Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B.

Neutrophil-directed motility is necessary for host defense, but its dysregulation can also cause collateral tissue damage. Actinopathies are monogenic disorders that affect the actin cytoskeleton and lead to immune dysregulation. Deficiency in ARPC1B, a component of the Arp2/3 complex, results in vascular neutrophilic inflammation; however, the mechanism remains unclear. Here, we generated human induced pluripotent stem cell (iPSC)-derived neutrophils (denoted iNeutrophils) that are deficient in ARPC1B and show impaired migration and a switch from forming pseudopodia to forming elongated filopodia. We show, using a blood vessel on a chip model, that primary human neutrophils have impaired movement across an endothelium deficient in APRC1B. We also show that the combined deficiency of ARPC1B in iNeutrophils and endothelium results in further reduction in neutrophil migration. Taken together, these results suggest that ARPC1B in endothelium is sufficient to drive neutrophil behavior. Furthermore, the findings provide support for using the iPSC system to understand human neutrophil biology and model disease in a genetically tractable system.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Lung cancer screening in primary care.

ABSTRACT: This article reviews the evidence supporting low-dose CT to screen for lung cancer, and the risks, costs, and challenges of implementing broad-based screening for eligible patients. Increased familiarity with lung cancer screening guidelines by primary care and specialty clinicians presents an opportunity to improve lung cancer screening rates and to save lives from the most common cause of cancer death in the United States.

The persistent-predation strategy of the red lionfish (Pterois volitans).

The pursuit of prey is vital to the biology of a predator and many aspects of predatory behaviour are well-studied. However, it is unclear how a pursuit can be effective when the prey is faster than a non-cryptic predator. Using kinematic measurements, we considered the strategy of red lionfish (Pterois volitans) as they pursued a faster prey fish (Chromis viridis) under laboratory conditions. Despite swimming about half as fast as C. viridis, lionfish succeeded in capturing prey in 61% of our experiments. This successful pursuit behaviour was defined by three critical characteristics. First, lionfish targeted C. viridis with pure pursuit by adjusting their heading towards the prey's position and not the anticipated point of interception. Second, lionfish pursued prey with uninterrupted motion. By contrast, C. viridis moved intermittently with variation in speed that included slow swimming. Such periods allowed lionfish to close the distance to a prey and initiate a suction-feeding strike at a relatively close distance (less than 9 cm). Finally, lionfish exhibited a high rate of strike success, capturing prey in 74% of all strikes. These characteristics comprise a behaviour that we call the 'persistent-predation strategy', which may be exhibited by a diversity of predators with relatively slow locomotion.

Imaging for Temporary Mechanical Circulatory Support Devices.

Heart failure is an important cause of mortality and morbidity in the world. Changes in organ allocation for solid thoracic (lung and heart) transplantation has increased the number of patients on mechanical circulatory support. Temporary mechanical support devices include devices tht support the circulation directly or indirectly such as extracorporeal membrane oxygenation (ECMO) and temporary support for right-sided failure, left-sided failure or biventricular failure. Most often, these devices are placed percutaneously and require either guidance with echocardiography, continuous radiography (fluoroscopy) or both. Furthermore, these devices need imaging in the intensive care unit to confirm continued accurate placement. This review contains the imaging views and nuances of the temporary assist devices (including ECMO) at the time of placement and the complications that can be associated with each individual device.

Association of family characteristics with health status and needs among children with congenital heart disease.

INTRODUCTION: Low socio-economic status is associated with poorer quality of life among children with congenital heart disease (CHD), but this finding is based on disparities among children remaining under cardiology follow-up. We used a population-based health survey data set to analyse the impact of socio-economic status on health and functional status among children with CHD. MATERIALS AND METHODS: We used 2007-2018 National Health Interview Survey data, selecting children 2-17 years of age who had been diagnosed with CHD. Outcomes included caregiver-rated general health, presence of functional limitations, number of missed school days, need for special education, and need for special equipment related to the child's health conditions. Socio-economic status measures included maternal educational attainment, food stamp programme participation, poverty status, and insurance coverage. RESULTS: Based on a sample of 233 children with CHD, 10% had fair or poor health, 38% reported having any health-related limitation on their usual activities, 11% needed special equipment, and 27% received special education services. On multivariable analysis, lower maternal educational attainment was correlated with worse caregiver-rated health, and children without insurance were especially likely to experience functional limitations. Black children with CHD had significantly worse caregiver-rated health compared to White children (ordered logit odds ratio: 0.19; 95% confidence interval: 0.08, 0.45; p < 0.001). CONCLUSIONS: In a population-based survey of children with CHD, race and several measures of socio-economic status disadvantage were associated with worse health outcomes. Further evaluation of social determinants of health during cardiology follow-up may help improve outcomes for children with CHD in socio-economically disadvantaged families.

Virtually Serving the Underserved: Resident Perceptions of Telemedicine Use While Training During Coronavirus Disease 2019.

Introduction: To adapt during the coronavirus disease 2019 (COVID-19) pandemic, a large safety-net hospital in Atlanta, Georgia and other hospitals across the United Sates, increased telemedicine (TM) for outpatient visits. The impact on resident physicians, including minority providers, had not yet been reported. We aimed to assess how primary care residents perceived increased TM in clinics during the pandemic, and assess resident burnout. Materials and Methods: An online survey was sent to 60 internal medicine (IM) and 18 family medicine (FM) residents who used TM to treat underserved patients, from March to May 2020, at the onset of the COVID-19 pandemic. The questionnaire included questions on resident demographics, satisfaction with TM, screening capability for COVID-19, effectiveness for patient education on COVID-19, impact on patient interactions and time management. Burnout was assessed with the Abbreviated Maslach Burnout Inventory. Results: A majority (62 of 78) eligible residents (79.5%) responded to the survey. Ninety-one percent of residents agreed that TM was a secure alternative to face-to-face encounters. Seventy-nine percent used it to screen for signs/symptoms of COVID-19 and 93% provided patient education on COVID-19. Average visit length decreased by 10-20 min with TM. Post-TM, scores for overall burnout were decreased (p = 0.0003) and less residents in total exhibited burnout (p = 0.0156). Discussion and Conclusions: IM and FM residents viewed TM as an efficient way to screen for and provide education on COVID-19, as well as a secure alternative to face-to-face encounters. With increased used of TM during COVID-19, there was decreased burnout among primary care residents.

Infectious Complications of Dorsal Root Ganglion Stimulation: A Systematic Review and Pooled Analysis of Incidence.

BACKGROUND AND OBJECTIVES: Dorsal root ganglion stimulation (DRGS) is a newer form of neuromodulation that targets the dorsal root ganglion. DRGS has superior efficacy in complex regional pain syndrome compared to spinal cord stimulation (SCS) and may have efficacy in other forms of chronic pain. While decades of safety data are available for SCS, there is less available safety information for DRGS. The objectives of this systematic review and pooled analysis of incidence are to determine the overall incidence of DRGS infections, incidence at each stage (trial vs implant vs revision), infection characteristics, and outcomes. MATERIALS AND METHODS: A comprehensive search of databases from January 1980 to January 2021 was conducted. RESULTS: Ten studies met inclusion criteria. Eight studies reported patients with trial data (n = 291), ten studies reported patients with implant data (n = 250), and seven studies reported data with revisions (n = 26). The pooled incidence of trial infections was 1.03% (95% CI 0.35-2.99%), implant infections was 4.80% (95% CI 2.77-8.20%), revision infections was 3.85% (95% CI 0.20-21.59%), and overall infections was 2.82% (95% CI 1.62-4.54%). There was a statistically significant difference in infection rates between the trial, implant, and revision stages, X2 (2, N = 567) = 8.9839, p = 0.01. CONCLUSIONS: This is the first systematic review and pooled analysis that followed PRISMA guidelines to report infectious complications of DRGS by stage (trial vs implant vs revision). DRGS trial appears to be low risk for infection but that risk is significantly increased with DRGS implant. Our findings highlight the need for further study of infectious complications, their risks, and optimal prophylaxis.

Management of Supraventricular Tachycardia in Pregnancy.

Supraventricular tachycardia is a common arrhythmia in pregnancy. During labor and delivery, neuraxial analgesia is important to prevent arrhythmia recurrence. We present the case of a 27-year-old gravida 2 para 1 woman at 35 weeks' gestation presenting with supraventricular tachycardia that converted to normal sinus rhythm with adenosine. To prevent recurrence of the arrhythmia, an early epidural was provided during labor to minimize catecholamine release.

The Visual Perception of Large-Scale Distances Outdoors.

The ability of 32 younger (ages ranged from 19 to 32 years) and older adults (ages ranged from 65 to 83 years) to visually perceive outdoor distances was evaluated; we used the method of equal-appearing intervals. On any given trial, the observers adjusted five distance intervals in depth so that they all appeared equivalent in magnitude (and equal to a standard initial egocentric distance of 6 m). The judgments of approximately two thirds of the younger and older observers exhibited varying degrees of perceptual compression, while those of the remaining one third were essentially accurate. Unlike a number of previous studies that evaluated the perception of shorter distances, no significant effects of age were obtained in the current experiment. In particular, there were no significant effects of age upon either accuracy or precision. The ability of human observers to evaluate large-scale distances outdoors is well maintained with increasing age.

Partner choice and fidelity stabilize coevolution in a Cretaceous-age defensive symbiosis.

Many insects rely on symbiotic microbes for survival, growth, or reproduction. Over evolutionary timescales, the association with intracellular symbionts is stabilized by partner fidelity through strictly vertical symbiont transmission, resulting in congruent host and symbiont phylogenies. However, little is known about how symbioses with extracellular symbionts, representing the majority of insect-associated microorganisms, evolve and remain stable despite opportunities for horizontal exchange and de novo acquisition of symbionts from the environment. Here we demonstrate that host control over symbiont transmission (partner choice) reinforces partner fidelity between solitary wasps and antibiotic-producing bacteria and thereby stabilizes this Cretaceous-age defensive mutualism. Phylogenetic analyses show that three genera of beewolf wasps (Philanthus, Trachypus, and Philanthinus) cultivate a distinct clade of Streptomyces bacteria for protection against pathogenic fungi. The symbionts were acquired from a soil-dwelling ancestor at least 68 million years ago, and vertical transmission via the brood cell and the cocoon surface resulted in host-symbiont codiversification. However, the external mode of transmission also provides opportunities for horizontal transfer, and beewolf species have indeed exchanged symbiont strains, possibly through predation or nest reuse. Experimental infection with nonnative bacteria reveals that--despite successful colonization of the antennal gland reservoirs--transmission to the cocoon is selectively blocked. Thus, partner choice can play an important role even in predominantly vertically transmitted symbioses by stabilizing the cooperative association over evolutionary timescales.

Congenital dystrophic epidermolysis bullosa (DEB) in Sprague Dawley rats: a case series.

BACKGROUND: Epidermolysis bullosa is a rare skin disease caused by defects in the basement membrane and/or other dermoepidermal junction components. HYPOTHESIS/OBJECTIVES: We describe a series of spontaneous cases of dystrophic epidermolysis bullosa (DEB) in a colony of Sprague Dawley rats investigated with histopathology, transmission electron microscopy (TEM) and inheritance pattern. ANIMALS: Four, 4-day-old pups from a litter of Sprague Dawley rats developed blistering, haemorrhagic skin lesions and were euthanized. Age-matched controls from the same litter were normal. Several months later two more litters presented with identical findings. All three litters had the same sire, suggesting a genetic component. METHODS: Skin from affected and control animals was evaluated histologically and with TEM. Unaffected sibling pairs from affected litters were bred in order to potentially reproduce the disease and determine the mode of inheritance. RESULTS: Histologically, there was significant dermoepidermal clefting below the basement membrane with variable amounts of haemorrhage and cellular debris within the clefts. Ultrastructurally, clefting occurred below the basement membrane with an intact lamina densa and normal hemidesmosomes. Anchoring filaments were strikingly absent. Litters produced from phenotypically unaffected sibling pairs resulted in a total of four more litters with approximately a quarter of pups affected. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on the gross lesions, histopathological features and TEM determination of separation below the lamina densa and lack of normal anchoring fibrils, these cases are most consistent with DEB. This is the first report of naturally occurring, localized and reproducible recessive DEB in Sprague Dawley rats.

Finding Identity and Meaning as a Nurse with a Mental Illness.

Through professional acculturation, nurses establish their identities as nurses. They also develop of an understanding what mental illness and associated phenomena mean. When nurses themselves develop mental illness, they must learn to establish a new identity as a patient and more specifically as a nurse-patient, and come to a new understanding of what mental illness means to them. This autoethnographic paper focuses on the author's own experience of finding an identity as nurse-patient and discovering what that really meant, at the same time incorporating analysis to connect the personal and the cultural.

A case for the use of autoethnography in nursing research.

AIMS: This paper discusses the basis for and potential usefulness of autoethnography as a research method in nursing. BACKGROUND: While qualitative research in nursing has traditionally involved the researcher taking an objective stance, autoethnography, with roots in the social sciences, is an emerging method that examines the researcher's own experience in a cultural context. DESIGN: Discussion paper. DATA SOURCES: Data sources from 1979-2013 in the CINAHL, Medline and PsycInfo databases were drawn on including articles from nursing and social science journals on autoethnography and related narrative-based approaches. DISCUSSION: Autoethnography is based on the assumption that reality is multifaceted and the role of culture and context is crucial in understanding human experience. The reader is engaged through the evocation of emotion and the stimulation of reflection. IMPLICATIONS FOR NURSING: While autoethnography has thus far been little used in the discipline of nursing, it is a methodology that offers novel insights and an opportunity to examine the impact of nurses' personal and professional cultural identity on their practice. CONCLUSION: Through the use of a subjective lens, autoethnography gives nurses the opportunity to tell stories that would otherwise not be heard. It involves a courageous laying bare of the self to gain new cultural understandings and it offers the potential for nurses to learn from the experiences and reflections of other nurses.

Primary cardiac angiosarcoma - a review.

Primary cardiac neoplasms are extremely rare. Angiosarcoma is the most commonly seen histological subtype and is characterized by its permeating and destructive nature. Unfortunately, primary cardiac angiosarcoma is often overlooked as an initial diagnosis because of its rarity. Since the time it was first identified in 1934, little progress has been made in improving survival outcome. Complete or partial surgical resection is still the best option for palliation, with little hope for cure. Improvements have been made in the ability to view and distinguish tumors. Echocardiography is one of the most useful diagnostic tools because of its high sensitivity; therefore, CT and MR images are often used to detect sites of metastatic disease. Immunohistochemistry staining can also be employed as an adjunctive diagnostic tool. CD31, CD34, FLI-1, and von Willebrand factor are the most commonly used markers in detecting tumors of endothelial origin. However, due to the vast heterogeneity within a tumor, immunohistochemistry staining can be quite variable. Surgical resection remains the standard modality of treatment. Primary cardiac angiosarcoma is largely resistant to chemotherapy and/or radiation. However, the exact benefit and its place in a multimodality treatment regimen are still under investigation.

Pneumomediastinum and the aortic nipple: the clinical relevance of the left superior intercostal vein.

This article discusses the appearance of the "aortic nipple" in chest radiography, and reviews the embryology and anatomy of the left superior intercostal vein which causes the appearance of an "aortic nipple." This radiological sign is useful in differentiating certain thoracic pathologies, such as pneumomediastinum, pneumopericardium, and medial pneumothorax. Pneumomediastinum is an encompassing term describing the presence of air in the mediastinum, and may arise from a wide range of pathological conditions. Despite the well-described imaging of pneumomediastinum, it is sometimes difficult to differentiate from other conditions such as pneumopericardium and medial pneumothorax. A separate finding, "aortic nipple" is the radiographic term used to describe the lateral nipple-like projection from the aortic knob present in a small number of individuals. The aortic nipple corresponds to the end-on appearance of the left superior intercostal vein coursing around the aortic knob, and may be mistaken radiologically for lymphadenopathy or a neoplasm. Despite their relative independence, the aortic nipple is defined by new contours in cases of pneumomediastinum, taking on an "inverted aortic nipple" appearance. In this position, the inverted aortic nipple may facilitate radiographic discrimination of pneumomediastinum from similar conditions. This study aims to review the common clinical and radiographic features of both pneumomediastinum and the aortic nipple. The radiologic appearance of the aortic nipple occurring in unison with pneumomediastinum, and its potential role as a tool in the differentiation of pneumomediastinum from similarly presenting conditions will also be described.

PTP1B phosphatase dampens iPSC-derived neutrophil motility and antimicrobial function.

Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited, as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration, and phagocytosis. In contrast, other effector functions like NETosis and reactive oxygen species production were reduced. PTP1B-deficient neutrophils were more responsive to Aspergillus fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine interleukin-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.