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BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions. METHODS: Wild-type and miR-30a-/- neonatal mice were exposed to hyperoxia [95% FiO2, postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a-/- mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a-/- male and female lung transcriptome data. RESULTS: Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a-/- mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a-/- female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand-receptor interaction. Gene expression signature in the miR-30a-/- female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium. CONCLUSIONS: miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.

Bronchopulmonary dysplasia (BPD) is a lung condition that affects babies born prematurely, causing problems with their lung development. Interestingly, BPD tends to affect boys more than girls, but we do not fully understand why. To investigate this, we conducted a study using mice. Female mice had better lung development and blood vessel formation when exposed to high oxygen levels. We found higher expression of a molecule called miR-30a in the female mice and seemed to be protective. So, we wanted to see if removing miR-30a would have the same effect on both male and female mice. To test this, we exposed newborn mice without miR-30a and normal mice to high oxygen levels or regular room air. Interestingly, the differences between normal males and females were no longer present in the mice without miR-30a. This suggested that miR-30a plays an important role in lung development. We also identified that the female mice without miR-30a, when exposed to high oxygen, had the greatest number of genes affected, and these gene changes were like those seen in blood samples from premature babies with BPD. Finally, we report that miR-30a was in a specific part of the lung called the bronchiolar epithelium. Overall, this study suggests that miR-30a is crucial in protecting premature lungs from damage caused by high oxygen levels. By understanding how miR-30a affects lung development, we may be able to develop new treatments for BPD in the future.

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Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the extant and anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) is likely to have greater value as an important diagnostic tool to inform public health. As the widespread adoption of WWS is relatively new at the scale employed for COVID-19, interpretation of data, including the relationship to clinical cases, has yet to be standardized. An in-depth analysis of the metrics derived from WWS is required for public health units/agencies to interpret and utilize WWS-acquired data effectively and efficiently. In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven different cities in Canada over periods ranging from 8 to 21 months. Significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing in these communities. The WC ratio decreased significantly during the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized communitys wastewater (40-60% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized communitys wastewater (40-60% allelic proportion). Finally, a rapid and significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variants greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when vaccine-induced community immunity was high. The WC ratio, used as an additional monitoring metric, complements clinical case counts and wastewater signals as individual metrics in its ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.

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On November 26, 2021, the World Health Organisation classified the B.1.1.529 SARS-CoV-2 variant as the Omicron variant of concern (VOC). Reports of higher transmissibility and potential immune evasion triggered flight bans and heightened health control measures across the world to stem its distribution. Wastewater-based surveillance has demonstrated to be a useful complement for community-based tracking of SARS-CoV-2 variants. Using design principles of our previous assays that detect VOCs (Alpha and Delta), here we report three allele-specific RT-qPCR assays that can quantitatively detect and discriminate the Omicron BA.1 and BA.2 variants in wastewater. The first assay targets the nine-nucleotide deletion at the L24-A27S of the spike protein for detection of BA.2. The second targets the six-nucleotide deletion at 69-70 of the spike protein for detection of the Omicron BA.1 variant, and the third targets the stretch of mutations from Q493R to Q498R for simultaneous detection of both Omicron BA.1 and BA.2. This method is open-sourced, can be implemented using commercially available RT-qPCR protocols, and would be an important tool for tracking the introduction and spread of the Omicron variants BA.1 and BA.2 in communities for informed public health responses.

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Wastewater-based epidemiology has emerged as a promising technology for population-level surveillance of COVID-19 disease. The SARS-CoV-2 virus is shed in the stool of infected individuals and aggregated in public sewers, where it can be quantified to provide information on population-level disease incidence that is unbiased by access to clinical testing. In this study, we present results from the largest nationwide wastewater monitoring system in the United States reported to date. We profile 55 locations with at least six months of sampling and highlight their wastewater data from April 2020 through May 2021. These locations represent over 12 million individuals across 19 states. Samples were collected approximately weekly by wastewater treatment utilities as part of a regular wastewater surveillance service and analyzed for SARS-CoV-2 concentrations using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Concentrations of SARS-CoV-2 (copies/mL) were normalized to pepper mild mottle virus (PMMoV), a stable and persistent indicator of feces concentrations in wastewater. Here, we show that wastewater data reflects temporal and geographic trends in clinical COVID-19 cases, demonstrating that wastewater surveillance is a feasible approach for nationwide population-level monitoring of COVID-19 disease. We also provide key lessons learned from our broad-scale implementation of wastewater-based epidemiology, which can be used to inform wastewater-based epidemiology approaches for future emerging diseases. With an evolving epidemic and effective vaccines against SARS-CoV-2, wastewater-based epidemiology can serve as an important passive surveillance approach to detect changing dynamics or resurgences of the virus. HighlightsO_LIWe present results from a nationwide wastewater monitoring network in the United States, which represents one of the broadest temporal and geographic wastewater-based epidemiology datasets to-date. C_LIO_LIWastewater concentrations measured within individual locations reflect temporal trends in reported COVID-19 cases in the associated communities. C_LIO_LIWastewater concentrations also reflect geographic patterns in reported COVID-19 cases across states throughout the pandemic. C_LIO_LINormalizing wastewater concentrations to a fecal marker virus improves the correlation between wastewater data and clinical cases across locations but not necessarily over time within individual locations. C_LIO_LIImplementing a nationwide wastewater monitoring system for SARS-CoV-2 is feasible, practical, and sustainable. C_LI

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The Delta (B.1.617.2) variant has caused major devastation in India and other countries around the world. First detected in October 2020, it has now spread to more than 100 countries, prompting WHO to declare it as a global variant of concern (VOC). The Delta (B.1.617.2), Delta plus (B.1.617.2.1) and Kappa (B.1.617.1) variants are all sub-lineages of the original B.1.617 variant. Prior to the inception of B.1.617, vaccine rollout, safe-distancing and timely lockdowns greatly reduced COVID-19 hospitalizations and deaths. However, the Delta variant, allegedly more infectious and for which existing vaccines seemed less effective, has catalyzed the resurgence of cases. Therefore, there is an imperative need for increased surveillance of the B.1.617 variants. While the Beta variant is increasingly outpaced by the Delta variant, the spread of the Beta variant remains of concern due to its vaccine resistance. Efforts have been made to utilize wastewater-based surveillance for community-based tracking of SARS-CoV-2 variants, however wastewater with its low SARS-CoV-2 viral titers and mixtures of viral variants, requires assays to be variant-specific yet accurately quantitative for meaningful interpretation. Following on the design principles of our previous assays for the Alpha variant, here we report allele-specific and multiplex-compatible RT-qPCR assays targeting mutations T19R, D80A, K417N, T478K and E484Q, for quantitative detection and discrimination of the Delta, Delta plus, Kappa and Beta variants in wastewater. This method is open-sourced and can be implemented using commercially available RT-qPCR protocols, and would be an important tool for tracking the spread of B.1.617 and the Beta variants in communities.

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Wastewater surveillance has emerged as a useful tool in the public health response to the COVID-19 pandemic. While wastewater surveillance has been applied at various scales to monitor population-level COVID-19 dynamics, there is a need for quantitative metrics to interpret wastewater data in the context of public health trends. We collected 24-hour composite wastewater samples from March 2020 through May 2021 from a Massachusetts wastewater treatment plant and measured SARS-CoV-2 RNA concentrations using RT-qPCR. We show that the relationship between wastewater viral titers and COVID-19 clinical cases and deaths varies over time. We demonstrate the utility of three new metrics to monitor changes in COVID-19 epidemiology: (1) the ratio between wastewater viral titers and clinical cases (WC ratio), (2) the time lag between wastewater and clinical reporting, and (3) a transfer function between the wastewater and clinical case curves. We find that the WC ratio increases after key events, providing insight into the balance between disease spread and public health response. We also find that wastewater data preceded clinically reported cases in the first wave of the pandemic but did not serve as a leading indicator in the second wave, likely due to increased testing capacity. These three metrics could complement a framework for integrating wastewater surveillance into the public health response to the COVID-19 pandemic and future pandemics.

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Wastewater-based epidemiology (WBE) has emerged as a critical public health tool in tracking the SARS-CoV-2 epidemic. Monitoring SARS-CoV-2 variants of concern in wastewater has to-date relied on genomic sequencing, which lacks sensitivity necessary to detect low variant abundances in diluted and mixed wastewater samples. Here, we develop and present an open-source method based on allele specific RT-qPCR (AS RT-qPCR) that detects and quantifies the B.1.1.7 variant, targeting spike protein mutations at three independent genomic loci highly predictive of B.1.1.7 (HV69/70del, Y144del, and A570D). Our assays can reliably detect and quantify low levels of B.1.1.7 with low cross-reactivity, and at variant proportions between 0.1% and 1% in a background of mixed SARS-CoV-2. Applying our method to wastewater samples from the United States, we track B.1.1.7 occurrence over time in 19 communities. AS RT-qPCR results align with clinical trends, and summation of B.1.1.7 and wild-type sequences quantified by our assays strongly correlate with SARS-CoV-2 levels indicated by the US CDC N1/N2 assay. This work paves the path for rapid inexpensive surveillance of B.1.1.7 and other SARS-CoV-2 variants in wastewater.

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Wastewater-based disease surveillance is a promising approach for monitoring community outbreaks. Here we describe a nationwide campaign to monitor SARS-CoV-2 in the wastewater of 159 counties in 40 U.S. states, covering 13% of the U.S. population from February 18 to June 2, 2020. Out of 1,751 total samples analyzed, 846 samples were positive for SARS-CoV-2 RNA, with overall viral concentrations declining from April to May. Wastewater viral titers were consistent with, and appeared to precede, clinical COVID-19 surveillance indicators, including daily new cases. Wastewater surveillance had a high detection rate (>80%) of SARS-CoV-2 when the daily incidence exceeded 13 per 100,000 people. Detection rates were positively associated with wastewater treatment plant catchment size. To our knowledge, this work represents the largest-scale wastewater-based SARS-CoV-2 monitoring campaign to date, encompassing a wide diversity of wastewater treatment facilities and geographic locations. Our findings demonstrate that a national wastewater-based approach to disease surveillance may be feasible and effective.

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Current estimates of COVID-19 prevalence are largely based on symptomatic, clinically diagnosed cases. The existence of a large number of undiagnosed infections hampers population-wide investigation of viral circulation. Here, we use longitudinal wastewater analysis to track SARS-CoV-2 dynamics in wastewater at a major urban wastewater treatment facility in Massachusetts, between early January and May 2020. SARS-CoV-2 was first detected in wastewater on March 3. Viral titers in wastewater increased exponentially from mid-March to mid-April, after which they began to decline. Viral titers in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 4-10 days earlier in wastewater than in clinical data. We inferred viral shedding dynamics by modeling wastewater viral titers as a convolution of back-dated new clinical cases with the viral shedding function of an individual. The inferred viral shedding function showed an early peak, likely before symptom onset and clinical diagnosis, consistent with emerging clinical and experimental evidence. Finally, we found that wastewater viral titers at the neighborhood level correlate better with demographic variables than with population size. This work suggests that longitudinal wastewater analysis can be used to identify trends in disease transmission in advance of clinical case reporting, and may shed light on infection characteristics that are difficult to capture in clinical investigations, such as early viral shedding dynamics.

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Wastewater surveillance may represent a complementary approach to measure the presence and even prevalence of infectious diseases when the capacity for clinical testing is limited. Moreover, aggregate, population-wide data can help inform modeling efforts. We tested wastewater collected at a major urban treatment facility in Massachusetts and found the presence of SARS-CoV-2 at high titers in the period from March 18 - 25 using RT-qPCR. We then confirmed the identity of the PCR product by direct DNA sequencing. Viral titers observed were significantly higher than expected based on clinically confirmed cases in Massachusetts as of March 25. The reason for the discrepancy is not yet clear, and until further experiments are complete, these data do not necessarily indicate that clinical estimates are incorrect. Our approach is scalable and may be useful in modeling the SARS-CoV-2 pandemic and future outbreaks.

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BACKGROUND: Caregiving can be stressful, potentially creating physical and psychological strain. Substantial evidence has shown that family caregivers suffer from significant health problems arising from the demands of caregiving. Although there are programs supporting caregivers, there is little evidence regarding their effectiveness. Acupressure is an ancient Chinese healing method designed to restore the flow of Qi (vital energy) by applying external pressure to acupoints. A randomized, wait-list controlled trial was developed to evaluate the effectiveness of a self-administered acupressure intervention on caregiver stress (primary objective) and stress-related symptoms of fatigue, insomnia, depression, and health-related quality of life (secondary objectives) in Chinese caregivers of older family members. METHODS: Two hundred Chinese participants, aged ≥ 21 years, who are the primary caregivers of an older family member and screen positive for caregiver stress and symptoms of fatigue/insomnia/depression will be recruited from a community setting in Hong Kong. Subjects will be randomized to receive either an immediate treatment condition (self-administered acupressure intervention) or a wait-list control condition. The self-administered acupressure intervention will include (i) an individual learning and practice session twice a week for 2 weeks, (ii) a home follow-up visit once a week for 2 weeks, and (iii) 15-min self-practice twice a day for 6 weeks. The wait-list control group will receive the same acupressure training after the intervention group has completed the intervention. We hypothesize that Chinese family caregivers in the intervention group will have lower levels of caregiver stress, fatigue, insomnia, depression, and higher health-related quality of life after completion of the intervention than participants in the wait-list control group. DISCUSSION: This study will provide evidence for the effectiveness of self-administered acupressure in reducing stress and improving symptoms of fatigue, insomnia, depression, and health-related quality of life in Chinese family caregivers. The findings will inform the design of interventions to relieve negative health effects of caregiving. Furthermore, the results can raise community awareness and serve as a basis for policymaking, planning, and allocation of resources regarding empowerment of family caregivers for self-care. TRIAL REGISTRATION: Current Controlled Trials NCT02526446 . Registered August 10, 2015.

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Intimate partner violence has long been recognized as a serious public health problem. However, relatively little is known about its occurrence in late life (age 60 or above). A better understanding of this complex phenomenon is needed, partly because of aging populations worldwide and partly because of the necessity to protect vulnerable older people from the harm a violent partner might cause. The current case study aims to illustrate the duality of experience and the dynamics of intimate partner violence of two older Chinese women. It is hoped that the women's accounts may stimulate dialogue on how policy, research, and practice can be directed to protecting vulnerable older adults and reducing intimate partner violence in late life.

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