystatin SN as a novel tumor marker for colorectal cancer.

The goal of this study was to investigate Cystatin SN, a cysteine protease inhibitor, as a novel tumor marker for colorectal cancer (CRC). Gene expression profiles of mRNA from normal tissues and cancer cell lines were performed. Twenty-eight monoclonal antibodies for Cystatin SN were generated and serum Cystatin SN was quantified using ELISA in sera from 159 patients with CRC and 40 healthy controls. Cystatin SN was highly expressed in colon cancer cells. Employing a receiver-operating characteristic curve, we obtained an area under the curve of 0.708 for Cystatin SN, 0.819 for carcinoembryonic antigen (CEA) and 0.703 for carbohydrate antigen 19-9 (CA19-9). The combination assay of Cystatin SN, CEA and CA19-9 showed 62.9% sensitivity and 90.0% specificity. Especially, the sensitivity of the combination assay in stages I and II detection, in which stages curative operation would be possible, was improved over that of the assay testing only for CEA and CA19-9 (from 37.5 to 42.5% in stage I, from 49.0 to 60.8% in stage II). Furthermore, Western blot analysis revealed that Cystatin SN was increased in the urine from patients with CRC. Our results suggest the possibility of utilizing this novel tumor marker that can be tested in urine samples. These observations suggest that Cystatin SN in combination with CEA and CA19-9 is a useful tumor marker for detecting early stage CRC and that it is a unique urinary excretory protein, suggesting that Cystatin SN might be a novel candidate for use in mass screening for CRC.

Gender differences in the age-stratified prevalence of erosive esophagitis and Barrett's epithelium in Japan.

BACKGROUND/AIMS: In contrast to Western countries where erosive esophagitis (EE) is more prevalent in males, there is a high incidence of EE in elderly females in Japan. We aimed to examine the gender differences in the age-stratified prevalence of EE and Barrett's epithelium. METHODOLOGY: The study population comprised 869 cases (463 men and 406 women) who had undergone an upper endoscopy at the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. EE was graded according to the Los Angeles Classification. Barrett's epithelium was diagnosed based on the Prague C & M Criteria. RESULTS: In contrast to the decrease of the proportion of EE with aging in males, that in females remained constant. The results suggest that the suppressive effect of the increased gastric mucosal atrophy associated with aging was wiped out by the age-related effect of the increased incidence of hiatal hernia. The proportions of Barrett's epithelium in both males and females increased with aging. CONCLUSIONS: In Japan, the prevalence of elderly females complicated with hiatal hernia, which was partly due to osteoporosis and kyphosis, may affect the proportion of EE and probably Barrett's epithelium.

Macroscopic extent of gastric mucosal atrophy: increased risk factor for esophageal squamous cell carcinoma in Japan.

BACKGROUND: We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection. METHODS: Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. RESULTS: Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma. CONCLUSION: Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy.

BACKGROUND: The antithrombotic effects of low-dose aspirin (LDA) are well established, and it is used for primary and secondary prevention of cardiovascular events. However, the small intestinal toxicity of LDA remains unclear. The aim of this study was to review the characteristics of small bowel injury in long-term LDA users with capsule endoscopy (CE). METHODS: We retrospectively reviewed all chronic LDA users (>3 months) who underwent CE for suspected small bowel diseases from May 2004 to May 2008 at two medical centers. RESULTS: At our institutions, a total of 22 patients (13 males and 9 females, mean age 66.3 years) taking LDA underwent a CE examination. The indications for CE were obscure gastrointestinal bleeding in 21 patients and 1 patient who had abdominal pain. Twenty-one patients (95.5%) had some small bowel mucosal injury. Small bowel erosions were identified in 14 patients (63.6%). This enteropathy was characterized by multiple petechiae, loss of villi, erosions, and ulcers with round, irregular, and punched-out shapes. Two patients had circumferential ulcers with stricture. In most patients, small bowel lesions were multifocal and were evenly distributed in the small bowel. No patients failed to pass the capsule. CONCLUSIONS: This is the first CE report that has studied the characteristics of small bowel injury in chronic LDA users. CE is useful to diagnose small bowel enteropathy associated with LDA.

Incidence of small bowel injury induced by low-dose aspirin: a crossover study using capsule endoscopy in healthy volunteers.

BACKGROUND AND AIMS: Small intestinal toxicity of low-dose aspirin remains unclear. The purpose of this capsule endoscopy study was to assess the incidence of small bowel injury in healthy volunteers treated with short-term low-dose aspirin. METHODS: Healthy subjects were randomly assigned to receive low-dose aspirin for 14 days (Aspirin group) or no drugs for 14 days (Control group). The two treatment occasions were separated by a washout period of at least 4 weeks. All subjects underwent capsule endoscopy at the end of each treatment period. RESULTS: After 2 weeks of treatment, the percentages of subjects with small bowel pathology were 80% in the Aspirin group compared with 20% in the Control group (p = 0.023). The incidence of small bowel mucosal breaks in the Aspirin group was higher than that in the Control group, although the difference was not significant (30 vs. 0%; p = 0.210). CONCLUSIONS: This is the first pilot study using capsule endoscopy to report on the relation between small bowel injury and low-dose aspirin. Among the healthy subjects, the short-term administration of low-dose aspirin was associated with a mild mucosal inflammation of the small bowel.

Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway.

Adiponectin is a peptide hormone secreted by adipose tissue. It is a key hormone responsible for insulin sensitization, and its circulating level is inversely associated with abdominal obesity. Recent studies have shown that a reduced plasma adiponectin level is significantly correlated with the risk of various cancers. However, there are few studies regarding the association of adiponectin and colorectal cancer. To address this issue, we investigated the effect of adiponectin on colorectal cancer cells. Three colorectal cancer cell lines express both AdipoR1 and AdipoR2 receptors. MTT assay revealed that adiponectin inhibited human colorectal cancer cell growth. Furthermore, Western blot analysis revealed that adiponectin activated adenosine monophosphate-activated protein kinase (AMPK) and suppressed mammalian target of rapamycin (mTOR) pathways. Selective AMPK inhibitor compound C abrogated the inhibitory effect of adiponectin on cell growth. Our results clearly demonstrate the novel findings that adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby down-regulating the mTOR pathway.

Association of visceral fat accumulation and plasma adiponectin with rectal dysplastic aberrant crypt foci in a clinical population.

The association between obesity and the risk of colorectal cancer (CRC) cannot be easily evaluated because CRC itself is associated with a gradual loss of bodyweight. Aberrant crypt foci (ACF) can be classified as dysplastic ACF or non-dysplastic ACF by magnifying colonoscopy, and dysplastic ACF are thought to be a biomarker of CRC. Ninety-four participants who underwent colonoscopy at Yokohama City University Hospital, Japan, were enrolled in the current study. We detected 557 ACF, including 67 dysplastic ACF (12.0%). Univariate regression analysis was conducted to determine correlations between the number of dysplastic ACF and various potential risk factors, including patient age, waist circumference, body mass index, visceral fat area (VFA), and plasma adiponectin level. The results of multiple regression analysis revealed that the number of dysplastic ACF correlated with age (correlation coefficient r=0.212, P=0.0383) and plasma adiponectin level (r=-0.201, P=0.0371), even after adjustments for sex, waist circumference, body mass index, and VFA. Our univariate correlation analysis data showed a significant correlation with the number of dysplastic ACF with VFA (r=0.238, P=0.0209), no correlation with subcutaneous fat area, and an inverse correlation with the plasma level of adiponectin (r=-0.258, P=0.0118). Thus, our results suggest that aging and visceral fat accumulation could correlate moderately with colorectal carcinogenesis. The novelty of our study lies in the finding that visceral fat accumulation and a low plasma adiponectin level may promote colorectal carcinogenesis; therefore, these obesity-related parameters may serve as novel targets for CRC prevention.