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BACKGROUND: Many uninsured patients do not receive Medicaid coverage until a cancer diagnosis, potentially delaying access to care for early cancer detection and treatment. We examine the association of Medicaid enrollment timing and patterns with survival among children and adolescents/young adults (AYAs) diagnosed with blood cancers, where disease onset can be acute and early detection is critical. METHODS: We identified 28,750 children and AYAs (0-39 years) newly diagnosed with blood cancers from the 2006-2013 SEER-Medicaid data. Enrollment patterns included continuous Medicaid (preceding through diagnosis), newly gained Medicaid (at/shortly after diagnosis), other noncontinuous Medicaid enrollment, and private/other insurance. We assessed cumulative incidence of death from diagnosis, censoring at last follow-up, five years post-diagnosis, or December 2018, whichever occurred first. Multivariable survival models estimated the association of insurance enrollment patterns with risk of death. RESULTS: One-fourth (26.1%) of the cohort were insured by Medicaid; of these, 41.1% had continuous Medicaid, 34.9% had newly gained Medicaid, and 24.0% had other noncontinuous enrollment. The cumulative incidence of all-cause death five-year post-diagnosis was highest in patients with newly gained Medicaid (30.2%, 95%CI = 28.4-31.9%), followed by other noncontinuous enrollment (23.2%, 95%CI = 21.3-25.2%), continuous Medicaid (20.5%, 95%CI = 19.1-21.9%), and private/other insurance (11.2%; 95%CI = 10.7-11.7%). In multivariable models, newly gained Medicaid was associated with a higher risk of all-cause (hazard ratio = 1.39, 95%CI = 1.27-1.53) and cancer-specific death (hazard ratio = 1.50, 95%CI = 1.35-1.68), compared to continuous Medicaid. CONCLUSIONS: Continuous Medicaid coverage is associated with survival benefits among pediatric and AYA patients diagnosed with blood cancers; however, less than half of Medicaid-insured patients have continuous coverage before diagnosis.

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BACKGROUND: CFTR modulators are approved for approximately 90% of people with cystic fibrosis in the USA and provide substantial clinical benefit. N1303K (Asn1303Lys), one of the most common class 2 CFTR defects, has not been approved for these therapies by any regulatory agency. Preclinical investigation by our laboratories showed N1303K CFTR activation with elexacaftor-tezacaftor-ivacaftor (ETI). In this trial, we evaluate whether ETI improves CFTR function, measured by sweat chloride and other clinical outcomes, in people with cystic fibrosis and CFTRN1303K. METHODS: In this prospective, open-label, single-arm trial, participants aged 12 years or older with cystic fibrosis encoding at least one N1303K variant and at least one CFTRN1303K allele who were ineligible for modulator therapy by US Food and Drug Administration labelling were given ETI for 28 days followed by a 28-day washout period at two cystic fibrosis centres in the USA. Participants received two orally administered pills of 100 mg elexacaftor, 50 mg tezacaftor, and 75 mg ivacaftor once daily in the morning, and 150 mg ivacaftor once daily in the evening. The primary endpoint was mean change in sweat chloride from baseline up to day 28 compared with mixed-effects models. Secondary endpoints were changes in percentage of predicted FEV1 (ppFEV1), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain, BMI, and weight after ETI therapy. Safety was assessed in all participants who received at least one dose of the study drug and primary and secondary analyses were performed in all participants who took the study drug per protocol. The trial was registered at ClinicalTrials.gov (NCT03506061) and remains open for reporting purposes. FINDINGS: Between June 7, 2022, and Oct 20, 2023, 20 participants (ten male and ten female) were enrolled and received ETI treatment. One participant was lost to follow-up but was included in intention-to-treat analyses. At 28 days, the mean sweat chloride reduction was -1·1 mmol/L (95% CI -5·3 to 3·1; p=0·61) with only one participant showing a sweat chloride decrease greater than 15 mmol/L. There was a mean increase in ppFEV1 from baseline at day 28 of 9·5 percentage points (6·7-12·3; p<0·0001) with 15 (75%) participants showing at least a 5% increase in ppFEV1. Improvements were also identified in mean CFQ-R respiratory domain score (20·8 increase [95% CI 11·9-29·8]; p<0·0001), BMI (0·4 kg/m2 increase [0·2-0·7]; p=0·0017), and weight (1·0 kg increase [0·4-1·7]; p=0·0020) after 28 days of ETI treatment. 14 (70%) of 20 participants had adverse events (12 [60%] mild, one [5%] moderate), with one (5%) serious adverse event of hospitalisation attributed to pneumonia. No deaths were recorded in the study. INTERPRETATION: Individuals with CFTRN1303K showed no change in sweat chloride after 28 days of treatment with ETI. However, there were improvements in secondary clinical endpoints, which suggest clinical efficacy. Our approach provides support for the use of in vitro model systems to inform clinical trials for rare CFTR variants. FUNDING: The Cystic Fibrosis Foundation and the US National Institutes of Health.

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We prospectively collected PROMIS©25 and PROMIS©29 surveys in the Sickle Cell Transplant Evaluation of Long Term and Late Effects Registry (STELLAR). Mobility and social participation T-scores were decreased; all other domains were within the norm.

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ETHNOPHARMACOLOGICAL RELEVANCE: Sinisan formula (SNSF), documented in the classic books Shanghan Lun, is known for its ability to regulate liver-qi and treat depression. However, its underlying mechanism, particularly its effects on dynamic real-time neuron activity and circuits remains to be fully elucidated. AIM OF THE STUDY: This study aimed to investigate the antidepressant effect of SNSF and its central nervous system mechanism on depression-like behaviors, focusing on the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) neural circuit in a stress-induced adolescent animal model. MATERIALS AND METHODS: SNSF comprised four herbs, the root of Bupleurum chinense DC., the root of Paeonia lactiflora Pall., the fruit of Citrus aurantium L., the rhizome of Glycyrrhiza uralensis Fisch., in equal propotions. The adolescent depression animal model was induced by maternal separation (MS) and chronic restraint stress (CRS). In-vivo multichannel physiological electrodes were implanted into the PFC on PND 28 and animals were recorded 5 times during PND 35-46. From PND 47, the behavioral tests were performed to evaluate the antidepressant efficacy of SNSF. Subsequently, brain tissue was collected for Western blot and immunofluorescence staining analysis. Retro virus was injected into the DRN to explore sources of projections received by serotonergic (5-HTergic) neurons. And the PFC-to-DRN circuit was activated or inhibited through chemogenetic techniques to investigate the effects of SNSF on depression-like behaviors. RESULTS: Administration of SNSF for 18 days effectively alleviated depression-like behaviors in MS&CRS adolescent mice. The PFC emerged as the primary glutamatergic projection source of the DRN5-HT neurons. Following SNSF administration for 13/15/18 days, there was an increase in the firing rate of excitatory neurons and excitatory/inhibitory (E/I) ratio in the PFC. MS&CRS stress let to a reduction in the density of 5-HT+ and CaMKII + neurons in the DRN, accompanied by an increase in the density of GAD + neurons in the DRN, while SNSF administration reversed the alterations. Chemogenetic activation of the PFC-to-DRN circuit rescued the depression-like behaviors induced by MS&CRS, whereas suppression of this circuit attenuated the antidepressant effect of SNSF. CONCLUSIONS: SNSF significantly mitigated depression-like behaviors in MS&CRS mice. SNSF exerts its antidepressant effects by increasing the E/I ratio in the PFC and enhancing glutamatergic projections from the PFC to the DRN.

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BACKGROUND: This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function of rats after oophorectomy. METHODS: Female 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. RESULTS: Rats 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. CONCLUSION: The 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.

With advancements in science and technology, ovarian transplantation techniques have become increasingly mature. However, there are still many questions that need to be addressed. For instance, the large size of the transplanted ovarian tissues may cause over-recruitment of the primordial follicles. When the transplanted ovarian tissue is too small, it can only exert limited functionality and may not meet the patient's needs. This study aimed to investigate the effects of different volumes of ovarian tissue transplantation on the reproductive endocrine function in rats after oophorectomy, and to provide a theoretical basis for determining the minimum effective volume of heterotopic ovarian tissue transplantation.

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Lung cancer causes the most cancer deaths and needs new treatment strategies urgently. Salvia miltiorrhiza is a classical Chinese herb and a strong candidate for tumor treatment. The study found that the aqueous extract of Salvia miltiorrhiza (DSAE), ethanol extract of Salvia miltiorrhiza (DSEE), and its active components danshensu (DSS) and dihydrotanshinone I (DHI), exhibited antineoplastic effects in vivo and in vitro. Meanwhile, DSAE, DSEE, DSS, and DHI reduced glycolysis metabolites (ATP, lactate, and pyruvate contents) production, decreased aerobic glycolysis enzymes, and inhibited Seahorse indexes (OCR and ECAR) in Lewis lung cancer cells (LLC). Data suggests that aerobic glycolysis could be inhibited by Salvia miltiorrhiza and its components. The administration of DSS and DHI further reduced the level of HKII in lung cancer cell lines that had been inhibited with HK-II antagonists (2-deoxyglucose, 2-DG; 3-bromo-pyruvate, 3-BP) or knocked down with siRNA, thereby exerting an anti-lung cancer effect. Although DSS and DHI decreased the level of HKII in HKII-Knock-In lung cancer cell line, their anti-lung cancer efficacy remained limited due to the persistent overexpression of HKII in these cells. Reiterating the main points, we have discovered that the anti-lung cancer effects of Salvia miltiorrhiza may be attributed to its ability to regulate HKII expression levels, thereby inhibiting aerobic glycolysis. This study not only provides a new research paradigm for the treatment of cancer by Salvia miltiorrhiza, but also highlights the important link between glucose metabolism and the effect of Salvia Miltiorrhiza.

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Rhodotorula spp. has been studied as one powerful source for a novel cell factory with fast growth and its high added-value biomolecules. However, its inadequate genome and genomic annotation have hindered its widespread use in cosmetics and food industries. Rhodotorula glutinis QYH-2023, was isolated from rice rhizosphere soil, and the highest quality of the genome of the strain was obtained at chromosome level (18 chromosomes) than ever before in red yeast in this study. Comparative genomics analysis revealed that there are more key gene copies of carotenoids biosynthesis in R. glutinis QYH-2023 than other species of Rhodotorula spp. Integrated transcriptome and metabolome analysis revealed that lipids and carotenoids biosynthesis was significantly enriched during fermentation. Subsequent investigation revealed that the over-expression of the strain three genes related to carotenoids biosynthesis in Komagataella phaffii significantly promoted the carotenoid production. Furthermore, in vitro tests initially confirmed that the longer the fermentation period, the synthesized metabolites controlled by R. glutinis QYH-2023 genome had the stronger anti-inflammatory properties. All of the findings revealed a high-quality reference genome which highlight the potential of R. glutinis strains to be employed as chassis cells for biosynthesizing carotenoids and other active chemicals.

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STUDY OBJECTIVE: This study aimed to evaluate the usability and feasibility of incorporating a cardiovascular risk assessment tool into adolescent reproductive health and primary care visits. DESIGN, SETTING, AND PARTICIPANTS: We recruited 60 young women ages 13-21 years to complete the HerHeart web-tool in 2 adolescent clinics in Atlanta, GA. MAIN OUTCOME MEASURES: Participants rated the tool's usability via the Website Analysis and Measurement Inventory (WAMMI, range 0-95) and their perceived 10-year and lifetime risk of cardiovascular disease (CVD) on a visual analog scale (range 0-10). Participants' perceived risk, blood pressure, and body mass index were measured at baseline and 3 months after enrollment. Health care providers (HCP, n = 5) completed the WAMMI to determine the usability and feasibility of incorporating the HerHeart tool into clinical practice. RESULTS: Adolescent participants and HCPs rated the tool's usability highly on the WAMMI with a median of 79 (interquartile range [IQR] 65, 84) and 76 (IQR 71, 84). At the baseline visit, participants' median perceived 10-year risk of a heart attack was 1 (IQR 0, 3), and perceived lifetime risk was 2 (IQR 0, 4). Immediately after engaging with the tool, participants' median perceived 10-year risk was 2 (IQR 1, 4.3), and perceived lifetime risk was 3 (IQR 1.8, 6). Thirty-one participants chose to set a behavior change goal, and 12 participants returned for follow-up. Clinical metrics were similar at the baseline and follow-up visits. CONCLUSION: HerHeart is acceptable to young women and demonstrates potential for changing risk perception and improving health habits to reduce risk of CVD. Future research should focus on improving retention in studies to promote cardiovascular health within reproductive health clinics.

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BACKGROUND: The COVID-19 pandemic have impacts on the prevalence of other pathogens and people's social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. METHODS: Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. RESULTS: Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis. CONCLUSIONS: The number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.

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ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

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BACKGROUND: An alternative surgical approach for hypoplastic left heart syndrome is the Hybrid pathway, which delays the risk of acute kidney injury outside of the newborn period. We sought to determine the incidence, and associated morbidity, of acute kidney injury after the comprehensive stage 2 and the cumulative incidence after the first two operations in the Hybrid pathway. DESIGN: A single centre, retrospective study was conducted of hypoplastic left heart patients completing the second-stage palliation in the Hybrid pathway from 2009 to 2018. Acute kidney injury was defined utilising Kidney Diseases Improving Global Outcomes criteria. Perioperative and post-operative characteristics were analysed. RESULTS: Sixty-one patients were included in the study cohort. The incidence of acute kidney injury was 63.9%, with 36.1% developing severe injury. Cumulatively after the Hybrid Stage 1 and comprehensive stage 2 procedures, 69% developed acute kidney injury with 36% developing severe injury. The presence of post-operative acute kidney injury was not associated with an increase in 30-day mortality (acute kidney injury 7.7% versus none 9.1%; p = > 0.9). There was a significantly longer median duration of intubation among those with acute kidney injury (acute kidney injury 32 (8, 155) hours vs. no injury 9 (0, 94) hours; p = 0.018). CONCLUSIONS: Acute kidney injury after the comprehensive stage two procedure is common and accounts for most of the kidney injury in the first two operations of the Hybrid pathway. No difference in mortality was detected between those with acute kidney injury and those without, although there may be an increase in morbidity.

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OBJECTIVE: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes. METHOD: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities. RESULTS: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions. SIGNIFICANCE: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care.

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BACKGROUND: This single-center, retrospective study evaluated the effects of de-escalating cystic fibrosis (CF) supportive therapies in patients on elexacaftor/tezacaftor/ivacaftor (ETI). For many with CF, the clinical benefit of ETI exceeds that of supportive therapies. Therefore, we anticipated patients would desire to discontinue many of their supportive therapies, leading to the creation of a de-escalation algorithm. If patients were clinically improved and stable on ETI, CF supportive therapies could be de-escalated quarterly in accordance with the algorithm. METHODS: The primary objective was to assess non-inferiority of supportive therapies de-escalation by comparing the absolute change in percent predicted (ppFEV1) from baseline to month 1 versus the absolute change from baseline to month 12 after initiating ETI with patients serving as their own control. A chart review of patients initiated on ETI from September 2019 through December 2020 was conducted. Inclusion criteria included those six years and older with at least one copy of F508del. RESULTS: The study included 174 patients. The mean ppFEV1 at baseline, month 1, and month 12 was 67%, 78%, and 87% respectively. The mean difference in absolute change in ppFEV1 from baseline to month 1 compared to baseline to month 12 after the initiation of ETI was 1.53% (95% CI: -0.49 to 3.55) CONCLUSION: De-escalating supportive therapies for those on ETI was non-inferior to remaining on all supportive therapies. This suggests that medications may be able to be discontinued under the context of a de-escalation algorithm, which may decrease medication burden and cost and increase quality of life.

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BACKGROUND: To study whether the four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of the Kazak children in Xinjiang, China. METHODS: Four single nucleotide polymorphisms about the 4 genes were genotyped in asthma group and control group of Han children and Kazak children respectively. The frequencies of different genotypes and alleles were compared between the asthma group and the control group in the two nationalities. Different risk genotypes for asthma were evaluated in the two nationalities. RESULTS: The differences about frequencies of genotypes in ADRB2 rs1042713 and IL4 rs2243250 and IL13 rs20541 between asthma group and control group were statistically significant in Han children, as were the frequencies of alleles in the 3 single nucleotide polymorphisms, but there were no statistical differences in FCER1B rs569108(P > 0.05). For the Kazak children, no differences were existed among all the genotypes and alleles in asthma group and control group. For the Han children, more children were asthma high risk genotype in the asthma group than those in the control group and no difference was found in the Kazak children. CONCLUSIONS: The four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of Han children but not for the Kazak children in Xinjiang, which illustrating that the difference of asthma prevalence between different races is closely related to the genetic background.

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Significance: Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking. Aim: We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults. Approach: Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5 cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA). Results: The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1 Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (Rs=0.59, p=0.010) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models. Conclusions: We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.

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BACKGROUND: Social connection and loneliness in adolescence are increasingly understood as critical influences on adult mental and physical health. The unique impact of the social isolation imposed by the COVID-19 lockdown on emerging adults is therefore expected to be especially profound. We sought to investigate the feasibility of using ecological momentary assessment (EMA) and wearable accelerometers to characterize the effects of social isolation and/or loneliness experienced by adolescents during the COVID-19 pandemic. METHODS: We recruited 19 participants aged 13-18 from an Adolescent Medicine practice in Atlanta, GA. Participants completed surveys at baseline and throughout a 2-week study period using EMA regarding their degree of social isolation, loneliness, family functioning, school climate, social media use, and COVID-19 experiences surrounding their physical, mental, and social domains. Six participants agreed to wear an activity tracker and heart rate measurement device for 14 days to monitor their emotional state and physical health. Participant feedback was collected via open-ended exit interviews. Feasibility of recruitment/retention, adherence, and outcome measures were investigated. Implementation was also assessed by evaluating the barriers and facilitators to study delivery. Associations between the social isolation and loneliness variables and all other variables were performed with univariate linear regression analysis with significance set at p < 0.05. The progression criteria were a recruitment rate of > 30% and a retention rate of > 80%. RESULTS: Progression criteria were met for recruitment (76%) of participants, but not retention (38%). Adherence to EMA survey completion was highly variable with only 54% completing ≥ 1 survey a day, and accelerometry use was not feasible. Social isolation was significantly correlated with lower school climate, higher COVID-19 experiences, higher depression scores, and lower sleep quality. Loneliness also showed a significant correlation with all these factors except COVID-19 experiences. CONCLUSIONS: EMA and wearable accelerometer use was not feasible in this longitudinal study of adolescents during the COVID-19 pandemic. Future research should further investigate barriers to conducting long-term research with adolescents and the potential effects of the pandemic on subject recruitment and retention.

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Background: Early life stress (ELS) is a major risk factor for depression in adolescents. The nucleus accumbens (NAc) is a key center of the reward system, and spine remodeling in the NAc contributes to the development of depression. The Si-Ni-San formula (SNS) is a fundamental prescription for treating depression in traditional Chinese medicine. However, little is known about the effects of SNS on behavioral abnormalities and spine plasticity in the NAc induced by ELS. Purpose: This study aimed to investigate the therapeutic effect and the modulatory mechanism of SNS on abnormal behaviors and spine plasticity in the NAc caused by ELS. Methods: We utilized a model of ELS that involved maternal separation with early weaning to explore the protective effects of SNS on adolescent depression. Depressive-like behaviors were evaluated by the sucrose preference test, the tail suspension test, and the forced swimming test; anxiety-like behaviors were monitored by the open field test and the elevated plus maze. A laser scanning confocal microscope was used to analyze dendritic spine remodeling in the NAc. The activity of Rac1 was detected by pull-down and Western blot tests. Viral-mediated gene transfer of Rac1 was used to investigate its role in ELS-induced depression-like behaviors in adolescence. Results: ELS induced depression-like behaviors but not anxiety-like behaviors in adolescent mice, accompanied by an increase in stubby spine density, a decrease in mushroom spine density, and decreased Rac1 activity in the NAc. Overexpression of constitutively active Rac1 in the NAc reversed depression-related behaviors, leading to a decrease in stubby spine density and an increase in mushroom spine density. Moreover, SNS attenuated depression-like behavior in adolescent mice and counteracted the spine abnormalities in the NAc induced by ELS. Additionally, SNS increased NAc Rac1 activity, and the inhibition of Rac1 activity weakened the antidepressant effect of SNS. Conclusion: These results suggest that SNS may exert its antidepressant effects by modulating Rac1 activity and associated spine plasticity in the NAc.

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Cerebrovascular reactivity (CVR), defined as the ability of cerebral vasculature to dilate in response to a vasodilatory stimulus, is an integral mechanism in brain homeostasis that is thought to be impaired in sickle cell disease (SCD). This study used diffuse correlation spectroscopy and a simple breath-hold stimulus to quantify CVR non-invasively in a cohort of 12 children with SCD and 14 controls. Median [interquartile range] CVR was significantly decreased in SCD compared to controls (2.03 [1.31, 2.44] versus 3.49 [3.00, 4.11] %/mmHg, p = 0.028). These results suggest DCS may provide a feasible means to routinely monitor CVR impairments in pediatric SCD.

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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.

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