Effect of Maternal Egg Intake During the Early Neonatal Period and Risk of Infant Egg Allergy at 12 Months Among Breastfeeding Mothers: A Randomized Clinical Trial.

Importance: Egg introduction in infants at age 4 to 6 months is associated with a lower risk of immunoglobulin E-mediated egg allergy (EA). However, whether their risk of EA at age 12 months is affected by maternal intake of eggs at birth is unknown. Objective: To determine the effect of maternal egg intake during the early neonatal period (0-5 days) on the development of EA in breastfed infants at age 12 months. Design, Setting, and Participants: This multicenter, single-blind (outcome data evaluators), randomized clinical trial was conducted from December 18, 2017, to May 31, 2021, at 10 medical facilities in Japan. Newborns with at least 1 of 2 parents having an allergic disease were included. Neonates whose mothers had EA or were unable to consume breast milk after the age of 2 days were excluded. Data were analyzed on an intention-to-treat basis. Interventions: Newborns were randomized (1:1) to a maternal egg consumption (MEC) group, wherein the mothers consumed 1 whole egg per day during the first 5 days of the neonate's life, and a maternal egg elimination (MEE) group, wherein the mothers eliminated eggs from their diet during the same period. Main Outcomes and Measures: The primary outcome was EA at age 12 months. Egg allergy was defined as sensitization to egg white or ovomucoid plus a positive test result in an oral food challenge or an episode of obvious immediate symptoms after egg ingestion. Results: Of the 380 newborns included (198 [52.1%] female), 367 (MEC: n = 183; MEE: n = 184) were followed up for 12 months. On days 3 and 4 after delivery, the proportions of neonates with ovalbumin and ovomucoid detection in breast milk were higher in the MEC group than in the MEE group (ovalbumin: 10.7% vs 2.0%; risk ratio [RR], 5.23; 95% CI, 1.56-17.56; ovomucoid: 11.3% vs 2.0%; RR, 5.55; 95% CI, 1.66-18.55). At age 12 months, the MEC and MEE groups did not differ significantly in EA (9.3% vs 7.6%; RR, 1.22; 95% CI, 0.62-2.40) or sensitization to egg white (62.8% vs 58.7%; RR, 1.07; 95% CI, 0.91-1.26). No adverse effects were reported. Conclusions and Relevance: In this randomized clinical trial, EA development and sensitization to eggs were unaffected by MEC during the early neonatal period. Trial Registration: UMIN Clinical Trials Registry: UMIN000027593.

Acute myelomonocytic leukemia negative for alpha-naphthyl acetate esterase stain in a Holstein cow.

A 4-year, 7-month-old Holstein cow presented with anorexia. Physical examination revealed masses in the interscapular region and vagina. Blast cells were detected in the masses and peripheral blood by fine needle aspiration cytology and hematological examination. By bone marrow aspiration, blast cells constituted up to 24.2% of all nucleated cells, and 22% and 2% of non-erythroid cells stained positive for myeloperoxidase and alpha-naphthyl acetate esterase (ANAE), respectively. Pathological examination revealed the mass lesions consisted of a proliferation of tumor cells, which were positive for monocytic markers (HLA-DR and Iba-1). The cow was diagnosed with acute myelomonocytic leukemia (AMML). Even when tumor cells are ANAE-negative, AMML cannot be completely ruled out and should be considered when diagnosing cattle with leukemia/lymphoma.

Comparisons Between Serum Levels of Hepcidin and Leptin in Male College-Level Endurance Runners and Sprinters.

Background: Hepcidin-25 is a 25 amino acid hepatokine and a key regulator of iron metabolism related to iron deficiency anemia. Recent studies have suggested that an elevated hepcidin level is correlated with low energy availability. Leptin is an appetite-suppressing adipokine and has been reported to stimulate hepcidin production in animals and cultured cells. While leptin is modulated by exercise, it is known that endurance runners and sprinters practice different types of exercise. This study investigated and compared the relationships between hepcidin and leptin levels, iron status, and body fat to understand better the risk of iron deficiency anemia in endurance runners and sprinters. Methods: Thirty-six male college track and field athletes (15 endurance runners and 21 sprinters) were recruited for this study. Dietary intake, body composition, and blood levels of ferritin, hepcidin-25, leptin, and adiponectin were measured. Correlations between hepcidin levels and ferritin, body fat, leptin, and adiponectin were evaluated using Pearson's correlation coefficient for each group. Results: The endurance runners had lower hepcidin levels and higher leptin and adiponectin levels compared with sprinters. Ferritin was positively correlated with hepcidin-25 levels in both the endurance and sprinter groups. A positive correlation was observed between hepcidin-25 and body fat or leptin levels only in sprinters. Conclusion: This is the first study investigating the relationship between blood levels of hepcidin and leptin in athletes. The positive correlation between hepcidin-25 and leptin was observed in sprinters but not endurance runners.

A clinical case of acute myelomonocytic leukemia in a Holstein cow.

A 2-year, 3-month-old Holstein cow presented with anorexia and enlarged superficial lymph nodes. Fine needle aspiration cytology of the superficial lymph nodes revealed large blast cells. Hematological examination revealed anemia, neutropenia, and blast cells in peripheral blood. Blast cells were the predominant cell type in bone marrow aspirates. Of the non-erythroid cells, 26%, 58%, and 18% were positive for myeloperoxidase, α-naphthyl acetate esterase, and naphthol AS-D chloroacetate esterase, respectively. Pathological examination revealed the proliferation of neoplastic cells, which were positive for monocytic markers, in the affected lymph nodes. The cow was diagnosed with acute myelomonocytic leukemia based on these findings. This report highlights the importance of performing bone marrow aspiration cytology and cytochemical staining when diagnosing bovine myeloid leukemia.

A clinical case of single left ventricle in a Holstein calf.

A 15-day-old Holstein calf with lethargy and tachypnea presented to the Veterinary Teaching Hospital at Obihiro University of Agriculture and Veterinary Medicine for evaluation of suspected congenital heart defect. A Levine grade 6 systolic murmur was noted at right apical site auscultation and phonocardiogram also recorded systolic a murmur. Electrocardiography findings include increased R and S waves, R wave split, and negative T waves without arrhythmia. Echocardiography revealed a single ventricle with a trace of the right ventricular wall, atrioventricular valve regurgitation, and turbulent in a single ventricle. Arterial blood analysis showed a marked decrease in oxygen saturation of 78% and oxygen partial pressure of 44 mmHg. Post-mortem examination confirmed the diagnosis of a single left ventricle.

A clinical case of presumed cerebellar medulloblastoma in a Japanese Black calf with increased neuron-specific enolase in cerebrospinal fluid.

A 2-day-old Japanese Black male calf that presented with opisthotonos with spastic extension of all four limbs and nystagmus was presented. Evaluation of cranial neurology revealed a horizontal slow nystagmus and absence of menace response in the left eye. Necropsy revealed a mass located between the posterior margin of the cerebrum and anterior margin of the cerebellum, and continuously with the cerebellar lesion. The brainstem was severely compressed by those lesions. Original structures of the cerebellum were mostly replaced by grayish-white and brownish tissues. Those lesions were diagnosed as presumed cerebellar medulloblastoma by histopathological and immunohistochemical examination. As neuron-specific enolase in the cerebrospinal fluid which is a biomarker for neuronal damage was increased compared with healthy calves.

One-month-old boy with group B streptococcal meningitis, subdural effusion, and high levels of interleukin-6.

Meningitis is associated with elevated levels of inflammatory cytokines in the blood, cerebrospinal fluid (CSF), and subdural fluid. Subdural effusion prolongs fever in patients with meningitis. However, the reason for this remains unclear. A healthy one-month-old boy was admitted after presenting with bacterial meningitis. He was administered meropenem, cefotaxime, and dexamethasone intravenously. On the 3rd day, blood and CSF cultures revealed the presence of Group B Streptococcus from samples collected on day 1. Subsequently, ampicillin and gentamicin replaced the previous combination of antimicrobials used. On the 4th day, brain magnetic resonance imaging with contrast showed bilateral cerebral ventriculitis and left subdural effusion. On the 11th day, since the subdural effusion had worsened, we performed a subdural puncture from the anterior fontanelle. Owing to the prolonged fever, he was intravenously injected immunoglobulin on day 13. He was afebrile on day 23. Antimicrobials were administered for 28 days. Levels of interleukin-6 (IL-6) in the serum and CSF were the highest on the 1st day at 20,600 pg/mL and 170,000 pg/mL, respectively, and decreased upon treatment. IL-6 concentration in the subdural fluid (30,000 pg/mL) was much higher than that in the serum (9 pg/mL) and CSF (2600 pg/mL). To the best of our knowledge, this is the first report on the cytokines in subdural fluid in patients with group B Streptococcal meningitis. Subdural effusion maintained high levels of IL-6 even after the levels in the blood and CSF decreased dramatically. This could explain why subdural effusion prolongs fever in patients with meningitis.

Easy to Swallow Rice Cake as a Carbohydrate Source during Endurance Exercise Suppressed Feelings of Thirst and Hunger without Changing Exercise Performance.

The present guidelines for sports nutrition recommend relatively higher doses of carbohydrates (CHO) for endurance exercise. There is a need for novel food products that are solid but easy to swallow and supply a large dose of CHO without gastrointestinal distress (ingesting a large amount of sugar solution may cause gastrointestinal distress because of its high osmolality). We prepared a modified rice cake (SPRC, sweet potato rice cake) and assessed its properties in swallowing and mastication; we also assessed the availability of this modified rice cake as a CHO source during endurance exercise. The number of chewing strokes with the SPRC tended to be lower compared to glutinous rice cakes. The exercise protocol consisted of 1 h at 80% VO2max plus a continuous time trial. The subjects were administered a commercially available jelly drink (CHO gel) or SPRC at 0 and 30 min during exercise and immediately after completing the time trial. Heart rate, oxygen consumption, blood glucose elevation, and the rate of perceived exertion did not differ among the trials during exercise. However, the visual analog scale rating revealed that SPRC significantly suppressed hunger and sweetness ratings (p<0.05) and tended to suppress thirst ratings (p<0.10) during exercise. The palatability rating did not differ between the SPRC and CHO gel during exercise at 80% VO2max and immediately after the time trial. In conclusion, pre- and during exercise ingestion of the SPRC suppressed sweetness, thirst, and hungry ratings without interfering with exercise performance.

Clinical Features of Febrile Urinary Tract Infection Caused by Extended-spectrum Beta-lactamase-producing Escherichia Coli in Children.

The global prevalence of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has been increasing. In children, ESBL-producing E. coli manifest mostly as febrile urinary tract infections (fUTIs). This study aimed to elucidate the clinical features of fUTI resulting from ESBL-producing E. coli in Japanese patients. The clinical features of children with E. coli-related fUTI were retrospectively examined. These children underwent treatment at the National Hospital Organization Saitama Hospital, Japan, between May 2010 and April 2018. Urine specimens were obtained by either bladder catheterization or the clean-catch method. All children having positive urine cultures (≥104 colony-forming unit/mL for catheter specimens and ≥105 colony forming unit/mL for clean-catch specimens) and a fever of ≥38°C were considered to have fUTI. During the study period, 171 patients were diagnosed with E. coli-related fUTI. Among these, 17 (9.9%) fUTI cases were caused by ESBL-producing E. coli. A significant difference was noted in the median age of the populations having ESBL-producing E. coli and non-ESBL-producing E. coli infections (2 and 5 months, respectively); other characteristics were not significantly different between the two patient groups. ESBL-producing E. coli infections markedly increased in our hospital between 2013 and 2018. In the present study, young age was the only risk factor for fUTI caused by ESBL-producing E. coli identified in Japanese children.

Disseminated thymic B-cell lymphoma in a Holstein heifer.

A 19-mo-old Holstein heifer was inactive and dyspneic. Physical examination revealed wheezing, exophthalmos, a cervical mass, and lymphadenopathy. Cytology of the cervical mass and lymph nodes showed predominantly large atypical lymphocytes. Lactate dehydrogenase and thymidine kinase activities were elevated. Although nested PCR for bovine leukemia virus (BLV) using blood was positive, quantitative PCR showed a low number of provirus copies. Autopsy revealed enlargement of most lymph nodes examined, as well as white masses of various sizes in muscles of the left hindlimb and thoracic and abdominal organs. Histopathology revealed severe infiltration with neoplastic lymphocytes in these organs. The cervical mass was immune-positive for B-cell markers. The final diagnosis was thymic B-cell lymphoma with BLV infection.

Effects of dietary protein contents and habitual endurance exercise on supplemental leucine oxidation in mice.

The effects of dietary protein contents and regular exercise on the oxidation of supplemented leucine were examined. In the short-term study, male BALB/cCrSlc mice were fed diets containing 0, 10, 20, 35, and 60% protein: energy ratios for 1 week. In the long-term study, exercised and sedentary mice were fed diets containing 20, 35, and 60% protein ratios for 9 weeks. After the feeding periods, the mice were a bolus administered oral supplements of l-[1-13C] leucine. Expired gas was analyzed, and oxidized leucine was expressed as a relative 13CO2/12CO2 ratio. In the short-term study, the peak 13CO2/12CO2 ratio significantly increased with diet protein concentrations. Moreover, the long-term study also showed that the peak 13CO2/12CO2 ratio was significantly increased by high protein diets in both exercised and sedentary mice. Our results indicate that supplemental leucine oxidation is associated with consumption of a high-protein diet, irrespective of exercise status. Abbreviations: AUC: area under the curve; EX: exercise; RQ: respiratory quotient; SED: sedentary; VO2/W: oxygen uptake per body weight.

Hepatic Fat Content Is Associated with Fasting-Induced Fibroblast Growth Factor 21 Secretion in Mice Fed Soy Proteins.

Previous studies suggest that circulating fibroblast growth factor 21 (FGF21) levels are elevated in patients with fatty liver, while fasting-induced secretion of FGF21 is lower in obese patients. It has been reported that soy protein prevents hepatic fat accumulation and induces FGF21 secretion. The present study was designed to evaluate the response of circulating FGF21 levels to feeding and fasting in mice fed soy protein-rich diets. For this, C57BL/6J mice were distributed into control, high-fat high-sucrose (HFHS)-casein protein, HFHS-soy protein, and HFHS-ß-conglycinin diet groups. Plasma samples were collected after 10 and 11 wk either in dark periods with feeding conditions or light periods under fasting conditions using a crossover design. After a 12-wk period of feeding, HFHS-induced hepatic fat accumulation was significantly reduced in the groups fed HFHS-soy protein and HFHS-ß-conglycinin as compared to that in the HFHS-casein-fed group (p<0.05). Plasma FGF21 concentration was significantly higher in the dark/feeding periods in the HFHS-casein group (p<0.05), while in the HFHS-ß-conglycinin group it was higher in the light/fasting periods (p<0.05). The amount of mesenteric fat was significantly lower in the HFHS-ß-conglycinin group than in the HFHS-casein and HFHS-soy protein groups (p<0.01). The fasting-induced FGF21 secretion was significantly and negatively correlated with hepatic fat content (p<0.05). The present study revealed that hepatic fat accumulation was associated with lower fasting-induced FGF21 secretion, which was regulated better by dietary intake of soy protein. These results support the preventive effects of soy protein on central obesity.

[A Cost-effectiveness Analysis of Sunitinib vs. Interferon-alpha in Patient with Advanced Renal Cell Carcinoma in Japan].

Sunitinib has been shown to offer clinical benefits during the treatment of advanced renal cell carcinoma. However, molecular targeting drugs are expensive and can have a significant impact on medical expenses. The purpose of this study was to assess the cost-effectiveness of sunitinib as a first-line therapy compared with interferon-alpha (IFN-α) in metastatic renal cell carcinoma patients. A Markov model was used to show the clinical courses of patients with metastatic renal cell carcinoma who received sunitinib or IFN-α. The transition probabilities and utilities employed in this Markov model were derived from two sources. This study focused on the perspective of public healthcare payer, as only direct medical costs were estimated from the treatment schedule for metastatic renal cell cancer. In the cost-effectiveness analysis, outcomes were valued in terms of life years (LYs) and quality-adjusted life years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) during the cost-effectiveness analysis. The results were tested using Monte Carlo simulations. Sunitinib and IFN-α treatment resulted in LYs of 2.40 years and 2.03 years, QALYs of 1.58 and 1.25, and expected costs of 13,572,629 yen and 6,083,002 yen, respectively. As a result, the ICER associated with replacing IFN-α with sunitinib was 22,695,839 yen/QALYs. Our results suggest that compared with IFN-α, sunitinib prolongs LYs and QALYs, but the increases in quality achieved by sunitinib are more expensive than those produced by IFN-α.

Radial stability of the actomyosin filament lattice in isolated skeletal myofibrils studied using atomic force microscopy.

The radial stability of the actomyosin filament lattice in skeletal myofibrils was examined by using atomic force microscopy. The diameter and the radial stiffness of the A-band region were examined based on force-distance curves obtained for single myofibrils adsorbed onto cover slips and compressed with the tip of a cantilever and with the Dextran treatment. The results obtained indicated that the A-band is composed of a couple of stiffness components having a rigid core-like component. It was further clarified that these radial components changed the thickness as well as the stiffness depending on the physiological condition of myofibrils. Notably, by decreasing the ionic strength, the diameter of the A-band region became greatly shrunken, but the rigid core-like component thickened, indicating that the electrostatic force distinctly affects the radial structure of actomyosin filament components. The results obtained were analyzed based on the elementary structures of the filament lattice composed of cross-bridges, thin filaments and thick filament backbones. It was clarified that the actomyosin filament lattice is radially deformable greatly and that (1), under mild compression, the filament lattice is stabilized primarily by the interactions of myosin heads with thin filaments and thick filament backbones, and (2), under severe compression, the electrostatic repulsive interactions between thin filaments and thick filament backbones became predominant.

Mechanical strength of sarcomere structures of skeletal myofibrils studied by submicromanipulation.

The mechanical strength of sarcomere structures of skeletal muscle was studied by rupturing single myofibrils of rabbit psoas muscle by submicromanipulation techniques. Microbeads coated with alpha-actinin were attached to the surface of myofibrils immobilized to coverslip. By use of either optical tweezers or atomic force microscope, the attached beads were captured and detached from the myofibrils. During the detachment of the beads, the actin filaments bound specifically to the beads were peeled off from the bulk structures of myofibrils, thus rupturing the peripheral components of the myofibrils bound to the actin filaments. By analyzing the ruptures thus produced in various myofibril preparations, it was found that the sarcomere structure of myofibrils is maintained by numerous molecular components having the mechanical strength sufficient to sustain the contractile force produced by the actomyosin system. The present techniques could be applied to study the mechanical strength of cellular organelles containing actin filaments as their component.

Transverse stiffness of myofibrils of skeletal and cardiac muscles studied by atomic force microscopy.

The transverse stiffness of single myofibrils of skeletal and cardiac muscles was examined by atomic force microscopy. The microscopic images of both skeletal and cardiac myofibrils in a rigor state showed periodical striation patterns separated by Z-bands, which is characteristic of striated muscle fibers. However, sarcomere patterns were hardly distinguishable in the stiffness distributions of the relaxed myofibrils of skeletal and cardiac muscles. Myofibrils in a rigor state were significantly stiff compared with those in a relaxed state, and in each state, cardiac myofibrils were significantly stiffer compared with skeletal myofibrils. By proteolytic digestions of sarcomere components of myofibrils, it was suggested that cardiac myofibrils are laterally stiffer than skeletal myofibrils because Z-bands, connectin (titin) filament networks, and other components of sarcomere structures for the former myofibrils are stronger than those for the latter.

Molecular organizations of myofibrils of skeletal muscle studied by atomic force microscopy.

By applying AFM technology, we studied mechanical characteristics of myofibrils of skeletal muscle. The obtained results indicate that (1) the Z-band is the most rigid sarcomere component stabilizing the myofibril structures, (2) various filamentous components are inter-connected in sarcomere with sufficient mechanical strength to support the contractile force, and (3) the molecular structure of the overlap region between actin and myosin filaments is anisotropic. In any case the present studies clearly indicate that the AFM technique is a powerful tool to investigate the mechanical characteristics of sarcomere structure of muscle fiber.