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BACKGROUND: To explore the predictive value of the Thompson score during the first 4 days of life for estimating short-term adverse outcomes in neonatal encephalopathy. METHODS: This observational study evaluated infants with neonatal encephalopathy (≥36 weeks of gestation) registered in a multicenter cohort of cooled infants in Japan. The Thompson score was evaluated at 0-24, 24-48, 48-72, and 72-90 h of age. Adverse outcomes included death, survival with respiratory impairment (requiring tracheostomy), or survival with feeding impairment (requiring gavage feeding) at discharge. RESULTS: Of the 632 infants, 21 (3.3%) died, 59 (9.3%) survived with respiratory impairment, and 113 (17.9%) survived with feeding impairment. The Thompson score throughout the first 4 days accurately predicted death, respiratory impairment, or feeding impairment. The 72-90 h score showed the highest accuracy. A cutoff of ≥15 had a sensitivity of 0.85 and specificity of 0.92 for death or respiratory impairment, while a cutoff of ≥14 had a sensitivity of 0.71 and a specificity of 0.92 for death, respiratory or feeding impairment. CONCLUSION: A high Thompson score during the first 4 days of life, especially at 72-90 h could thus be useful for estimating the need for prolonged life support. IMPACT: The Thompson score on days 1-4 of age was useful in predicting death and respiratory or feeding impairments. The 72-90 h Thompson score showed the highest predictive capability. Owing to the rarity of withdrawal of life-sustaining treatment in Japan, 43% of infants with persistent severe encephalopathy with a Thompson score of ≥15 at 72-90 h of age could regain spontaneous breathing, be extubated, and survive without tracheostomy. Meanwhile, approximately 50% of infants who survived without tracheostomy required gavage feeding. Our results could provide useful information for clinical decision making regarding infants with persistent severe encephalopathy.
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Encefalopatias , Hipotermia Induzida , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Humanos , Hipotermia Induzida/métodos , Doenças do Recém-Nascido/terapia , Encefalopatias/diagnóstico , Encefalopatias/terapia , Tomada de Decisão Clínica , JapãoRESUMO
AIM: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia. METHODS: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age. RESULTS: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85). CONCLUSION: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia.
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Asfixia Neonatal , Encefalopatias , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Recém-Nascido , Lactente , Criança , Humanos , Nutrição Enteral , Estudos Retrospectivos , Respiração Artificial , Asfixia Neonatal/terapia , Encefalopatias/etiologia , Doenças do Recém-Nascido/terapia , Hipotermia Induzida/efeitos adversos , Hipóxia-Isquemia Encefálica/terapiaRESUMO
Purpose: This study aimed to explore whether umbilical cord-derived mesenchymal stem cells (UC-MSCs) could be used as a therapeutic resource for endometriosis. Methods: Of seven cynomolgus monkeys with endometriosis, five were administered UC-MSCs (intervention group) and two were administered saline (control group). First, intravenous US-MSC treatment was administered for three months. Second, weekly intravenous US-MSC administration combined with monthly intraperitoneal US-MSC administration was conducted for 3 months. Finally, weekly intraperitoneal US-MSC administration was conducted for 3 months. The dose of UC-MSCs was set to 2 × 106 cells/kg for all administration routes. Laparoscopic findings and serum cancer antigen 125 (CA125) levels were also evaluated. The Revised American Society for Reproductive Medicine classification was used for laparoscopic evaluation. Results: Laparoscopic findings showed exacerbation of endometriosis after intraperitoneal UC-MSC administration, although no changes were observed in the control group. Intravenous UC-MSC administration decreased the level of CA125 in all monkeys; however, the difference was not significant. Intraperitoneal UC-MSC administration significantly exacerbated endometriosis compared with intravenous administration (p = 0.02). Conclusions: This study revealed that intraperitoneal UC-MSC administration exacerbates endometriosis in a nonhuman primate model of the disease.
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BACKGROUND: Therapeutic hypothermia is a standard of care for neonatal encephalopathy; however, approximately one in two newborn infants fails to respond to this treatment. Recent studies have suggested potential relationships between body temperature, heart rate and the outcome of cooled infants. METHODS: The clinical data of 756 infants registered to the Baby Cooling Registry of Japan between January 2012 and December 2016 were analysed to assess the relationship between body temperature, heart rate and adverse outcomes (death or severe impairment at 18 months corrected age). RESULTS: A lower body temperature at admission was associated with adverse outcomes in the univariate analysis (P < 0.001), the significance of which was lost when adjusted for the severity of encephalopathy and other covariates. A higher body temperature during cooling and higher heart rate before and during cooling were associated with adverse outcomes in both univariate (all P < 0.001) and multivariate (P = 0.012, P < 0.001 and P < 0.001, respectively) analyses. CONCLUSIONS: Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling, whereas causal relationships between slightly higher temperatures during cooling and adverse outcomes need to be elucidated in future studies. IMPACT: In a large cohort of encephalopathic newborn infants, dual roles of body temperature to the outcome were shown; adverse outcomes were associated with a lower body temperature at admission and higher body temperature during cooling. A higher heart rate before and during cooling were associated with adverse outcomes. Severe hypoxia-ischaemia might be a common causative of faster heart rates before and during cooling and low body temperature before cooling. The exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes remains unknown, which needs to be elucidated in future studies.
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Encefalopatias , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Temperatura Corporal , Encefalopatias/terapia , Frequência Cardíaca , Humanos , Hipotermia Induzida/efeitos adversos , Hipóxia/terapia , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/terapia , Lactente , Recém-NascidoRESUMO
Traumatic central nervous system (CNS) injury often causes irreversible impairment, and new alternative therapies for the treatment of CNS injury and sequelae are expected to be developed. Recently, mesenchymal stromal cells (MSCs) have started being used as cell therapy for neurological disorders such as traumatic CNS injury based on their immunomodulatory, neuroprotective, and neurorestorative abilities. Based on the premise of basic research, numerous clinical trials using MSCs for the treatment of traumatic CNS injury have been performed, and the feasibility and efficacy of this therapy have been reported. In this review we aimed to shed light on the characteristics of MSCs and to discuss the basic and clinical research and recent progress in clinical studies using MSCs to treat various traumatic neurological injuries.
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Células-Tronco Mesenquimais , Traumatismos do Sistema Nervoso , Terapia Baseada em Transplante de Células e Tecidos , Sistema Nervoso Central , HumanosRESUMO
Neonatal hypoxic-ischemic encephalopathy (HIE) causes permanent motor deficit "cerebral palsy (CP)," and may result in significant disability and death. Therapeutic hypothermia (TH) had been established as the first effective therapy for neonates with HIE; however, TH must be initiated within the first 6 hours after birth, and the number needed to treat is from 9 to 11 to prevent brain damage from HIE. Therefore, additional therapies for HIE are highly needed. In this review, we provide an introduction on the mechanisms of HIE cascade and how TH and cell therapies such as umbilical cord blood cells and mesenchymal stromal cells (MSCs), especially umbilical cord-derived MSCs (UC-MSCs), may protect the brain in newborns, and discuss recent progress in regenerative therapies using UC-MSCs for neurological disorders.The brain damage process "HIE cascade" was divided into six stages: (1) energy depletion, (2) impairment of microglia, (3) inflammation, (4) excitotoxity, (5) oxidative stress, and (6) apoptosis in capillary, glia, synapse and/or neuron. The authors showed recent 13 clinical trials using UC-MSCs for neurological disorders.The authors suggest that the next step will include reaching a consensus on cell therapies for HIE and establishment of effective protocols for cell therapy for HIE. KEY POINTS: · This study includes new insights about cell therapy for neonatal HIE and CP in schema.. · This study shows precise mechanism of neonatal HIE cascade.. · The mechanism of cell therapy by comparing umbilical cord blood stem cell with MSC is shown.. · The review of recent clinical trials of UC-MSC is shown..
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Lesões Encefálicas , Paralisia Cerebral , Hipóxia-Isquemia Encefálica , Células-Tronco Mesenquimais , Humanos , Recém-Nascido , Hipóxia-Isquemia Encefálica/prevenção & controle , Hipóxia-Isquemia Encefálica/etiologia , Sangue Fetal , Cordão Umbilical , Lesões Encefálicas/complicações , EncéfaloRESUMO
BACKGROUND: Neuroinflammation plays an important role in neonatal hypoxic-ischemic encephalopathy (HIE). Although microglia are largely responsible for injury-induced inflammatory response, they play beneficial roles in both normal and disease states. However, the effects of microglial depletion on neonatal HIE remain unclear. METHODS: Tamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ (microglia-depleted model) and Cx3cr1CreER/+Rosa26DTA/- (control) mice at P8 and P9 to assess the effect of microglial depletion. The density of microglia was quantified using Iba-1 staining. Moreover, the proportion of resident microglia after the HI insult was analyzed using flow cytometric analysis. At P10, the HI insult was conducted using the Rice-Vannucci procedure at P10. The infarct size and apoptotic cells were analyzed at P13. Cytokine analyses were performed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at P13. RESULTS: At P10, tamoxifen administration induced > 99% microglial depletion in DTA+ mice. Following HI insult, there was persisted microglial depletion over 97% at P13. Compared to male DTA- mice, male DTA+ mice exhibited significantly larger infarct volumes; however, there were no significant differences among females. Moreover, compared to male DTA- mice, male DTA+ mice had a significantly higher density of TUNEL+ cells in the caudoputamen, cerebral cortex, and thalamus. Moreover, compared to female DTA- mice, female DTA+ mice showed a significantly greater number of TUNEL+ cells in the hippocampus and thalamus. Compared to DTA- mice, ELISA revealed significantly lower IL-10 and TGF-ß levels in both male and female DTA+ mice under both normal conditions and after HI (more pronounced). CONCLUSION: We established a microglial depletion model that aggravated neuronal damage and apoptosis after the HI insult, which was predominantly observed in males.
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Hipóxia-Isquemia Encefálica/patologia , Microglia , Neurônios/patologia , Caracteres Sexuais , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos TransgênicosAssuntos
Síndromes Mielodisplásicas , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Feminino , Humanos , Recém-Nascido , Mães , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Trombocitopenia/diagnóstico , Trombocitopenia/etiologiaRESUMO
BACKGROUND AIMS: The human umbilical cord (UC) is a rich source of mesenchymal stromal cells (MSCs), which have been reported to have multi-lineage potential. The objectives of this study were to investigate the characteristics and capacity of UC-MSC neurosphere formation and whether this event enhances the propensity of UC-MSCs to undergo neural differentiation. METHODS: UC-MSCs were collected by the improved explant method. UC-MSCs and neurosphere-forming UC-MSCs (UC-MSC-neurospheres) were induced to undergo neurogenic differentiation, the latter of which were induced by suspension culturing in the presence of epidermal growth factor and basic fibroblast growth factor. The differentiation and migratory capacities of the individual cultures were then compared on the basis of the expression of neural markers, as measured by immunocytochemistry, immunoblotting and quantitative real-time polymerase chain reaction and transwell assays, respectively. RESULTS: Both UC-MSCs and UC-MSC-neurospheres were capable of differentiating into neurogenic cells when cultured in neurogenic differentiation medium. However, pre-conditioned UC-MSC-neurospheres exhibited significantly higher expression of neural markers--including microtubule-associated protein (MAP2), MUSASHI1, glial fibrillary acidic protein (GFAP), and NESTIN--compared with those derived from UC-MSCs directly. Moreover, UC-MSC-neurospheres expressed significantly higher levels of the stemness markers NANOG, KLF4 and OCT4 than did UC-MSCs. Migration assays also revealed that both UC-MSCs and UC-MSC-neurospheres actively migrate toward glucose-depleted cells. CONCLUSIONS: Neurogenic differentiation potential probably is greater in UC-MSC-neurospheres than in UC-MSCs. Thus, UC-MSC-neurospheres may serve as a better source of cells for neurogenic regenerative medicine.
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Células-Tronco Mesenquimais/citologia , Neurogênese/fisiologia , Esferoides Celulares/citologia , Cordão Umbilical/citologia , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Movimento Celular/fisiologia , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Proteína Glial Fibrilar Ácida/biossíntese , Proteínas de Homeodomínio/biossíntese , Humanos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/biossíntese , Proteínas Associadas aos Microtúbulos/biossíntese , Proteína Homeobox Nanog , Proteínas do Tecido Nervoso/biossíntese , Nestina/biossíntese , Fator 3 de Transcrição de Octâmero/biossíntese , Proteínas de Ligação a RNA/biossíntese , Reação em Cadeia da Polimerase em Tempo RealRESUMO
The 22q11.2 deletion syndrome has many complications; one of them is immunodeficiency. However, the time of onset and the degree of immunodeficiency can vary. We report a case of a preterm infant with congenital cytomegalovirus infection complicated with 22q11.2 deletion syndrome and immunological abnormalities. Ultrasonography revealed pulmonary atresia, ventricular septal defect, major aortopulmonary collateral artery, and thymic hypoplasia. His serum chemistry tests on admission revealed immunoglobulin G, A, and M levels of 1,547 mg/dL, 70 mg/dL, and 274 mg/dL, respectively. A surface antigen analysis of the peripheral lymphocytes using flow cytometry revealed the following: relatively low CD4-positive T-cell levels (18.1%; 1,767/µL), very high CD8-positive T-cell levels (58.9%; 5,751/µL), and CD4/CD8 ratio of 0.31. The level of T-cell receptor excision circles was relatively low at 17.5 copies/µL. After birth, the CD8-positive T-cell level began to gradually decrease, whereas the CD4/CD8 ratio began to increase. Thrombocytopenia, neutropenia, and skin petechiae were observed on admission. However, the condition improved. Treatment for congenital cytomegalovirus infection was not provided due to the absence of viremia. Unfortunately, the patient died suddenly on the 158th day of life, and the cause of death was unknown. To the best of our knowledge, no association between 22q11 deletion syndrome and cCMV has been described in the recent medical literature. According to the calculation, around one newborn infant who have both 22q11 deletion syndrome and cCMV infection will be born each year in Japan. Healthcare providers should pay more attention to this medical situation in the future.
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Infecções por Citomegalovirus , Síndrome de DiGeorge , Cardiopatias Congênitas , Atresia Pulmonar , Lactente , Humanos , Recém-Nascido , Síndrome de DiGeorge/complicações , Recém-Nascido Prematuro , Infecções por Citomegalovirus/complicaçõesRESUMO
Ectopia cordis is a rare condition with expected low survival rate based on past studies. We encountered a case of a preterm and low birth weight infant with ectopia cordis. When the infant cried, the prolapse of the heart, liver, and intestinal tract worsened. A pressure-applying protector was used to protect the organs and reduce the prolapse. Upon application, the infant's tachypnea and desaturation worsened. Fluoroscopic examination suggested that the pressure from the prolapsed regions was impeding pulmonary expansion and negatively affecting circulation. It is essential to carefully design a protector that accommodates the infant's growth.
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Introduction: Mesenchymal stromal cells (MSCs) are activated upon inflammation and/or tissue damage and migrate to suppress inflammation and repair tissues. Migration is the first important step for MSCs to become functional; however, the migration potency of umbilical cord-derived MSCs (UC-MSCs) remains poorly understood. Thus, we aimed to assess the migration potency of UC-MSCs in comparison with those of bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) and investigate the influence of chemotactic factors on the migration of these cells. Methods: We compared the migration potencies of UC-, BM-, and AD-MSCs toward allogeneic stimulated mononuclear cells (MNCs) in mixed lymphocyte reaction (MLR). The number of MSCs in the upper chamber that migrated toward the MLR in the lower chamber was counted using transwell migration assay. Results and discussion: UC-MSCs showed significantly faster and higher proliferation potencies and higher migration potency toward unstimulated MNCs and MLR than BM- and AD-MSCs, although the migration potencies of the three types of MSCs were comparable when cultured in the presence of fetal bovine serum. The amounts of CCL2, CCL7, and CXCL2 in the supernatants were significantly higher in UC-MSCs co-cultured with MLR than in MLR alone and in BM- and AD-MSCs co-cultured with MLR, although they did not induce the autologous migration of UC-MSCs. The amount of CCL8 was higher in BM- and AD-MSCs than in UC-MSCs, and the amount of IP-10 was higher in AD-MSCs co-cultured with MLR than in UC- and BM-MSCs. The migration of UC-MSCs toward the MLR was partially attenuated by platelet-derived growth factor, insulin-like growth factor 1, and matrix metalloproteinase inhibitors in a dose-dependent manner. Conclusion: UC-MSCs showed faster proliferation and higher migration potency toward activated or non-activated lymphocytes than BM- and AD-MSCs. The functional chemotactic factors may vary among MSCs derived from different tissue sources, although the roles of specific chemokines in the different sources of MSCs remain to be resolved.
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BACKGROUND: Inherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17. METHOD: Clinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. RESULTS: The patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency. CONCLUSION: This is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.
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Glicosilfosfatidilinositóis , Dissomia Uniparental , Humanos , Masculino , Hidrolases de Éster Carboxílico , Mutação da Fase de Leitura , Glicosilfosfatidilinositóis/deficiência , Glicosilfosfatidilinositóis/genética , Homozigoto , Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/patologia , Distúrbios do Metabolismo do Fósforo/genética , Distúrbios do Metabolismo do Fósforo/patologia , Receptores de Superfície Celular , Convulsões , Dissomia Uniparental/genética , Dissomia Uniparental/patologia , Recém-NascidoRESUMO
Meconium, a non-invasive biomaterial reflecting prenatal substance accumulation, could provide valuable insights into neonatal health. However, the comprehensive protein profile of meconium across gestational ages remains unclear. Here, we conducted an extensive proteomic analysis of first meconium from 259 newborns across varied gestational ages to delineate protein composition and elucidate its relevance to neonatal diseases. The first meconium samples were collected, with the majority obtained before feeding, and the mean time for the first meconium passage from the anus was 11.9 ± 9.47 h. Our analysis revealed 5370 host-derived meconium proteins, which varied depending on sex and gestational age. Specifically, meconium from preterm infants exhibited elevated concentrations of proteins associated with the extracellular matrix. Additionally, the protein profiles of meconium also exhibited unique variations depending on both specific diseases, including gastrointestinal diseases, congenital heart diseases, and maternal conditions. Furthermore, we developed a machine learning model to predict gestational ages using meconium proteins. Our model suggests that newborns with gastrointestinal diseases and congenital heart diseases may have immature gastrointestinal systems. These findings highlight the intricate relationship between clinical parameters and meconium protein composition, offering potential for a novel approach to assess neonatal gastrointestinal health.
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Idade Gestacional , Aprendizado de Máquina , Mecônio , Proteômica , Humanos , Mecônio/metabolismo , Recém-Nascido , Feminino , Masculino , Proteômica/métodos , Recém-Nascido Prematuro/metabolismo , Gastroenteropatias/metabolismo , Cardiopatias Congênitas/metabolismo , Gravidez , Proteoma/metabolismoRESUMO
When treating patients with EBV encephalitis, the possibility of XLP should be considered. Once the diagnosis of XLP is made, aggressive treatment such as rituximab, and other immunosuppressive agents are desired for rapid transition to HSCT.
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ALCAPA should be considered in the differential diagnosis of myocarditis, and contrast-enhanced CT or catheterization should be considered even if coronary artery abnormalities are not detected on echocardiography.
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Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social communication, repetitive behaviors, and restricted interests, with onset early in life. The prevalence of ASD has increased worldwide in the last two decades. However, there is currently no effective therapy for ASD. Therefore, it is important to develop new strategies for ASD treatment. Evidence for the relationship between ASD and neuroinflammation, ASD and microglia, and ASD and glucose metabolism has increased rapidly in recent decades. We reviewed 10 clinical studies on cell therapies for individuals with ASD. Almost all studies showed good outcomes and no remarkable adverse events. Over the past decades, the neurophysiological characteristics of ASD have been shown to be impaired communication, cognition, perception, motor skills, executive function, theory of mind, and control of emotions. Recent studies have focused on the roles of immune pathology, such as neuroinflammation, microglia, cytokines, and oxidative stress, in ASD. We also focused on glucose metabolism in patients with ASD. The significance of gap junction-mediated cell-cell interactions between the cerebral endothelium and transplanted cells was observed in both bone marrow mononuclear cells and mesenchymal stromal cells transplantation. Owing to the insufficient number of samples, cell therapies, such as umbilical cord blood cells, bone marrow mononuclear cells, and mesenchymal stromal cells, will be a major challenge for ASD. As a result of these findings, a new paradigm for cell therapy for autism may emerge.
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Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/psicologia , Doenças Neuroinflamatórias , Cognição , Citocinas , GlucoseRESUMO
The patient was a female newborn. Ultrasonography performed at 35 weeks and 3 days of gestation revealed honeycomb-like dilatation and peri-intestinal strong echo patterns in the gastrointestinal tract. Nonreassuring fetal status was also diagnosed, leading to an emergency Cesarean section. The baby's birth weight was 2,127â g, whereas the Apgar 1â min and 5â min scores were 8 and 9, respectively. The amniotic fluid showed fecal and hematogenous turbidity. After delivery, there was hematogenous intragastric residue and defecation. Thereafter, the bloody intragastric residue and fecal discharge improved. Aggregations of eosinophils in the stool were observed, and gastrointestinal allergy was suspected. Enteral feeding with the hydrolyzed protein formula was initiated and symptoms did not recur. The allergen-specific lymphocyte stimulation test was positive for lactoferrin, and the patient was suspected with neonatal cow's milk allergy or neonatal transient eosinophilic colitis. After her condition stabilized, an oral challenge test was performed using breast milk without dairy products, and the test was negative. Gastrointestinal allergy is rare even in utero, and when gastrointestinal bleeding is suspected in utero, hemorrhagic or surgical gastrointestinal diseases should be ruled out first; however, the possibility of gastrointestinal allergy should also be kept in mind.
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Reports on the clinical course of fetal umbilical vein varix in premature infants are limited. We report a case of an extremely low body weight infant with intra-abdominal umbilical vein varix who developed disseminated intravascular coagulation, polycythemia, and hyperbilirubinemia after birth; late-onset neonatal hepatitis; and fetal thrombotic vasculopathy confirmed by placental histopathology. Ultrasonography after birth showed a dilated portion of the umbilical vein at the hepatic hilum with thrombi inside. We speculate that the umbilical vein varix caused the fetal thrombotic vasculopathy, and the presence of umbilical vein varix and fetal thrombotic vasculopathy in combination with prematurity caused coagulopathy, polycythemia, hyperbilirubinemia, and hepatitis. Despite the favorable outcomes reported in the literature, premature infants with umbilical vein varix may require careful observation and management for coagulopathy and late-onset hepatitis. Furthermore, placental histopathology could aid in the understanding of various clinical outcomes in infants with umbilical vein varices.
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Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attention-deficit/hyperactive disorder and autism spectrum disorder, as well as cerebral palsy, for which no prophylactic measure exists. Neuroinflammation in fetuses and neonates plays a major pathogenic role in NDDs. Meanwhile, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) exhibit immunomodulatory properties. Therefore, we hypothesized that systemic administration of UC-MSCs in the early postnatal period may attenuate neuroinflammation and thereby prevent the emergence of NDDs. The LBW pups born to dams subjected to mild intrauterine hypoperfusion exhibited a significantly lesser decrease in the monosynaptic response with increased frequency of stimulation to the spinal cord preparation from postnatal day 4 (P4) to P6, suggesting hyperexcitability, which was improved by intravenous administration of human UC-MSCs (1 × 105 cells) on P1. Three-chamber sociability tests at adolescence revealed that only LBW males exhibited disturbed sociability, which tended to be ameliorated by UC-MSC treatment. Other parameters, including those determined via open-field tests, were not significantly improved by UC-MSC treatment. Serum or cerebrospinal fluid levels of pro-inflammatory cytokines were not elevated in the LBW pups, and UC-MSC treatment did not decrease these levels. In conclusion, although UC-MSC treatment prevents hyperexcitability in LBW pups, beneficial effects for NDDs are marginal.