Integrating multi-wet laboratory diagnostics to study staphylococci in animals in Uganda.

BACKGROUND: Several diagnostic environments in Uganda lack real-time, robust and high-throughput technologies for comprehensive typing of microbes, which is a setback to infectious disease surveillance. This study combined various wet laboratory diagnostics to understand the epidemiology of pathogenic staphylococci isolated from animals in Uganda and the implications for global health security priorities. METHODS: A retrospective study was conducted employing records and pathogenic staphylococci (from animals) archived at the Central Diagnostic Laboratory (CDL), Makerere University, Uganda, between January 2012 and December 2019. The bacteria were speciated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and tested for virulence factors [beta lactamases, lecithinase, deoxyribonuclease (DNase), haemolysins] and resistance to ten antimicrobials of clinical and veterinary relevance. Tetracycline and methicillin resistance genes were also tested. RESULTS: The prevalent diseases were mastitis in cattle and skin infections in dogs. Of the 111 staphylococci tested by MALDI-TOF MS, 79 (71.2%) were Staphylococcus aureus, 27 (24.3%) were Staphylococcus pseudintermedius and 5 (4.5%) were Staphylococcus schleiferi. All these strains expressed haemolysins. The prevalence of strains with lecithinase, penicillinase, cephalosporinase and DNase was 35.9% (14/39), 89.7% (35/39), 0.0% (0/39) and 87.2% (34/39), respectively. Staphylococci were primarily resistant to early penicillins (over 80%), tetracycline (57.7%), and chloramphenicol (46.2%). Minimal resistance was noted with cloxacillin (0.0%), ciprofloxacin (9.6%), and cefoxitin (3.8%). The prevalence of multidrug resistance (MDR) was 78.8% for general staphylococci, 82.2% for S. aureus, 73.1% for S. pseudintermedius, and 60.0% for S. schleiferi. Multidrug resistant staphylococci were significantly more prevalent in the cattle isolates than in the dog isolates (P < 0.05). The prevalence of methicillin-resistant staphylococci (MRS) tested by resistance to cefoxitin and mecA carriage was 3.8%. These four strains were all isolated from dog skin infections. The tetK gene was the most predominant (35.4%), followed by tetM (25.0%). CONCLUSION: In resource-constrained settings, the approach of integrated diagnostics promises sustainable disease surveillance and the addressing of current capacity gaps. The emergence of MRS (zoonotic bacteria) in companion animals creates a likelihood of reduced treatment options for related human infections, a threat to global health.

Within-individual relationships between mother-to-infant bonding and postpartum depressive symptoms: a longitudinal study.

BACKGROUND: Although the importance of the dynamic intra-individual relationship between mother-to-infant bonding and postpartum depressive symptoms has been widely recognized, the complex interplay between them is not well understood. Furthermore, the potential role of prenatal depressive symptoms and infant temperament in this relationship remains unclear. This study aims to examine the bidirectional influence of mother-to-infant bonding on postpartum depressive symptoms within individuals and to elucidate whether prenatal depressive symptoms and infant temperament would influence deviations from stable individual states. METHODS: Longitudinal data were collected from 433 women in early pregnancy. Of these, 360 participants completed the main questionnaires measuring impaired mother-to-infant bonding and postpartum depressive symptoms at least once during the postpartum period. Data were collected at early and late pregnancy and several postpartum time points: shortly after birth and at one, four, ten, and 18 months postpartum. We also assessed prenatal depressive symptoms and infant temperament. A random-intercept cross-lagged panel model was used. RESULTS: Within-individual variability in mother-to-infant bonding, especially anger and rejection, significantly predicted subsequent postpartum depressive symptoms. However, the inverse relationship was not significant. Additionally, prenatal depressive symptoms and difficult infant temperament were associated with greater within-individual variability in impaired mother-to-infant bonding and postpartum depressive symptoms. CONCLUSIONS: The present study demonstrated that the within-individual relationship between mother-to-infant bonding and postpartum depressive symptoms is likely non-bidirectional. The significance of the findings is underscored by the potential for interventions aimed at improving mother-to-infant bonding to alleviate postpartum depressive symptoms, suggesting avenues for future research and practice.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Effect of nausea and vomiting during pregnancy on mother-to-infant bonding and the mediation effect of postpartum depression: the Japan Environment and Children's Study.

BACKGROUND: Mother-to-infant bonding (MIB) is critical for the health and well-being of the mother and child. Furthermore, MIB has been shown to boost the social-emotional development of infants, while also giving mothers a sense of happiness in raising their children. Nausea and vomiting during pregnancy (NVP) is a normal complication of pregnancy, occurring in approximately 50-90% of pregnant women in the early stages of pregnancy. Despite widespread knowledge of MIB and postpartum depression, little research attention has been given to the effects of NVP on MIB. This study aimed to investigate the relationship between NVP and MIB and the mediating effects of postpartum depression. METHODS: We analyzed the data of 88,424 infants and 87,658 mothers from the Japan Environment and Children's Study (JECS), which is a government-funded nationwide birth prospective cohort study. The Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) was used to assess MIB, and the Edinburgh Postpartum Depression Scale (EPDS) was utilized to assess postpartum depression. We divided participants into four groups according to a self-reported questionnaire assessing NVP (No NVP, Mild NVP, Moderate NVP, and Severe NVP). MIB disorder was defined as a MIBS-J score ≥ 5. Logistic analysis was performed to evaluate the effect of NVP on MIB disorder at one year after delivery. A mediation analysis was conducted to examine whether postpartum depression mediated the association between NVP and MIBS-J scores. RESULTS: The logistic regression analysis results revealed reduced risks of MIB disorder among mothers with Moderate NVP (adjusted OR 0.93; 95% confidence interval, 0.86-0.99) and Severe NVP (adjusted OR 0.81; 95% confidence interval, 0.74-0.89), compared to those with No NVP. The mediation analysis revealed that NVP positively correlated with MIBS-J score in the indirect effect via postpartum depression, while NVP (Mild NVP, Moderate NVP, and Severe NVP) negatively correlated with MIBS-J score in the direct effect. CONCLUSION: The risks of MIB disorder were reduced in the Moderate NVP and Severe NVP mothers, although NVP inhibited the development of MIB via postpartum depression. The development of effective interventions for postpartum depression is important to improve MIB among mothers with NVP.

Vitamin D Receptor Mediates Attenuating Effect of Lithocholic Acid on Dextran Sulfate Sodium Induced Colitis in Mice.

Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.

[Elderly Advanced Breast Cancer Effectively Treated with Locoregional Therapy-A Case Report].

We report a case of advanced breast cancer in an elderly patient effectively treated with locoregional therapy. The patient was an 81-year-old woman who presented with an increasing right breast lump. The tumor was 55 mm in diameter, accompanied by fixation to pectoral muscle. A core needle biopsy for right breast tumor led to a diagnosis of mucinous carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), negative for HER2/neu. The Ki-67 positive cell index was 10%. A bone scintigraphy revealed multiple bone metastases, so, we confirmed the diagnosis as T4cN2aM1, Stage Ⅳ. She initiated endocrine therapy by letrozole. By changing the endocrine therapy to toremifene followed by fulvestrant, the therapy achieved a partial response. However, the size of the primary tumor increased accompanied by bleeding, and surgical resection of the right breast was performed for local control. The locoregional surgery was effective, improving the patient's quality of life. She was administered lapatinib as anti-HER2 therapy in addition to the endocrine therapy. Two years and 6 months after surgery, there has been no worsening of bone metastasis or appearance of visceral metastasis.

[Permissibility of Stoma Closure Surgery in Patients with Colorectal Cancer Who Underwent Primary Tumor Resection Including in Cancer-Bearing Conditions].

From 2006 to 2021, 27 patients who underwent stoma construction during colorectal cancer resection followed by stoma closure were grouped into 2 groups: Group A(7 patients with cancer)and Group B(20 patients without cancer). The male- to-female ratio were 6:1 for Group A and 13:7 for Group B. The average ages were 63.7 and 65.0 years, respectively. The ratios(Group A:Group B)of the causes for stoma construction were 5:13 for bowel obstruction due to colorectal cancer, 2:2 for abdominal wall invasion/dissemination and 0:5 for covering stoma. The causes of non-curative resection for Group A were peritoneal dissemination(4 patients), liver metastasis(1 patient), bladder infiltration(1 patient), and periaortic lymph node metastasis(1 patient). For Groups A and B, Hartmann surgery was performed in 4 and 10, colectomy and stoma construction in 3 and 5, and low anterior resection and covering stoma in 0 and 5 patients, respectively. The median time to stoma closure was 10 months for Group A and 6 months for Group B(p<0.05). There was no case of anastomotic leakage and 1 case of anastomotic stenosis(case not treated with anticancer drugs). No patient died of cancer within 1 year after stoma closure(median survival time after stoma closure was >26.0 months for Group A). Although stoma closure in patients with cancer was significantly delayed compared with patients without cancer, it was performed safely.

[Recurrent Breast Cancer with Bone Metastasis Effectively Treated with Abemaciclib plus Endocrine Therapy-A Case Report].

We report a case of recurrent breast cancer with bone metastasis in a premenopausal woman. A 46-year-old woman underwent mastectomy for right breast cancer 6 years ago. Histopathological diagnosis was invasive ductal carcinoma, T2N3aM0, stage ⅢC. She received adjuvant chemotherapy and irradiation followed by tamoxifen. Four and a half years after surgery, serum tumor marker levels elevated, and bone metastasis in the sacral region was revealed by PET-CT scan. After suppressing ovarian function with LH-RH agonist, we switched the endocrine therapy from tamoxifen to letrozole with a CDK4/6 inhibitor. Five months after starting administration of abemaciclib, the bone metastasis disappeared on PET-CT. The elevated tumor markers normalized and have continued to decrease. Abemaciclib combined with endocrine therapy was significantly effective as first-line treatment for premenopausal women with metastatic breast cancer.

Effect of Neonicotinoid Pesticides on Japanese Water Systems: Review with Focus on Reproductive Toxicity.

Neonicotinoid pesticides (NPs) are neurotoxic substances. They are highly effective as insecticides owing to their water solubility, permeability, and long-lasting activity. These molecules are structurally similar to nicotine and act as nicotinic acetylcholine receptor agonists. The administration of NPs to experimental animals reportedly causes neuromuscular and reproductive disorders. Moreover, recently reported problems caused by NPs include damage to land-dwelling creatures (such as mammals and birds), hydrobiology, and ecosystems. This review summarizes the recent reports on NP concentrations detected in river systems in several Japanese regions. These values were lower than the environmental standard values; however, seasonal variations were observed. Furthermore, reports on NP-induced testicular and ovarian toxicity were examined, revealing that the mechanism of injury is mainly driven by oxidative stress. The use of NPs is declining worldwide, except in Japan; therefore, continuous monitoring remains necessary.

Neurological development in 36-month-old children conceived via assisted reproductive technology: The Japan Environment and Children's Study.

Purpose: This study aimed to investigate neurodevelopment in children conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with several types of embryo transfers. Methods: We analyzed data for 77 928 children and their mothers included in a Japanese birth cohort study. Among the included children, 4071 were conceived via IVF, while 1542 were conceived via ICSI. Neurodevelopmental delay at the age of 3 years was assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition. Results: In the crude model, the odds ratios for developmental delay in 1-4 domains were higher among children conceived via IVF, ICSI, and non-ART (ovulatory induction or intrauterine insemination) than in spontaneously conceived children. After adjusting for parental background factors and the child's sex, there were no differences in the risk of developmental delay when comparing singletons conceived by IVF, ICSI, or non-ART and those conceived spontaneously. Higher odds ratios for developmental delay in one domain were observed in singleton girls conceived via IVF when compared with those who were spontaneously conceived. Conclusion: Most cases of developmental delay may be associated with multiple pregnancies and factors related to infertility, such as parental age, irrespective of the use of ART.

[Clinicopathological Examination of Resected Case of Primary Duodenal Cancer at Our Hospital].

Primary duodenal cancer is a rare disease. We examined 8 resected cases of duodenal cancer at our hospital from June 2003 to February 2022. Patients with resected duodenal cancer had an average age of 69.3 years(45-84 years), with a male-female ratio of 3 : 5. Of the 8 cases, 6 cases were adenocarcinomas and 2 were neuroendocrine carcinomas. Among those with adenocarcinomas, 3 cases were Stage Ⅰ, while Stage ⅡA, ⅢA, and ⅢB accounted for one case each(UICC 8th edition). Five patients underwent a pancreaticoduodenectomy(PD), while 1 underwent partial duodenal resection. Except for 1 case of Stage ⅢB(death from tumor recurrence in 1 year), tumor recurrence was not observed in the 5 remaining cases(survival period; >1 month to >97 months). The patient with a pT3pN1M0, Stage Ⅲ neuroendocrine carcinoma underwent a partial duodenal resection due to poor cardiac and renal function. Meanwhile, the patient with a pT4pN0M0, Stage Ⅲ neuroendocrine carcinoma underwent a PD. The survival time was 123 months for the former(death from other diseases, no tumor recurrence)and 7 months for the latter(death from recurrence).

[A 10-Year Survivor with Multidisciplinary Treatment for Pancreatic Carcinoma That Recurred 17 Months after Pancreatoduodenectomy].

Postoperative recurrence of invasive pancreatic ductal carcinoma(PC)has a poor prognosis. We experienced a case of PC that relapsed 17 months after pancreaticoduodenectomy(PD)and survived for more than 10 years after PD. A 51-year-old man underwent PD in December 2011(pT3pN1bM0, pStage Ⅱb). Gemcitabine(GEM)16 cycles were performed as postoperative adjuvant chemotherapy, and a 1 cm nodule was found in the liver on abdominal CT scan, and partial liver resection was performed. After that, adjuvant chemotherapy with S-1 was performed for 12 months. Abdominal CT scan revealed abdominal lymph node metastasis, and radiation therapy(39.6 Gy)was requested from another hospital. Then, the combination therapy of 5-FU/l-LV plus L-OHP(or CPT-11)was started in September 2014. To date, a total of 131 cycles of chemotherapy have been given. 10 years and 5 months after pancreaticoduodenectomy and 9 years after hepatectomy, although recurrence around the superior mesenteric artery plexus was observed, outpatient visits are continued.

[Function of the Puborectalis Muscle in Patients with or without Fecal Incontinence Three Years after Low Anterior Resection for Lower Rectal Cancer].

To clarify the function of the puborectalis muscle(PM)in fecal incontinence(FI)prevention after low anterior resection (LAR)for lower rectal cancer(LRC), PM function at 3 years after LAR was studied. A total of 29 patients aged 40-79 years (19 men and 10 women, mean age: 63.9 years)who underwent LAR for LRC were enrolled in the present study. Based on the presence of postoperative FI, these patients were divided into 2 groups[group A: patients with FI(n=13), 11 men and 2 women aged 43-75 years(mean age: 64.8 years)and group B: patients without FI(continence, n=16), 8 men and 8 women aged 41-79 years(mean age: 62.9 years)]. These groups were compared with group C of control subjects[n=38; 28 men and 10 women aged 42-76 years(mean age: 64.5 years)]. Magnetic stimulation at the S2-4 sacral levels has been shown to activate the sacral motor nerve(SMN)root of the cauda equina. SMN latency(SMNL)was determined on the right, left, and posterior sides of the upper anal canal. FI after LAR was also evaluated using the Wexner score(WS), with a score of 8 or more being associated with FI according to our data. All patients had pathological Stage Ⅰ disease(19 patients: T1, N0, M0; 10 patients: T2, N0, M0). Group A had a larger proportion of men than group B(p<0.1). The distance of anastomosis from the anal verge(DAAV)was significantly shorter in group A(2.2±1.2 cm)than in group B(4.6 ±1.3 cm)(p<0.001). Regarding WS of group A, 23.1% patients had a score of 8-10(mean: 9.0), 53.8% of 11-15 (mean: 13.4), and 30.7% of 16-20(mean: 17.0). All patients in group A(WS: 8 or more)were incontinent. In contrast, all patients in groups B(WS: 0)and C(WS: 0)were continent. Patients with preoperative defecation ability(WS: 0)were also continent. As for SMNL on the right(9 o'clock), left(15 o'clock), and posterior(18 o'clock)sides of the PM located in the upper anal canal, conduction delay was significantly longer in group A(8.4±0.6 ms, 8.2±1.9 ms, and 8.3±0.9 ms, respectively)than in groups B(4.4±0.5 ms, 4.3±0.7 ms, and 4.4±0.9 ms, respectively)and C(4.1±0.5 ms, 4.0±0.5 ms, and 4.2±0.7 ms, respectively)(p<0.001, all). FI after LAR with a short DAAV, especially in men, may cause PM dysfunction due to operative damage of the SMN.

[Long-Term Survival of Patient Having Advanced Esophageal Cancer with Cirrhosis after Overcoming Anastomotic Leakage, Purulent Osteomyelitis, Cervical Lymph Node Recurrence, and Systemic Edema-A Surgical Case].

We report the surgical case of advanced esophageal cancer with cirrhosis in a patient who has been cancer-free for 6 years after overcoming anastomotic leakage, purulent osteomyelitis, cervical lymph node recurrence, and systemic edema. A 69-year-old woman visited our hospital and presented with the complaint of a food sticking sensation. Endoscopic findings showed a type 3 tumor in the middle thoracic esophagus. Esophagectomy was subsequently performed. Histopathological findings revealed poorly differentiated squamous cell carcinoma, Mt, 17×15 mm, type 3, pT3, pIM0, pPM0, pDM0, pRM0, pN2(7/18), pStage Ⅲ, and liver cirrhosis(F4, A1-2). Postoperative suture failure was observed; however, it conservatively improved in approximately 2 months. The patient had lower back pain since approximately 6 weeks after the surgery, and she was diagnosed with purulent spondylitis and was administered antibiotics. The patient was subsequently discharged 67 days after the surgery. One course of 5-FU+CDDP was administered as postoperative adjuvant chemotherapy. However, renal function deteriorated, and chemotherapy was discontinued. Four months after the surgery, cervical echography revealed recurrence in the left cervical lymph node, and docetaxel(DTX)was administered. Five DTX doses were administered, because of which the left cervical lymph nodes markedly shrunk. Moreover, the sixth dose of DTX resulted in febrile neutropenia and a large amount of abdominal pleural effusion. Consequently, the patient was hospitalized. Tolvaptan treatment was extremely effective, and the thoracic ascites disappeared. Esophageal cancer has not recurred, and the patient is being observed at an outpatient clinic 6 years after the surgery.

[A Long-Term Recurrence-Free Survivor after Resection for Hepatopulmonary Metastases found within One Year after Rectal Cancer Surgery].

We observed a case of long-term survival without recurrence following hepatectomy and lung resection in a patient with hepatopulmonary metastases, which appeared 7 months after rectal cancer surgery. We report the case of a 68-year-old man whose chief complaint was anal pain. The patient was referred to our hospital because of a suspected rectal cancer. He was diagnosed with rectal cancer without distant metastasis, and abdominoperineal excision was then performed. Histopathological findings revealed Rb, type 2, 85×60 mm, tub 2, ly1, v1, pPM0, pDM0, pRM0, pT3(A), pN0(0/27), cM0, and pStage Ⅱa. Seven months after the surgery, abdominal computed tomography(CT)revealed a 3 cm nodule in segment 7 of the liver. In addition, chest CT detected a 2 mm nodule in segment 3 of the upper lobe of the left lung. Hepatectomy was immediately performed, whereas lung nodules were to be followed up. Three months later, chest CT showed that the lung nodules had increased in size(approximately 5 mm); therefore, the patient was diagnosed with lung metastasis, and thoracoscopic partial lung resection was performed. The histopathological findings of the hepatic tumor and lung tumor were similar to those of rectal cancer. The postoperative course was good, and the patient has been alive without recurrence for 8 years since the final surgery(lung resection)without postoperative adjuvant chemotherapy.

Participant mothers' attitudes toward genetic analysis in a birth cohort study.

To conduct a long-term birth cohort study that includes genetic analysis, it is crucial to understand the attitudes of participants to genetic analysis and then take appropriate approaches for addressing their ambiguous and negative attitudes. This study aimed to explore participants' attitudes toward genetic analysis and associated background factors among mothers who were enrolled in a large Japanese birth cohort. A questionnaire was sent to participants' households, and the responses of 1762 mothers (34.0%) were used for the study. The majority of mothers recognized genetic analysis for themselves and their children and sharing of genetic data as beneficial. A low knowledge level of genomic terminology was associated with ambiguous attitudes toward genetic analysis and data sharing. Education level was positively associated with the recognition of the benefits of genetic analysis. Concern about handling genetic information was associated with the unacceptability of data sharing. Trust was associated with the approval of genetic analysis. Most mothers preferred that genetic analysis results be returned. These findings suggest the need for multiple efforts to maximize participants' acceptance of genetic analysis, such as utilizing an educational approach to encourage familiarity with genetics/genomics, optimizing explanations for different educational levels, and explicitly disclosing the handling policy for genetic information.

Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia.

BACKGROUND: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. METHODS: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. RESULTS: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). CONCLUSIONS: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.

[Hereditary Breast and Ovarian Cancer(HBOC)in a Young Adult-A Case Report].

We report a case of hereditary breast and ovarian cancer(HBOC)in a young adult. A 31-year-old woman consulted at our hospital for a lump on her left breast. Ultrasonography revealed an irregular-shaped mass. A core needle biopsy was performed, and the pathological diagnosis was invasive ductal carcinoma. There were multiple enlarged lymph nodes in the axilla and internal mammary areas but no evidence of metastasis. She underwent mastectomy and axially dissection. The pathological findings from the surgically resected specimens showed scirrhous carcinoma positive for ER and PgR and negative for HER2/neu protein expression. The tumor size was 16 mm, and 3 axillary lymph node metastases were seen. We identified the pathological stage as T1cN3bM0, stage ⅢC. She received chemotherapy, radiotherapy, and endocrine therapy after surgery. At present, 1 year after surgery, the patient is alive without recurrence. With a low age of onset and a family history of ovarian cancer, she was diagnosed with HBOC as a result of breast cancer susceptibility gene(BRCA)genetic testing. In addition to the recommended surveillance, prophylactic surgery will be performed in the future.

[Prediction of Prognosis in Breast Carcinoma Using Klotho Immunohistochemistry].

Klotho is one of the known anti-aging genes, and functions as an inhibitor of the insulin-like growth factor 1(IGF-1) pathway. However, the clinical significance of Klotho expression in cancer tissues have not been elucidated yet. In this study, we aimed to investigate the clinical significance of Klotho expression in breast cancer patients. We evaluated Klotho expression through immunohistochemical analysis and evaluating Ki-67 positive cell index in 142 patients who underwent surgery for breast cancer in our hospital. There was no significant correlation between age, menopausal state, historical type, hormone status, HER2 status, and distant metastases. High expression of Klotho was observed in the non-invasive compared to the invasive ductal carcinomas. The number of metastatic lymph nodes, clinical stage, and tumor size were correlated to Klotho expression level in the cancer tissues. The Klotho positive group exhibited low score for Ki-67 positive cell index than the Klotho negative group. No significant correlation in cumulative survival rates between Klotho positive and Klotho negative groups was observed. The Klotho negative group exhibited good prognosis than the Klotho positive group for the disease- free survival after the operation. These results suggest that the analysis Klotho expression in the breast cancer tissues using immunohistochemistry is a useful tool to assess the disease-free survival for breast cancer patients.

[Relationships Gastric Stasis in the Remnant Stomach and Interdigestive Migrating Motor Complex in Patients after Pylorus-Preserving Gastrectomy for Early Gastric Cancer].

The demerit of pylorus-preserving gastrectomy(PPG)is the postprandial abdominal fullness(PAF)with gastric stasis in the remnant stomach(GSRS). We investigated the relationship between clinical findings and GSRS, and between GSRS and interdigestive migrating motor complex(IMMC)in PPG patients. A total of 30 patients(17 men and 13 women, mean age of 62.3 years)after PPG for early gastric cancer(Billroth Ⅰ)were divided into 2 groups(group A; 18 patients with GSRS, group B; 12 patients without GSRS). The relationship between GSRS including clinical findings and IMMC was studied from 1.5 to 3 years after operation. A catheter equipped with a micro-tip force transducer was inserted transnassally into the remnant stomach and duodenum in a supine position, and the IMMC was studied. All patients were Stage ⅠA(mucosal cancer, no lymph node metastasis, no distant metastasis). The remnant stomach was 1/3 compared with stomach size before operation. The length of the antral cuff in group A(1.5±0.2 cm)was significantly shorter than group B(3.2±0.3 cm)(p =0.0004). Appetite was significantly recognized in group B compared with group A(p=0.0067). PAF was significantly recognized in group A compared with group B(p=0.0001). Reflux esophagitis was found in group A more than group B. Early dumping syndroms did not found significant differences in both groups. In endoscopic esophagogastric finding of the remnant stomch, gastritis with GSRS was significantly found in group A compared with group B(p=0.0001). The IMMC was significantly recognized in group B compared with group A(p<0.0001). The occurrence of the PAF due to the GSRS may be caused by abscens of the IMMC.