Profound Treg perturbations correlate with COVID-19 severity.

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.

Investigation of social support as a mediator of the relationship between physical and psychological health among hospitalised patients.

AIM: To investigate the self-reported levels of social support from friends and family and from nurses as mediators of the relationship between self-rated physical and psychological condition in hospitalised patients. DESIGN: Cross-sectional study of adult inpatients at a large tertiary-care hospital in the northeast United States. METHODS: Multiple mediation analysis of survey data. RESULTS: In surveys received from 324 inpatients, one fourth of the variation in patients' self-rated psychological condition was explained by self-rated physical condition. Social support from family and friends mediated a significant proportion (11.0%) of the relationship between self-rated physical and psychological condition, however social support from nurses did not. CONCLUSION: Social support from family and friends can positively influence the psychological health of inpatients, but nurses are not an adequate replacement for the social support provided by family and friends. IMPLICATIONS FOR NURSING: Although nurses cannot replace the social support provided by family and friends, the assessment of social isolation and care planning of interventions to support patients is a fundamental nursing role. Technology to connect patients with friends and family should be used to mitigate isolation for hospitalised patients unable to receive in-person visits from loved ones. IMPACT: The influence of social support from family and friends and nurses was addressed. The study found social support from family and friends, but not nurses, to influence the relationship between physical and psychological ratings. This finding has implications for the role of nurses in the hospital setting. REPORTING METHOD: Strengthening the Reporting of Observational Studies in Epidemiology guidelines were followed.

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

The Neurologic Exam.

For most of human history, diseases preying upon the nervous system could only be identified indirectly through neurological signs-making the neurology clinician's examination the principal diagnostic tool. While advanced imaging and electrophysiology of today's practice provides greater diagnostic precision, the wide array of tools available and their applications emphasizes the accuracy that the neurological examination provides to localization, which in turn enables our technology's precision to effectively and efficiently aid one's diagnosis.

Hypnic headache secondary to haemangioblastoma of the cerebellum.

We report a case of secondary hypnic headache in a patient with a haemangioblastoma of the cerebellum. The number of secondary cases is steadily increasing in the medical literature and magnetic resonance imaging of the brain should be considered mandatory after arriving at a presumptive diagnosis.

Profound Treg perturbations correlate with COVID-19 severity.

The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in both Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, which correlated with poor outcomes. Accordingly, these Tregs over-expressed a range of suppressive effectors, but also pro-inflammatory molecules like IL32. Most strikingly, they acquired similarity to tumor-infiltrating Tregs, known to suppress local anti-tumor responses. These traits were most marked in acute patients with severe disease, but persisted somewhat in convalescent patients. These results suggest that Tregs may play nefarious roles in COVID-19, via suppressing anti-viral T cell responses during the severe phase of the disease, and/or via a direct pro-inflammatory role.

Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children.

Background: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. Methods: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. Results: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. Conclusions: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

CE: Original Research: Midlife Hypertension and Hypercholesterolemia in Relation to Cognitive Function Later in Life in Black Women.

: Purpose: This study sought to evaluate midlife hypertension and hypercholesterolemia in relation to cognitive function later in life among black women. METHODS: Participants were drawn from the Nurses' Health Study and the Women's Health Study databases. In these studies, health professionals reported health information by questionnaire at baseline and at regular follow-up intervals, including diagnoses of hypertension, hypercholesterolemia, or both; and they completed telephone-based cognitive assessments later in life. Multivariable-adjusted linear regression models were used to estimate mean differences in global cognition and executive function scores, comparing women with and without a history of hypertension at midlife and women with and without a history of hypercholesterolemia at midlife. RESULTS: Data for 363 black female health professionals were analyzed. Those with a history of hypertension or hypercholesterolemia at midlife did not have lower global cognition and executive function scores later in life compared with those without such a history, although there were trends in this direction. CONCLUSION: In the study sample, a history of hypertension or hypercholesterolemia at midlife was not related to worse cognitive function in later life. But there was a suggestive pattern of trends that warrants further exploration in larger studies.

scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling.

Loss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to differentiated hair cells. scRNA-Seq of lateral line organs uncovered five different support cell types, including quiescent and activated stem cells. Ordering of support cells along a developmental trajectory identified self-renewing cells and genes required for hair cell differentiation. scRNA-Seq analyses of fgf3 mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. The data is searchable and publicly accessible via a web-based interface.

Value of Patient-Directed Brain Magnetic Resonance Imaging Scan with a Diagnosis of Migraine.

BACKGROUND: The objective of this study was to determine whether a brain magnetic resonance imaging (MRI) scan in patients with a diagnosis of migraine, who insist on the performance of imaging, is of more benefit in detecting clinically significant unsuspected structural abnormalities than would be expected by chance. METHODS: This prospective, observational, single-center study was performed from January 1, 2010 to December 31, 2012 and included 100 subjects with a diagnosis of migraine and normal results on neurologic examination. A brain MRI scan was performed on all patients, solely at their request, to detect an unsuspected clinically significant structural lesion. RESULTS: Of the 100 patients, 86 were female, and the average age was 31.5 years. Forty-five patients experienced migraine without aura, 41 chronic migraine, and 14 migraine with aura. All of the patients had normal results on neurologic examination. The duration of headaches ranged from 4 months to 40 years. In all, 82 of the MRI scans showed normal results, and 17 revealed clinically insignificant abnormalities. One MRI in a patient with chronic migraine without aura revealed a meningioma that subsequently required surgery and radiation therapy. The 1% prevalence of tumor in this study was then compared with 2 large cohorts of MRI abnormalities in the general asymptomatic population, in which tumor was found in 35 out of 3000. Fisher's exact test was used to compare the prevalence of tumor in the study population with the combined cohorts, and there was no statistical difference between these rates (P > .99). CONCLUSIONS: Brain MRI obtained at the specific request of patients with a diagnosis of migraine in the presence of normal neurologic examination results has a yield that is equivalent to that of the general asymptomatic population. Patients do not seem to have more insight than the examining clinician with regard to detecting underlying structural abnormalities, and brain MRI should not performed as part of the routine evaluation of migraine without a clear clinical indication.

Single-cell transcriptome analysis of avian neural crest migration reveals signatures of invasion and molecular transitions.

Neural crest cells migrate throughout the embryo, but how cells move in a directed and collective manner has remained unclear. Here, we perform the first single-cell transcriptome analysis of cranial neural crest cell migration at three progressive stages in chick and identify and establish hierarchical relationships between cell position and time-specific transcriptional signatures. We determine a novel transcriptional signature of the most invasive neural crest Trailblazer cells that is consistent during migration and enriched for approximately 900 genes. Knockdown of several Trailblazer genes shows significant but modest changes to total distance migrated. However, in vivo expression analysis by RNAscope and immunohistochemistry reveals some salt and pepper patterns that include strong individual Trailblazer gene expression in cells within other subregions of the migratory stream. These data provide new insights into the molecular diversity and dynamics within a neural crest cell migratory stream that underlie complex directed and collective cell behaviors.