Longitudinal impacts of the COVID-19 pandemic on adolescents living with HIV in New York City.

Adolescents living with HIV (ALWH) are particularly susceptible to disruptions in care, which may lead to poor HIV-related health outcomes. Here, we report the results of a longitudinal phone-based study investigating impacts of the COVID-19 pandemic on ALWH in New York City. Participants (N = 10, mean age 21.2 years, 50% female) demonstrated substantial COVID-19 knowledge and identified Instagram as their primary source of COVID-19 information. Nearly all participants reported loss of income, and 50% reported experiencing food insecurity as a result of the pandemic. These findings highlight existing vulnerabilities among ALWH that may threaten the continuum of care.

In the Global Epicenter: Social Work Leadership in a New York City Hospital.

The Mount Sinai Hospital in New York City was in the epicenter of the COVID-19 pandemic and had to transform from a tertiary to crisis care hospital and increase its bed capacity by 50 percent to care for COVID-19 patients. The size, scope, complexity and uncertainty of this crisis was unparalleled. This article describes the comprehensive response of the Department of Social Work Services, one of the largest hospital social work departments in the country. The response was informed by four Departmental principles, as well as crisis intervention strategies. This article describes organizational structures, practice models, policies, and protocols developed to respond quickly and effectively, given infection prevention mandates, to patient, population and workforce needs. Finally, it includes how social workers addressed COVID-19 related physical and psychosocial needs and applied and modified interprofessional communication and collaboration. Lessons learned and clinical and administrative changes that will assist in navigating "new normal" operations are discussed.

Neurobehavioral outcomes in young adults with perinatally acquired HIV.

BACKGROUND: With combination antiretroviral therapy (cART), infants with perinatally acquired HIV (pHIV) are living into adolescence and adulthood. Worldwide, many have not received cART in the first years of life, and challenges of adolescence complicate transition to adulthood. Neurobehavioral outcomes in pHIV young adults (pHIVAd) are infrequently reported. OBJECTIVES: To examine neurobehavioral characteristics of pHIVAd ages 21-30 years, and to compare them with age-matched young adults infected in the second or third decade of life (HIVagematch), and older adults with similar duration HIV disease (HIVOA). METHODS: A comprehensive neuropsychological test battery and questionnaires to determine cognitive function and mood, and reviews of neuromedical and behavioral records were undertaken in three groups of 13 individuals each. Descriptive analysis and bivariate techniques were used for comparisons. RESULTS: Rates of cognitive impairment were highest in pHIVAd (85%) compared with HIVagematch (38%) and HIVOA (62%). pHIVAd had the worst scores in global cognition, speed of information processing, working memory, and verbal fluency (0.5--1.0 SD below other groups). There was a trend for higher rates of psychiatric dysfunction (predominantly mood disorders) in pHIVAd (85%) compared with HIV-agematch (46%) and HIVOA (54%). Only four pHIVAd reported employment or enrollment in school. Four had autoimmune disorders. CONCLUSION: These pHIVAd displayed high rates of cognitive, psychiatric, and autoimmune dysfunction, greater than age-matched or HIV duration-matched comparators. Although this small study is largely descriptive in nature, it suggests that a lack of cART in early life may result in long-term neurobehavioral and immune abnormalities manifesting into adulthood.

Outcomes of a Comprehensive Retention Strategy for Youth With HIV After Transfer to Adult Care in the United States.

BACKGROUND: The retention of youth living with HIV (YLHIV) in adult care after transfer from pediatric care in the United States is a challenge. A targeted comprehensive retention strategy (CRS) may improve retention among YLHIV. METHODS: A retrospective cohort study of YLHIV after transfer from pediatric to adult care for patients with at least 1 adult visit at 2 urban HIV care programs in the United States employing CRSs with internal medicine/pediatrics-trained providers, peer navigators, social workers and mental health resources. Primary outcomes were successful retention in care after transfer (≥2 provider visits in the adult clinic ≥90 days apart within 1 year of transfer) and successful transition (successful retention plus a stable HIV viral load (VL) defined as VL 1 year after transfer that was less than or equal to the VL obtained at or immediately before transfer). Logistic regression assessed factors associated with successful transition. A subgroup analysis was performed to examine rates of successful transfer and linkage from pediatric to adult clinics (attending at least 1 adult visit after transition). RESULTS: Of the 89 patients included in the study, 79 (89%) patients had successful retention and 53 (60%) had successful transition to the adult program. Factors associated with successful transition included non-African American race [adjusted odds ratio (aOR) = 11.26, 95% confidence interval (CI): 1.32-95.51], perinatal HIV (aOR = 8.00, 95% CI: 1.39-46.02) and CD4 count > 500 cells/mm (aOR = 5.22, 95% CI: 1.54-17.70). Of those who were retained, 53/79 (67%) had stable or improved virologic control at 1 year after transition. In a subgroup analysis, 54/56 (96%) patients who were targeted to transition successfully linked to adult care. CONCLUSIONS: Overall, YLHIV in the United States engaged in a CRS program appear to have high retention rates but suboptimal virologic control after transfer from pediatric HIV care.

Maternal Perinatal HIV Infection Is Associated With Increased Infectious Morbidity in HIV-exposed Uninfected Infants.

BACKGROUND: The aging population of females with perinatally-acquired HIV (PHIV) are having their own children. HIV-exposed uninfected infants (HEU-N) born to women living with non-perinatally-acquired HIV (NPHIV) experience higher infectious morbidity compared with HIV-unexposed infants (HUU). Little is known about the infectious morbidity risk of HIV-exposed uninfected infants (HEU-P) born to PHIV women. METHODS: We evaluated prevalence of infectious cause hospitalizations (ICH) during the first year of life among HEU-P, HEU-N and HUU infants in a United States (U.S) tertiary care center. Maternal HIV status was categorized as PHIV vs. NPHIV vs. HIV-uninfected. Generalized Estimating Equation models were fit to evaluate the association between maternal HIV status and infant ICH. RESULTS: ICH was evaluated among 205 infants, 28 HEU-P infants, 112 HEU-N infants, and 65 HUU infants. PHIV women were younger compared with NPHIV and HIV-uninfected women (median age 22 years vs. 29 and 23 respectively, p<0.01). Overall, 21% of HEU-P, 4% of HEU-N and 12% of HUU infants experienced at least one ICH event (p<0.01) in the first year of life. After adjusting for confounders, HEU-P infants were at increased ICH risk compared with HEU-N infants [adjusted odds ratio (aOR)=7.45, 95% Confidence Interval (CI):1.58-35.04]. In sub-group analysis of HEU infants, excluding HUU infants, this relationship persisted after adjustment for maternal CD4 and HIV RNA level (aOR=10.24, 95% CI:1.66-63.31) CONCLUSIONS:: In a small U.S. cohort, HEU-P infants experienced increased ICH risk. Differences in intrauterine environments, social factors, or access to care may be important factors to assess in future larger studies.

Psychosocial snapshots: perinatally infected HIV+ adolescents' sexual behaviors and pregnancies.

Perinatally infected HIV+ adolescents are confronted with unique psychosocial challenges as they navigate sexual behaviors and pregnancies. How their health and the nature of their chronic illness affect the normal developmental challenges of adolescence is explored through case vignettes taken from social workers' clinical practice at an East Harlem Medical Center. The successes and difficulties faced by both the patient and the practitioner are illustrated.

Pediatric HIV adherence: an ever-evolving challenge.

Providers working with children living with HIV strive to achieve "good adherence," often viewed only as consistent pill taking by the infected child. This goal, while important, needs to be expanded with a thorough examination of the many biopsychosocial factors impacting the HIV affected family. The complexity of the issues affecting adherence to a pediatric HIV medical regimen can overwhelm both the practitioner and the patient. By utilizing a developmental framework and emphasizing the critical importance of the relationship between provider, patient and family, the authors (both of whom are social workers who have worked over a period of many years with children and families living with terminal and serious chronic illnesses) describe a developmental approach that includes comprehensive assessment to address the multiple challenges faced by individuals and families they have worked with.

Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: evidence from knockout mice and growth factor administration.

Vascular endothelial growth factor-B (VEGFB) is an angiogenic and neuroprotective protein that reduces hypoxic and ischemic neuronal injury. To determine if VEGFB also regulates neurogenesis in the adult brain, we studied the effects of VEGFB administration in vitro and in vivo, as well as the effect of VEGFB gene knockout (KO) in mice, on bromodeoxyuridine (BrdU) incorporation and expression of immature neuronal markers in the subgranular zone (SGZ) of the hippocampal dentate gyrus and the forebrain subventricular zone (SVZ). Intracerebroventricular VEGFB administration increased BrdU incorporation into cells of neuronal lineage both in vitro and in vivo, and VEGFB-KO mice showed impaired neurogenesis, consistent with a neurogenesis-promoting effect of VEGFB. In addition, intraventricular administration of VEGFB restored neurogenesis to wild-type levels in VEGFB-KO mice. These results suggest a role for VEGFB in the regulation of adult neurogenesis, which could have therapeutic implications for diseases associated with central neuronal loss.

Neuronal nitric oxide synthase and ischemia-induced neurogenesis.

Nitric oxide (NO) influences infarct size after focal cerebral ischemia and also regulates neurogenesis in the adult brain. These observations suggest that therapeutic approaches to stroke that target NO signaling may provide neuroprotection and also enhance brain repair through cell replacement. However, ischemic injury and neurogenesis are both affected differently depending on which isoform of NO synthase is the source of NO. In addition, ischemia itself stimulates neurogenesis, and ischemia-induced neurogenesis may be regulated differently than neurogenesis in nonischemic brain. To determine how neuronal NO synthase affects ischemia-induced neurogenesis, transient focal cerebral ischemia was produced in wild-type mice and in knockout mice lacking neuronal NO synthase, and BrdU incorporation and doublecortin immunoreactivity were measured in the principal neuroproliferative regions of the adult brain. Knockout of neuronal NO synthase reduced infarct size and increased both basal and ischemia-induced neurogenesis, suggesting that NO from this source is an inhibitory regulator of neurogenesis in the ischemic brain. 7-Nitroindazole, an NO synthase inhibitor that preferentially affects the neuronal isoform, also increased neurogenesis in rats when administered by the intracerebroventricular route. Selective inhibition of neuronal NO synthase may have the potential to both reduce infarct size and enhance neurogenesis in stroke.

Effect of aging on neuroglobin expression in rodent brain.

Neuroglobin (Ngb), a recently discovered O2-binding heme protein related to hemoglobin and myoglobin, protects neurons from hypoxic-ischemic injury in vitro and in vivo. In immunostained mouse brain sections, we found widespread expression of Ngb protein in neurons, but not astrocytes, of several brain regions that are prominently involved in age-related neurodegenerative disorders. Western blots from young adult (3 month), middle-aged (12 month), and aged (24 month) rats showed an age-related decline in Ngb expression in cerebral neocortex, hippocampus, caudate-putamen, and cerebellum. Loss of this neuroprotective protein may have a role in increasing susceptibility to age-related neurological disorders.

Increased severity of cerebral ischemic injury in vascular endothelial growth factor-B-deficient mice.

Vascular endothelial growth factor-B (VegfB) is an angiogenic protein related to VegfA, although it acts on a different set of tyrosine kinase receptors. Like VegfA, VegfB is expressed in the brain and is induced at sites of brain injury. VegfA has neuroprotective and angiogenic effects, but VegfA-knockout mice die in utero, so the effect of endogenous VegfA signaling in neuropathologic states, such as cerebral ischemia, cannot be tested directly. In contrast, VegfB-knockout mice survive to adulthood with little abnormality in the absence of pathologic stresses. To determine if VegfB regulates the severity of cerebral ischemia, the middle cerebral artery was occluded in VegfB-knockout, heterozygous, and wild-type mice, and the volume of the resulting cerebral infarcts and associated impairment of neurologic function were measured. Infarct volume was increased by approximately 40% and neurologic impairment was more severe in VegfB-knockout mice, implying that endogenous VegfB acts to protect the brain from ischemic injury. VegfB also protected cultured cerebral cortical neurons from hypoxic injury, suggesting that its protective action is mediated at least in part through a direct effect on neurons.

Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice.

Pharmacological studies suggest a role for CB1 cannabinoid receptors (CB1R) in regulating neurogenesis in the adult brain. To investigate this possibility, we measured neurogenesis by intraperitoneal injection of bromodeoxyuridine (BrdU), which labels newborn neurons, in wild-type and CB1R-knockout (CB1R-KO) mice. CB1R-KO mice showed reductions in the number of BrdU-labeled cells to approximately 50% of wild-type (WT) levels in dentate gyrus and subventricular zone (SVZ), suggesting that CB1R activation promotes neurogenesis. To test this further, WT mice were given the CB1R antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A) before measuring neurogenesis with BrdU. SR141716A paradoxically increased the number of BrdU-labeled cells by approximately 50% in SVZ; another CB1R antagonist, 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251), had a similar effect. To investigate this discrepancy, SR141716A was given to CB1R-KO mice, in which it still stimulated neurogenesis, indicating involvement of a non-CB1 receptor. Action at one such non-CB1, SR141716A-sensitive site, the VR1 vanilloid receptor, was tested by administering SR141716A to VR1-KO mice, in which the ability of SR141716A to enhance neurogenesis was abolished. Thus, CB1 and VR1 receptors both seem to have roles in regulating adult neurogenesis.

Post-ischemic administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) reduces infarct size and modifies neurogenesis after focal cerebral ischemia in the rat.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hypoxia-inducible, neuroprotective protein that also stimulates proliferation of neuronal precursor cells. Accordingly, HB-EGF may contribute to recovery from cerebral injury through direct neuroprotective effects, by enhancing neurogenesis, or both. When administered by the intracerebroventricular route 1-3 days after focal cerebral ischemia in adult rats, HB-EGF decreased the volume of the resulting infarcts and reduced post-ischemic neurological deficits. HB-EGF also increased the incorporation of bromodeoxyuridine into cells expressing the immature neuronal marker protein TUC-4 in the dentate subgranular and rostral subventricular zones, consistent with increased proliferation of neuronal precursors. However, HB-EGF decreased the number of newborn neurons that migrated into the ischemic striatum, perhaps partly because reduction of infarct size by HB-EGF also reduced the stimulus to migration. To determine if HB-EGF might also directly inhibit migration of neuronal precursors, we co-cultured subventricular zone (SVZ) explants treated with HB-EGF or vehicle together with hypoxic cerebral cortical explants, and measured cell migration from the former toward the latter. HB-EGF reduced directed migration of SVZ cells toward the cortical explants, possibly due to a local chemoattractant effect on neuronal precursor cells, which may be mediated through the HB-EGF-specific receptor, N-arginine dibasic convertase. The delayed neuroprotective effect of HB-EGF may have implications for efforts to prolong the therapeutic window for intervention in stroke.

Proteomic and immunochemical characterization of a role for stathmin in adult neurogenesis.

Stathmin is a developmentally regulated cytosolic protein expressed at high levels in the brain. Two-dimensional differential in-gel electrophoresis and mass spectroscopy of proteins expressed in immature and mature cultures from embryonic rat cerebral cortex identified stathmin among several differentially expressed proteins, consistent with a possible role in neurogenesis. Stathmin immunohistochemistry in adult rodent brain revealed prominent expression in neuroproliferative zones and neuronal migration pathways, a pattern that resembles the expression of doublecortin, which is implicated in neuronal migration. Stathmin immunoreactivity was also associated with neurons undergoing ectopic chain migration into the ischemic striatum and cerebral cortex following focal cerebral ischemia. Reducing the expression of stathmin or doublecortin with an antisense oligonucleotide inhibited the migration of new neurons from the subventricular zone to the olfactory bulb via the rostral migratory stream. These results suggest a role for stathmin in the migration of newborn neurons in the adult brain.

VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia.

Vascular endothelial growth factor (VEGF) is an angiogenic protein with therapeutic potential in ischemic disorders, including stroke. VEGF confers neuroprotection and promotes neurogenesis and cerebral angiogenesis, but the manner in which these effects may interact in the ischemic brain is poorly understood. We produced focal cerebral ischemia by middle cerebral artery occlusion for 90 minutes in the adult rat brain and measured infarct size, neurological function, BrdU labeling of neuroproliferative zones, and vWF-immunoreactive vascular profiles, without and with intracerebroventricular administration of VEGF on days 1-3 of reperfusion. VEGF reduced infarct size, improved neurological performance, enhanced the delayed survival of newborn neurons in the dentate gyrus and subventricular zone, and stimulated angiogenesis in the striatal ischemic penumbra, but not the dentate gyrus. We conclude that in the ischemic brain VEGF exerts an acute neuroprotective effect, as well as longer latency effects on survival of new neurons and on angiogenesis, and that these effects appear to operate independently. VEGF may, therefore, improve histological and functional outcome from stroke through multiple mechanisms.

Cerebral neurogenesis is induced by intranasal administration of growth factors.

Neurogenesis persists in the adult brain, where it may contribute to repair and recovery after injury, but the lack of methods for noninvasive stimulation of cerebral neurogenesis limits its potential for clinical application. We report that intranasal administration of either fibroblast growth factor-2 or heparin-binding epidermal growth factor-like growth factor increases neurogenesis, measured by the incorporation of bromodeoxyuridine into cells that express the early neuronal marker protein doublecortin in the subventricular zone of mouse brain. These findings indicate that intranasal growth factors may have potential as neurogenesis-promoting therapeutic agents.