Congenital heart disease (CHD) is common in trisomy 13 (T13) and trisomy 18 (T18), but surgical repair has not been offered in most centers. Data on outcomes of congenital heart surgery (CHS) for T13 ...and T18 are lacking. We sought to determine the impact of CHS on in-hospital mortality in T13 and T18.
Data from the 2004 to 2015 Pediatric Health Information System database were used to identify inpatients with T13 or T18 and CHD. Data were restricted to newborns with T13 or T18 admitted at ≤14 days of age. Hospital readmissions were examined to analyze longer-term in-hospital mortality. In-hospital mortality and length of stay were compared between infants with and without CHD and with and without CHS.
The study cohort included 1020 infants with T18 and 648 infants with T13. CHD was present in 91% of infants with T18 and 86% of infants with T13. CHS was performed in 7% of each group. In-hospital mortality was decreased in those who underwent CHS (64% lower in T18
<.001; 45% lower in T13
= .003) and remained decreased throughout the 24 months of follow-up. In-hospital mortality was decreased in infants with higher weight, female sex, and older age at admission.
CHS is associated with decreased in-hospital mortality in T18 and T13. These results suggest CHS may be beneficial in select cases.
X-linked Charcot-Marie-Tooth neuropathy (CMTX) is caused by mutations in the gene encoding Gap Junction Protein Beta-1 (GJB1)/Connexin32 (Cx32) in Schwann cells. Neurotrophin-3 (NT-3) is an important ...autocrine factor supporting Schwann cell survival and differentiation and stimulating axon regeneration and myelination. Improvements in these parameters have been shown previously in a CMT1 model, Trembler
mouse, with NT-3 gene transfer therapy. For this study, scAAV1.tMCK.NT-3 was delivered to the gastrocnemius muscle of 3-month-old Cx32 knockout (KO) mice. Measurable levels of NT-3 were found in the serum at 6-month post gene delivery. The outcome measures included functional, electrophysiological and histological assessments. At 9-months of age, NT-3 treated mice showed no functional decline with normalized compound muscle action potential amplitudes. Myelin thickness and nerve conduction velocity significantly improved compared with untreated cohort. A normalization toward age-matched wildtype histopathological parameters included increased number of Schmidt-Lanterman incisures, and muscle fiber diameter. Collectively, these findings suggest a translational application to CMTX1.
The integration of psychological services in medical settings has numerous benefits but a process for systematic integration and system wide evaluation is needed. A process model was created and ...evaluated for integrating services in 32 outpatient subspecialty clinics. Levels of satisfaction in caregivers (n = 98), physicians (n = 27), and non-physicians (n = 45) were assessed. Most caregivers rated psychology services at the highest level of satisfaction (85%) and would recommend these services to others (100%). Teammates indicated that services should continue in their clinic (85% non-physician; 96% physician) and have improved patient care (71% non-physician; 81% physician). These findings demonstrate positive outcomes associated with the process model and support its utility in integrating psychology services across a health system.
More than 300 million people suffer from depressive disorders globally. People under early-life stress (ELS) are reportedly vulnerable to depression in their adulthood, and synaptic plasticity can be ...the molecular mechanism underlying such depression. Herein, we simulated ELS by using a maternal separation (MS) model and evaluated the behavior of Sprague-Dawley (SD) rats in adulthood through behavioral examination, including sucrose preference, forced swimming, and open-field tests. The behavior tests showed that SD rats in the MS group were more susceptible to depression- and anxiety-like behaviors than did the non-MS (NMS) group. Nissl staining analysis indicated a significant reduction in the number of neurons at the prefrontal cortex and hippocampus, including the CA1, CA2, CA3, and DG regions of SD rats in the MS group. Immunohistochemistry results showed that the percentages of synaptophysin-positive area in the prefrontal cortex and hippocampus (including the CA1, CA2, CA3, and DG regions) slice of the MS group significantly decreased compared with those of the NMS group. Western blot analysis was used to assess synaptic-plasticity protein markers, including postsynaptic density 95, synaptophysin, and growth-associated binding protein 43 protein expression in the cortex and hippocampus. Results showed that the expression levels of these three proteins in the MS group were significantly lower than those in the NMS group. LC-MS/MS analysis revealed no significant differences in the peak areas of sex hormones and their metabolites, including estradiol, testosterone, androstenedione, estrone, estriol, and 5β-dihydrotestosterone. Through the application of nontargeted metabolomics to the overall analysis of differential metabolites, pathway-enrichment results showed the importance of arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In summary, the MS model caused adult SD rats to be susceptible to depression, which may regulate synaptic plasticity through arginine and proline metabolism; pantothenate and CoA biosyntheses; glutathione metabolism; and phenylalanine, tyrosine, and tryptophan biosyntheses.
•SNS improves depression-like behavior in MS-combined CUMS rats.•SNS increases CaSR expression and synaptic plasticity in the hippocampus and PFC.•SNS regulates the CaSR-PKC-ERK signaling pathway in ...rats.
Adverse stress in early life negatively influences psychiatric health by increasing the risk of developing depression and suicide in adulthood. Clinical antidepressants, such as fluoxetine, exhibit unsatisfactory results due to their low efficacy or intolerable side effects. SiNiSan (SNS), a traditional Chinese herbal formula, has been proven to have affirmatory antidepressive effects. However, the underlying mechanism remains poorly understood. Therefore, this study aimed to explore the impact and molecular mechanism of SNS treatment in rats exposed to neonatal maternal separation (MS)-combined young–adult chronic unpredictable mild stress (CUMS).
Seventy-two neonatal male Sprague–Dawley rats were randomly divided into six groups of 12 rats each: control + ddH2O, model + ddH2O, positive (fluoxetine: 5 mg/kg), SNS-low dose (2.5 g/kg), SNS-medium dose (5 g/kg), and SNS-high dose (10 g/kg). Behavioral tests included sucrose preference test, open-field test, and forced swimming test. Calcium sensitive receptor (CaSR), protein kinase C (PKC), ERK1/2, and synapse-associated proteins (PSD-95, GAP-43, and synaptophysin Syn) in the hippocampus (HIP) and prefrontal cortex (PFC) were assayed using Western blot. CaSR and Syn protein expression was measured by immunohistochemistry.
MS-combined CUMS rats exhibited depression-like behavior. SNS exerted antidepressant effects on stress-induced depression-like behavior. The levels of CaSR, PKC, and p-ERK1/2 in the HIP and PFC decreased in stressed rats. SNS treatment significantly upregulated the expression of CaSR, PKC, and p-ERK1/2 in the HIP and PFC of adult stressed rats.
MS-combined CUMS could develop depression-like behavior in adult. SNS exhibited antidepressive effects accompanied by improving synaptic plasticity by activation of the CaSR-PKC-ERK signaling pathway.
Objective To evaluate test proficiency and the receipt of special education services in school-age children who had undergone surgery for congenital heart disease (CHD) at age <1 year. Study design ...Data from Arkansas-born children who underwent surgery for CHD at Arkansas Children's Hospital at age <1 year between 1996 and 2004 were linked to state birth certificates and the Arkansas Department of Education longitudinal database containing achievement test scores in literacy and mathematics for grades 3-4 and special education codes. The primary negative outcome was not achieving grade-level proficiency on achievement tests. Logistic regression accounting for repeated measures was used to evaluate for associations between achieving proficiency and demographic data, maternal education, and clinical factors. Results A total of 362 of 458 (79%) children who underwent surgery for CHD were matched to the Arkansas Department of Education database, 285 of whom had grade 3 and/or 4 achievement tests scores. Fewer students with CHD achieved proficiency in literacy and mathematics ( P < .05) compared with grade-matched state students. Higher 5-minute Apgar score, shorter duration of hospitalization, and higher maternal education predicted proficiency in literacy ( P < .05). White race, no cardiopulmonary bypass, and shorter hospitalization predicted proficiency in mathematics ( P < .05). Sex, gestational age, age at surgery, CHD diagnosis, and type and number of surgeries did not predict test proficiency. Compared with all public school students, more children with CHD received special education services (26.9% vs 11.6%; P < .001). Conclusion Children with CHD had poorer academic achievement and were more likely to receive special education services than all state students. Results from this study support the need for neurodevelopmental evaluations as standard practice in children with CHD.
BACKGROUNDThis study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy.METHODSFemale rats were ...selected to establish a castration model and then underwent different volumes of ovarian tissue transplantation. Group I served as the sham operation group. The transplantation group was divided into five subgroups based on the calculated ratio of ovarian weight to body weight in normal female rats, δ = (2.52 ± 0.17) ×10-4: Group II: transplanted ovarian volume was δ; Group III: 0.75δ; Group IV: 0.5δ; Group V: 0.25δ; Group VI: without ovarian transplantation. The post-transplant oestrous cycle recovery was observed, and blood samples were collected every 2 weeks to measure serum hormone levels. Histological evaluation was performed at the end of the observation period.RESULTSRats in Group V exhibited disrupted oestrous cycles after transplantation, which were significantly longer than those in Group I. Rats in Groups II, III, and IV showed no cyclic changes. At 6 weeks post-transplantation, rats in Group V had lower E2 and AMH levels and higher FSH levels compared to Group I. The uterine wet weight and the number of normal follicles in Group V were significantly lower than those in Group I, but the number of atretic follicles was higher than in Group I.CONCLUSIONThe larger ovarian tissue transplantation resulted in a faster recovery with a higher survival rate of the uterus and normal follicles, compared to smaller ovarian tissue transplantation.
Nasal intermittent positive pressure ventilation (NIPPV) is a widely used mode of support in neonates, during which ventilator inflations may or may not coincide with spontaneous breathing.
We tested ...the hypothesis that inflations delivered with NIPPV via RAM
cannula and not accompanied by patient effort produce minimal tidal volume as measured by respiratory inductance plethysmography.
Fourteen subjects were monitored while receiving NIPPV. We compared tidal volumes during ventilator-supported breaths, unsupported breaths, and ventilator inflations not accompanied by patient effort (defined using electrical activity of the diaphragm).
Mean tidal volumes in arbitrary units were 0.30 ± 0.22 in NIPPV inflations associated with patient effort and 0.27 ± 0.15 in spontaneous breaths without ventilator assistance (p = 0.82). Tidal volumes during ventilator-only inflations were 0.06 ± 0.04 (p < 0.005 vs. both ventilator-assisted and unassisted efforts).
NIPPV via RAM cannula produces minimal, clinically insignificant tidal volumes during non-spontaneous inflations.
Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, ...but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.
Social isolation (SI) is a major risk factor for mood disorders in adolescents. The nucleus accumbens (NAc) is an important reward center implicated in psychiatric disorders. Resveratrol (RSV) is one ...of the most effective natural polyphenols with anti-anxiety and depression effects. However, little is known about the therapeutic effects and mechanisms of RSV on behavioral abnormality of adolescent social stress. Therefore, this study aimed to investigate the underlying mechanism of RSV on the amelioration of SI-induced behavioral abnormality. We found that SI induced anxiety-like behavior and social dysfunction in isolated female rats. Moreover, SI reduced mitochondrial number and ATP levels and increased thin spine density in the NAc. RNA sequencing results showed that SI changed the transcription pattern in the NAc, including 519 upregulated genes and 610 downregulated genes, especially those related to mitochondrial function. Importantly, RSV ameliorated behavioral and spine abnormalities induced by SI and increased NAc ATP levels and mitochondria number. Furthermore, RSV increased the activity of cytochrome C oxidase (COX) and upregulated mRNA levels of Cox5a, Cox6a1 and Cox7c. These results demonstrate that the modulation of spine plasticity and mitochondrial function in the NAc by RSV has a therapeutic effect on mood disorders induced by social isolation.
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