Body Size, Cerebral Blood Flow, Ambient Temperature, and Relative Brain Temperatures in Newborn Infants under Incubator Care.

Subtle changes in body temperature affect the outcomes of ill newborns. However, the temperature profile of neonatal brains remains largely unknown. In open-cot care, increased cerebral perfusion is correlated with higher superficial brain temperatures. This study investigated the dependence of brain temperature (relative to rectal temperature) on ambient temperature, body size, cerebral perfusion, and metabolism in infants receiving incubator care. Rectal, scalp, and brain temperatures, superior vena cava flow, and brain oxygenation were assessed using echocardiography, thermo-compensatory temperature monitoring, and near-infrared spectroscopy in 60 newborns. These infants had a mean postconceptional age of 36.9 (2.2) weeks and weighed 2348 (609) g at the time of evaluation. The ambient temperature was maintained at 30.0 (1.0) °C. A higher rectal temperature was associated with greater postconceptional age (p = 0.002), body weight (p < 0.001), and head circumference (p < 0.001). Relative scalp, superficial brain, and deep brain temperatures were associated with smaller head circumference (p < 0.001, p = 0.030, and p = 0.015, respectively) and superior vena cava flow (p = 0.002, p = 0.003, and p = 0.003, respectively). In infants receiving incubator care, larger head sizes and increased brain perfusion were associated with lower relative scalp and brain temperatures. When considered alongside previous reports, cerebral perfusion may contribute to maintaining stable cerebral tissue temperature against ambient temperature changes.

Comparative pharmacokinetics of new curcumin preparations and evidence for increased bioavailability in healthy adult participants.

OBJECTIVE: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted. MATERIALS AND METHODS: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) 0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of Cmax. TS-P1 tended to have a higher Cmax than CR-033P, CR-043P tended to have a slightly lower Cmax than CR-033P, and TS-P1 tended to have a higher Cmax than CR-043P. CONCLUSION: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

The Oral Administration of Highly-Bioavailable Curcumin for One Year Has Clinical and Chondro-Protective Effects: A Randomized, Double-Blinded, Placebo-Controlled Prospective Study.

Purpose: The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment. Methods: We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy. Results: The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy. Conclusions: The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo. Level of Evidence: Level I, double-blinded, placebo-controlled, prospective study.

Influence of extreme prematurity and bronchopulmonary dysplasia on cardiac function.

OBJECTIVE: Prematurity and bronchopulmonary dysplasia (BPD) are associated with poorly understood abnormalities of ventricular function. We therefore comprehensively compared biventricular function in infants with and without BPD. METHODS: Prospective observational study in extremely preterm infants with (n = 20) and without (n = 38) BPD using conventional and advanced echocardiography at 28 days (T1) and near-term (T2). RESULTS: Infants with BPD had lower birth gestational age (26.7±1.9 vs 27.4±1.1 weeks, p = 0.047) and weight (884±207 vs 1108±190 g, p = 0.0001). BPD was associated with larger right ventricles (RV) and reduced RV systolic strain rate at T1 and pulmonary hypertensive indicators at T2 (pulmonary artery acceleration time BPD 51±17 vs no BPD 63±12 ms, p = 0.017). At T1/T2, infants with BPD had lower RV tissue Doppler velocities (e', a' and s) and higher E/e' ratios (T1: BPD 10.4±2.4 vs no BPD 6.2±3.1 cm/sec, p = 0.001; T2: BPD 8.0±3.1 vs no BPD 5.6±2.6 cm/sec, p = 0.02), altered LV diastolic function (apical circumferential T1 early diastolic strain rate BPD 2.8±0.8 vs no BPD 3.6±1.0 /sec, p = 0.04; T2 late diastolic strain rate, BPD 2.29 ± 0.99 vs no BPD 1.67±0.84 /sec, p = 0.03) and LV rotational mechanics (T1: twist rate BPD 90±16 vs no BPD 130±48 deg/sec, p = 0.008; untwist rate (UTR) BPD -69±90 vs no BPD -147±68 deg/sec, p = 0.008; torsion BPD 2.78±0.56 vs no BPD 4.48±1.74 deg/cm, p = 0.009; and T2: UTR BPD -132±69 vs no BPD -179±57 deg/sec, p = 0.013). CONCLUSION: BPD is associated with altered RV diastolic function that persists near term, with elevated pulmonary vascular resistance, and with persistent alterations in LV apical strain rate and rotational mechanics.

The Perinatal Transition and Early Neonatal Period in Hypoplastic Left Heart Syndrome Is Associated With Reduced Systemic and Cerebral Perfusion.

BACKGROUND: The impact of the striking perinatal circulatory changes on blood flow distribution have not to date been well examined in hypoplastic left heart syndrome (HLHS). This study aimed to document perinatal redistribution of cardiac output in HLHS compared with healthy control subjects, to further understand the impact of the perinatal transition on cerebral and systemic blood flow. METHODS: Prospectively recruited HLHS case subjects (n = 31) and healthy control subjects (n = 19) underwent serial echocardiography from late fetal stages to 96 hours after birth. Combined cardiac output (CCO), systemic, pulmonary, cerebrovascular, and splanchnic flow data were compared between neonates with HLHS and control subjects, and the impact of vasoactive support and positive pressure ventilation in HLHS patients was examined. RESULTS: In late gestation, CCO was similar between HLHS and control subjects, whereas middle cerebral artery (MCA) pulsatility index (PI) in HLHS was consistent with low cerebral vascular resistance. In the 96 hours after birth, CCO and pulmonary blood flow progressively increased in HLHS compared with control subjects (P < 0.001), and CCO was further increased in neonates with HLHS receiving vasoactive support (P = 0.01). Neonates with HLHS had reduced systemic and 6-24-hour superior vena cava (SVC) flow compared with control subjects (P < 0.001). Low systemic flow was further suggested by increased MCA and celiac artery PI at 6-48 hours in neonates with HLHS (P < 0.001). Systemic and SVC flow did not differ between those with and without vasoactive support. CONCLUSIONS: We provide quantitative echocardiographic evidence associating impaired cerebral and systemic blood flow with perinatal hemodynamic changes in the preoperative neonate with HLHS.

Simple method to distinguish the type of fetal premature contraction using arterial Doppler time interval measurements.

AIM: The purpose of this study was to establish a simple method to distinguish premature ventricular contractions (PVC) from premature atrial contractions (PAC) using a fetal Doppler ultrasound arterial pulse waveform to measure time intervals between sinus node restarting. METHODS: We retrospectively identified 14 fetuses with premature contraction (8 with PAC, 6 with PVC). We measured two distinct parts of time intervals using an arterial pulsed-wave Doppler: the two consecutive waveforms just before the premature contraction (2-V interval) and two consecutive waveforms including the premature contraction (XV interval) to measure time intervals between sinus node restarting. We then evaluated the time difference between the 2-V and XV intervals in PVC compared to PAC. RESULTS: For PVC, the difference between the 2-V interval and the XV interval was significantly shorter than that for PAC. A cut-off point of 33 ms, where a difference ≤33 ms was clearly shown to be associated with a PVC and a difference more than 33 ms signified a PAC was demonstrated. CONCLUSION: The 2-V and XV interval measurements, used to measure time intervals between sinus node restarting, could easily distinguish PVC from PAC in utero. Therefore, this study could potentially be a feasible and effective method for obstetricians or sonographers to employ usefully.

Branch pulmonary artery Doppler parameters predict early survival-non-survival in premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membrane (pPROM) leads to high neonatal mortality due in part to severe lung hypoplasia (LH). In other causes of severe LH, fetal echo-based parameters of smaller branch pulmonary arteries (PA), shorter acceleration to ejection time ratio (AT/ET), increased peak early diastolic reverse flow (PEDRF), and higher pulsatility index (PI) are predictive of worse neonatal outcome. We sought to determine whether these parameters correlated with worse clinical outcome in pPROM. METHODS: Twenty-five pregnancies complicated by pPROM were prospectively recruited. Fetal echocardiography was used to evaluate branch PA diameters and Doppler parameters. Clinical records were reviewed. Fetal echo findings were compared between early survivors and non-survivors. RESULTS: Of 25 pPROM cases, 5 had early neonatal demise (≤3 days) due to respiratory insufficiency. While gestational age at pPROM, fetal echo, and at birth did not differ, amniotic fluid index (AFI) was significantly lower in early non-survivors compared to survivors (p = 0.05). No difference was observed in PA diameter, PEDRF, or PI; however, branch PA AT/ET was significantly shorter in non-survivors (right PA median 0.12 (0.11-0.16) vs. survivors 0.17 (0.14-0.21), p = 0.046 and left PA 0.12 (0.09-0.13) vs. survivors 0.16 (0.11-0.21), p = 0.042). CONCLUSIONS: We found a significantly lower AFI and shorter fetal bilateral branch PA AT/ET to be associated with early neonatal demise following pPROM.

Associations between caries experience, dietary habits, and metabolic syndrome in Japanese adults.

Dental caries could be a risk factor for metabolic syndrome (MetS); however, there is limited evidence of such a relationship in the literature. This cross-sectional study investigated the relationships among dental caries experience, dietary habits, and MetS in Japanese adults. A total of 937 participants aged 40-74 years underwent a health check, including dental examination. Decayed, missing, and filled teeth (DMFT) were used as an index of caries experience. The mean DMFT score was 14, and 12% of the participants had MetS in this study. Multivariate logistic regression analyses showed that the prevalence of MetS was significantly related to DMFT (first vs. fourth quartile, odds ratio [OR] = 1.80; P < 0.05). In addition, the OR of DMFT for MetS was found to be greater in each successively higher DMFT quartile. The prevalence of MetS was significantly related to daily coffee consumption (OR = 0.51, P < 0.01), and the relationship between DMFT and MetS was noted after adjusting for daily coffee consumption. There appears to be a positive association between caries experience and MetS in Japanese adults. This relationship increased with the increase in DMFT regardless of dietary habits.

Self-reported behavior of eating quickly is correlated with visceral fat area in Japanese non-obese adults.

BACKGROUND AND OBJECTIVES: This cross-sectional study investigated the relationship between eating speed and fat accumulation in Japanese non-obese adults. METHODS AND STUDY DESIGN: In total, 381 non-obese participants aged 35-74 years underwent a health checkup including fat distribution. All participants underwent magnetic resonance imaging to quantify visceral fat area (VFA) and subcutaneous fat area (SFA). Information on eating speed was obtained using a self-administrated questionnaire. RESULTS: The numbers of participants with self-reported behavior of eating slowly, medium, or quickly were 24 (6.3%), 180 (47.2%), and 177 (46.5%), respectively. The prevalence of VFA ≥100 cm2 was higher in the eating quickly group than in the eating slowly (p<0.05) or medium groups (p<0.05). On the other hand, no significant differences in SFA ≥100 cm2 were observed between groups. In addition, multiple stepwise regression analysis showed that eating quickly was positively correlated with VFA (standard ß=0.068, p<0.05), but not with SFA. CONCLUSIONS: Although eating quickly was positively correlated with bigger VFA in Japanese non-obese adults, no associations were found between eating speed and SFA.

Association between eating behavior and poor glycemic control in Japanese adults.

This study investigated the relationship between eating behavior and poor glycemic control in 5,479 Japanese adults with hemoglobin A1c (HbA1c) <6.5% who participated in health checks. Respondents to a 2013 baseline survey of eating behavior, including skipping breakfast and how quickly they consumed food were followed up until 2017. We defined poor glycemic control after follow-up as HbA1c ≥6.5%, or increases in HbA1c of ≥0.5% and/or being under medication to control diabetes. We identified 109 (2.0%) respondents who met these criteria for poor glycemic control. After adjusting for sex, age, smoking status, body mass index (BMI), and eating behavior, the risk of poor glycemic control was increased in males (odds ratio [OR], 2.38; 95% confidence interval [CI] 1.37-4.12; p < 0.01), and associated with being older (OR, 1.07; 95% CI, 1.04-1.11; p < 0.001), having a higher BMI (OR, 1.29; 95% CI 1.23-1.35; p < 0.001), skipping breakfast ≥3 times/week (OR, 2.44; 95% CI, 1.35-4.41; p < 0.01), and changing from eating slowly or at medium speed to eating quickly (OR, 2.11; 95% CI, 1.04-4.26; p < 0.05). In conclusion, Japanese adults who were male, older, had a high BMI, skipped breakfast ≥3 times/week and ate quickly were at increased risk for poor glycemic control.

Correlation between ultrasound-diagnosed non-alcoholic fatty liver and periodontal condition in a cross-sectional study in Japan.

This cross-sectional study investigated the relationship between periodontal condition and ultrasound-diagnosed non-alcoholic fatty liver disease (NAFLD) in a Japanese oral health check population. A total of 1226 consecutive participant were enrolled in the study. Abdominal ultrasonography was applied to diagnose NAFLD. Of the study participants, 339 (27.7%) had ultrasonography-diagnosed NAFLD. The participants with NAFLD had a significantly higher prevalence of probing pocket depth (PPD) ≥ 4 mm (86.7%) than those without NAFLD (72.9%) (p < 0.05). After adjusting for gender, age, Brinkman index, regular exercise habits, body mass index, number of teeth present, presence of periodontitis, blood pressure, and serum parameters, there was a statistically significant difference in the adjusted odds ratios of having PPD ≥ 4 mm for NAFLD (Odds ratio = 1.881, 95% confidence interval 1.184-2.987, p < 0.01). Having PPD ≥ 4 mm may be a risk factor for ultrasound-diagnosed NAFLD in this cross-sectional study of a Japanese oral health check population.

Expression of Salivary miR-203a-3p Was Related with Oral Health-Related Quality of Life in Healthy Volunteers.

Oral health-related quality of life (OHRQoL) is a multidimensional construct that involves subjective evaluation of an individual's oral health. Although it is difficult to evaluate OHRQoL biologically, recently, it has been reported that circulating microRNAs (miRNAs) in several body fluids could reflect various health conditions. The aim of this pilot study was to investigate whether salivary miRNAs expression differs according to OHRQoL in healthy volunteers. Forty-six volunteers (median age, 23.0 years) were recruited, and their OHRQoL was assessed using the Japanese version of the Oral Health Impact Profile (OHIP-J). Then, we compared salivary microRNA profiles of the high-OHRQoL group (≤25th percentile score of OHIP-J) and the low-OHRQoL group (≥75th percentile score of OHIP-J) using the polymerase chain reaction (PCR) array and the quantitative real-time PCR. There were no significant differences between the two groups in terms of oral health status. In the PCR array, miR-203a-3p and miR-30b-5p were significantly more expressed in the low-OHRQoL group (p < 0.05). Quantitative real-time PCR assay also showed that miR-203a-3p was more highly expressed in the low-OHRQoL group than in the high-OHRQoL group (p < 0.05). These observations suggest that expression of salivary miR-203a-3p was related with OHRQoL in healthy volunteers.

Evolution of left ventricular function in the preterm infant.

BACKGROUND: The aim of this study was to evaluate left ventricular function in preterm infants from 28 days to near term using echocardiography. METHODS: Thirty clinically stable preterm infants delivered at <30 weeks' gestational age were prospectively enrolled. At 28 days, conventional, tissue Doppler, and speckle-tracking echocardiography evaluations of left ventricular function were performed, with comparison made to findings in 30 healthy term infants of similar postnatal age. Sixteen preterm infants underwent repeat examinations near term. RESULTS: Compared with controls, preterm infants at 28 days had decreased peak mitral valve (MV) E-wave velocities (P < .01), E/A ratios (P < .0001), annular e' velocities (P < .0001), and e'/a' ratios (P < .0001); increased MV E/e' ratios (P < .01); and lower basal circumferential early diastolic and higher late diastolic strain rates. No significant differences were found in fractional shortening, ejection fraction, and longitudinal or circumferential strain and strain rate between preterm infants and controls. Although preterm infants at 28 days had higher heart rates compared with controls (161 ± 15 vs 142 ± 16 beats/min), no significant correlations existed between heart rate and MV E, E/A ratio, e', e'/a' ratio, and E/e' ratio. Near term, the differences in diastolic function persisted, including decreased MV e'/a' ratio (P < .05), increased E/e' ratio (P < .01), and increased late diastolic strain rate. CONCLUSIONS: Clinically stable preterm infants have normal left ventricular systolic function but altered diastolic function, with greater dependence on atrial contraction, the latter of which persists despite nearing term. These findings may be relevant to the management of preterm infants and may relate to the longer term myocardial dysfunction observed in affected adults.

Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome.

Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.

Levothyroxine replacement therapy and refractory hypotension out of transitional period in preterm infants.

BACKGROUND: Recent studies suggest that refractory hypotension from causes other than septicaemia or cardiac failure is common in extremely preterm infants even out of the transitional period. Marked response to low-dose cortisol suggests underlying adrenal insufficiency, although the exact mechanism remains unknown. METHODS: To investigate potential triggers for and related short-term outcomes of early-onset (

Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway.

Although increased vascular permeability is known to be a major characteristic of diabetic vasculopathy, the precise mechanisms and relevance of advanced glycation end products (AGE) to hyperpermeability of vessels remains unclear. Here, we studied changes in cytoskeletal configuration and the signaling mechanism induced by AGE in human endothelial cells. AGE-BSA stimulation induced Rho activation, intercellular gap formation, prominent actin stress fiber and cell contraction without changing VE-cadherin, and subsequently transendothelial diffusion of FITC-labeled dextran. These processes induced by AGE-BSA were inhibited by either Rho-kinase inhibitor Y27632 or anti-RAGE antibody. We also showed that RhoA and RAGE spontaneously formed a complex. These findings suggest that activation of RAGE/Rho is involved in AGE-BSA-induced hyperpermeability through gap formation and actin reorganization in diabetes.

Fetal arrhythmia: prenatal diagnosis and perinatal management.

The importance of managing fetal arrhythmia has increased over the past three decades. Although most fetal arrhythmias are benign, some types cause fetal hydrops and can lead to fetal death. With the aim of improving the outcome in such cases, various studies for prenatal diagnosis and perinatal management have been published. Detailed analysis of the type of arrhythmia in utero is possible using M-mode and Doppler echocardiography. In particular, a simultaneous record of Doppler waveform at the superior venous cava and the ascending aorta has become an important and useful method of assessing the interval between atrial and ventricular contractions. Common causes of fetal tachycardia (ventricular heart rate faster than 180 bpm), are paroxysmal supraventricular tachycardia (SVT) with 1:1 atrioventricular (AV) relation and atrial flutter with 2:1 AV relation. Of fetal SVT, short ventriculo-atrial (VA) interval tachycardia due to atrioventricular reentrant tachycardia is more common than long VA interval. Most fetuses with tachycardia are successfully treated in utero by transplacental administration of antiarrhythmic drugs. Digoxin is widely accepted as a first-line antiarrhythmic drug. Sotalol, flecainide and amiodarone are used as second-line drugs when digoxin fails to achieve conversion to sinus rhythm. Fetal bradycardia is diagnosed when the fetal ventricular heart rate is slower than 100 bpm, mainly due to AV block. Approximately half of all cases are caused by associated congenital heart disease, and the remaining cases that have normal cardiac structure are often caused by maternal SS-A antibody. The efficacy of prenatal treatment for fetal AV block is limited compared with treatment for fetal tachycardia. Beta stimulants and steroids have been reported as effective transplacental treatments for fetal AV block. Perinatal management based on prospective clinical study protocol rather than individual experience is crucial for further improvement of outcome in fetuses with tachycardia and bradycardia.

Brain-type natriuretic peptide at birth reflects foetal maturation and antenatal stress.

AIM: Antenatal stress, maturation and other foetal conditions affect the postnatal cardiovascular function. Atrial- (ANP) and brain-type natriuretic peptide (BNP) play important roles in regulating extracellular fluid volume and blood pressure, which may surrogate the foetal cardiovascular condition. The aim of this study was to investigate the dependence of serum ANP and BNP at birth on antenatal variables in high-risk infants. METHODS: Plasma ANP and BNP levels in the umbilical cord blood were compared with antenatal clinical information in 280 infants. RESULTS: High levels of ANP and BNP were associated with multiple pregnancy, antenatal magnesium sulphate and foetal distress. Caesarean section (CS) was paradoxically associated with low ANP and high BNP; low ANP was related with CS before labour whereas high BNP was related with CS after the commencement of labour. High BNP levels further correlated with younger gestational age and intrauteral growth restriction. With regard to short-term postnatal variables, high BNP levels were associated with low Apgar scores and respiratory failure whereas high ANP only correlated with the latter. CONCLUSION: High natriuretic peptide levels were associated with prematurity at birth, uteral contraction and antenatal stress: cord blood ANP and BNP may be a useful surrogate marker for hidden antenatal stress.