Influence of maternal psychological distress during COVID-19 pandemic on placental morphometry and texture.

The Coronavirus Disease 2019 (COVID-19) pandemic has been accompanied by increased prenatal maternal distress (PMD). PMD is associated with adverse pregnancy outcomes which may be mediated by the placenta. However, the potential impact of the pandemic on in vivo placental development remains unknown. To examine the impact of the pandemic and PMD on in vivo structural placental development using advanced magnetic resonance imaging (MRI), acquired anatomic images of the placenta from 63 pregnant women without known COVID-19 exposure during the pandemic and 165 pre-pandemic controls. Measures of placental morphometry and texture were extracted. PMD was determined from validated questionnaires. Generalized estimating equations were utilized to compare differences in PMD placental features between COVID-era and pre-pandemic cohorts. Maternal stress and depression scores were significantly higher in the pandemic cohort. Placental volume, thickness, gray level kurtosis, skewness and run length non-uniformity were increased in the pandemic cohort, while placental elongation, mean gray level and long run emphasis were decreased. PMD was a mediator of the association between pandemic status and placental features. Altered in vivo placental structure during the pandemic suggests an underappreciated link between disturbances in maternal environment and perturbed placental development. The long-term impact on offspring is currently under investigation.

Artificial Lipid Biomembranes for Full-Length SARS-CoV-2 Receptor.

The angiotensin-converting enzyme 2 (ACE2), as a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for assessing potential hosts and treatments. However, many studies are based on its truncated version but not full-length structure. Indeed, a single transmembrane (TM) helix presents in the full-length ACE2, influencing its interaction with SARS-CoV-2. Therefore, synthesis of the full-length ACE2 is an urgent requirement. Here, cell-free membrane protein synthesis systems (CFMPSs) are constructed for full-length membrane proteins. MscL is screened as a model among ten membrane proteins based on their expression and solubility. Next, CFMPSs are constructed and optimized based on natural vesicles, vesicles with four membrane proteins removed or two chaperonins added, and 37 types of nanodiscs. They all increase membrane protein solubility to over 50%. Finally, the full-length ACE2 of 21 species are successfully expressed with yields between 0.4 and 0.9 mg mL-1 . The definite functional differences from the truncated version suggest that the TM region affects ACE2's structure and function. CFMPSs can be extended to more membrane proteins, paving the way for further applications.

Impact of the COVID-19 pandemic on the treatment and prognosis of acute myocardial infarction in Xuzhou, China.

INTRODUCTION: The treatment of acute myocardial infarction (AMI) during the COVID-19 pandemic has been affected to varying degrees. This study is the first to explore the impact of COVID-19 on the treatment and prognosis of rural and urban AMI in developing countries. METHODOLOGY: A total of 128 patients with AMI in our hospital during the COVID-19 pandemic were enrolled. A total of 197 patients diagnosed with AMI before the COVID-19 pandemic were selected as the control group and one year of follow-up was performed. RESULTS: Hospital stay and the proportion of Killip class ≥ 2 patients were increased among rural AMI patients in the 'during COVID-19' group, compared with the 'before COVID-19' group. Among ST-segment elevation myocardial infarction (STEMI) total and rural STEMI patients, the treatment time in the during-COVID-19 group was longer than that in the before-COVID-19 group, whereas only the symptom to door (S to D) total and door to balloon (D to B) were extended in urban STEMI patients. In AMI total and rural AMI patients, major adverse cardiovascular events (MACEs) and all-cause mortality were increased in the during-COVID-19 group compared with the before-COVID-19 group. Kaplan-Meier analysis revealed that the survival and occurrence of MACEs in AMI total and rural AMI patients were significantly higher in the during-COVID-19 group. CONCLUSIONS: The COVID-19 pandemic led to delayed treatment and worse prognosis in AMI patients. Rural areas appear to be at a greater risk.

Maternal psychological distress during the COVID-19 pandemic and structural changes of the human fetal brain.

Background: Elevated maternal psychological distress during pregnancy is linked to adverse outcomes in offspring. The potential effects of intensified levels of maternal distress during the COVID-19 pandemic on the developing fetal brain are currently unknown. Methods: We prospectively enrolled 202 pregnant women: 65 without known COVID-19 exposures during the pandemic who underwent 92 fetal MRI scans, and 137 pre-pandemic controls who had 182 MRI scans. Multi-plane, multi-phase single shot fast spin echo T2-weighted images were acquired on a GE 1.5 T MRI Scanner. Volumes of six brain tissue types were calculated. Cortical folding measures, including brain surface area, local gyrification index, and sulcal depth were determined. At each MRI scan, maternal distress was assessed using validated stress, anxiety, and depression scales. Generalized estimating equations were utilized to compare maternal distress measures, brain volume and cortical folding differences between pandemic and pre-pandemic cohorts. Results: Stress and depression scores are significantly higher in the pandemic cohort, compared to the pre-pandemic cohort. Fetal white matter, hippocampal, and cerebellar volumes are decreased in the pandemic cohort. Cortical surface area and local gyrification index are also decreased in all four lobes, while sulcal depth is lower in the frontal, parietal, and occipital lobes in the pandemic cohort, indicating delayed brain gyrification. Conclusions: We report impaired fetal brain growth and delayed cerebral cortical gyrification in COVID-19 pandemic era pregnancies, in the setting of heightened maternal psychological distress. The potential long-term neurodevelopmental consequences of altered fetal brain development in COVID-era pregnancies merit further study.

E-waste dismantling-related occupational and routine exposure to melamine and its derivatives: Estimating exposure via dust ingestion and hand-to-mouth contact.

Melamine (MEL) and its derivatives are increasingly applied as nitrogenous flame retardants in consumer products. Nevertheless, limited information is available on their environmental occurrence and subsequent human exposure via multiple exposure pathways. In this study, we analysed MEL and its derivatives in dust (indication of the dust ingestion route) and hand wipe samples (indication of the hand-to-mouth route) collected in various microenvironments. The levels of ∑MELs in both dust (median: 24,100 ng/g) and participant hand samples (803 ng/m2) collected in e-waste dismantling workshops were significantly higher than those in samples collected in homes (15,600 ng/g and 196 ng/m2, respectively), dormitories (13,100 ng/g and 227 ng/m2, respectively) and hotel rooms (11,800 ng/g and 154 ng/m2, respectively). Generally, MEL dominated in dust samples collected in e-waste dismantling workshops, whereas cyanuric acid dominated in hand wipe samples. This may occur partly because the latter is an ingredient in disinfection products, which are more frequently employed in daily lives during the COVID-19 pandemic. Exposure assessment suggests that dust ingestion is an important exposure pathway among dismantling workers and the general population, whereas hand-to-mouth contact could not be overlooked in certain populations, such as children and dismantling workers not wear gloves at work.

The worldwide impact of telemedicine during COVID-19: current evidence and recommendations for the future.

During the COVID-19 pandemic, telemedicine has emerged worldwide as an indispensable resource to improve the surveillance of patients, curb the spread of disease, facilitate timely identification and management of ill people, but, most importantly, guarantee the continuity of care of frail patients with multiple chronic diseases. Although during COVID-19 telemedicine has thrived, and its adoption has moved forward in many countries, important gaps still remain. Major issues to be addressed to enable large scale implementation of telemedicine include: (1) establishing adequate policies to legislate telemedicine, license healthcare operators, protect patients' privacy, and implement reimbursement plans; (2) creating and disseminating practical guidelines for the routine clinical use of telemedicine in different contexts; (3) increasing in the level of integration of telemedicine with traditional healthcare services; (4) improving healthcare professionals' and patients' awareness of and willingness to use telemedicine; and (5) overcoming inequalities among countries and population subgroups due to technological, infrastructural, and economic barriers. If all these requirements are met in the near future, remote management of patients will become an indispensable resource for the healthcare systems worldwide and will ultimately improve the management of patients and the quality of care.

Inequality in Social Support Associated With Mild Cognitive Impairment: A Cross-Sectional Study of Older (≥60 Years) Residents in Shanghai, China.

Objective: Social support plays a critical role in the detection and management of mild cognitive impairment (MCI). However, socioeconomic inequalities exist in both social support and health care services. Our study aimed to compare the level of social support received by MCI patients in comparison with those without MCI and to determine its link with income. Methods: Secondary data analyses were performed. Social support was measured using the Duke Social Support Index (DSSI) and satisfaction ratings. Multivariate logistic regression models were constructed to determine the associations of personal income and MCI with social support after adjustment for variations in the sociodemographic and health characteristics of the respondents. The multiplicative and additive interaction effects of income and MCI were further examined through introducing the MCI*Income variable to the regression models and using the relative excess risk due to interaction (RERI) analysis, respectively. Results: The logistic regression models showed that the respondents with MCI had significantly lower social support as measured by the DSSI scores (AOR = 33.03, p < 0.001) and satisfaction ratings (AOR = 7.48, p < 0.001) compared with those without MCI. Similarly, social support decreased with lower personal income (p < 0.001). There existed a significant multiplicative interaction effect between personal income and MCI on social support (AOR = 0.30-0.32, p < 0.01). The gap in social support between those with and without MCI was higher in the higher income group compared with the lower income group (p < 0.001). No significant additive interaction effects on social support were found between MCI and income. Conclusions: There are significant disparities in social support between people living with and without MCI. Such a gap is more profound in people with higher income. The inequality in social support associated with MCI may present a significant challenge to the successful implementation of community MCI detection and management.

Tracking Self-reported Symptoms and Medical Conditions on Social Media During the COVID-19 Pandemic: Infodemiological Study.

BACKGROUND: Harnessing health-related data posted on social media in real time can offer insights into how the pandemic impacts the mental health and general well-being of individuals and populations over time. OBJECTIVE: This study aimed to obtain information on symptoms and medical conditions self-reported by non-Twitter social media users during the COVID-19 pandemic, to determine how discussion of these symptoms and medical conditions changed over time, and to identify correlations between frequency of the top 5 commonly mentioned symptoms post and daily COVID-19 statistics (new cases, new deaths, new active cases, and new recovered cases) in the United States. METHODS: We used natural language processing (NLP) algorithms to identify symptom- and medical condition-related topics being discussed on social media between June 14 and December 13, 2020. The sample posts were geotagged by NetBase, a third-party data provider. We calculated the positive predictive value and sensitivity to validate the classification of posts. We also assessed the frequency of health-related discussions on social media over time during the study period, and used Pearson correlation coefficients to identify statistically significant correlations between the frequency of the 5 most commonly mentioned symptoms and fluctuation of daily US COVID-19 statistics. RESULTS: Within a total of 9,807,813 posts (nearly 70% were sourced from the United States), we identified a discussion of 120 symptom-related topics and 1542 medical condition-related topics. Our classification of the health-related posts had a positive predictive value of over 80% and an average classification rate of 92% sensitivity. The 5 most commonly mentioned symptoms on social media during the study period were anxiety (in 201,303 posts or 12.2% of the total posts mentioning symptoms), generalized pain (189,673, 11.5%), weight loss (95,793, 5.8%), fatigue (91,252, 5.5%), and coughing (86,235, 5.2%). The 5 most discussed medical conditions were COVID-19 (in 5,420,276 posts or 66.4% of the total posts mentioning medical conditions), unspecified infectious disease (469,356, 5.8%), influenza (270,166, 3.3%), unspecified disorders of the central nervous system (253,407, 3.1%), and depression (151,752, 1.9%). Changes in posts in the frequency of anxiety, generalized pain, and weight loss were significant but negatively correlated with daily new COVID-19 cases in the United States (r=-0.49, r=-0.46, and r=-0.39, respectively; P<.05). Posts on the frequency of anxiety, generalized pain, weight loss, fatigue, and the changes in fatigue positively and significantly correlated with daily changes in both new deaths and new active cases in the United States (r ranged=0.39-0.48; P<.05). CONCLUSIONS: COVID-19 and symptoms of anxiety were the 2 most commonly discussed health-related topics on social media from June 14 to December 13, 2020. Real-time monitoring of social media posts on symptoms and medical conditions may help assess the population's mental health status and enhance public health surveillance for infectious disease.

Development and comparison of cell-free protein synthesis systems derived from typical bacterial chassis.

Cell-free protein synthesis (CFPS) systems have become an ideal choice for pathway prototyping, protein production, and biosensing, due to their high controllability, tolerance, stability, and ability to produce proteins in a short time. At present, the widely used CFPS systems are mainly based on Escherichia coli strain. Bacillus subtilis, Corynebacterium glutamate, and Vibrio natriegens are potential chassis cells for many biotechnological applications with their respective characteristics. Therefore, to expand the platform of the CFPS systems and options for protein production, four prokaryotes, E. coli, B. subtilis, C. glutamate, and V. natriegens were selected as host organisms to construct the CFPS systems and be compared. Moreover, the process parameters of the CFPS system were optimized, including the codon usage, plasmid synthesis competent cell selection, plasmid concentration, ribosomal binding site (RBS), and CFPS system reagent components. By optimizing and comparing the main influencing factors of different CFPS systems, the systems can be optimized directly for the most influential factors to further improve the protein yield of the systems. In addition, to demonstrate the applicability of the CFPS systems, it was proved that the four CFPS systems all had the potential to produce therapeutic proteins, and they could produce the receptor-binding domain (RBD) protein of SARS-CoV-2 with functional activity. They not only could expand the potential options for in vitro protein production, but also could increase the application range of the system by expanding the cell-free protein synthesis platform. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40643-021-00413-2.

Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With the Risk of Hospitalization and Death in Hypertensive Patients With COVID-19.

Background Despite its clinical significance, the risk of severe infection requiring hospitalization among outpatients with severe acute respiratory syndrome coronavirus 2 infection who receive angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) remains uncertain. Methods and Results In a propensity score-matched outpatient cohort (January-May 2020) of 2263 Medicare Advantage and commercially insured individuals with hypertension and a positive outpatient SARS-CoV-2, we determined the association of ACE inhibitors and ARBs with COVID-19 hospitalization. In a concurrent inpatient cohort of 7933 hospitalized with COVID-19, we tested their association with in-hospital mortality. The robustness of the observations was assessed in a contemporary cohort (May-August). In the outpatient study, neither ACE inhibitors (hazard ratio [HR], 0.77; 0.53-1.13, P=0.18) nor ARBs (HR, 0.88; 0.61-1.26, P=0.48) were associated with hospitalization risk. ACE inhibitors were associated with lower hospitalization risk in the older Medicare group (HR, 0.61; 0.41-0.93, P=0.02), but not the younger commercially insured group (HR, 2.14; 0.82-5.60, P=0.12; P-interaction 0.09). Neither ACE inhibitors nor ARBs were associated with lower hospitalization risk in either population in the validation cohort. In the primary inpatient study cohort, neither ACE inhibitors (HR, 0.97; 0.81-1.16; P=0.74) nor ARBs (HR, 1.15; 0.95-1.38, P=0.15) were associated with in-hospital mortality. These observations were consistent in the validation cohort. Conclusions ACE inhibitors and ARBs were not associated with COVID-19 hospitalization or mortality. Despite early evidence for a potential association between ACE inhibitors and severe COVID-19 prevention in older individuals, the inconsistency of this observation in recent data argues against a role for prophylaxis.

Engagement With COVID-19 Public Health Measures in the United States: A Cross-sectional Social Media Analysis from June to November 2020.

BACKGROUND: COVID-19 has continued to spread in the United States and globally. Closely monitoring public engagement and perceptions of COVID-19 and preventive measures using social media data could provide important information for understanding the progress of current interventions and planning future programs. OBJECTIVE: The aim of this study is to measure the public's behaviors and perceptions regarding COVID-19 and its effects on daily life during 5 months of the pandemic. METHODS: Natural language processing (NLP) algorithms were used to identify COVID-19-related and unrelated topics in over 300 million online data sources from June 15 to November 15, 2020. Posts in the sample were geotagged by NetBase, a third-party data provider, and sensitivity and positive predictive value were both calculated to validate the classification of posts. Each post may have included discussion of multiple topics. The prevalence of discussion regarding these topics was measured over this time period and compared to daily case rates in the United States. RESULTS: The final sample size included 9,065,733 posts, 70% of which were sourced from the United States. In October and November, discussion including mentions of COVID-19 and related health behaviors did not increase as it had from June to September, despite an increase in COVID-19 daily cases in the United States beginning in October. Additionally, discussion was more focused on daily life topics (n=6,210,255, 69%), compared with COVID-19 in general (n=3,390,139, 37%) and COVID-19 public health measures (n=1,836,200, 20%). CONCLUSIONS: There was a decline in COVID-19-related social media discussion sourced mainly from the United States, even as COVID-19 cases in the United States increased to the highest rate since the beginning of the pandemic. Targeted public health messaging may be needed to ensure engagement in public health prevention measures as global vaccination efforts continue.

Immune dysfunction following COVID-19, especially in severe patients.

The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4+ T cell, CD8+ T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4+ cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.

A Cyclodextrin-Stabilized Spermine-Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency.

Ion-pairing a lifesaving drug such as theophylline with a targeting moiety could have a significant impact on medical emergencies such as status asthmaticus or COVID-19 induced pneumomediastinum. However, to achieve rapid drug targeting in vivo the ion-pair must be protected against breakdown before the entry into the target tissue. This study aims to investigate if inserting theophylline, when ion-paired to the polyamine transporter substrate spermine, into a cyclodextrin (CD), to form a triplex, could direct the bronchodilator to the lungs selectively after intravenous administration. NMR demonstrates that upon the formation of the triplex spermine protruded from the CD cavity and this results in energy-dependent uptake in A549 cells (1.8-fold enhancement), which persists for more than 20 min. In vivo, the triplex produces a 2.4-fold and 2.2-fold increase in theophylline in the lungs 20 min after injection in rats and mice, respectively (p < 0.05). The lung targeting is selective with no increase in uptake into the brain or the heart where the side-effects of theophylline are treatment-limiting. Selectively doubling the concentration of theophylline in the lungs could improve the benefit-risk ratio of this narrow therapeutic index medicine, which continues to be important in critical care.