Disorders of oxygen transport are commonly attributed to inadequate carrying capacity (anemia) but may also relate to inefficient gas exchange by red blood cells (RBCs), a process that is poorly characterized yet assumed to be rapid. Without direct measurements of gas exchange at the single-cell level, the barriers to O2...

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster. Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.

Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 10⁸ CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 10⁹ CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 10⁸-CFU standard dose (n = 50) or a ≥2 x 10⁹-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

We previously produced a heavy-chain-only antibody (Ab) VH domain (V_HH)-displayed phage library from two alpacas that had been immunized with ricin toxoid and nontoxic mixtures of the enzymatic ricin toxin A subunit (RTA) and binding ricin toxin B subunit (RTB) (D. J. Vance, J. M. Tremblay, N. J. Mantis, and C. B. Shoemaker, J Biol Chem 288:36538–36547, 2013, https://doi.org/10.1074/jbc.M113.519207). Initial and subsequent screens of that library by direct enzyme-linked immunosorbent assay (ELISA) yielded more than two dozen unique RTA- and RTB-specific V_HHs, including 10 whose structures were subsequently solved in complex with RTA. To generate a more complete antigenic map of ricin toxin and to define the epitopes associated with toxin-neutralizing activity, we subjected the V_HH-displayed phage library to additional "pannings" on both receptor-bound ricin and antibody-captured ricin. We now report the full-length DNA sequences, binding affinities, and neutralizing activities of 68 unique V_HHs: 31 against RTA, 33 against RTB, and 4 against ricin holotoxin. Epitope positioning was achieved through cross-competition ELISAs performed with a panel of monoclonal antibodies (MAbs) and verified, in some instances, with hydrogen-deuterium exchange mass spectrometry. The 68 V_HHs grouped into more than 20 different competition bins. The RTA-specific V_HHs with strong toxin-neutralizing activities were confined to bins that overlapped two previously identified neutralizing hot spots, termed clusters I and II. The four RTB-specific V_HHs with potent toxin-neutralizing activity grouped within three adjacent bins situated at the RTA-RTB interface near cluster II. These results provide important insights into epitope interrelationships on the surface of ricin and delineate regions of vulnerability that can be exploited for the purpose of vaccine and therapeutic development.

Objective

To identify and characterize myeloid cell populations within the CSF of patients with MS and anti-myelin oligodendrocyte glycoprotein (MOG) disorder by high-resolution single-cell gene expression analysis.

Methods

Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells of CSF and blood from 2 subjects with relapsing-remitting MS (RRMS) and one with anti-MOG disorder. Publicly available scRNA-seq data from the blood and CSF of 2 subjects with HIV were also analyzed. An informatics pipeline was used to cluster cell populations by transcriptomic profiling. Based on gene expression by CSF myeloid cells, a flow cytometry panel was devised to examine myeloid cell populations from the CSF of 11 additional subjects, including individuals with RRMS, anti-MOG disorder, and control subjects without inflammatory demyelination.

Results

Common myeloid populations were identified within the CSF of subjects with RRMS, anti-MOG disorder, and HIV. These included monocytes, conventional and plasmacytoid dendritic cells, and cells with a transcriptomic signature matching microglia. Microglia could be discriminated from other myeloid cell populations in the CSF by flow cytometry.

Conclusions

High-resolution single-cell gene expression analysis clearly distinguishes distinct myeloid cell types present within the CSF of subjects with neuroinflammation. A population of microglia exists within the human CSF, which is detectable by surface protein expression. The function of these cells during immunity and disease requires further investigation.

Objective

To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines.

Methods

Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia.

Results

Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6–15.5 years). Median follow-up was 12.6 months (IQR 10.2–24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, p = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, p < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, p = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders.

Conclusion

In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.

Cellular heterogeneity in gene expression is driven by cellular processes, such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed characterization of gene expression heterogeneity and can thus shed new light on the processes driving heterogeneity. Here, we combined fluorescence imaging with scRNA-seq to measure cell cycle phase and gene expression levels in human induced pluripotent stem cells (iPSCs). By using these data, we developed a novel approach to characterize cell cycle progression. Although standard methods assign cells to discrete cell cycle stages, our method goes beyond this and quantifies cell cycle progression on a continuum. We found that, on average, scRNA-seq data from only five genes predicted a cell's position on the cell cycle continuum to within 14% of the entire cycle and that using more genes did not improve this accuracy. Our data and predictor of cell cycle phase can directly help future studies to account for cell cycle–related heterogeneity in iPSCs. Our results and methods also provide a foundation for future work to characterize the effects of the cell cycle on expression heterogeneity in other cell types.

Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be approximately 10–100x higher than the in vivo replication mutation rate. Here, we present RETrace, a method for simultaneously capturing both microsatellites and methylation-informative cytosines to characterize both lineage and cell type, respectively, from the same single cell. An important unique feature of RETrace was the introduction of linear amplification of microsatellites in order to reduce in vitro amplification noise. We further coupled microsatellite capture with single-cell reduced representation bisulfite sequencing (scRRBS), to measure the CpG methylation status on the same cell for cell type inference. When compared to existing retrospective lineage tracing methods, RETrace achieved higher accuracy (88% triplet accuracy from an ex vivo HCT116 tree) at a higher cell division resolution (lowering the required number of cell division difference between single cells by approximately 100 divisions). Simultaneously, RETrace demonstrated the ability to capture on average 150,000 unique CpGs per single cell in order to accurately determine cell type. We further formulated additional developments that would allow high-resolution mapping on microsatellite-stable cells or tissues with RETrace. Overall, we present RETrace as a foundation for multi-omics lineage mapping and cell typing of single cells.

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of >300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0–12 months), followed by those diagnosed at ages >1–18 years (40.3%) and >18–25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in >50% of eligible candidates, with C-peptide >252 pmol/L emerging as the best prognostic factor.

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in patients with metastatic pancreatic cancer who were enrolled in two phase II randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase IIa patient subcohort (N = 38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and a lower abundance of CD14⁺CD33⁺CD85j⁺ cells had improved overall survival [median overall survival, range (days) 271, 43–1,247] compared with patients with a lower abundance of CD8⁺CD45RO^–CCR7^–CD57⁺ cells and higher abundance of CD14⁺CD33⁺CD85j⁺ cells (77, 24–1,247 days; P = 0.0442). The results from this prospective–retrospective biomarker analysis were validated by flow cytometry in 200 patients with pancreatic cancer enrolled in a phase IIb study (P = 0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC_0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed.

In the past few decades, enterovirus A71 (EVA71) has caused devastating outbreaks in the Asia-Pacific region, resulting in serious sequelae in infected young children. No preventive or therapeutic interventions are currently available for curing EVA71 infection, highlighting a great unmet medical need for this disease. Here, we showed that one novel single-domain antibody (sdAb), F1, isolated from an immunized llama, could alleviate EVA71 infection both in vitro and in vivo. We also confirmed that the sdAb clone F1 recognizes EVA71 through a novel conformational epitope comprising the highly conserved region of VP3 capsid protein by using competitive-binding and overlapping-peptide enzyme-linked immunosorbent assays (ELISAs). Because of the virion’s icosahedral structure, we reasoned that adjacent epitopes must be clustered within molecular ranges that may be simultaneously bound by an engineered antibody with multiple valency. Therefore, two single-domain binding modules (F1) were fused to generate an sdAb-in-tandem design so that the capture of viral antigens could be further increased by valency effects. We showed that the tetravalent construct F1xF1-hFc, containing two sdAb-in-tandem on a fragment crystallizable (Fc) scaffold, exhibits more potent neutralization activity against EVA71 than does the bivalent sdAb F1-hFc by at least 5.8-fold. We also demonstrated that, using a human scavenger receptor class B member 2 (hSCARB2) transgenic mouse model, a half dose of the F1xF1-hFc provided better protection against EVA71 infection than did the F1-hFc. Thus, our study furnishes important insights into multivalent sdAb engineering against viral infection and provides a novel strategic deployment approach for preparedness of emerging infectious diseases such as EVA71.

Genomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog. However, the scRNA-seq analysis revealed that the neuroendocrine epithelial cells in the liver metastasis were less differentiated and expressed relatively little SSTR2, the predominant somatostatin receptor. There were also differences in the tumor microenvironments. RNA expression of vascular endothelial growth factors was higher in the primary tumor cells, reflected by an increased number of endothelial cells. Interestingly, vascular expression of the major VEGF receptors was considerably higher in the liver metastasis, indicating that the metastatic vasculature may be primed for expansion and susceptible to treatment with angiogenesis inhibitors. The patient eventually progressed on Sandostatin, and although consideration was given to adding an angiogenesis inhibitor to her regimen, her disease progression involved non-liver metastases that had not been characterized. Although in this specific case comparative scRNA-seq did not alter treatment, its potential to help guide therapy of metastatic disease was clearly demonstrated.

The Milky Way ate another galaxy called Gaia-Enceladus, and the waves passing through a star have shown us that it happened at most 11.6 billion years ago

A new computational method for assigning the donor in single cell RNA sequencing experiments provides an accurate way to unravel data from a mixture of people. The Souporcell method could help study how genetic variants in different people affect which genes are expressed during infection or response to drugs, and help research into transplants, personalized medicine and malaria.

A protein-coding gene called GB45239 is responsible for thelytokous parthenogenesis — the ability to produce daughters asexually — in the Cape honeybee (Apis mellifera capensis), a subspecies of honeybee found in the two southern provinces of South Africa, according to a new paper published in the journal Current Biology. The female worker caste of the [...]

A manually constructed 3D atlas offers a cellular-level view of the entire mouse brain. This reference brain, called the Allen Mouse Brain Common Coordinate Framework (CCFv3), is derived from serial two-photon tomography images of 1,675 mice.

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Photosynthetic systems in nature transport energy very efficiently towards a reaction center, where it is converted into a useful form for the organism. Scientists have been using this as inspiration to learn how to transport energy efficiently in, for example, molecular electronics. Physicist Richard Hildner from the University of Groningen and colleagues have investigated energy transport in an artificial system made from nanofibres. The results were published in the Journal of the American Chemical Society.

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by Annie Waldman

Last September, over pancakes at a diner in central Massachusetts, Molly Baldwin told her husband, Jonathan, they were going to have a baby. He cried into his coffee mug, elated and a little surprised. They had only been trying for about a week, and they had yearned for a summer baby, ideally in June, which would enable their parents to spend more time with their first grandchild.

“We thought we had the best timing,” she said.

But as the novel coronavirus began to spread through the country this year, Baldwin realized in early March that it was only a matter of time before the virus hit her town, Fitchburg, and the nursing home where she’s a social worker. Her patients would be among the most vulnerable: Some had battled addiction, many had experienced homelessness and most were elderly. Flu seasons were always hard on her patients, and she dreaded the havoc a more lethal disease would wreak.

Baldwin also worried about her baby. She spent hours looking up the prenatal effects of COVID-19, and the lack of evidence-based research concerned her. She called her obstetrician, who cautioned that because of the unknowns, she should consider working from home to limit her exposure to the virus.

So Baldwin made a plan for when COVID-19 arrived at her nursing home: She would swap shifts with a colleague to work fewer hours and request to work from home, as many of her duties are paperwork or computer-based.

She would work from the comfort of her kitchen table. She would avoid catching the virus. She would keep visiting her doctor until it was time to deliver, her belly swelling with a baby girl she knew was healthy and safe.

None of it, not a single thing, would go according to plan.

Baldwin said her supervisor and the human resources representative from the facility verbally agreed in mid-March to let her work from home. (Baldwin spoke with ProPublica on the condition that her workplace not be named; ProPublica contacted her employers with questions for this story.)

Then, on April 16, one of the residents at her facility tested positive for the virus. Baldwin sought testing at a walk-in clinic, and the results came back negative. But when she called her obstetrician’s office, she got a warning: If she continued to work at the facility, potentially exposing herself to the virus, they would not allow her to enter their office for prenatal appointments unless she could prove with a test, before each visit, that she was negative for COVID-19.

She understood their caution; her job was beginning to feel at odds with her pregnancy. It was time for her work-from-home plan to go into action.

She called her employer and asked to start the accommodations she had requested the month before. But they told her that now the plan would not be feasible, she said. Other pregnant employees were continuing to work at the facilities, and she would have to as well, she said she was told.

“The services provided at a nursing home do not typically allow for remote working,” a company spokesperson told ProPublica. “However, we have made changes to accommodate our staff whenever possible, provided there is no impact on patient care.”

After finding out her request to work from home would not be granted, Baldwin panicked. “I’m not even a mom yet,” she said. “This is my first baby, and I already feel like I’m doing everything wrong.”

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Baldwin is one of dozens of pregnant workers who ProPublica has heard from who are navigating the risks of COVID-19 while in the field of health care.

“There are plenty of pregnant women across the country who are trying to figure out what to do to protect themselves, given the uncertainty,” said Emily Martin, vice president for education and workplace justice at the National Women’s Law Center. “If you feel like you can’t do your job because there aren’t certain accommodations and you feel like you’re at risk, it’s difficult to see where to go next.”

About half of the states have laws that allow pregnant women to request reasonable accommodations, including Massachusetts, Martin said.

According to the Massachusetts Pregnant Workers Fairness Act, signed into state law in July 2017, employers must grant reasonable accommodations to their pregnant employees that allow them to continue to do their job, “unless doing so would impose an ’undue hardship’ on the employer.” An employer also “cannot make an employee accept a particular accommodation if another reasonable accommodation would allow the employee to perform the essential functions of the job.”

Both the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists have stated that based on the data available, pregnant women do not face a higher risk of infection or severe morbidity related to COVID-19. That said, both the CDC and ACOG have suggested that health care facilities may want to consider reducing the exposure of pregnant health care workers to patients with confirmed or suspected COVID-19, if staffing permits.

“In the overwhelming majority of pregnancies, the person who is pregnant recovered well with mild illness,” said Dr. Neel Shah, an obstetrician and assistant professor at Harvard Medical School, echoing the current guidance. But, he cautioned, there is a lot we still don’t know about how the virus impacts bodies, let alone those that are pregnant. “We can’t say that it’s completely safe — we don’t know.”

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Baldwin and her husband went through their options.

She couldn’t quit because they needed her paycheck. They had a mortgage, student loans and a new baby on the way. She also loved her job and cared deeply for her patients, whom she wanted to continue to serve. Her employer, trying to manage understaffing, had discouraged employees from taking time off, she said. She didn’t want to take any additional sick days, because she needed to save them for her maternity leave.

They decided that she would have to return to work.

Her employer told her to wear a mask and gloves, use hand sanitizer and remain in her small, boxy office, which has three desks for four people. Though she didn’t have contact with the residents, her office mates still did.

Even though she was scared, she tried to stay optimistic. “I was grateful for what I had because I have friends that are out of work right now,” she said. But she remained perplexed about why her requests had been denied. “I was sitting in my office doing work that would have easily been done from a laptop on my kitchen table.”

The company spokesperson did not respond to a question about whether it had originally given Baldwin verbal approval to work from home. When asked why she couldn’t have done the same work remotely, he said, “Based on your questions, our HR and Risk Management are anticipating action and would prefer to not comment at all.”

The next day, the Massachusetts National Guard delivered testing kits to the nursing home, and every resident was checked for the virus. When the results came back, at least 22 residents and 20 other staff members tested positive.

“We are conducting cleanings and infection control measures multiple times per day, with extra focus on high touch areas,” the company spokesperson said. “We screen and take the temperature of anyone entering our building, and we have increased monitoring of our residents.”

Public data shows the facility has more than 30 cases among residents and staff, the maximum number that the state reports publicly.

“I thought if I just keep working, stay in my office, use hand sanitizer, wear my mask, go home and shower right away, disinfect my clothes, then I will be fine, and I can keep my baby safe, and I can shed all this guilt,” she said.

Then on April 24, two of her office mates texted to tell her they had the virus.

And that morning, she’d felt a tickle in her throat.

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“I know I’m positive,” she thought to herself, as she left work midday and drove to a CVS drugstore testing site an hour away that was offering free rapid tests for front-line and health care workers. Hundreds of cars were already lined up.

She waited alone in her Jeep Wrangler for three hours, wearing her mask as required, which muffled her nagging cough. She shifted around constantly, to keep blood from pooling in her swelling feet. At the front of the line, she received a 6-inch cotton swab, wedged it deep in her nasal cavity, and returned it to the technicians. They directed her into a side parking lot, and 30 minutes later, she got a phone call with her results.

“We’re sorry to tell you that you’re positive,” the voice on the line told her. Baldwin’s mind stalled, engulfed in a wave of anxiety, which gave way to seething frustration.

“This was so preventable,” she said. “Now here I am, 33 weeks pregnant and positive. My most important job is to keep the baby safe, and my actual job wasn’t making that happen.”

When she called her co-workers and supervisor to tell them she tested positive, she said they were “all very caring and compassionate.” They told her to stay home for at least a week, or until her symptoms subsided. The Families First Coronavirus Response Act requires most employers to provide their workers with two weeks of paid leave if the employee is quarantined or experiencing COVID-19 symptoms. Baldwin said she would have to exhaust her sick days first; she’d been saving them for her maternity leave. Her husband, who works as a correctional officer at a county jail, was allowed to take 14 days of paid leave to tend to his wife, without using his own sick days.

She could no longer go to her normal obstetrician for in-person appointments, and instead, she would have to rely on telemedicine. Her doctor connected her with an obstetrician specializing in COVID-19 cases, with whom she planned to meet this week.

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Last Saturday, Baldwin’s mother had planned to throw her daughter a baby shower. She had invited 50 of their closest friends to celebrate at a new restaurant and had ordered dozens of pink favors from Etsy.

Because of the stay-at-home order, her shower morphed into a drive-by celebration, where her friends and family passed by her house, honking their horns and holding celebratory signs, balloons and streamers. They dropped gifts in front of her house, including first aid kits and a handsewn pink mask for an infant.

Her symptoms have, so far, been relatively mild, similar to a normal flu: headaches, a stuffy nose, a sore throat and muscle pains. She’s spent most of the past week resting in bed and taking baths to soothe her body aches. While taking care of Baldwin, her husband has also contracted the virus and is experiencing severe body aches as well.

In addition to her disappointment that the hypnobirthing and breastfeeding classes she had signed up for are canceled, her time in quarantine is now filled with anxious questions about how the disease may impact her baby.

Will the stress of this experience damage her baby neurologically? Will her baby be born early? Will she have to deliver by cesarean section to relieve pressure on her body and lungs, like so many stories she had read? Will she have to be secluded from her baby for days or weeks after birth? And what if her own symptoms worsen?

“This is our first baby, and it was so planned and wanted,” she said. “But had we known this awful thing would happen, would we have tried when we did?”

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Yokogawa Electric Corporation (TOKYO: 6841) announces that it has developed the SU10 Single Cellome Unit, a device that uses a nanopipette to inject substances such as genes and drugs and aspirate intracellular materials at target locations in individual cells.