Nut consumption during pregnancy is associated with decreased risk of peer problems in 5-year-old Japanese children.

OBJECTIVES: Nuts are nutrient-dense foods rich in unsaturated fatty acids, protein, dietary fiber, vitamins, and minerals. The present prebirth cohort study examined the association between maternal nut intake during pregnancy and the risk of childhood behavioral problems in 5-year-old Japanese children. METHODS: Study subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, peer problems, and low prosocial behavior were assessed using the parent-reported version of the Strengths and Difficulties Questionnaire. Adjustments were made for a priori-selected nondietary confounders and potentially related dietary factors. RESULTS: Compared with mothers who had not eaten nuts during pregnancy, mothers who had eaten nuts had a significantly reduced risk of peer problems in children; the adjusted odds ratio was 0.64 (95% confidence interval: 0.42-0.97). There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of childhood emotional problems, conduct problems, hyperactivity problems, and low prosocial behavior. CONCLUSIONS: Maternal consumption of nuts during pregnancy may be associated with a decreased risk of peer problems in 5-year-old children.

Human milk-specific fat components enhance the secretion of ghrelin by MGN3-1 cells.

Triacylglycerols (TAGs) are a major fat component in human milk. Since gastric lipase produces 1,2-diacylglycerol from TAGs, we focused on the bioactivity of human milk-derived diacylglycerols in stomach cells. Ghrelin is produced in the stomach and acts as an important regulator of growth hormone secretion and energy homeostasis. In this study, we showed that 1-oleoyl-2-palmitoylglycerol (OP) increased ghrelin secretion, whereas 1,3-dioleoyl-2-palmitoylglycerol (OPO), a major component of human milk TAGs, did not increase ghrelin secretion in the ghrelin-secreting cell line, MGN3-1. Therefore, diacylglycerol OP may directly contribute to the regulation of ghrelin secretion. We also found that 2-palmitoylglycerol and 1- and 2-oleoylglycerol increased ghrelin secretion. Finally, we demonstrated that intracellular cAMP levels and preproghrelin and ghrelin O-acyl transferase expression levels were enhanced by OP treatment in MGN3-1 cells. This may represent an example of a novel mother-infant interaction mediated by fat components derived from human breast milk.

Absolute quantification of bovine lactadherin to screen the anti-rotavirus activity of dairy ingredients.

The anti-rotavirus components in breast milk and infant formulas play an important role in the prevention of rotavirus infection. The present study examined whether the levels of phospholipids and bovine lactadherin, which are the major components and proteins of the milk fat globule membrane complex, are useful indices of the anti-rotavirus activity of dairy ingredients used in infant formulas. We compared the anti-rotavirus activity of 2 types of dairy ingredients enriched in the milk fat globule membrane complex: high-fat whey protein concentrate (high-fat WPC) and butter milk powder (BMP), using 50% inhibition concentration (IC50) and linear inhibition activity to determine levels of solid contents, total proteins, phospholipids, and bovine lactadherin. Here, we developed a quantification method using full-length isotope-labeled proteins to measure bovine lactadherin levels in these dairy ingredients. The evaluation of anti-rotavirus activity showed that the difference in IC50 was the smallest when the 2 dairy ingredients were compared at the bovine lactadherin level, among other indices in this study. Additionally, no significant difference was observed between the inhibition linearity of 2 dairy ingredients when evaluating only bovine lactadherin levels. These results indicated that the level of bovine lactadherin was more strongly associated with anti-rotavirus activity than the level of phospholipids. Our results suggest that bovine lactadherin levels can be used to estimate the anti-rotavirus activity of dairy ingredients and can be a criterion used in selecting ingredients for infant formulas.

[A Resected Case of Intraperitoneal Foreign Body Granuloma Mimicking Peritoneal Dissemination].

Foreign body granuloma(FBG)is a granuloma that occurs due to chronic inflammation caused by various residual foreign objects. In the field of gastrointestinal surgery, intraperitoneal foreign body granulomas(IPFBGs)are often caused by sutures materials or residual gauzes, but those caused by food residue are extremely rare. We present an IPFBG case of food residue caused by anastomotic leakage, which was difficult to be distinguished from peritoneal dissemination. The patient is a 74- year-old male. Anastomotic leakage occurred following low anterior resection for rectal cancer, peritoneal drainage and ileostomy were performed. 1.5 years after rectal resection, liver metastasis was diagnosed by CT and peritoneal dissemination was diagnosed by PET-CT. Both lesions were resected at the same time. The pathological findings were liver metastasis and FBG. It was presumed to be an FBG formed by food residue left behind after anastomotic leakage. It has reported that FBG caused by residual gauzes were shown a ring-shaped uptake by PET-CT, but that was not observed in our case. In addition, since a nodule suspected of liver metastasis was observed simultaneously, we considered no differential diagnosis other than peritoneal dissemination. IPFBG resembling peritoneal dissemination, occurred after anastomotic leakage. A food residue can cause IPFBG, it is necessary to consider IPFBG in decision making treatment strategy for peritoneal nodule.

Characteristics and etiology of infection in febrile infants aged ≤90 days.

BACKGROUND: Infants ≤90 days old can exhibit non-specific signs of infection, even in cases of serious bacterial infection (SBI). METHODS: This prospective study included infants aged ≤90 days hospitalized for fever from June 2017 to August 2019. Nasopharyngeal swabs were tested using multiplex real-time polymerase chain reaction (PCR) tests and 16S ribosomal RNA analysis of whole blood to determine causative microorganisms. Data pertaining to inflammatory markers, maximum body temperature (BT), and respiratory symptoms of infants and their cohabiting families were collected at admission. RESULTS: A total of 110 infants were enrolled (age range, 9-90 days), 17 (15.5%) of whom presented with SBIs. White blood cell (WBC) count and absolute neutrophil count (ANC) were significantly higher in patients with SBIs than in those without, although maximum BT did not significantly differ between the SBI and non-SBI groups (n = 93). One or more viruses were detected in 82 infants (74.5%). Viruses were detected more frequently in infants with respiratory symptoms than in those without respiratory symptoms (P = 0.038), and patients with SBIs experienced significantly less respiratory symptoms than those without SBIs (P = 0.049). Moreover, viruses were more often detected in infants from cohabiting families with respiratory symptoms than in those whose family members did not exhibit respiratory symptoms (P = 0.0018). CONCLUSION: White blood cell count, and ANC were significantly higher, and respiratory symptoms were less in infants ≤90 days old with SBIs than in those without SBIs. Microorganisms from nasopharyngeal by multiplex real-time PCR swabs could not be judged as SBI or non-SBI.

Highest concentration of breast-milk-derived exosomes in colostrum.

BACKGROUND: Exosomes are nanosized extracellular vesicles, that play important roles in intercellular immune regulation. They have potential therapeutic utility for neonatal diseases including necrotizing enterocolitis. Breast-milk-derived exosomes have recently shown beneficial effects on intestinal damage in vitro and in vivo. However, the chronological change in breast-milk-derived exosome concentrations after delivery are unclear. METHODS: In this prospective study, we enrolled 17 mothers who delivered premature infants admitted to a neonatal intensive care unit in Japan. We measured the consecutive concentrations of breast-milk-derived exosomes in the mothers for 48 weeks after delivery. RESULTS: The median concentration of breast-milk-derived exosomes was 1.62 × 108 particles/ml in colostrum, showing a significant decrease after 2 weeks (P < 0.01). There was no association between the exosome concentration in colostrum and maternal perinatal factors including parity, mode of delivery, maternal age, and gestational age at delivery. CONCLUSIONS: We concluded that breast-milk-derived exosomes were the richest in colostrum. Our basic data regarding breast-milk-derived exosomes are expected to aid in the clinical application of exosomes for treating neonatal diseases.

[A Strategy of Treatment for Perforated Gastric Cancer].

In past reports, the incidence of gastric perforation accounts for 0.08 to 3.6% of all gastric cancers, and the proportion of perforated gastric cancer(PGC)in gastric perforations is 26 to 32%. In the treatment of PGC, critical care for peritonitis, diagnosis of gastric cancer and curability for gastric cancer are required simultaneously, so it is not easy to decide the treatment strategies. Therefore, for the purpose to consider treatment strategies for PGC, we conducted a clinicopathological study on PGC in our hospital for the past 12 years. There were 22 cases of PGC, and we analyzed clinicopathologically 19 cases excluding perforation during endoscopic resection and perforation during chemotherapy. The R0 surgery group tended to have a good prognosis even in PGC cases, and there was surgery-related death in the one-stage gastrectomy group. So it was considered desirable to perform radical surgery after the general condition was stable by the treatment of peritonitis was given priority in the PGC.

Calcium intake during pregnancy is associated with decreased risk of emotional and hyperactivity problems in five-year-old Japanese children.

Background: Recently, more attention has been paid to behavioral problems in children. However, for the most part, risk factors for these problems have yet to be determined.Objective: The current prebirth cohort study investigated the relationship between maternal calcium consumption during pregnancy and behavioral problems in five-year-old Japanese children.Methods: Subjects were 1199 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Strengths and Difficulties Questionnaire. Logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Results: Compared with the lowest quartile of maternal calcium intake, the highest was significantly associated with decreased risk of childhood emotional problems: the adjusted OR (95% CIs) was 0.46 (0.27-0.79, P for trend = 0.01). Higher maternal calcium intake during pregnancy was also independently associated with decreased risk of childhood hyperactivity problems; the adjusted ORs (95% CIs) in the first, second, third, and fourth quartiles of maternal calcium intake during pregnancy were 1 (reference), 0.52 (0.31-0.84), 0.58 (0.35-0.93), and 0.60 (0.37-0.97), respectively (P for trend = 0.046). No such inverse associations were observed for childhood conduct problems or peer problems; the adjusted ORs (95% CIs) in the highest quartile of maternal calcium intake were 0.97 (0.64-1.47) for conduct problems and 1.11 (0.61-2.01) for peer problems.Conclusions: Maternal calcium intake during pregnancy may decrease the risk of childhood emotional and hyperactivity problems.

Recent acute reduction in macrolide-resistant Mycoplasma pneumoniae infections among Japanese children.

INTRODUCTION: Mycoplasma pneumoniae contributes to numerous pneumonia cases among children and young adults. Therefore, this study aimed to investigate the prevalence of M. pneumoniae infections among Japanese children, occurring since 2008. METHODS: Nasopharyngeal swab specimens were obtained from all cases, following which real-time PCR was performed to identify M. pneumoniae. Further, the p1 genotypes of isolates were determined using the PCR restriction fragment length polymorphism typing method. RESULTS: The annual rate of macrolide-resistant M. pneumoniae (MRMP) infections peaked at 81.8% in 2012 and decreased annually until 2015. Although the infection rate increased to 65.3% in 2016, it decreased again to 14.3% in 2018. Although >90% of isolates harbored the type 1 genotype until 2012, this rate decreased, and approximately 80% harbored p1 genotypes other than type 1 in 2018. Furthermore, the occurrence rate of MRMP among the type 1 isolates was very high (82.4%), whereas that among p1 genotypes other than type 1 was very low (6.5%). CONCLUSIONS: MRMP occurrence potentially decreased owing to changes in not only antibiotic usage but also in the distribution of p1 genotype among isolates.

[Clinicopathological Examination of 81 Cases Added Gastrectomy for Early Gastric Cancer after ESD].

As a general rule, our department has performed additional gastrectomy with lymph node dissection(radical surgery: RS) for non-curative endoscopic submucosal dissection(ESD)cases. This time, we performed a clinicopathological study on 81 patients who underwent RS after ESD for 10 years from May 2009 to April 2019. Lymph node metastasis(LNM)was observed in 5 cases and local cancer residue(LCR)was observed in 8 cases. Examination of the presence or absence of LNM and LCR by clinicopathological factors(histopathological type, tumor size, lymphatic invasion[ly], venous invasion[v], horizontal margin[HM], vertical margin[VM], submucosal invasion, ulceration[scar])revealed no significant risk factor for LNM, however, tumor size and HM were significant risk factors for LCR. The relationship between the eCura system and the case rate associated with LNM in our hospital was similar to that in the original report. Regarding the prognosis, there was one local recurrence and no death from the primary disease.

Expression and characterization of l-arabinose isomerase from Geobacillus stearothermophilus for improved activity under acidic condition.

A low-calorie sugar-substituting sweetener, d-tagatose, can be produced by l-arabinose isomerase (l-AI) from the substrate d-galactose. However, this process suffers from a Maillard reaction when performed at alkaline pH and high temperature. For industrial applications, therefore, a reaction under slightly acidic conditions is desirable to minimize the Maillard reaction. Previously, we obtained a mutant of l-AI, H18T, from Geobacillus stearothermophilus with greater substrate specificity. Although H18T possessed excellent thermostability, its activity under acidic conditions was not optimal. Here, we successfully obtained a potential variant of the H18T protein, H18T-Y234C, which achieved improved activity at pH 6.0, based on random mutagenesis using error-prone PCR around the binding pocket area of H18T. This double H18T-Y234C mutant possessed 1.8-fold and 3-fold higher activity at pH 6.0 than the parent H18T and the wild type, thereby broadening the optimal pH range to 6.0-8.0. Mutation from Tyr to Cys at residue 234 had little effect on the secondary structure of L-AI. Furthermore, the formation of disulfide bonds was not detected. Thus, the improvement of activity at pH 6.0 is probably caused by the change in the binding pocket area involving residue 234. This study offers insight into the importance of residue 234 in improving the activity under acidic conditions.

Growth of term infants fed a commercial infant formula with a protein content of 2.2 g/100 kcal: an observational follow-up study.

To evaluate the suitability of the new nutritional composition of renewed commercial Formula A (protein reduced to 2.2 g/100 kcal, arachidonic acid increased to 13.2 mg/100 kcal, and docosahexaenoic acid maintained at 20 mg/100 kcal), we examined whether the growth of Formula A-fed infants was equivalent to that of breastfed infants. In this observational study, 1,053 infants were followed-up to 12 months. Growth, stool consistency, and the health condition of 99 infants fed with Formula A and 295 breastfed infants were compared. Body weight, body mass index, and head circumference of Formula A-fed infants were similar to those of breastfed infants. Additionally, there were no differences in the stool consistency and the health condition (infection and allergy prevalence) between the two groups. Formula A-fed infants grew as well as breastfed infants, suggesting the appropriate nutritional composition of Formula A. The findings may contribute to further improvements in infant formulas.

Daily protein and energy intakes of infants fed a commercial infant formula with a reduced protein concentration of 2.2 g/100 kcal: an impact of feeding interval on energy intake.

We evaluated the protein and energy intakes of infants fed commercial infant Formula A (protein, 2.2 g/100 kcal; energy, 68 kcal/100 mL) and examined whether changes in feeding intervals are involved in constant energy intake. Daily nutritional intake of 378 Formula A-fed infants was assessed using reference values and compared to that of infants fed Formulas B (protein: 2.3 g/100 kcal, energy: 68 kcal/100 mL) and C (protein: 2.4 g/100kcal, energy: 70 kcal/100 mL). From 15 to 149 days of age, the mean formula volume and protein intake were 758-887 mL/day and 11.4-13.3 g/day, respectively, higher than the protein intake of breast-fed infants. Daily energy intake (86-129 kcal/kg/day) was comparable to the estimated energy requirements. Feeding intervals were shorter in infants fed Formulas A and B than in those fed Formula C, whereas energy intake was similar. The protein intake of infants decreased as the protein concentration per energy in infant formula was reduced, and accordingly the protein intake of Formula A-fed infants was significantly lower than that of Formula C-fed infants. In conclusion, the new composition of Formula A is suitable in protein and energy intake of infants, and daily energy intake remains constant by shortening in feeding intervals when the energy concentration in infant formula is reduced.Clinical Trial Registration: UMIN000023110.

Low prevalence of Chlamydia pneumoniae infections during the Mycoplasma pneumoniae epidemic season: Results of nationwide surveillance in Japan.

OBJECTIVE: Chlamydia pneumoniae and Mycoplasma pneumoniae are both common causes of atypical pneumonia. We conducted an annual national survey of Japanese children to screen them for C. pneumoniae infections during the M. pneumoniae epidemic season. METHODS: Nasopharyngeal swab specimens were collected from children aged 0-15 years with suspected acute lower respiratory tract infection due to atypical pathogens, at 85 medical facilities in Japan from June 2008 to March 2018. Specimens were tested for infection using real-time polymerase chain reaction assays. RESULTS: Of 5002 specimens tested, 1822 (36.5%) were positive for M. pneumoniae alone, 42 (0.8%) were positive for C. pneumoniae alone, and 20 (0.4%) were positive for both organisms. In children with C. pneumoniae infection, the median C. pneumoniae DNA copy number was higher in those with single infections than in those with M. pneumoniae coinfection (p = 0.08); however it did not differ significantly according to whether the children had received antibiotics prior to sample collection (p = 0.34). CONCLUSIONS: The prevalence of C. pneumoniae infection was substantially lower than that of M. pneumoniae infection during the study period. The change in prevalence of C. pneumoniae was not influenced by that of M. pneumoniae. Children with single C. pneumoniae infection are likely to have had C. pneumoniae infection, while those with coinfection are likely to have been C. pneumoniae carriers.

Differential Diagnosis of COVID-19: Importance of Measuring Blood Lymphocytes, Serum Electrolytes, and Olfactory and Taste Functions.

Coronavirus disease 2019 (COVID-19) is associated with various symptoms and changes in hematological and biochemical variables. However, clinical features, which can differentiate COVID-19 from non-COVID-19, are not clear. We therefore examined the key clinical features of COVID-19 and non-COVID-19 patients. This study included 60 COVID-19 patients and 100 non-COVID-19 patients, diagnosed by PCR, and no significant differences in the age and sex were seen between the two groups. The frequencies of fatigue, loose stool, diarrhea, nasal obstruction, olfactory dysfunction, taste dysfunction, underlying hyperlipidemia, and the prescription of angiotensin II receptor blocker (ARB) were significantly higher in COVID-19 patients than those in non-COVID-19 patients. The counts of leucocytes, neutrophils, lymphocytes, eosinophils, monocytes, and basophils and the levels of chloride and calcium in blood of COVID-19 patients were significantly lower than those of non-COVID-19 patients. The frequencies of atypical lymphocytes and the levels of lactate dehydrogenase (LDH) and potassium were significantly higher in COVID-19 than those in non-COVID-19. The C-reactive protein (CRP) level in COVID-19 patients was significantly lower than that in non-COVID-19 patients, when we compared CRP levels among patients with elevated CRP. This study is the first to indicate that electrolyte levels and the frequency of atypical lymphocytes in COVID-19 are significantly different from those in non-COVID-19. Fatigue, loose stool, diarrhea, nasal obstruction, olfactory dysfunction, and taste dysfunction were the key symptoms of COVID-19. Furthermore, hyperlipidemia and ARB may be risk factors of COVID-19. In conclusion, leucocytes, leucocyte fractions, CRP, LDH, and electrolytes are useful indicators for COVID-19 diagnosis.

[A Case of Primary Gastric Adenocarcinoma with Enteroblastic Differentiation(GAED)].

Gastric adenocarcinoma with enteroblastic differentiation(GAED)is a rare disease that is classified as a special type in the 15th edition Japanese Classification of Gastric Carcinoma. GAED is considered to have a poor prognosis. We report about a 76-year-old man with GAED who presented with complaints of poor appetite and weight loss. He was suspected of having gastric cancer based on ultrasonography and computed tomography findings and was referred to our hospital by his home doctor. Upper gastrointestinal endoscopy revealed a gastric cancer in the lesser curvature of the gastric antrum. Distal gastrectomy was performed. Histopathology showed a moderately differentiated adenocarcinoma with a clear cytoplasm. Immunostaining was positive for Sal-like protein 4(SALL4)and negative for α-fetoprotein(AFP). The patient was diagnosed as having GAED. Vascular and lymphatic invasion were not observed. He was discharged on the 9th day after surgery. At 5 months postoperatively, he was treated with adjuvant chemotherapy, and no recurrence was noted. GAED is a rare disease with a poor prognosis. We report this case and discuss relevant literature.

Comparing Antimicrobial Susceptibilities among Mycoplasma pneumoniae Isolates from Pediatric Patients in Japan between Two Recent Epidemic Periods.

We compared the antimicrobial susceptibility of Mycoplasma pneumoniae isolates from pediatric patients in Japan in 2011-2012 and 2015-2016, when epidemics occurred. The antimicrobial activity of macrolides and tetracyclines against M. pneumoniae infection tended to be restored in 2015-2016. There was no change in the antimicrobial activity of quinolones against M. pneumoniae infection.

[A Case of Early Gastric Cancer with Multiple Lymph Node Metastases Revealed by Additional Surgical Resection after ESD].

A 74-year-old man was referred to our hospital for further investigation of a cystic lesion in the pancreatic body, which had been detected by ultrasonography at a local hospital. He was diagnosed as intraductal papillary mucinous neoplasm(IPMN) and further preoperative examinations were conducted. Upper gastrointestinal endoscopy demonstrated a type 0-II c tumor of the greater curvature in the upper third of the stomach. Endoscopic ultrasonography showed no sign of submucosal invasion. Endoscopic submucosal dissection(ESD)was carried out and pathological examination of a specimen revealed well differentiated adenocarcinoma with submucosal invasion, which fulfilled the indication for additional gastrectomy with lymph node dissection. Laparoscopy-assisted proxymal gastrectomy with D1 plus lymph node dissection and distal pancreatectomy with splenectomy was performed. Pathological examination demonstrated intraductal papillary mucious adenoma(IPMA)in the pancreatic body and no residual gastric cancer in a specimen, however 7lymph node metastases from gastric cancer was confirmed(pN3a), including 3 metastatic lymph nodes incidentally-detected adjacent to the pancreatic parenchyma. We report a rare case of early gastric cancer with N3 lymph node metastases, with a brief literature review.

[The Actual State of Treatment of Gastrointestinal Cancer with Abdominal Aortic Aneurysm in Our Department over the Past Five Years].

With the aging of the population of Japan and Westernization of the dietary life, the number of cases in which cardiovascular diseases are merged in non-cardiac surgery is increasing year by year.Many of the abdominal aortic aneurysms are asymptomatic and it is not uncommon to be discovered accidentally in preoperative examination of non-cardiac surgery.When gastrointestinal surgery involves malignant diseases of the gastrointestinal tract and abdominal aortic aneurysm, the two life prognosis-related diseases are merged, depending on the severity and urgency of the disease for each case, its treatment to determine the priority order.Abdominal aortic aneurysm occurred at the time of malignant disease surgery in 14 cases of gastrointestinal cancer patients who underwent surgery at the department during the 5 years from 2012 to 2016.T he actual condition of treatment for these cases was investigated.

[Cases of Oncologic Emergency Associated with Colorectal Cancer].

The clinical condition of oncologic emergency associated with colorectal cancer includes hemorrhage, perforation and obstruction. Obstructive colorectal cancer is an oncologic emergency commonly observed in our daily clinical practice. Colonic stent placement for obstructive colorectal cancer is relatively easy and safe and may be considered as an effective treatment method that enables favorable intestinal decompression preoperatively and one-stage resection. Colonic stent use can be a bridge to surgery, enabling shorter duration of hospitalization, and reduced postoperative complications, and colostomy rates, as compared to emergency surgery. From January 2009 to December 2016, this study was designed to evaluate the clinical outcomes of 68 patients who underwent surgery for obstructive colorectal cancer. The patients were divided into 2 groups: 32 cases receiving colonic stent placement(the S group), 36 cases receiving ileus tube and emergency surgery(the NS group). There was no significant difference in terms of morbidity or survival rate between the 2 groups. For the S group, 31 out of 32 could one-stage resection(94%). The colostomy rate in the S group was significantly lower than that in the NS group(3% vs 33%). In the S group, number of dissected lymph nodes was significantly larger and the duration of postoperative stay was shorter than that in the NS Group.