The impact of teleneonatology on the Transport Risk Index of Physiologic Stability score for outborn neonates: A prospective, observational study.

INTRODUCTION: Teleneonatology (TN) allows neonatologists to use real-time, audio-video telemedicine to manage critically ill neonates located in community hospitals (CHs). The California Transport Risk Index of Physiologic Stability (Ca-TRIPS) score is a validated metric that predicts the risk of 7-day mortality for neonates undergoing medical transport. We hypothesized that neonates born in CHs who received TN consults would have lower (better) Ca-TRIPS scores upon arrival of the transport team than those who did not. METHODS: Neonates born in CHs between 8 December 2018 and 31 July 2022 who were transported to the neonatal intensive care unit were screened for eligibility. TN was available at 50% (12/24) of CHs, where care teams decided when to activate the service. Study data were abstracted from the electronic health record and used to calculate Ca-TRIPS scores. Scores were evaluated using zero-inflated negative binomial regression. RESULTS: Forty-two percent (161/385) of neonates received a TN consult. Neonates that received TN had lower birth weight, gestational age, and Apgar scores and were more often admitted with respiratory distress syndrome and respiratory failure. Neonates who received TN were less likely to have a Ca-TRIPS score of zero (odds ratio 0.51; 95% confidence interval 0.33, 0.78). When adjusted for baseline characteristics, this difference was no longer significant. Non-zero Ca-TRIPS scores were not different between groups. DISCUSSION: In this observational study, neonates that received TN did not have lower (better) Ca-TRIPS scores. Findings may be limited by confounding bias given between-group differences in baseline patient characteristics. Randomized studies are needed to determine whether TN impacts the physiologic stability of neonates requiring medical transport.

Sociodemographic factors and family use of remote infant viewing in neonatal intensive care.

OBJECTIVE: We aimed to determine whether the use of remote infant viewing (RIV) in a neonatal intensive care unit (NICU) differed based on maternal sociodemographic factors. METHODS: The number of RIV camera views and view duration were obtained for NICU patients between 10/01/2019 and 3/31/2021 and standardized relative to patient days. Maternal sociodemographic and neonatal characteristics were obtained from institutional databases. RESULTS: Families in which mothers were unmarried (aOR 1.42, 95% CI 1.03-1.95), did not require an interpreter (aOR 2.86, 95% CI 1.54-5.32), were multiparous (aOR 1.56, 95% CI 1.16-2.10), delivered prior to 37 weeks' gestation (aOR 1.57, 95% CI 1.17-2.12), or resided ≥50 miles from the NICU (aOR 1.38, 95% CI 1.02-1.87) were significantly more likely to use RIV. CONCLUSION: Family use of RIV in the NICU varied by multiple sociodemographic factors. Further investigation to understand and to address potential equity gaps revealed or created by RIV are warranted.

Family Use of Remote Infant Viewing in the Neonatal Intensive Care Unit: Impact of the COVID-19 Pandemic and Patient Room Type.

Background: Remote infant viewing (RIV) uses a bedside camera to allow families to view a livestream video of their neonate 24/7 from anywhere with internet access. Objective: The aim of this study was to evaluate family use of RIV for infants in the neonatal intensive care unit (NICU) during the COVID-19 pandemic and whether RIV use varied by patient room type. Study Design: Use of RIV was evaluated for NICU patients between October 1, 2019, and March 31, 2021. The date, time, and duration of every RIV were exported from the RIV database and linked to the patient's room type. Results: Among 980 patients, 721 (73.6%) were viewed using RIV. The median (interquartile range) number of views per patient-days was 12.5 (5.4-26.0). Based on monthly aggregate data, the proportion of patients with at least one RIV increased during the pandemic from 71.6% in April 2020 to 94.3% in March 2021 (p < 0.001). The monthly number of views and view duration per patient-days also increased (p = 0.003; p = 0.029, respectively). When evaluating patient-level data by room type, the median number of views per patient-days was higher for open-bay than single-family rooms (13.5 vs. 10.5; p < 0.001) and median view duration (minutes) per patient-days was longer (21.8 vs. 12.1; p < 0.001). Conclusions: Use of RIV in the NICU increased during the COVID-19 pandemic. RIV was used more frequently and for longer duration by families with newborns in an open-bay room. RIV allows families to observe their newborn when visitor restrictions are in place or when in-person visits may be less private or do not allow for physical distancing.

Food-induced dopamine signaling in AgRP neurons promotes feeding.

Obesity comorbidities such as diabetes and cardiovascular disease are pressing public health concerns. Overconsumption of calories leads to weight gain; however, neural mechanisms underlying excessive food consumption are poorly understood. Here, we demonstrate that dopamine receptor D1 (Drd1) expressed in the agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons of the arcuate hypothalamus is required for appropriate responses to a high-fat diet (HFD). Stimulation of Drd1 and AgRP/NPY co-expressing arcuate neurons is sufficient to induce voracious feeding. Delivery of a HFD after food deprivation acutely induces dopamine (DA) release in the ARC, whereas animals that lack Drd1 expression in ARCAgRP/NPY neurons (Drd1AgRP-KO) exhibit attenuated foraging and refeeding of HFD. These results define a role for the DA input to the ARC that encodes acute responses to food and position Drd1 signaling in the ARCAgRP/NPY neurons as an integrator of the hedonic and homeostatic neuronal feeding circuits.

Non-Endoplasmic Reticulum-Based Calr (Calreticulin) Can Coordinate Heterocellular Calcium Signaling and Vascular Function.

OBJECTIVE: In resistance arteries, endothelial cell (EC) extensions can make contact with smooth muscle cells, forming myoendothelial junction at holes in the internal elastic lamina (HIEL). At these HIEL, calcium signaling is tightly regulated. Because Calr (calreticulin) can buffer ≈50% of endoplasmic reticulum calcium and is expressed throughout IEL holes in small arteries, the only place where myoendothelial junctions form, we investigated the effect of EC-specific Calr deletion on calcium signaling and vascular function. APPROACH AND RESULTS: We found Calr expressed in nearly every IEL hole in third-order mesenteric arteries, but not other ER markers. Because of this, we generated an EC-specific, tamoxifen inducible, Calr knockout mouse (EC Calr Δ/Δ). Using this mouse, we tested third-order mesenteric arteries for changes in calcium events at HIEL and vascular reactivity after application of CCh (carbachol) or PE (phenylephrine). We found that arteries from EC Calr Δ/Δ mice stimulated with CCh had unchanged activity of calcium signals and vasodilation; however, the same arteries were unable to increase calcium events at HIEL in response to PE. This resulted in significantly increased vasoconstriction to PE, presumably because of inhibited negative feedback. In line with these observations, the EC Calr Δ/Δ had increased blood pressure. Comparison of ER calcium in arteries and use of an ER-specific GCaMP indicator in vitro revealed no observable difference in ER calcium with Calr knockout. Using selective detergent permeabilization of the artery and inhibition of Calr translocation, we found that the observed Calr at HIEL may not be within the ER. CONCLUSIONS: Our data suggest that Calr specifically at HIEL may act in a non-ER dependent manner to regulate arteriolar heterocellular communication and blood pressure.

Chlamydia induces anchorage independence in 3T3 cells and detrimental cytological defects in an infection model.

Chlamydia are gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI) Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV). We have previously shown chlamydial infection results in centrosome amplification and multipolar spindle formation leading to chromosomal instability. Many studies indicate that centrosome abnormalities, spindle defects, and chromosome segregation errors can lead to cell transformation. We hypothesize that the presence of these defects within infected dividing cells identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. Here we demonstrate that infection with Chlamydia trachomatis is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time Chlamydia infects actively replicating cells in vivo. Infection of mice with Chlamydia results in significantly increased cell proliferation within the cervix, and in evidence of cervical dysplasia. Confocal examination of these infected tissues also revealed elements of chlamydial induced chromosome instability. These results contribute to a growing body of data implicating a role for Chlamydia in cervical cancer development and suggest a possible molecular mechanism for this effect.

Chlamydia trachomatis infection causes mitotic spindle pole defects independently from its effects on centrosome amplification.

Chlamydiae are Gram negative, obligate intracellular bacteria, and Chlamydia trachomatis is the etiologic agent of the most commonly reported sexually transmitted disease in the United States. Chlamydiae undergo a biphasic life cycle that takes place inside a parasitophorous vacuole termed an inclusion. Chlamydial infections have been epidemiologically linked to cervical cancer in patients previously infected by human papillomavirus (HPV). The inclusion associates very closely with host cell centrosomes, and this association is dependent upon the host motor protein dynein. We have previously reported that this interaction induces supernumerary centrosomes in infected cells, leading to multipolar mitotic spindles and inhibiting accurate chromosome segregation. Our findings demonstrate that chlamydial infection causes mitotic spindle defects independently of its effects on centrosome amplification. We show that chlamydial infection increases centrosome spread and inhibits the spindle assembly checkpoint delay to disrupt centrosome clustering. These data suggest that chlamydial infection exacerbates the consequences of centrosome amplification by inhibiting the cells' ability to suppress the effects of these defects on mitotic spindle organization. We hypothesize that these combined effects on mitotic spindle architecture identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation.

Giant cell arteritis of the female genital tract: report of a case and review of the literature.

A 65-year-old female presented with constitutional symptoms of fever and weight loss with bilateral adnexal masses on physical examination. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed and subsequently revealed giant cell arteritis involving numerous small arteries in the ovaries, fallopian tubes, paraovarian and paratubal soft tissues, myometrium, and cervix. After surgery, the patient continued to have constitutional symptoms. Corticosteroid therapy led to a significant improvement and eventual resolution of symptoms. Several similar cases of giant cell arteritis of the female genital tract have been described, both with and without concomitant temporal arteritis. Implications for diagnosis and treatment are discussed.

PI3K/AKT signaling and systemic autoimmunity.

The phosphoinositide 3-kinase (PI3K)/Akt signaling axis plays an important role in cellular proliferation and growth signaling. With respect to the immune system, a growing body of data is helping to elucidate the role of this pathway in lymphocyte development, as well as to show how perturbations that lead to unregulated activation in this pathway may produce systemic autoimmunity or malignancy. Various knockout and transgenic murine models have been described for key mediators of this signaling pathway. Many of these models resulting in the activation of this pathway demonstrate features of systemic autoimmunity, linking this pathway to autoimmune disease. Here, we review recently described murine models that exhibit activated PI3K/Akt signaling and the potential role this pathway in autoimmune disease, and also discuss the therapeutic implications of these findings.

Transverse myelitis in systemic sclerosis.

BACKGROUND: Neurological involvement occurs rarely with systemic sclerosis (SSc). Only a few cases of transverse myelopathy have been reported in the setting of SSc. OBJECTIVE: To describe a patient with SSc who developed transverse myelitis that improved during a course of immunosuppression. RESULTS: A 30-year-old woman with SSc presented with subacute onset of bilateral lower extremity weakness and numbness. Results of magnetic resonance imaging and cerebrospinal fluid studies supported a diagnosis of transverse myelitis. The patient responded favorably to a course of corticosteroids and cyclophosphamide. No overlapping autoimmune disorders were evident. Clinical follow-up showed significant recovery, with resolution of radiological abnormalities. CONCLUSION: Transverse myelitis can occur as a rare manifestation of SSc and may respond favorably to immunosuppressive therapy.