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BACKGROUND: AGEs, their receptor (RAGE), and the extracellular newly identified receptor for AGEs product-binding protein (EN-RAGE) are implicated in the pathogenesis of inflammation. AIM: We analyzed serum EN-RAGE, soluble RAGE (sRAGE), and their isoforms: endogenous secretory - esRAGE and cleaved - cRAGE concentrations in lean controls (n = 74) and in patients with obesity (n = 71) treated for three weeks with moderate calorie restriction (CR) combined with physical activity in a hospital condition. METHODS: Using the ELISA method, serum sRAGE, esRAGE, and EN-RAGE were measured before and after CR. RESULTS: The serum level of sRAGE and esRAGE in patients with obesity was lower than that in non-obese individuals, contrary to cRAGE. EN-RAGE concentration was about three times higher in obese patients. Gradually, a rise in BMI resulted in sRAGE, esRAGE reduction, and EN-RAGE increase. The sRAGE concentration was sex-dependent, indicating a higher value in lean men. A moderate negative correlation was observed between BMI and all RAGE isoforms, whereas EN-RAGE displays a positive correlation. CR resulted in an expected decrease in anthropometric, metabolic, and proinflammatory parameters and EN-RAGE, but no RAGE isoforms. The ratio EN-RAGE/sRAGE was higher in obese humans than in control and was not modified by CR. CONCLUSION: Obesity decreases sRAGE and esRAGE and increases EN-RAGE concentration. Moderate CR and physical activity by decreasing inflammation reduces EN-RAGE but is insufficient to increase sRAGE and esRAGE to the extent observed in lean patients. EN-RAGE instead of sRAGE could be helpful to indicate a better outcome of moderate dietary intervention in obese subjects.
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Restricción Calórica , Obesidad , Isoformas de Proteínas , Receptor para Productos Finales de Glicación Avanzada , Humanos , Restricción Calórica/métodos , Masculino , Obesidad/sangre , Obesidad/dietoterapia , Obesidad/terapia , Femenino , Receptor para Productos Finales de Glicación Avanzada/sangre , Adulto , Persona de Mediana Edad , Isoformas de Proteínas/sangre , Índice de Masa Corporal , Ejercicio Físico/fisiología , Receptores Inmunológicos/sangre , Actividad Motora/fisiología , Antígenos de Neoplasias , Proteínas Quinasas Activadas por MitógenosRESUMEN
BACKGROUND: Breast milk, nature's optimum source of nutrition for infants, can contain undesirable microorganisms that cause severe morbidity. After an outbreak of multidrug-resistant Escherichia coli among neonates receiving breast milk donated by another mother in our neonatal intensive care unit (NICU), we were motivated to develop a high-grade breast milk pasteurizer (BMP) designed to thaw and pasteurize breast milk at 63°C for 30 min in a sealed bag without having to open the bag or immerse it in water. METHODS: Pre-existing bacteria and spiked cytomegalovirus (CMV) were measured pre- and post-pasteurization in frozen breast milk donated by mothers of children admitted to the NICU. RESULTS: Among 48 breast milk samples (mean ± standard deviation [SD]), pre-existing bacterial counts of 5.1±1.1 × 104 colony forming units (cfu)/mL decreased to less than 10 cfu/mL (below detection level) in 45 samples after pasteurization for 30 min. In three samples, 10-110 cfu/mL persisted. As no CMV was detected in any of the 48 samples, CMV at ≥5 × 104 pfu/mL was spiked into 11 breast milk samples. After just 10 min of pasteurization, infectious CMV was not detected (threshold <50 pfu/mL) in any sample. CONCLUSION: A new BMP was shown to pasteurize milk effectively with more than a 3-log reduction of microorganisms. Compared to conventional pasteurizers, this device reduces the effort involved in pasteurizing breast milk, avoids various contamination risks, and may reduce the risk of infectious disease transmission via breast milk.
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Infecciones por Citomegalovirus , Leche Humana , Recién Nacido , Lactante , Femenino , Niño , Humanos , Madres , Citomegalovirus , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/prevención & control , Esterilización , Escherichia coliRESUMEN
BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD. METHODS: A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006). CONCLUSIONS: Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants. IMPACT: This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.
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Displasia Broncopulmonar , Enfermedades del Prematuro , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Displasia Broncopulmonar/diagnóstico , Recien Nacido Prematuro , Peso al Nacer , BiomarcadoresRESUMEN
Dualisms are pervasive. The divisions between the rational mind, the physical body, and the external natural world have set the stage for the successes and failures of contemporary cognitive science and artificial intelligence.1 Advanced machine learning (ML) and artificial intelligence (AI) systems have been developed to draw art and compose music. Many take these facts as calls for a radical shift in our values and turn to questions about AI ethics, rights, and personhood. While the discussion of agency and rights is not wrong in principle, it is a form of misdirection in the current circumstances. Questions about an artificial agency can only come after a genuine reconciliation of human interactivity, creativity, and embodiment. This kind of challenge has both moral and theoretical force. In this article, the authors intend to contribute to embodied and enactive approaches to AI by exploring the interactive and contingent dimensions of machines through the lens of Japanese philosophy. One important takeaway from this project is that AI/ML systems should be recognized as powerful tools or instruments rather than as agents themselves.
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Inteligencia Artificial , Música , Creatividad , Humanos , Imaginación , Aprendizaje AutomáticoRESUMEN
Various biological processes show seasonal variations in humans, including important metabolic pathways. Seasonal changes in gene expression may affect annual differences in human immunity. We hypothesized that seasonal changes occur in clock gene expression levels that are associated with body mass index. Six non-obese men and five obese men participated in summer and winter. Two milliliters of saliva were collected, and total RNA was isolated from buccal epithelial cells in saliva. The clock gene expression levels of CLOCK, BMAL1, PER1, CRY2, REV-ERB-α, and REV-ERB-ß were examined by real-time PCR. Blood samples were measured HbA1c, glucose, insulin, adiponectin, IL-6, and TNF-α. Participants were asked about their sleeping hours and seasonal pattern. In the present study, CLOCK, BMAL1, and REV-ERB-ß gene expression levels were significantly lower in winter than in summer; BMAL1 expression level was significantly lower in obese men than in non-obese. Concentrations of adiponectin and insulin were significantly different between obese and non-obese. No significant seasonal effects were observed in HbA1c, glucose, insulin, adiponectin, IL-6, or TNF-α concentrations. Sleep duration did not significantly differ between summer and winter. The short photoperiod during winter might contribute to seasonal alterations in the expression of clock genes in men. In the present results, revealed seasonal differences in clock gene expression levels might be associated with obesity. These results also showed the potential for measuring clock gene expression in a non-invasive manner using saliva samples.
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Ritmo Circadiano , Obesidad , Proteínas CLOCK/genética , Ritmo Circadiano/genética , Células Epiteliales , Expresión Génica , Humanos , Masculino , Obesidad/genética , Proyectos Piloto , Estaciones del AñoRESUMEN
BACKGROUND: During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non-oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF-n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed. STUDY DESIGN AND METHODS: To assess the performance of PAF-n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre-filtration and serial post-filtration (0-30 mL, 30-60 mL, 60-90 mL, and 90-120 mL) samples from 8 RBC components. RESULTS: The average potassium adsorption rate of the PAF-n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%. CONCLUSION: The PAF-n showed an effective potassium ability with negligible RBC dilution.
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Transfusión de Eritrocitos , Hiperpotasemia/prevención & control , Potasio/sangre , Adsorción , Humanos , Hiperpotasemia/sangre , Recién NacidoRESUMEN
To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time-international normalized ratio correlated with intraventricular hemorrhage (p = 0.000; ß = 0.180) and placental abruption (PA; p = 0.000; ß = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p = 0.000; ß = - 0.217), gestational age (GA; p = 0.000; ß = - 0.282), and PA (p = 0.000; ß = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome (p = 0.007; ß = - 0.114), pregnancy-induced hypertension (p = 0.000; ß = - 0.141), and Apgar score at 1 minute (p = 0.043; ß = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes (p = 0.049). Finally, antithrombin III levels positively correlated with GA (p = 0.000) and BW (p = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates.
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Factores de Coagulación Sanguínea/análisis , Recién Nacido/sangre , Recien Nacido Prematuro/sangre , Antitrombinas/sangre , Peso al Nacer , Hemorragia Cerebral Intraventricular/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Edad Gestacional , Humanos , Relación Normalizada Internacional , Análisis Multivariante , Tiempo de Tromboplastina Parcial , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Estudios Retrospectivos , Nacimiento a TérminoRESUMEN
CONTEXT: Amaranth and canola oils have been used traditionally. Amaranth has been identified as being of interest because of its outstanding nutritive value. Amaranth oil is a rich source of highly unsaturated fats and so could be a valuable dietary alternative for individuals affected with obesity. Reactive oxygen species (ROS) are postulated to be involved in systemic inflammation and oxidative stress. Activated polymorphonuclear neutrophils (PMNs) generate high amounts of reactive oxygen species. OBJECTIVE: Our study investigates the impact of amaranth and canola oils supplementation on oxidative metabolism in patients with obesity. We hypothesized that, due to its lipid-lowering and antioxidant properties, amaranth and canola oil would protect against oxidative stress. MATERIALS AND METHODS: We tested 19 obese patients [body mass index (BMI) = 41.1 ± 7.8 kg/m2, (mean ± SD)]. The protocol consisted of two stages: a run-in phase of 2 weeks and an experimental stage - canola or amaranth oil supplementation (20 mL/d) with calorie restriction diet for 3 weeks. The neutrophil oxidative burst was expressed by fluorescence intensity (IF). RESULTS: The oxidative burst had increased significantly at the end of treatment in both groups IF: (21.4 ± 11.15 vs. 35.9 ± 20.3; mean ± SD) p < 0.05. The levels of IF were significantly higher in neutrophils of patients who received canola oil (41.05 ± 25.3) compared to those who received amaranth oil (28.4 ± 11.8) p < 0.05. CONCLUSIONS: Canola oil exerts possible effects on oxidative burst activity in neutrophils in vivo conditions.
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Amaranthus/química , Neutrófilos/efectos de los fármacos , Obesidad/sangre , Obesidad/dietoterapia , Aceite de Brassica napus/farmacología , Adulto , Anciano , Antioxidantes/farmacología , Brassica napus/química , Suplementos Dietéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Aceites de Plantas/farmacología , Estallido Respiratorio/efectos de los fármacosRESUMEN
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.
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Anomalías Múltiples/sangre , Síndrome de Beckwith-Wiedemann/sangre , Cara/anomalías , Enfermedades Hematológicas/sangre , Hiperinsulinismo/sangre , Hipoglucemia/sangre , Síndrome de Sotos/sangre , Enfermedades Vestibulares/sangre , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/epidemiología , Puntaje de Apgar , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/epidemiología , Femenino , Pruebas Genéticas , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/epidemiología , Pruebas Hematológicas , Humanos , Recién Nacido , Japón/epidemiología , Masculino , Fenotipo , Vigilancia de la Población , Embarazo , Complicaciones del Embarazo/epidemiología , Síndrome de Sotos/diagnóstico , Síndrome de Sotos/epidemiología , Encuestas y Cuestionarios , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/epidemiologíaRESUMEN
Light is the strongest synchronizer controlling circadian rhythms. The intensity and duration of light change throughout the year, thereby influencing body weight, food preferences, and melatonin secretion in humans and animals. Although the expression of clock genes has been examined using human samples, it currently remains unknown whether bright light during the daytime affects the expression of these genes in humans. Therefore, we herein investigated the effects of bright light exposure during the daytime on clock gene expression in the hair follicular and root cells of the human scalp. Seven healthy men (20.4 ± 2.2 years old; 172.3 ± 5.8 cm; 64.3 ± 8.5 kg; BMI 21.7 ± 3.1 kg/m2, mean ± SD) participated in this study. Subjects completed 3-day experimental sessions twice in 1 month during which they were exposed to bright and dim light conditions. The mRNA expression of Per1-3, Cry1-2, Rev-erb-α (Nr1d1), Rev-erb-ß (Nr1d2), and Dec1 was analyzed using branched DNA probes. No significant changes were observed in the expression of Per1, Per2, Per3, Cry1, Cry2, Rev-erb-α (Nr1d1), or Dec1 following exposure to bright light conditions. However, the expression of Rev-erb-ß (Nr1d2) tended to be stronger under bright light than dim light conditions. These results suggest that the bright light stimulus did not influence the expression of clock genes in humans. Long-lasting bright light exposure during the daytime may be required to change the expression of clock genes in humans.
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Péptidos y Proteínas de Señalización del Ritmo Circadiano/genética , Expresión Génica/efectos de la radiación , Luz , Adolescente , Adulto , Folículo Piloso/citología , Folículo Piloso/metabolismo , Humanos , Masculino , ARN Mensajero/metabolismo , Adulto JovenRESUMEN
Aim We determined whether the bacteria in the lower respiratory tract (LRT) in extremely premature infants with severe bronchopulmonary dysplasia (BPD) are different from those with nonsevere BPD. Study Design We conducted a retrospective study of extremely premature infants who were admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Japan between April 2005 and March 2014. We screened for the bacterial colonization of the LRT using tracheobronchial aspirate fluid. Results A total of 169 extremely premature infants were included. Overall, 102 did not experience severe BPD, whereas the remaining 67 experienced severe BPD. Corynebacterium species (Cs) were more frequently detected in the severe BPD than nonsevere BPD infants (p = 0.03). There were significant differences between infants with and without severe BPD in the duration of endotracheal ventilation (p = 0.00, odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), the duration of supplemental oxygen (p = 0.00, OR, 1.02; 95% CI, 1.01-1.03) before 36 weeks of postmenstrual age, and the frequency of sepsis after 7 postnatal days (p = 0.01, OR, 1.73; 95% CI, 1.18-2.54). Conclusion Cs are more likely to be present in the severe BPD infants with longer duration of endotracheal ventilation.
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Bronquios/microbiología , Displasia Broncopulmonar/microbiología , Microbiota , Tráquea/microbiología , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/fisiopatología , Candida/aislamiento & purificación , Estudios de Casos y Controles , Hemorragia Cerebral Intraventricular/epidemiología , Corynebacterium/aislamiento & purificación , Enterococcus faecalis/aislamiento & purificación , Femenino , Bacterias Gramnegativas/aislamiento & purificación , Humanos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Tiempo de Internación , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Sepsis Neonatal/epidemiología , Terapia por Inhalación de Oxígeno , Neumonía/epidemiología , Respiración Artificial , Retinopatía de la Prematuridad/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Staphylococcus/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificación , Streptococcus agalactiae/aislamiento & purificación , Factores de Tiempo , Estreptococos Viridans/aislamiento & purificaciónRESUMEN
BACKGROUND: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants. METHODS: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W. RESULTS: Intotal, 30 infants were included. Themediangestationalageoftheinfantswas 26 weeks 5 days (range, 23 weeks 1 day-28 weeks 6 days), and the median birth weight was 731 g (range, 398-1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05 -0.59) in infants on admission and constantly < 0.05 in those between Day 10 and Day 56 after birth. There was no correlation of GV/W with clinical variables after birth. CONCLUSION: It is considered that GB volume is not affected by serial changes without nonfavor-able course of enteral nutrition.
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Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-ß1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-ß1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-ß1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-ß1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis.
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Síndrome de Down/sangre , Síndrome de Down/complicaciones , Reacción Leucemoide/sangre , Reacción Leucemoide/complicaciones , Factor de Crecimiento Transformador beta1/sangre , Citocinas/sangre , Resultado Fatal , Femenino , Humanos , Lactante , Masculino , EmbarazoRESUMEN
While the significance of obesity as a serious health problem is well recognized, little is known about whether and how biometerological factors and biorhythms causally contribute to obesity. Obesity is often associated with altered seasonal and daily rhythmicity in food intake, metabolism and adipose tissue function. Environmental stimuli affect both seasonal and daily rhythms, and the latter are under additional control of internal molecular oscillators, or body clocks. Modifications of clock genes in animals and changes to normal daily rhythms in humans (as in shift work and sleep deprivation) result in metabolic dysregulation that favours weight gain. Here, we briefly review the potential links between biorhythms and obesity in humans.
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Relojes Biológicos , Ritmo Circadiano , Modelos Biológicos , Obesidad/fisiopatología , Periodicidad , Estaciones del Año , Tejido Adiposo/fisiopatología , Proteínas CLOCK/metabolismo , Fenómenos Cronobiológicos , Ingestión de Alimentos , Metabolismo Energético , Humanos , Intestinos/fisiopatología , SueñoRESUMEN
While atrial septal defect (ASD) may contribute to right ventricular decompression in patients with severe pulmonary hypertension (PH), the pulmonary vasculature might be compromised by increased pulmonary blood flow, even though pulmonary vasodilators successfully reduce resistance. ASD closure is a treatment option that may ameliorate PH symptoms associated with bronchopulmonary dysplasia (BPD) in infants. However, the feasibility of ASD closure is obscure in patients with BPD-PH causing right-to-left shunting. Here, we present an eight-month-old girl with ASD complicated by BPD-PH, in which the pulmonary pressure exceeded the systemic pressure; the ASD was successfully closed after pulmonary preconditioning with dexamethasone and high-dose diuretics. Our patient was delivered as the third baby in triplets at a gestational age of 25 weeks, with a birth weight of 344 g. She was diagnosed with BPD at three months of age (37 weeks of postmenstrual age) with a body weight of 1.4 kg. Mild pulmonary hypertension was identified at the age of five months, and oral sildenafil was initiated. While her atrial septal defect was small at the time of PH diagnosis, it became hemodynamically significant when she grew up to 3.4 kg of body weight, at seven months after birth. Her estimated right ventricular pressure was apparently more than the systemic pressure, and oxygen saturation fluctuated between 82% and 97% under oxygen supplementation due to bidirectional interatrial shunt with predominant right-to-left shunting. Pulmonary preconditioning lowered the estimated right ventricular pressure to almost equal the systemic pressure and elevated arterial oxygen saturation while also suppressing right-to-left shunting. Cardiac catheterization after preconditioning revealed a ratio of pulmonary blood pressure to systemic blood pressure ratio (Pp/Ps) of 0.9, pulmonary resistance of 7.3 WU-m2, and a pulmonary to systemic blood flow ratio (Qp/Qs) of 1.3 (approximately 1.0 in the normal circulation without significant shunt), with the cardiac index of 2.8 L/min/m2. The acute pulmonary vasoreactivity test against the combination of 20 ppm nitric oxide and 100% oxygen was negative, although the patient had consistently high pulmonary flow with makeshift improvements after preconditioning. Despite the high pulmonary resistance even after preconditioning, aggressive ASD closure was performed so that pulmonary flow could be consistently suppressed regardless of the pulmonary condition. Her Pp/Ps under 100% oxygen with 20 ppm nitric oxide was 0.7 immediately after closure. After two years of follow-up, her estimated right ventricular pressure was less than half of the systemic pressure with the use of three pulmonary vasodilators, including sildenafil, macitentan, and beraprost. A strategy to temporarily improve PH and respiratory status aimed at ASD closure could be a treatment option for the effective use of multiple pulmonary vasodilators, by which intensive treatment of BPD can be achieved.
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Comorbid Alzheimer's disease (AD) neuropathology is common in Lewy body disease (LBD); however, AD comorbidity in the prodromal phase of LBD remains unclear. This study investigated AD comorbidity in the prodromal and symptomatic phases of LBD by analyzing plasma biomarkers in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and individuals at risk of LBD (NaT-PROBE cohort). Patients with PD (PD group, n = 84) and DLB (DLB group, n = 16) and individuals with LBD with ≥ 2 (high-risk group, n = 82) and without (low-risk group, n = 37) prodromal symptoms were enrolled. Plasma amyloid-beta (Aß) composite was measured using immunoprecipitation-mass spectrometry assays. Plasma phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and alpha-synuclein (aSyn) were measured using a single-molecule array. Plasma p-tau181 levels were higher in the PD and DLB groups than in the low-risk group. Aß composite level was higher in the DLB group than in the high-risk group. AD-related biomarker levels were not elevated in the high-risk group. NfL levels were higher in the high-risk, PD, and DLB groups than in the low-risk group. In the PD group, Aß composite was associated with cognitive function, p-tau181 with motor function and non-motor symptoms, and NfL with cognitive and motor functions and non-motor symptoms. In the high-risk group, NfL was associated with metaiodobenzylguanidine scintigraphy abnormalities. The PD and DLB groups exhibited comorbid AD neuropathology, though not in the prodromal phase. Elevated plasma NfL levels, even without elevated AD-related plasma biomarker levels, may indicate aSyn-induced neurodegeneration in the LBD prodromal phase.
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Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation.
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BACKGROUND: Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown. OBJECTIVES: The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and ß in the whole blood of preterm and term infants. STUDY DESIGN: The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA. RESULTS: GRß mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRß isoforms were detected at a ratio of 1:0.0002. GRß mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRß ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRß/GAPDH expression and birth weight (rs=-0.296, p=0.030). Furthermore, in preterm infants, GRß/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022). CONCLUSION: Importantly, in preterm infants, both the expression of GRß and the GRα/GRß ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants.
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Recien Nacido Prematuro/sangre , Receptores de Glucocorticoides/sangre , Adulto , Estudios de Casos y Controles , Femenino , Expresión Génica/fisiología , Humanos , Recién Nacido , Recien Nacido Prematuro/metabolismo , Masculino , Parto/sangre , Parto/genética , Parto/metabolismo , Embarazo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Nacimiento a Término/sangre , Nacimiento a Término/genética , Nacimiento a Término/metabolismo , Adulto JovenRESUMEN
The effects of environmental temperature on blood pressure and hormones in obese subjects in Japan were compared in two seasons: summer vs winter. Five obese (BMI, 32 ± 5 kg/m(2)) and five non-obese (BMI, 23 ±3 kg/m(2)) men participated in this experiment at latitude 35°10' N and longitude 136°57.9' E. The average environmental temperature was 29 ± 1 °C in summer and 3 ± 1 °C in winter. Blood samples were analyzed for leptin, ghrelin, catecholamines, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total cholesterol, triglycerides, insulin and glucose. Blood pressure was measured over the course of 24 h in summer and winter. A Japanese version of the Profile of Mood States (POMS) questionnaire was also administered each season. Systolic and diastolic blood pressures in obese men were significantly higher in winter (lower environmental temperatures) than in summer (higher environmental temperatures). Noradrenaline and dopamine concentrations were also significantly higher at lower environmental temperatures in obese subjects, but ghrelin, TSH, fT3, fT4, insulin and glucose were not significantly different in summer and winter between obese and non-obese subjects. Leptin, total cholesterol and triglyceride concentrations were significantly higher in winter in obese than non-obese men. Results from the POMS questionnaire showed a significant rise in Confusion at lower environmental temperatures (winter) in obese subjects. In this pilot study, increased blood pressure may have been due to increased secretion of noradrenaline in obese men in winter, and the results suggest that blood pressure control in obese men is particularly important in winter.
Asunto(s)
Obesidad/sangre , Obesidad/fisiopatología , Temperatura , Adulto , Glucemia/análisis , Presión Sanguínea , Catecolaminas/sangre , Colesterol/sangre , Ghrelina/sangre , Humanos , Insulina/sangre , Japón , Leptina/sangre , Masculino , Proyectos Piloto , Estaciones del Año , Tirotropina/sangre , Tiroxina/sangre , Triglicéridos/sangre , Triyodotironina/sangre , Adulto JovenRESUMEN
During the past several decades, obesity has been increasing globally. In Japan, obesity is defined by a BMI of 25 kg/m² or over; 28.6 % of men and 20.6 % of women are obese. Obese people have an increased incidence of developing cardiovascular, renal, and hormonal diseases and sleep disorders. Obese people also have shortened sleep durations. We investigated seasonal differences in melatonin concentrations, heart rates, and heart rate variability during sleep in obese subjects in Japan. Five obese (BMI, 32.0 ± 4.9 kg/m²) and five non-obese (BMI, 23.2 ± 2.9 kg/m²) men participated in this study in the summer and winter. Electrocardiograms were measured continuously overnight in a climatic chamber at 26 °C with a relative humidity of 50 %. Saliva samples for melatonin were collected at 2300 hours, 0200 hours, and 0600 hours. We found that melatonin concentrations during sleep in obese subjects were significantly lower than those in non-obese subjects in the winter. Heart rate during sleep in winter was significantly higher than that in summer in both obese and non-obese subjects. Heart rate variability was not significantly different in the summer and winter in both obese and non-obese subjects. Our results show that decreased nocturnal melatonin concentrations during winter in obese men may be related to higher heart rates, and this may suggest that obese men are at an increased risk of a cardiovascular incident during sleep, especially in the winter.