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Background Low birthweight infants have high risk of developing chronic kidney disease (CKD) in later in life, however, the pathogenesis of this disease remains unclear. This study aimed to investigate the underlying mechanism using a low birthweight-non-obese hyperglycemic adulthood mouse model. Methods Pregnant ICR-strain mice underwent uterine artery ligation at day 16.5 of gestation to induce fetal hypoxia (ischemic group, I). Female newborns were weaned at 4 weeks of age and fed a normal diet until 8 weeks of age ( n  = 10). The group I was compared to the control group (C) regarding the body weight, tubular injury markers, renal function, pathology, and metabolome analysis. Results Group I were born with a low birth weight (group I: C = 1.4:1.9 g, p  < 0.01), which persisted after birth. By 8 weeks of age, there were minimal changes in kidney histopathology between the two groups. However, group I showed an increase in markers for detection of CKD, such as urinary β2-microglobulin levels (group I: C = 116:26 µg/L), albumin levels (group I: C=0.14:0.07 mg/gCr) (both p  < 0.01) and serum creatinine levels (group I: C= 0.18:0.12 mg/dL, p  < 0.05). Furthermore, kidney metabolomic analysis revealed notable differences between the two groups, particularly in succinic acid, S-adenosylmethionine, and N1-methyl-4-pyridone-5-carboxamide (4PY), which are closely linked to kidney injury. Conclusion The low birthweight-non-obese hyperglycemic mouse model may develop CKD in adulthood, potentially caused by increased renin activity related to succinic acid and tissue injury related to S-adenosylmethionine and 4PY. Clinical trial number Not applicable.

This study investigated the mechanism of reducing body fat via whey protein diet. Pregnant mice were fed whey or casein, and their offspring were fed by birth mothers. After weaning at 4 weeks, male pups received the diets administered to their birth mothers (n = 6 per group). At 12 weeks of age, body weight, fat mass, fasting blood glucose (FBG), insulin (IRI), homeostatic model assessment of insulin resistance (HOMA-IR), cholesterol (Cho), triglyceride (TG), the expression levels of lipid metabolism-related genes in liver tissues and metabolomic data of fat tissues were measured and compared between the groups. The birth weights of pups born were similar in the two groups. Compared to the pups in the casein group, at 12 weeks of age, pups in the whey group weighed less, had significantly lower fat mass, HOMA-IR and TG levels (p < 0.01, p = 0.02, p = 0.01, respectively), and significantly higher levels of the antioxidant glutathione and the anti-inflammatory 1-methylnicotinamide in fat tissues (p < 0.01, p = 0.04, respectively). No differences were observed in FBG, IRI, Cho levels (p = 0.75, p = 0.07, p = 0.63, respectively) and expression levels of lipid metabolism-related genes. Whey protein has more antioxidant and anti-inflammatory properties than casein protein, which may be its mechanism for reducing body fat.

This study examined whey protein’s impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

We previously reported the 95th percentile cutoff value of the serum procalcitonin (PCT) reference curve for diagnosing early-onset bacterial infection. We aimed to verify the effectivity of these novel diagnostic criteria by comparing antibiotic use and incidence of early-onset bacterial infection between pre- and post-introduction periods. We included newborns admitted to our neonatal intensive care unit who underwent blood tests within 72 h after birth between 2018 and 2022. The neonates were divided into the pre-intervention (admitted before the introduction, n = 737) or post-intervention (admitted after the introduction, n = 686) group. The days of antibiotics therapy (DOT) per 1000 patient days up to 6 days after birth, percentage of antibiotic use, and incidence of early-onset bacterial infection were compared between the groups. The post-intervention group had significantly lower DOT per 1000 patient days (82.0 days vs. 211.3 days, p < 0.01) and percentage of newborns receiving antibiotics compared with the pre-intervention group (79 (12%) vs. 280 (38%), respectively, p < 0.01). The incidence of early-onset bacterial infections did not differ between the groups (2% each, p = 0.99). In conclusion, our diagnostic criteria using the 95th percentile cutoff value of the serum PCT reference curve for early-onset bacterial infection were proven safe and effective, promoting appropriate use of antibiotics.

We aimed to create percentile-based reference values of the umbilical cord blood insulin-like growth factor-1 (IGF-1) levels in Japanese newborns, as these values have not yet been established. A total of 259 newborns were classified into four gestational-age-at-birth (GA) groups: extremely preterm (<28 weeks); early preterm (28–33 weeks); late preterm (34–36 weeks); and term (≥37 weeks). They were further subclassified as small-for-gestational-age (SGA) or non-SGA. The 10th, 25th, 50th, 75th, and 90th percentiles of the umbilical cord blood IGF-1 levels were calculated and compared between the groups by using reference values of 9, 18, 33, 52, and 71 ng/mL, respectively. In the extremely preterm group, the IGF-1 levels were significantly lower than those in the early preterm, late preterm, and term groups (13.5, 24.0, 44.5, and 47.5 ng/mL, respectively; p < 0.001). The umbilical cord blood IGF-1 levels in the SGA newborns were significantly lower than those in the non-SGA newborns in all subgroups. In multivariate analyses, the GA and birth weight standard deviation scores were independent determinant factors for the umbilical cord blood IGF-1 levels. Thus, we established percentile-based reference values of umbilical cord blood IGF-1 in Japanese newborns; these reference values can be applied on the basis of the extent of prematurity and the SGA status.

In the original publication [...]

To date, no clinical studies have compared the accuracy of serum procalcitonin (PCT) reference curves. We aimed to validate the diagnostic accuracy of previously reported serum PCT reference curves and to determine which biomarkers among a cut-off value over the 95th percentile in the serum PCT reference curve, white blood cell (WBC) count, and C-reactive protein (CRP) and immunoglobulin M (IgM) levels, have the highest diagnostic accuracy for early-onset neonatal bacterial infections. This retrospective cohort study assessed 16 preterm and 23 term infants with suspected bacterial infections within 72 h after birth. Each infant group was divided into two subgroups: confirmed- and non-infection. The diagnostic accuracy was determined using the Youden index. The reference curves by Fukuzumi et al. in preterm and term infants had the highest Youden indexes: 1.000 and 0.324, respectively. Among preterm infants, the Youden index for PCT was 1.000. Among term infants, the Youden index for a combination of PCT, CRP, and WBC and/or IgM was 1.000. In conclusion, a serum PCT level over the 95th percentile on the reference curve for preterm infants and a combination of PCT and CRP levels with WBC count and/or IgM levels for term infants provided sufficient diagnostic accuracy.