Urbanization, self-harm, and suicidal ideation in left-behind children and adolescents in China: a systematic review and meta-analysis.

PURPOSE OF REVIEW: Economic development and urbanisation have prompted many Chinese parents to move from rural to urban regions for better job opportunities. Their children, who remain behind in rural regions, become left-behind children (LBC). With absent parents, children and adolescents are unable to maintain the secure attachment required for healthy social and emotional development, increasing the risk of mental illness. This study aimed to compare risk of self-harm and suicidal ideation in LBC and non-LBC in China. RECENT FINDINGS: Greater risks for poor mental health outcomes including worse depression, loneliness and anxiety have been identified in LBC in cross-sectional studies. Previous studies have also identified higher prevalence of bullying victimization, poorer school performance and worse school attendance amongst LBC. SUMMARY: Findings indicate that prolonged separation from parents put LBC at greater risks of poor mental health. Policy changes to allow children to migrate with their parents and policies to reduce inequalities in job opportunities between urban and rural regions are needed.

Validating real-time three-dimensional echocardiography against cardiac magnetic resonance, for the determination of ventricular mass, volume and ejection fraction: a meta-analysis.

INTRODUCTION: Real-time three-dimensional echocardiography (RT3DE) is currently being developed to overcome the challenges of two-dimensional echocardiography, as it is a much cheaper alternative to the gold standard imaging method, cardiac magnetic resonance (CMR). The aim of this meta-analysis is to validate RT3DE by comparing it to CMR, to ascertain whether it is a practical imaging method for routine clinical use. METHODS: A systematic review and meta-analysis method was used to synthesise the evidence and studies published between 2000 and 2021 were searched using a PRISMA approach. Study outcomes included left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left ventricular mass (LVM), right ventricular end-systolic volume (RVESV), right ventricular end-diastolic volume (RVEDV) and right ventricular ejection fraction (RVEF). Subgroup analysis included study quality (high, moderate), disease outcomes (disease, healthy and disease), age group (50 years old and under, over 50 years), imaging plane (biplane, multiplane) and publication year (2010 and earlier, after 2010) to determine whether they explained the heterogeneity and significant difference results generated on RT3DE compared to CMR. RESULTS: The pooled mean differences for were - 5.064 (95% CI - 10.132, 0.004, p > 0.05), 4.654 (95% CI - 4.947, 14.255, p > 0.05), - 0.783 (95% CI - 5.630, 4.065, p > 0.05, - 0.200 (95% CI - 1.215, 0.815, p > 0.05) for LVEF, LVM, RVESV and RVEF, respectively. We found no significant difference between RT3DE and CMR for these variables. Although, there was a significant difference between RT3DE and CMR for LVESV, LVEDV and RVEDV where RT3DE reports a lower value. Subgroup analysis indicated a significant difference between RT3DE and CMR for studies with participants with an average age of over 50 years but no significant difference for those under 50. In addition, a significant difference between RT3DE and CMR was found in studies using only participants with cardiovascular diseases but not in those using a combination of diseased and healthy participants. Furthermore, for the variables LVESV and LVEDV, the multiplane method shows no significant difference between RT3DE and CMR, as opposed to the biplane showing a significant difference. This potentially indicates that increased age, the presence of cardiovascular disease and the biplane analysis method decrease its concordance with CMR. CONCLUSION: This meta-analysis indicates promising results for the use of RT3DE, with limited difference to CMR. Although in some cases, RT3DE appears to underestimate volume, ejection fraction and mass when compared to CMR. Further research is required in terms of imaging method and technology to validate RT3DE for routine clinical use.

Quality of childcare and delayed child development in left-behind children in China.

BACKGROUND: Inequalities in job opportunities and income prompts many Chinese parents to leave rural regions to work in urban regions. Their children are left behind in rural regions, subjected to worse quality of childcare that jeopardizes their development. This study aimed to examine the association between quality of childcare and delayed child development in under-three years children left behind in China. METHODS: Cross-sectional national survey was conducted in children left behind in rural China in 2017. Exploratory and confirmatory factor analysis was used to develop a quality of childcare index. Mutlilevel analyses determined factors associated with quality of childcare and child development on a province and individual level. RESULT: The largest population of at-risk children left behind were found in higher-GDP provinces. Children left behind had the lowest mean quality of childcare score. Multilevel analysis found that province level accounted for a great proportion of variance observed. CONCLUSIONS: While migration to urban regions for work may improve household income, a trade-off in worse quality of childcare and developmental delays exists. With improving household income often being the greatest contributing factor for parental migration, policies to reduce inequalities in job opportunities and wealth between rural and urban regions are required. IMPACT: Previous studies identified higher prevalence of developmental delays in children left behind in China. However, quality of childcare has not been examined. Based on WHO's Nurturing Care Framework, we developed a quality of childcare index to assess its association with child development in children left behind. Greatest proportion of children left behind at-risk of developmental delays resided in higher-GDP states, indicating a trade-off in worse quality of childcare and developmental delays. Since improving household income is the main factor for parental migration, policies to close inequalities in job opportunities and wealth between rural and urban regions are required.

A Vocal Hygiene Program for Mitigating the Effects of Occupational Vocal Demand in Primary School Teachers.

PURPOSE: Teachers are occupational voice users with significant vocal demand. This study examined if a vocal hygiene program could mitigate the effects of occupational vocal demand in primary school teachers across 1 month. METHOD: Sixty female teachers participated, with 30 in an experimental group receiving vocal hygiene education plus daily home practice for 1 month and 30 in a control group with no intervention. Their vocal changes across the month were quantified with (a) acoustic measures on fundamental frequency (fo), vocal intensity, jitter and shimmer, harmonics-to-noise ratio, and smoothed cepstral peak prominence and (b) Voice Handicap Index (VHI-10) and Vocal Fatigue Index (VFI) scores. RESULTS: Analysis of covariance showed significantly larger changes (significant decreases) in conversational fo and in jitter for the experimental group relative to the control group. Post hoc pairwise comparisons following repeated-measures analysis of variance showed significant decreases in conversational fo and in jitter across the month for the experimental group. No significant differences in VHI-10 and VFI scores were found between the groups. CONCLUSIONS: Vocal demand-related changes in acoustic measures could be partially mitigated with the vocal hygiene program. Future studies with a more refined intervention program and more long-term follow-up are recommended to better understand the long-term benefits of vocal hygiene programs on primary school teachers.

Mapping the quality of prenatal and postnatal care and demographic differences on child mortality in 26 low to middle-income countries.

BACKGROUND: Closing the gap between child mortality in low- and middle-income countries (LMICs) and high-income countries is a priority set by the WHO in sustainable development goals (SDGs). We aimed to examine poor nutrition and prenatal and postnatal care that could increase the risk of child mortality in LMICs. METHODS: The Demographic and Health Survey (DHS) was used to examine data from 26 countries to compare prenatal, postnatal, nutritional, and demographic factors across LMICs. Outcome of child death was classified into death before one month of age, between 1 to 11 months, between one to two years, between three to five years, and overall death before five years. Chi-square analyses identified differences in prenatal care, postnatal care, nutrition, and demographic factors between children who died and those who survived. Logistic regression identified factors that increased child mortality risk. RESULTS: The majority of deaths occurred before the ages of one month and one year. Considerably poorer quality of prenatal care, postnatal care, and nutrition were found in low-income and low-middle-income countries in the contemporary 2020s. High child mortality and poor quality of prenatal and postnatal care coincide with low income. Children in LMICs were exposed to less vitamin A-rich foods than children in higher-middle-income countries. The use of intestinal parasite drugs and the absence of postpartum maternal vitamin A supplementation significantly increased child mortality risk. Significant socio-demographic risk factors were associated with an increased mortality rate in children, including lack of education, maternal marital status, family wealth index, living rurally, and financial problems hindering access to healthcare. CONCLUSIONS: Poor nutrition remains a vital factor across all LMICs, with numerous children being exposed to foods low in iron and vitamin A. Significantly, most deaths occur in neonates and infants, indicating an urgent need to address risk factors associated with early child death.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in the United States: Living Density, Viral Load, and Disproportionate Impact on Communities of Color.

BACKGROUND: Households are hot spots for severe acute respiratory syndrome coronavirus 2 transmission. METHODS: This prospective study enrolled 100 coronavirus disease 2019 (COVID-19) cases and 208 of their household members in North Carolina though October 2020, including 44% who identified as Hispanic or non-White. Households were enrolled a median of 6 days from symptom onset in the index case. Incident secondary cases within the household were detected using quantitative polymerase chain reaction of weekly nasal swabs (days 7, 14, 21) or by seroconversion at day 28. RESULTS: Excluding 73 household contacts who were PCR-positive at baseline, the secondary attack rate (SAR) among household contacts was 32% (33 of 103; 95% confidence interval [CI], 22%-44%). The majority of cases occurred by day 7, with later cases confirmed as household-acquired by viral sequencing. Infected persons in the same household had similar nasopharyngeal viral loads (intraclass correlation coefficient = 0.45; 95% CI, .23-.62). Households with secondary transmission had index cases with a median viral load that was 1.4 log10 higher than those without transmission (P = .03), as well as higher living density (more than 3 persons occupying fewer than 6 rooms; odds ratio, 3.3; 95% CI, 1.02-10.9). Minority households were more likely to experience high living density and had a higher risk of incident infection than did White households (SAR, 51% vs 19%; P = .01). CONCLUSIONS: Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color.

Assessment of the Field Utility of a Rapid Point-of-Care Test for SARS-CoV-2 Antibodies in a Household Cohort.

Point-of-care (POC) tests to detect SARS-CoV-2 antibodies offer quick assessment of serostatus after natural infection or vaccination. We compared the field performance of the BioMedomics COVID-19 IgM/IgG Rapid Antibody Test against an ELISA in 303 participants enrolled in a SARS-CoV-2 household cohort study. The rapid antibody test was easily implemented with consistent interpretation across 14 users in a variety of field settings. Compared with ELISA, detection of seroconversion lagged by 5 to 10 days. However, it retained a sensitivity of 90% (160/177, 95% confidence interval [CI] 85-94%) and specificity of 100% (43/43, 95% CI 92-100%) for those tested 3 to 5 weeks after symptom onset. Sensitivity was diminished among those with asymptomatic infection (74% [14/19], 95% CI 49-91%) and early in infection (45% [29/64], 95% CI 33-58%). When used appropriately, rapid antibody tests offer a convenient way to detect symptomatic infections during convalescence.

Effects of Polyphenol Supplementations on Improving Depression, Anxiety, and Quality of Life in Patients With Depression.

Background: Increased prevalence of mental disorders has become a significant public health concern. Recent studies have linked nutrition to depression and anxiety, suggesting that dietary changes or nutritional supplementation may be beneficial in improving mental disorders. Polyphenols have anti-inflammatory and antioxidant properties that may counteract physiological changes in depression and anxiety. This study examined the effectiveness of polyphenol supplementation in improving depression, anxiety and quality of life (QoL). Methods: Randomized controlled trials in English and with polyphenol supplementation as the intervention were searched. The primary outcome was depression, and secondary outcomes were anxiety and QoL. Only studies of at least moderate quality based on the Physiotherapy Evidence Database tool were included. Comprehensive systematic review and meta-analysis were then used to determine the effect of polyphenol supplementations on improving depression, anxiety and quality of life (QoL) in patients with depression. Results: Nineteen studies with 1,523 participants were included; 18 studies (n = 1,523) were included in the depression meta-analysis, and 5 (n = 188) and 6 (n = 391) in the QoL and anxiety meta-analyses, respectively. Twelve of the 18 studies found significant improvements in depression with polyphenol use, while the meta-analyses results also indicated that polyphenol supplementation significantly improved depression score as compared to control conditions (MD: -2.280, 95% CI: -1.759, -0.133, I 2 = 99.465). Although subgroup analyses were conducted a significantly high heterogeneity was still found amongst subgroups. Only 2 of the 5 studies found significant improvements in QoL following polyphenol supplementation and meta-analyses found that polyphenol use did not benefit QoL (MD: -1.344, p < 0.05, I 2 = 55.763). For anxiety, 5 of the 6 studies found significant reductions in depression score following polyphenol use but meta-analyses found no significant differences in anxiety score (MD: -0.705, CI: -1.897, 0.487, I 2 = 84.06) between polyphenol supplementation and control. Conclusion: The results suggest that polyphenol supplementation is effective in improving depression. Physical illness may act as a risk factor that worsens depression, suggesting the need for preventative supplementation to improve depression. Polyphenol types may have varying effects, which suggests that different populations with depression may benefit from different polyphenols.

Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings.

Alternatives to nasopharyngeal sampling are needed to increase capacity for SARS-CoV-2 testing. Among 275 participants, we piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including polyester flocked swabs as well as 3D-printed plastic lattice swabs, placed into viral transport media or an RNA stabilization agent. Flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), missing those with low viral load (<106 viral copies/mL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into RNA preservative, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. We also evaluated pooling strategies that involved pooling specimens in the lab versus pooling swabs at the point of collection, finding both successfully detected samples with >105 viral copies/mL.

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color.

Background: Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color. Methods and Findings: This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05). Conclusions: SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.

Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings.

BACKGROUND: Standard nasopharyngeal swab testing for SARS-CoV-2 detection by PCR is not always feasible due to limitations in trained personnel, personal protective equipment, swabs, PCR reagents, and access to cold chain and biosafety hoods. METHODS: We piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including both standard polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into either viral transport media or an RNA stabilization agent. Quantitative SARS-CoV-2 viral detection by RT-qPCR was compared to that obtained by nasopharyngeal sampling as the reference standard. Pooling specimens in the lab versus pooling swabs at the point of collection was also evaluated. RESULTS: Among 275 participants, flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), mostly missing those with low viral load (<10^3 viral copies/uL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into an RNA stabilizer, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. Pooling sample specimens or swabs both successfully detected samples >102 viral copies/uL. CONCLUSIONS: Nasal swabs are likely adequate for clinical diagnosis of acute infections to help expand testing capacity in resource-constrained settings. When collected into an RNA preservative that also inactivates infectious virus, nasal swabs yielded quantitative viral loads approximating those obtained by nasopharyngeal sampling.

Perioperative, functional, and oncologic outcomes of partial adrenalectomy for multiple ipsilateral pheochromocytomas.

OBJECTIVE: Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting. MATERIALS AND METHODS: We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010. Patients were included if multiple tumors were excised from the ipsilateral adrenal gland in the same operative setting. Perioperative, functional, and oncologic outcomes of PA for multiple pheochromocytomas are shown. RESULTS: Of 121 partial adrenalectomies performed, 10 procedures performed in eight patients for synchronous multiple ipsilateral pheochromocytomas were identified. All eight patients were symptomatic at presentation. The mean patient age was 30.6 years, median follow up was 12 months. The average surgical time was 228 minutes, average blood loss of 125 mL, and average number of tumors removed was 2.6 per adrenal. In total, 26 tumors were removed, 24 were pathologically confirmed pheochromocytomas, while two were adrenal cortical hyperplasia. After surgery, all patients had resolution of their symptoms, one patient required steroid replacement postoperatively. On postoperative imaging, one patient had evidence of ipsilateral adrenal nodule at the prior resection site 2 months postoperatively, which was consistent with incomplete resection. CONCLUSIONS: Minimally invasive surgical resection of synchronous multiple pheochromocytomas is feasible with acceptable perioperative, functional, and short-term oncologic outcomes.

The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth of EGFRvIII-activated glioblastomas.

PURPOSE: mTOR pathway hyperactivation occurs in approximately 90% of glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the clinic. Here, we examine the efficacy of the newly discovered ATP-competitive mTOR kinase inhibitors CC214-1 and CC214-2 in glioblastoma, identifying molecular determinants of response and mechanisms of resistance, and develop a pharmacologic strategy to overcome it. EXPERIMENTAL DESIGN: We conducted in vitro and in vivo studies in glioblastoma cell lines and an intracranial model to: determine the potential efficacy of the recently reported mTOR kinase inhibitors CC214-1 (in vitro use) and CC214-2 (in vivo use) at inhibiting rapamycin-resistant signaling and blocking glioblastoma growth and a novel single-cell technology-DNA Encoded Antibody Libraries-was used to identify mechanisms of resistance. RESULTS: Here, we show that CC214-1 and CC214-2 suppress rapamycin-resistant mTORC1 signaling, block mTORC2 signaling, and significantly inhibit the growth of glioblastomas in vitro and in vivo. EGFRvIII expression and PTEN loss enhance sensitivity to CC214 compounds, consistent with enhanced efficacy in strongly mTOR-activated tumors. Importantly, CC214 compounds potently induce autophagy, preventing tumor cell death. Genetic or pharmacologic inhibition of autophagy greatly sensitizes glioblastoma cells and orthotopic xenografts to CC214-1- and CC214-2-induced cell death. CONCLUSIONS: These results identify CC214-1 and CC214-2 as potentially efficacious mTOR kinase inhibitors in glioblastoma, and suggest a strategy for identifying patients most likely to benefit from mTOR inhibition. In addition, this study also shows a central role for autophagy in preventing mTOR-kinase inhibitor-mediated tumor cell death, and suggests a pharmacologic strategy for overcoming it.

Outcomes of patients with surgically treated bilateral renal masses and a minimum of 10 years of followup.

PURPOSE: Nephron sparing surgery has been advocated for patients with bilateral renal masses but long-term functional and oncological outcomes are lacking. We report the outcomes of patients with bilateral renal masses and a minimum 10-year followup. MATERIALS AND METHODS: Patients with bilateral renal masses evaluated at our institution who were treated with initial surgery at least 10 years ago and underwent interventions on each renal unit were included in the analysis. Collected data included demographics, hereditary diagnosis, number of renal interventions, renal function and mortality status. Overall and renal cell carcinoma specific survival was assessed. Comparisons were made of renal function and overall survival between groups with 2 renal units and a surgically solitary kidney. RESULTS: A total of 128 patients met study inclusion criteria. Median followup in our cohort was 16 years (mean 17, range 10 to 49). The median number of surgical interventions was 3 (range 2 to 10). Of the patients 87 (68%) required repeat interventions on the ipsilateral renal unit at last followup with a median of 6.2 years (range 0.7 to 21) between interventions. Overall and renal cell cancer specific survival was 88% and 97%, respectively. Six patients (4.7%) ultimately underwent bilateral nephrectomy. Although renal function was better preserved in patients with 2 kidneys (70 vs 53 ml/minute/1.73 m(2), p = 0.0002), there was no difference in overall survival between those with bilateral kidneys or a surgically solitary kidney. CONCLUSIONS: At a minimum 10-year followup after initial surgery, nephron sparing surgery allowed for excellent oncological and functional outcomes. Despite the need for repeat surgical interventions, nephron sparing surgery enabled dialysis to be avoided in more than 95% of patients.

EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy.

Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma, their clinical relevance is poorly understood. Studies of tumors from patients treated with the EGFR inhibitor lapatinib revealed that EGFR induces the cleavage and nuclear translocation of the master transcriptional regulator of fatty acid synthesis, sterol regulatory element-binding protein 1 (SREBP-1). This response was mediated by Akt; however, clinical data from rapamycin-treated patients showed that SREBP-1 activation was independent of the mammalian target of rapamycin complex 1, possibly explaining rapamycin's poor efficacy in the treatment of such tumors. Glioblastomas without constitutively active EGFR signaling were resistant to inhibition of fatty acid synthesis, whereas introduction of a constitutively active mutant form of EGFR, EGFRvIII, sensitized tumor xenografts in mice to cell death, which was augmented by the hydroxymethylglutaryl coenzyme A reductase inhibitor atorvastatin. These results identify a previously undescribed EGFR-mediated prosurvival metabolic pathway and suggest new therapeutic approaches to treating EGFR-activated glioblastomas.