Telehealth Initiation of Buprenorphine for Opioid Use Disorder: Patient Characteristics and Outcomes.

BACKGROUND: The COVID-19 pandemic exacerbated access barriers for patients with opioid use disorder. Telehealth presents an opportunity to improve access, treatment quality, and patient outcomes. OBJECTIVE: To determine patient characteristics associated with initiating buprenorphine treatment via telehealth and to examine how telehealth initiation is associated with access, treatment quality, and health outcomes. DESIGN AND PARTICIPANTS: This cross-sectional study used deidentified insurance claims to identify opioid use disorder adult patients initiating buprenorphine treatment between March 1, 2020, and November 30, 2021. Multivariable logistic regression assessed determinants of telehealth initiation. Propensity score matching addressed observed differences between in-person and telehealth initiators. MAIN MEASURES: Treatment quality outcomes included initiation within 14 days of diagnosis, engagement (at least 2 opioid use disorder-related visits), and any buprenorphine refill during the study period. Health outcomes included opioid overdose and opioid use disorder-related emergency department and inpatient visits. KEY RESULTS: We identified 23,565 adult buprenorphine initiators, including 3314 (14.1%) patients using telehealth. Younger patients (OR 0.91 to 0.77), females (OR 1.18), South (OR 1.63) and Midwest (OR 1.27) regions, rural area (OR 1.12), and higher-income (OR 1.16) neighborhood residents were more likely to use telehealth. Telehealth patients were more likely than in-person patients (54.5% vs. 48.4%; adjusted odds ratio (AOR), 1.29; 95% CI, 1.19-1.40) to stay engaged with opioid use disorder treatment, and more likely to refill buprenorphine during the study period (83.6% vs. 79.0%, AOR 1.37; 95% CI, 1.23-1.52). Telehealth initiation of buprenorphine was associated with 36% lower overdose rate than in-person initiation (adjusted incidence rate ratio 0.64; 95% CI, 0.45-0.94). The two groups evidenced no significant differences in opioid use disorder-related ED visit and hospitalization. CONCLUSIONS: Our findings suggest that telehealth-initiated buprenorphine treatment is associated with reduced opioid overdose rate and improved patient engagement. Our findings strengthen the case for extending telehealth exemptions and prescribing flexibilities for treatment.

Brønsted Acid-Catalyzed Reaction of N-arylnaphthalen-2-amines with Quinone Esters for the Construction of Carbazole and C-N Axially Chiral Carbazole Derivatives.

We demonstrated here an efficient synthetic method of carbazole derivatives from readily available N-arylnaphthalen-2-amines and quinone esters catalyzed by Brønsted acid. With this strategy, a series of carbazole derivatives were obtained in good to excellent yields (76 to >99) under mild conditions. Large scale reaction illustrated the synthetic utility of this protocol. Meanwhile, a series of C-N axially chiral carbazole derivatives were also constructed in moderate to good yields (36-89% yield) with moderate to excellent atroposelectivities (44-94% ee) by using chiral phosphoric acid as a catalyst, which provides a novel strategy for the atroposelective construction of C-N axially chiral compounds and a new member of the C-N atropisomers.

Long Noncoding RNA lncR17454 Regulates Metamorphosis of Silkworm Through let-7 miRNA Cluster.

A number of long noncoding RNAs (lncRNAs) have been identified in silkworm, but little is known about their functions. Recent study showed that the let-7 miRNA cluster (contains let-7, miR-2795, and miR-100) was transcribed from the last exon of lncRNA lncR17454 in silkworm. To investigate the functional role of lncR17454, dsRNAs of lncR17454 were injected into the hemolymph of 1-d-old third-instar larvae of Bombyx mori, repression of lncR17454 led to molting arrestment during the larval-larval and larval-pupal transition of silkworm, which was consistent to the result as let-7 knockdown in other studies. The expression level of mature let-7, miR-100, and miR-2795 decreased 40%, 36%, and 40%, respectively, while the mRNA level of two predicted target genes of let-7, the Broad Complex isoform 2 (BR-C-Z2) and the BTB-Zinc finger transcription repression factor gene Abrupt (Ab), increased significantly after lncR17454 knockdown. In contrast, when adding the 20-Hydroxyecdysone (20E) to silkworm BmN4 cell lines, the expression level of lncR17454 and let-7 cluster all increased significantly, but the expression of Abrupt, the predicted target gene of let-7, was repressed. Dual-luciferase reporter assays confirmed Abrupt was the real target of let-7. Here we found that the lncRNA lncR17454 can play regulator roles in the metamorphosis of silkworm through let-7 miRNA cluster and the ecdysone signaling pathway, which will provide new clues for lepidopteran pest control.

Health impacts of parental migration on left-behind children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. FINDINGS: Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. INTERPRETATION: Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. FUNDING: Wellcome Trust.

Impact of parental migration on psychosocial well-being of children left behind: a qualitative study in rural China.

BACKGROUND: Tens of millions of rural "left-behind children (LBC)" in China grow up experiencing prolonged separation from their migrant worker parents. This study aimed to explore how children are affected by parental migration, from the perspectives of children, parents, and grandparents, focusing on the experiences of prolonged parent-child separation and relationship dynamics in the extended family. METHODS: Qualitative in-depth interviews were conducted in a migrant-sending rural area of eastern China. Participants included 25 children (aged 7 to 14), 17 parents, and 13 grandparents, from 30 families, as well as 24 key informants from the communities. Data analysis followed a grounded theory approach. RESULTS: The results showed that despite the original purpose of benefiting children, parental migration resulted in challenges in child psychosocial well-being, due to the emotional impacts from prolonged parent-child separation. Parental absence also led to inadequate care and support for left-behind children. The negative effects of parental migration may be exacerbated by other vulnerabilities such as parents' divorce, poverty and grandparent caregivers' frailty. Concerns about child well-being made some migrants decide to return home permanently, because of the altered trade-offs of migration. CONCLUSION: Prolonged separation following migration often disrupts parent-child relationships and results in psychosocial difficulties in LBC, especially among those who live with multiple adversities in the family. Community-based interventions may help migrant parents and co-resident caregivers to better engage children and promote their resilience.

Long-term impacts of parental migration on Chinese children's psychosocial well-being: mitigating and exacerbating factors.

PURPOSE: Prolonged separation from migrant parents raises concerns for the well-being of 60 million left behind children (LBC) in rural China. This study aimed to investigate the impact of current and previous parental migration on child psychosocial well-being, with a focus on emotional and behavioral outcomes, while considering factors in family care and support. METHODS: Children were recruited from schools in migrant-sending rural areas in Zhejiang and Guizhou provinces by random stratified sampling. A self-administered questionnaire measured children's psychosocial well-being, demographics, household characteristics, and social support. Multiple linear regression models examined the effects of parental migration and other factors on psychosocial difficulties. RESULTS: Data from 1930 current, 907 previous, and 701 never LBC were included (mean age 12.4, SD 2.1). Adjusted models showed both previous and current parental migration was associated with significantly higher overall psychosocial difficulties, involving aspects of emotion, conduct, peer relationships, hyperactivity, and pro-social behaviors. Parental divorce and lack of available support demonstrated a strong association with greater total difficulties. While children in Guizhou had much worse psychosocial outcomes than those in Zhejiang, adjusted subgroup analysis showed similar magnitude of between-province disparities regardless of parental migration status. However, having divorced parents and lack of support were greater psychosocial risk factors for current and previous-LBC than for never LBC. CONCLUSIONS: Parental migration has an independent, long-lasting adverse effect on children. Psychosocial well-being of LBC depends more on the relationship bonds between nuclear family members and the availability of support, rather than socioeconomic status.

Cause of death among infants in rural western China: a community-based study using verbal autopsy.

OBJECTIVES: To determine the causes of death among infants in high-mortality areas of western China with the use of globally recognized methods. STUDY DESIGN: A survey of all infant deaths identified over 1 year in 4 counties in Yunnan and Xinjiang in which combined verbal autopsy was combined with a physician's diagnosis of the cause to calculate the local infant mortality rate. RESULTS: Among 470 completed investigations, a cause of death was assigned to 423 cases (90%). Overall, pneumonia (34.5%), preterm birth complications (16.5%), diarrhea (10.4%), birth asphyxia (10.3%), and congenital abnormalities (8.5%) were the main causes, with 56.6% of deaths occurring in the neonatal period. Deaths were attributable predominantly to prematurity or birth asphyxia in the early neonatal period, whereas infection accounted for more than 60% and 80% of deaths in the late and postneonatal periods, respectively. Calculated infant mortality was 21.9 in 1000 live births. CONCLUSIONS: The pattern of infant mortality observed in the surveyed counties differs markedly from that reported previously at the national level, with a high proportion the result of causes that may be preventable with globally recommended interventions. Financial and political support is needed to promote improved cause of death surveillance and newborn and infant health care in China's western region.

Outcome assessment of different reward stimuli in Internet gaming disorder by event-related potentials.

An imbalance in sensitivity to different types of reward stimuli may be an important cause of addiction that is mainly manifested in high sensitivity to addictive substance rewards and blunting of natural rewards. However, contradictions remain in the research results on the sensitivity of individuals with Internet gaming disorder (IGD) to different reward stimuli. Based on participants' neural responses to win and loss feedback (in door task), the event-related potential (ERP) technique was used to investigate the effects of different types of reward stimuli on the assessment of reward-processing outcomes in individuals with IGD. The results showed that in the gain condition, the FB-P3 amplitude induced by game stimuli in the IGD group was significantly higher than that in the control group, and the FN amplitude induced by money stimuli was significantly lower than that in the control group. However, the FB-P3 and FN amplitudes induced by food were not significantly different from those in the control group. In the loss condition, there were no between-group differences in the FB-P3 and FN amplitudes evoked by the three reward stimuli. This indicates that the IGD group showed increased hedonic responses to game stimuli and decreased hedonic responses to money but no differences in hedonic responses to food during the reward assessment phase. Therefore, heightened sensitivity to game rewards and diminished sensitivity to monetary rewards during outcome assessment may play a crucial role in the development of IGD.

Influence of reinforcement learning on the inhibitory control of Internet gaming disorder.

Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences on the cognitive inhibitory control of IGD. This study compared the differences between an IGD group and healthy people without game experiences in the probability selection task and the subsequent stop signal task by the method of behavioral experiments, in order to explore whether the reward learning ability is impaired in the IGD group. We also discuss the influence of previous reward learning on subsequent inhibition control. The results showed that (1) during the reward learning phase, the IGD group's accuracy was significantly lower than that of the control group; (2) compared with the control group, the IGD group's reaction times were longer in the transfer phase; (3) for no-go trials of the inhibitory control phase after reward learning, the accuracy of the reward-related stimulation in the IGD group was lower than that of punishment-related or neutral stimulation, but there was no significant difference among the three conditions in the control group. These findings indicated that the reinforcement learning ability of the IGD group was impaired, which further caused the abnormal response to reinforcement stimuli.

Novel IARS1 variants cause syndromic developmental disorder with epilepsy in a Chinese patient and the literature review.

BACKGROUND: Isoleucinyl-tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. OBJECTIVE: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype-phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1-related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. METHODS: Clinical data of the proband were collected, and trio whole-exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. RESULTS: A 17-month-old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120-1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. CONCLUSION: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1-related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants.

lncR26319/miR-2834/EndophilinA axis regulates oogenesis of the silkworm, Bombyx mori.

Oocyte maturation is critical for insect reproduction. Vitellogenesis, the timely production and uptake of vitellogenin (Vg), is crucial for female fecundity. Vg is synthesized in fat body and absorbed by the oocytes through endocytosis during insect oogenesis. In the silkworm, Bombyx mori, we discovered that a nucleus-enriched long-noncoding RNA (lncRNA) lncR26319 regulates Endophilin A (EndoA) - a member of the endophilin family of endocytic proteins - through competitive binding to miR-2834. The lncR26319-miR-2834-EndoA axis was required for Vg endocytosis in the silkworm; loss of EndoA or overexpression of miR-2834 significantly reduced egg numbers in virgin moths. In addition, accumulation of miR-2834 resulted in pupal and adult deformation and reduced fecundity in females. The expression of Vg, 30-kDa (30K) protein, and egg-specific protein (Esp) decreased after knockdown of EndoA or overexpression of miR-2834, while knockdown of miR-2834 had an opposite effect on the expression of Vg, 30K protein gene, and Esp. These results suggest that the lncR26319-miR-2834-EndoA axis contributes to the endocytic activity in the Vg uptake and leads to the normal progression of oogenesis in the silkworm. Thus, miR-2834 and EndoA are crucial for female reproduction and could be potential targets for new pest management strategies in lepidopterans.

Thermally activated delayed fluorescence with dual-emission and pressure-induced bidirectional shifting: cooperative effects of intramolecular and intermolecular energy transfer.

Different from the conventional piezochromic materials with a mono-redshift of single emission, our well-designed molecule demonstrates a sensitive turn-on and color-tunable piezochromic luminescence in response to the hydrostatic pressure. The molecule PXZ-W-SOF possesses dual-emission and pressure-induced bidirectional shifting characteristics. On the basis of in-depth experimental studies, on one hand, it is confirmed that the origin of the dual-emission behavior is the intramolecular charge transfer, namely thermally activated delayed fluorescence (TADF), and the intermolecular excimer; on the other hand, the emission of the excimer exhibits three-step variations with increasing pressure, which is mainly attributed to the molecular structure and its crystal packing state. The remarkable color change of PXZ-W-SOF from sky-blue to green to deep-blue during the whole process of boosting and releasing pressure is a result of intramolecular and intermolecular energy-transfer interactions. The PXZ-W-SOF molecular model is an extremely rare example of highly sensitive fluorescence tuning driven by TADF and excimer conversion under mechanical stimulation, thus providing a novel mechanism for the field of piezochromism. The unique molecular design also offers a new idea for rare deep-blue and ultraviolet TADF materials.

Prenatal diagnosis in a fetuses with a clenched hands, overlapping fingers, and clubfoot due to MED12 deficiency in three affected siblings: A case report.

A fetal clenched hand with overlapping fingers is more common in aneuploidy syndrome and was not well-documented in MED12 deficiency. This study reports the clinical and genetic findings of three affected siblings from a Chinese family. The chromosome karyotype analysis diagram shows that karyotypes of the three children were normal. Trio whole-exome sequencing and Sanger sequencing verification found that there was a MED12 R296Q variant in normal mothers and their two offspring. A pattern of clenched hand with overlapping fingers (clinodactyly) and clubfoot was found in all the three affected siblings by three-dimensional ultrasound. The discovery of this case shows that even if the chromosome karyotype is normal, comprehensive prenatal genetic diagnosis is required when the ultrasound results show a clenched hand with clinodactyly and clubfoot symptoms.

Association of the Labor Migration of Parents With Nonsuicidal Self-injury and Suicidality Among Their Offspring in China.

Importance: The labor migration of parents in China often leaves children behind, which may be adversely associated with children's health. However, few studies have assessed the association of parental migration with nonsuicidal self-injury (NSSI) or with suicidality among their offspring. Objective: To examine the associations of parental labor migration with NSSI and with suicidality as well as potential differential associations by sex among offspring left behind. Design, Setting, and Participants: This nationwide cross-sectional study was conducted from February to October 2015 among individuals aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from November 1, 2020, to March 1, 2021. Exposures: Parental labor migration, including parental migration status (yes vs no), migration pattern (father, mother, or both), and the child's age at the initial parent-child separation. Main Outcomes and Measures: Less frequent (1-4 episodes) NSSI, more frequent (≥5 episodes) NSSI, suicidal ideation, and suicide attempt in the past year were measured using validated questionnaires. Multinomial or binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of the associations between parental migration and NSSI, suicidal ideation, or suicide attempt. Potential covariates (demographic, family-level, and psychological characteristics) were adjusted for in 3 sequential models. Results: A total of 15 312 participants (7904 male [51.6%] and 7408 female [48.4%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of those participants, 5963 (23.3%) experienced parental migration. The 12-month prevalence of less frequent NSSI was 17.2% (2635 of 15 312), the 12-month prevalence of more frequent NSSI was 11.6% (1783 of 15 312), the 12-month prevalence of suicidal ideation was 15.2% (2335 of 15 312), and the 12-month prevalence of suicide attempt was 3.5% (535 of 15 312). Parental migration was associated with less frequent NSSI (adjusted odds ratio [aOR], 1.13; 95% CI, 1.03-1.24); no significant association of parental migration with more frequent NSSI (aOR, 1.01; 95% CI, 0.90-1.13), suicidal ideation (aOR, 1.00; 95% CI, 0.90-1.10), or suicide attempt (aOR, 1.09; 95% CI, 0.90-1.33) was identified. Compared with children whose parents did not migrate, the aOR for less frequent NSSI for participants whose father migrated was 1.18 (95% CI, 1.06-1.31), and the aOR for less frequent NSSI for participants having both parents migrate was 1.12 (95% CI, 1.01-1.28). Compared with children whose parents did not migrate, participants who experienced initial separation from 1 or both parents at preschool age had an aOR for less frequent NSSI of 1.16 (95% CI, 1.03-1.31). No sex disparities were found in these associations except for participants who experienced initial separation from 1 or both migrant parents at preschool age, for which the aOR for more frequent NSSI was higher among male (aOR, 1.27; 95% CI, 1.04-1.55) than female (aOR, 0.96; 95% CI, 0.77-1.19) participants. Conclusions and Relevance: This cross-sectional study found that parental migration, mainly of the father or of both parents, or an initial separation of children at preschool age from 1 or both parents who migrated was associated with higher odds of experiencing 1 to 4 NSSI episodes in 1 year among offspring. Overall, the associations of parental migration with NSSI and suicidality were similar between male and female participants.

Cognitive impact of early separation from migrant parents: A spectrum of risk and key mechanisms in child development contexts. A commentary on Hou et al., (2020).

Prolonged separation from migrant parents may lead to child development risks, despite the potential benefits from improved financial circumstances. Within the substantial literature on the health and well-being of the so-called left-behind children, the cognitive impact of parental migration has been inconclusive across different settings globally. In this issue, Hou et al.'s study in rural China focused on school-age children who experience persistent absence of both migrant parents since infancy, and revealed disadvantages in language comprehension outcomes among these children, despite the mitigating effect of higher household income. While results from this study are limited to the ongoing parent-child separation, previous absence of migrant parents has been suggested to have long-lasting negative effects in studies of adolescents in reunited families. Findings from Hou and colleagues' study highlight the needs to better understand migration-related parent-child separation during sensitive developmental periods in infancy and early childhood. A spectrum of risk due to parental migration should be established, accounting for the timing and duration of migration and care arrangements, in order to better identify the at-risk children in communities affected by out-migration. Future research should further explore the mediating and moderating factors in child's environments, and evaluate post-separation adjustment among reunited families after parents' return migration. Research evidence on these aspects will inform the development of tailored intervention programs for left-behind children, and strengthen the abilities of families and communities in best serving the needs of children affected by prolonged parental absence.