Preconception vitamin D intake and obstetric outcomes in women using assisted reproductive technology: the Japan Environment and Children's Study.

BACKGROUND: In reproductive medicine, vitamin D (VitD) is of particular interest because its deficiency has been linked to various infertility issues. Thus, preconception care, including appropriate VitD supplementation, is essential, especially in women using assisted reproductive technology (ART). Despite the therapeutic benefits of VitD, adverse events due to a high daily intake may influence obstetric outcomes. However, the effects of either low or high preconception VitD intake on obstetric outcomes, including the outcomes in women who used ART, remain unclear. Therefore, the aim of this study was to examine the association between pre-pregnancy daily VitD intake and obstetric outcomes in Japanese women, including those who conceived through ART. METHODS: Data were obtained from the Japan Environment and Children's study database comprising 92,571 women recruited between January 2011 and March 2014 in Japan. Participants were categorized into five quintiles according to pre-pregnancy VitD intake (Q1 and Q5 had the lowest and highest VitD intake, respectively) and stratified according to the use of ART. Multiple logistic regression was performed to identify the effects of pre-pregnancy VitD intake on preterm birth (PTB), low-birth weight infant (LBW), and small for gestational age (SGA). RESULTS: Using Q3 (middle VitD intake) as a reference, our analysis revealed that Q5 (highest VitD intake) showed an increased risk of LBW < 1500 g (adjusted odds ratio [aOR]: 1.09, 95% confidence interval [CI]: 1.00-1.18) and SGA (aOR: 1.26, 95% CI: 1.14-1.39) among women who conceived without ART. Among women who conceived with ART, we found that Q5 (highest VitD intake) showed an increased risk of PTB at < 37 weeks (aOR: 2.05, 95% CI: 1.27-3.31). CONCLUSION: The present study revealed that higher VitD intake before pregnancy may affect perinatal outcomes, particularly in women using ART. Our findings may facilitate personalized preconceptional counseling regarding VitD intake based on the method of conception, especially among women using ART.

Effective sound therapy using a hearing aid and educational counseling in patients with chronic tinnitus.

OBJECTIVE: This study aimed to assess the effectiveness of our sound therapy with appropriate hearing aid fitting and periodic hearing aid adjustment in patients with chronic tinnitus. METHODS: We conducted a retrospective study. The study included 490 individuals who received treatment with hearing aids for chronic tinnitus at least for 3 months. To determine the effects of tinnitus on patients' quality of life, the participants completed a series of questionnaires, including the Tinnitus Handicap Inventory (THI), Visual Analogue Scale (VAS) for loudness and annoyance, and questionnaires of subjective symptom improvement. Data were collected at entry and 3 months and 1 year after treatment initiation. RESULTS: All 490 participants completed the questionnaires at 3 months; however, only 312 completed them at 1 year. The mean ± standard deviation THI score before treatment decreased significantly at 3 months (490 participants: 53 ± 25 to 11 ± 16 and 312 participants: 55 ± 24 to 12 ± 16) and 1 year (55 ± 24 to 9 ± 14) (P < 0.01). The mean VAS score for tinnitus loudness before treatment decreased significantly at 3 months (490 participants: 70 ± 22 to 25 ± 27 and 312 participants: 71 ± 22 to 27 ± 26) and 1 year (71 ± 22 to 21 ± 28) (P < 0.01). In addition, the mean VAS score for tinnitus annoyance before treatment decreased significantly at 3 months (490 participants: 75 ± 26 to 20 ± 26 and 312 participants: 75 ± 25 to 23 ± 27) and 1 year (75 ± 25 to 17 ± 26) (P < 0.01). Approximately 80% of patients noticed improvements in their tinnitus annoyance and loudness, as determined by their responses to the questionnaires of subjective symptom improvement. CONCLUSION: The results of this study suggest that treatment with sound therapy may ameliorate the symptoms of chronic tinnitus associated with hearing loss.

Effect of immunonutrition on infectious complications in low skeletal muscle mass patients after pancreaticoduodenectomy.

BACKGROUND & AIMS: Sarcopenia is considered a risk factor of postoperative complications among patients undergoing abdominal surgery. However, few studies have demonstrated an effective strategy for reducing complications in sarcopenic patients. This study aimed to examine retrospectively the effect of preoperative immunonutrition on postoperative complications, especially infectious complications, in low skeletal muscle mass patients undergoing pancreaticoduodenectomy (PD). METHODS: This was a retrospective, consecutive cohort study conducted in our institution. Skeletal muscle mass was assessed using preoperative computed tomography images in 298 consecutive patients who underwent PD between May 2009 and May 2016. Cross-sectional areas at the third lumbar vertebrae normalized for stature (cm2/m2) were defined as the skeletal muscle mass index (SMI). Low SMI was defined as the lowest sex-specific quartile of SMI. Risk factors for postoperative infectious complications and the effect of preoperative immunonutrition on low SMI patients who underwent PD were evaluated. RESULTS: Results of multivariate analysis showed that the presence of low SMI and absence of preoperative immunonutrition were independent risk factors for postoperative infectious complications after PD (odds ratio [OR], 3.17 and 3.10, respectively; P < 0.001). In high SMI patients, the rate of postoperative infectious complications was significantly lower in those who received immunonutrition than in those who did not receive immunonutrition (31.9 vs. 46.1%, respectively; OR, 1.82; P = 0.045). Further, similar findings were exhibited in low SMI patients (26.3 vs. 83.6%, respectively; OR, 14.31; P < 0.001), even though OR was markedly higher in low vs. high SMI patients. CONCLUSION: There is a stronger association with reduced infectious complications in patients who have low SMI and receive immunonutrition (UMIN-CTR Identifier: UMIN000035775.).

A survey of hypercalciuria during chemotherapy in acute lymphoblastic leukemia.

BACKGROUND: Urolithiasis is an extremely rare complication in childhood acute lymphoblastic leukemia (ALL), and some reports have implicated corticosteroids during chemotherapy as a risk factor for it. However, only a few reports have analyzed urinary electrolytes in this context. METHODS: We retrospectively analyzed 55 patients with ALL who underwent chemotherapy between October 2007 and January 2019. Their median age was 9.3 years (range, 0.3-24.0 years) with 30 males and 25 females. Lineages were B-cell precursor ALL (BCP-ALL) in 42 patients, T-cell in nine and others in four patients. All patients received chemotherapy based on the Berlin-Frankfurt-Münster regimen. RESULTS: Forty-nine out of the 55 ALL patients exhibited hypercalciuria at least once during chemotherapy. Moreover, 36 patients with BCP-ALL, who were receiving identical Berlin-Frankfurt-Münster-based regimens, exhibited significantly high urinary calcium excretion immediately following high-dose glucocorticoid administration. Among the 55 ALL patients, urolithiasis was observed in one patient, a 6-year-old boy with BCP-ALL who developed urolithiasis at reinduction chemotherapy just after cessation of high-dose dexamethasone administration. CONCLUSIONS: Nearly 90% of the ALL patients studied developed hypercalciuria during chemotherapy in strong association with corticosteroid administration.

Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: A randomized, controlled trial.

BACKGROUND: We have reported that perioperative and preoperative immunonutrition reduced infectious complications in patients undergoing pancreaticoduodenectomy; however, it is unclear whether perioperative immunonutrition has additional effects compared with preoperative immunonutrition. The present study evaluated whether perioperative, compared with preoperative, immunonutrition has additional effects on cell-mediated immunity and the infection rate after pancreaticoduodenectomy. MATERIALS AND METHODS: This was a prospective, randomized clinical trial conducted in our institution. Oral supplementation enriched with arginine, ω-3 fatty acids, and dietary nucleotides was given by enteral infusion to 30 patients before and after surgery (perioperative group); 30 patients received the same enriched formula before surgery and standard enteral nutrition following surgery (preoperative group). The primary endpoint was concanavalin (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation on postoperative day (POD) 7, which is an index of cell-mediated immunity; the secondary endpoint was the postoperative infection rate. RESULTS: There were no significant differences in Con A- or PHA-stimulated lymphocyte proliferation on POD 7 between the groups. There was no significant difference in the postoperative infection rate between the two groups. In the post hoc subgroup analysis, with respect to the effect on the infection rate, a significant interaction was found only between a long operative time and perioperative immunonutrition. CONCLUSIONS: There were no additional effects of perioperative, compared with preoperative, immunonutrition on postoperative immunity and infectious complications in patients undergoing pancreaticoduodenectomy.

Study Protocol for the Effects of Formula Diet with Dapagliflozin on Metabolic Improvement and Body Composition in Type 2 Diabetes Mellitus.

INTRODUCTION: Sodium-dependent glucose transporter-2 (SGLT2) inhibitors such as dapagliflozin induce weight loss, but the mechanism is thought to involve loss of both body fat and skeletal muscle mass. The decrease in skeletal muscle mass may lead to worsening of insulin resistance in type 2 diabetes patients. On the other hand, formula diet (FD) is a low-calorie food containing low carbohydrates, low fat, and sufficient protein, vitamins, and minerals to support a healthy and balanced diet, and is used for the treatment of obesity or diabetes. Therefore, we examine whether the protein supplementation is superior to the fat supplementation in metabolic improvement of the poorly controlled type 2 diabetes patients treated with SGLT2 inhibitor. We compare the therapeutic effects using two types of FD; a high protein FD and a high fat FD. Patients are prescribed dapagliflozin and replacement of one of three meals with FD. We compare high protein FD and high fat FD with respect to improvement of glycemic control while maintaining skeletal muscle mass. METHODS: We conduct a prospective, multicenter, double-blinded, randomized, controlled, investigator-initiated clinical trial. Patients who satisfy the eligibility criteria will be randomized to two groups (1:1) and prescribed 5 mg of dapagliflozin once daily together with a high protein FD or high fat FD (same number of calories) to replace one of three meals a day (one meal with FD only and two normal meals). The observation period for both groups is 24 weeks. The primary endpoint is the change in HbA1c. PLANNED OUTCOMES: This study is ongoing and scheduled to complete in June 2019. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) 000024580. FUNDING: This study was carried out under contract with the specified nonprofit corporation Hokkaido Institute of Health Sciences, based on a grant from AstraZeneca Co., Ltd. and Ono Pharmaceutical Co., Ltd. for an investigator-initiated clinical trial. The authors funded the journals article processing charges.

Clinical efficacy of piperacillin/tazobactam in the treatment of complicated skin and soft tissue infections.

INTRODUCTION: Complicated skin and soft tissue infections (cSSTIs) are skin and soft tissue infections (SSTIs) that involve deep soft tissue. cSSTIs often require surgical intervention and/or hospitalization. cSSTIs are associated with significant mortality and morbidity, and carry a significant burden on health care systems. Piperacillin/tazobactam has been regarded as a standard treatment for cSSTIs because of its antibiotic spectrum, safety and clinical efficacy. Several antibiotics, as compared to piperacillin/tazobactam, have been evaluated in the treatment of cSSTIs. Areas covered: This review summarizes randomized controlled trials (RCTs) evaluating the clinical efficacy of piperacillin/tazobactam for the treatment of cSSTIs. Expert opinion: Piperacillin/tazobactam, which covers most causative organisms in cSSTIs, is the drug of choice for the treatment of cSSTIs. Other options such as ertapenem and moxifloxacin may be reasonable where multiple daily dosing or intravenous administration is inappropriate. But in general, they should be avoided as an empirical treatment because of their highly association with resistant bacteria, which are becoming a global threat. Therefore, piperacilin/tazobactam is appropriate as an empirical therapy for the treatment of SSTIs and should be de-escalated as soon as causative organisms are identified, their drug-sensitivity results are available, and clinical condition becomes stable.

Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection.

BACKGROUND: Although several studies have reported the effects of immunonutrition on clinical outcomes, detailed mechanisms of immunonutrition after an operation are still unclear. It was recently reported that resolvin E1, a novel lipid mediator generated from eicosapentaenoic acid (EPA), activates factors that reduce inflammation. This randomized clinical trial was designed to investigate not only the effect of immunonutrition on postoperative complications but also the participation of resolvin E1 on anti-inflammatory effects of immunonutrition in patients undergoing major hepatobiliary resection. METHODS: Forty patients who underwent major hepatobiliary resection were divided into 2 groups. Twenty patients received oral supplementation enriched with EPA, arginine, and nucleotides before the operation (group IN). Twenty patients (control group) received no artificial nutrition before the operation (group C). RESULTS: The rate of infectious complications and severity of complications in group IN was significantly lower than in group C (P < .05). Immediately after the operation, plasma resolvin E1 levels were significantly higher in group IN than in group C (P < .05), and plasma interleukin-6 levels were significantly lower in group IN than in group C (P < .05). Preoperative serum EPA levels correlated with plasma resolvin E1 levels immediately after the operation. Plasma resolvin E1 levels correlated with plasma interleukin-6 levels immediately after the operation. CONCLUSION: Preoperative immunonutrition reduced inflammatory responses and protected against the aggravation of postoperative complications in patients undergoing major hepatobiliary resection. Resolvin E1 may play a key role in the resolution of acute inflammation when immunonutrition is supplemented with EPA. (ClinicalTrials.gov Identifier: NCT01256047.).

Preoperative immunonutrition decreases postoperative complications by modulating prostaglandin E2 production and T-cell differentiation in patients undergoing pancreatoduodenectomy.

BACKGROUND: An immune-enhancing diet has been used to alter eicosanoid synthesis, cytokine production, and immune function in an attempt to limit the undesired immune reactions after injury from surgery. This prospective randomized study was designed to investigate the effect of preoperative immunonutrition on operative complications, and the participation of prostaglandin E2 (PGE2) on T-cell differentiation in patients undergoing a severely stressful surgery. METHODS: The enrolled patients who were scheduled to undergo pancreatoduodenectomy were randomized into two groups. Patients in the immunonutrition group (n = 25) received oral supplementation containing arginine, ω-3 fatty acids, and RNA for 5 days before the procedure in addition to a 50% reduction in the amount of regular food. Patients in the control group (n = 25) received no artificial nutrition and were allowed to consume regular food before surgery. All patients received early postoperative enteral infusion of a standard formula intended to provide 25 kcal/kg/day. The primary endpoint was the rate of infectious complications; the secondary endpoint was immune responses. This study is registered with ClinicalTrials.gov (NCT01256034). RESULTS: Infectious complication rate and severity of complications (Clavien-Dindo classification) were lesser in the immunonutrition group than in the control group. mRNA expression levels of T-bet were greater in the immunonutrition group than in the control group (P < .05). Serum eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratios were greater in the immunonutrition group than in the control group (P < .05). The levels of plasma PGE2 were lesser in the immunonutrition group than in the control group (P < .05). CONCLUSION: Preoperative immunonutrition modulates PGE2 production and T-cell differentiation and may protect against the aggravation of operative complications in patients undergoing pancreatoduodenectomy.

Osteosclerosis and inhibition of human hematopoiesis in NOG mice expressing human Delta-like 1 in osteoblasts.

NOD/Shi-scid IL2rγnull (NOG) mice with severe immunodeficiency are excellent recipients to generate "humanized" mice by the transplantation of human CD34(+) hematopoietic stem cells (HSCs). In this study, we developed NOG mice carrying a human Delta-like1 (DLL1) gene, which is a ligand of the Notch receptor and is known to be important in HSC maintenance and self-renewal. We also analyzed the effect of DLL1 signaling on human hematopoiesis and HSC maintenance using humanized DLL1 transgenic NOG mice. To develop DLL1 transgenic NOG (NOG-D1-Tg) mice, a transgenic vector consisting of a human DLL1 complementary DNA fragment placed downstream of the α1(I) collagen (Col1a1) promoter for expression specifically in osteoblasts was constructed. Human CD34(+) HSCs were transplanted into NOG-D1-Tg mice, and differentiation of lymphoid or myeloid lineage cells from human HSCs and maintenance of HSCs in bone marrow were analyzed. Severe osteosclerosis accompanied by increased bone mass and a decreased number of bone marrow cells were observed in NOG-D1-Tg mice. After human HSC transplantation, development of human B lymphocytes, but not T lymphocytes, was significantly suppressed in both bone marrow and the periphery of NOG-D1-Tg mice. Contrary to the initial expectation, retention of human CD34(+) HSCs was inhibited in the bone marrow of NOG-D1-Tg mice. In conclusion, our data suggest that the development of human B lymphocytes and HSC maintenance in osteosclerotic bone may be suppressed by introducing DLL1. These unique humanized mice with sclerotic bone reconstituted by human HSCs are useful models of hematopoiesis in patients with osteosclerosis, such as osteopetrosis, and for investigation of osteogenesis via Notch signaling.

Polyphasic characterization of two microbial consortia with wide dechlorination spectra for chlorophenols.

Two soil-free anaerobic dechlorinating cultures (3-CP and 35-DCP) were enriched from a pentachlorophenol (PCP)-to-phenol dechlorinating soil-dependent culture, using 3-chlorophenol (3-CP) and 3,5-dichlorophenol (3,5-DCP) as specific respective substrates, and characterized polyphasically. Physiological characterization indicated that the 3-CP and 35-DCP cultures had similar features, but with some variations. Both cultures utilized formate or acetate preferably as optimum electron donors for reductive dechlorination, and they shared similar patterns of dechlorination spectra for chlorophenols ranging from mono-CPs to a tetra-CP, with preferred dechlorination pathways in the ortho and meta positions. Alternative electron acceptors such as NO(3)(-) but not SO(4)(2-) inhibited the dechlorination activity in both cultures, while amorphous iron oxides (FeOOH) suppressed dechlorination activity only in the 35-DCP culture. Complete inhibition of dechlorination was observed in both cultures supplemented with chloramphenicol and vancomycin. The addition of 2-bromoethanesulfonate resulted in delayed dechlorination activity in the 35-DCP culture but not in the 3-CP culture; molybdate did not exert any inhibitory effect in either culture. Phylogenetic analysis based on 16S rRNA genes confirmed that the two cultures exhibited similar bacterial species but with varied responsible dechlorinators. Dehalobacter spp. were the likely dechlorinators in the 3-CP culture versus Sulfurospirillum spp. in the 35-DCP culture, with Clostridium and Clostridium-like spp. as candidate dechlorinators in both cultures.

Combined application of alpha-track and fission-track techniques for detection of plutonium particles in environmental samples prior to isotopic measurement using thermo-ionization mass spectrometry.

The fission track technique is a sensitive detection method for particles which contain radio-nuclides like (235)U or (239)Pu. However, when the sample is a mixture of plutonium and uranium, discrimination between uranium particles and plutonium particles is difficult using this technique. In this study, we developed a method for detecting plutonium particles in a sample mixture of plutonium and uranium particles using alpha track and fission track techniques. The specific radioactivity (Bq/g) for alpha decay of plutonium is several orders of magnitude higher than that of uranium, indicating that the formation of the alpha track due to alpha decay of uranium can be disregarded under suitable conditions. While alpha tracks in addition to fission tracks were detected in a plutonium particle, only fission tracks were detected in a uranium particle, thereby making the alpha tracks an indicator for detecting particles containing plutonium. In addition, it was confirmed that there is a linear relationship between the numbers of alpha tracks produced by plutonium particles made of plutonium certified standard material and the ion intensities of the various plutonium isotopes measured by thermo-ionization mass spectrometry. Using this correlation, the accuracy in isotope ratios, signal intensity and measurement errors is presumable from the number of alpha tracks prior to the isotope ratio measurements by thermal ionization mass spectrometry. It is expected that this method will become an effective tool for plutonium particle analysis. The particles used in this study had sizes between 0.3 and 2.0 µm.

Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy.

BACKGROUND: The mechanisms of immunonutrition on reducing infectious complications are still poorly understood. This prospective randomized study was designed to determine whether immunonutrition influences the following factors: cell-mediated immunity, differentiation of T helper type 1 (Th1) and Th2 cells, interleukin (IL)-17-producing CD4(+) helper T (Th17) cell response, and infectious complication rate after pancreaticoduodenectomy. METHODS: Thirty patients who underwent pancreaticoduodenectomy were divided into 3 groups. Ten patients in the perioperative group received immune-enhancing diets enriched with arginine, omega-3 fatty acids, and RNA for 5 days before operative resection, which was prolonged after operative resection by enteral infusion. Ten patients in the postoperative group received early postoperative enteral infusion of the same enriched formula with no artificial nutrition before operative resection. Ten patients in the control group received total parenteral nutrition postoperatively. The primary endpoint was immune responses; the secondary endpoint was the rate of infectious complications. RESULTS: Concanavalin A (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and natural killer cell activity were significantly higher in the perioperative group than in the other groups. Messenger RNA (mRNA) expression levels of T-bet, interferon-gamma (IFN-gamma), related orphan receptor gammat (RORgammat), and interleukin-17F (IL-17F) were significantly higher in the perioperative group than in the other groups. In the perioperative group, the rate of infectious complications was significantly reduced compared with that in the other groups. CONCLUSION: Perioperative immunonutrition reduced stress-induced immunosuppression after a major stressful operative resection. The modulation of Th1/Th2 differentiation and Th17 response may play important roles in this immunologic effect.

Does distal tibiofibular joint mobilization decrease limitation of ankle dorsiflexion?

Limitation of ankle motion is in many cases treated by joint mobilization (JM), a kind of manual physical therapy technique. Until now, the JM approach has mainly focused on the talocrural joint, with less attention to the distal tibiofibular joint. We applied cyclic loading to the lateral malleolus as in JM in order to clarify the relationship between the dorsiflexion angle and the excursion of the lateral malleolus. Seven normal, fresh-frozen cadaver legs were used. To each specimen, cyclic loading with a 30N force was applied 1000 times to the lateral malleolus at a speed of 15N/s. The displacement of the lateral malleolus was measured with a magnetic tracking system. The maximum dorsiflexion angle was measured before and after cyclic loading. After the first 100 and 1000 times of cyclic loading, the tibia was displaced 0.44+/-0.30mm and 0.75+/-0.36mm, respectively, and the fibula was displaced 0.44+/-0.28mm and 0.92+/-0.39mm, respectively. The average dorsiflexion angle increased from 14.36+/-7.51 degrees to 16.74+/-7.21 degrees after cyclic loading (P<0.05). Movement of the distal tibiofibular joint led to a significant increase in the range of ankle dorsiflexion. These results suggest that tibiofibular JM would be effective for limitation of ankle dorsiflexion.

Allergic potency of Japanese cedar pollen Cry j 1 is reduced by a low concentration of hypochlorous acid generated by electolysis.

BACKGROUND: Although Japanese cedar (Cryptomeria japonica) pollinosis has developed into a health problem, few methods eradicate indoor allergens completely. In a recent study, however, the effectiveness of inactivation with sodium hypochlorite (NaOCl) treatment was revealed. Therefore, the present study aimed to elucidate the ability of chlorine bleach (NaOCl) to reduce the immunogenicity of the major allergenic protein of Japanese cedar (Cry j 1). METHODS: Sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blotting, enzyme-linked immunosorbant assay, and skin testing were carried out in 7 individuals. RESULTS: The allergenic protein was undetectable using sodium dodecyl sulfate polyacrylamide gel electrophoresis and silver staining at a sodium hypochlorite/allergenic protein molar ratio of 457. Western blotting with human sera showed the same dose-dependent efficacy. The immunogenicity of the purified protein and cedar pollen was also demonstrated on enzyme-linked immunosorbant assay to be reduced by sodium hypochlorite treatment in a dose- and time-dependent manner. Moreover, sodium hypochlorite-treatment inhibited the skin test response to the protein in all 7 individuals. CONCLUSIONS: Hypochlorous acid generated by electrolysis is an effective method for significantly reducing the immunogenicity of Cry j 1.