The Impact of COVID-19 on Transportation of Adults With Visual Impairments.

Introduction: Access to efficient and affordable transportation options has long been a challenge for many individuals with vision loss. In spring 2020, the COVID-19 pandemic caused a quick shift in the availability and safety of transportation. Methods: Using the constant comparison method, open-ended responses from 1,162 participants in the Flatten Inaccessibility study were coded. Responses were from participants who had concerns about transportation. Results: Ten themes and corresponding subthemes emerged from the data. Themes were interdependent in that the extent of concerns differed based on respondents' support networks, transportation availability, and financial circumstances. Discussion: The COVID-19 pandemic brought to the forefront both systemic and COVID-19 transportation challenges about which those with visual impairments experienced or had concerns or both. Implications for Practitioners: It is imperative that professionals support those with visual impairments to develop alternative plans for when their typical transportation options are disrupted.

Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

PURPOSE: To compare the pattern of gene-specific involvement and the spectrum of variants observed in prenatal and postnatal (mean ± SD, 8.9 ± 9.4 years) cohorts tested for Noonan syndrome and related conditions. METHODS: Outcomes of sequencing panel testing were compared between prenatal (n = 845) and postnatal (n = 409) cohorts. RESULTS: PTPN11 and SOS1 harbored the majority of observed variants in both prenatal and postnatal cohorts, and BRAF, HRAS, KRAS, MAP2K1, MAP2K2, RAF1, and SHOC2 had similarities in their pattern of involvement in both cohorts. PTPN11 was the largest contributor of pathogenic variants and had the lowest frequency of variants of uncertain significance (VUS). SOS1 had the highest VUS frequency in both cohorts. The overall VUS frequency was twice as high in prenatal specimens (58.1 vs. 29.3%). PTPN11 and SOS1 had a 1.5-fold higher VUS frequency in the prenatal cohort (10.7 vs. 7.4% and 95 vs. 61.1%, respectively). The diagnostic yield was 3.7% for prenatal samples, with a higher yield of 12.3% in fetuses with cystic hygroma as a sole finding, and 21.3% for postnatal. CONCLUSION: Comparison of prenatal versus postnatal specimens demonstrates that the pattern of specific gene involvement is similar, whereas the classification spectrum of observed variants differs considerably.

Correction: Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

The original version of this Article contained an error in the spelling of the author N. T. Leach, which was incorrectly given as N. L. Leach. This has been corrected in both the PDF and HTML versions of the Article.

Sumoylation of the astroglial glutamate transporter EAAT2 governs its intracellular compartmentalization.

EAAT2 is a predominantly astroglial glutamate transporter responsible for the majority of synaptic glutamate clearance in the mammalian central nervous system (CNS). Its dysfunction has been linked with many neurological disorders, including amyotrophic lateral sclerosis (ALS). Decreases in EAAT2 expression and function have been implicated in causing motor neuron excitotoxic death in ALS. Nevertheless, increasing EAAT2 expression does not significantly improve ALS phenotype in mouse models or in clinical trials. In the SOD1-G93A mouse model of inherited ALS, the cytosolic carboxy-terminal domain is cleaved from EAAT2, conjugated to SUMO1, and accumulated in astrocytes where it triggers astrocyte-mediated neurotoxic effects as disease progresses. However, it is not known whether this fragment is sumoylated after cleavage or if full-length EAAT2 is already sumoylated prior to cleavage as part of physiological regulation. In this study, we show that a fraction of full-length EAAT2 is constitutively sumoylated in primary cultures of astrocytes in vitro and in the CNS in vivo. Furthermore, the extent of sumoylation of EAAT2 does not change during the course of ALS in the SOD1-G93A mouse and is not affected by the expression of ALS-causative mutant SOD1 proteins in astrocytes in vitro, indicating that EAAT2 sumoylation is not driven by pathogenic mechanisms. Most interestingly, sumoylated EAAT2 localizes to intracellular compartments, whereas non-sumoylated EAAT2 resides on the plasma membrane. In agreement, promoting desumoylation in primary astrocytes causes increased EAAT2-mediated glutamate uptake. These findings could have implications for optimizing therapeutic approaches aimed at increasing EAAT2 activity in the dysfunctional or diseased CNS.

A qualitative study of the ASPECT Patient Engagement Program designed to teach storytelling and advocacy skills to individuals with visual impairments and allies.

PURPOSE/OBJECTIVE: This study examined the impact of the ASPECT (Advocacy, Support, Perspective, Empowerment, Communication, and Training) Patient Engagement Program on its alumni in order to understand how they used the storytelling and advocacy skills they learned, determine the strengths of the program, and identify recommendations for strengthening the program. RESEARCH METHOD/DESIGN: In spring 2023, eight focus groups and one interview were conducted with ASPECT Program alumni. Inductive coding was used to identify themes. RESULTS: Eight themes emerged and included: (a) reasons alumni joined the ASPECT Program, (b) value of combining persons with visual impairments and allies in one cohort, (c) reflections on personal growth, (d) developing and telling one's story, (e) networking with others, (f) advocacy activities, (g) strengths of the ASPECT Program, and (h) recommendations for improving the ASPECT Program. CONCLUSIONS/IMPLICATIONS: The ASPECT Program provided alumni the opportunity to better understand their own eye health and/or the eye health of others, learn to impactfully tell their story to diverse stakeholders, develop their advocacy skills, and network with others. The use of a training program that includes those with visual impairments and allies is an effective method for providing high-quality training to a diverse group. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Concerns on healthcare access, utilization, and safety due to COVID-19 among American adults with vision loss.

BACKGROUND: Limited studies have indicated that Americans with vision loss are differentially impacted by COVID-19. OBJECTIVE: We examined concerns with healthcare and safety among Americans with vision loss during the early phase of the pandemic (April 2020). METHODS: The Flatten Inaccessibility Survey assessed the impact of COVID-19 on healthcare (pharmacy access, maintenance of eyecare regimen, caregiver access, and resource denial) and safety (social distancing, clean surfaces, and touching public signage) concerns among Americans with low vision or who were blind. Multivariable logistic regression was used to determine associations between respondent characteristics and each concern. RESULTS: A total of 1921 adults responded to the survey, of whom 65% were blind and 35% had low vision. Most respondents were female (63%) and white (74%). Respondents with additional disabilities/comorbidities were more likely to report healthcare access concerns (pharmacy access, eyecare regimen, caregiver access, and ventilator access) and safety concerns (social distance, clean surfaces, and touching signage) than those with vision loss alone. In addition, females, those identifying as "other" gender, older individuals, and people with adult onset of vision impairment were more likely to experience COVID-19-related concerns and challenges related to healthcare and overall safety. CONCLUSION: These results suggest that while Americans with vision loss have been differentially impacted by COVID-19, adults with vision loss and additional disabilities/comorbidities are more likely to have concerns with healthcare and safety than those with vision loss alone.

Depression in infant monkeys separated from their mothers.

The mothers of four pigtail (Macaca nemestrina) infants living in a group were removed for 4 weeks. All infants reacted initially with agitation. Three of the four infants then became severely depressed. The depression lasted about a week and was strikingly similar to the "anaclitic depression" of human infants who lost their mothers. When they were reunited, all four dyads showed a marked and prolonged intensification of the mother-infant relationship.

Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants.

Multiple human immunodeficiency virus type-1 sequences from the V3 and V4-V5 regions of the envelope gene were analyzed from three mother-infant pairs. The infants' viral sequences were less diverse than those of their mothers. In two pairs, a proviral form infrequently found in the mother predominated in her infant. A conserved N-linked glycosylation site within the V3 region, present in each mother's sequence set, was absent in all of the infants' sequence sets. These findings demonstrate that a minor subset of maternal virus is transmitted to the infant.

Clinical improvement with fluoxetine therapy and noradrenergic function in patients with panic disorder.

BACKGROUND: Central noradrenergic (NA) dysregulation has provided a major theoretical framework for understanding the pathogenesis of panic disorder (PD). Using clonidine, an alpha 2-adrenergic receptor agonist, as a probe of NA function, we investigated the hypothesis that the antipanic efficacy of the selective serotonin reuptake inhibitors may be associated with normalization of a putatively dysregulated NA system. METHODS: We report further analyses on data from 17 subjects with PD and 16 healthy volunteers who underwent measurement of the plasma NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) immediately before and after oral clonidine administration. Thirteen patients with PD were rechallenged after 12 weeks during open fluoxetine hydrochloride treatment using the same clonidine paradigm; 13 healthy volunteers were rechallenged at 12 weeks, not having received treatment between challenges. RESULTS: Patients with PD, compared with healthy volunteers, have markedly elevated plasma MHPG volatility during the first clonidine challenge. Volatility describes the magnitude of within-subject plasma MHPG oscillatory activity as assessed by the root of the mean square successive difference. A greater degree of clinical global improvement was predicted by a greater magnitude of basal MHPG reduction with fluoxetine treatment. Antipanic response to fluoxetine was accompanied by a significant decrease of MHPG volatility to volunteer levels. Volunteer MHPG volatility remained unchanged from the first to second clonidine challenge. CONCLUSIONS: Further evidence is provided for the hypothesis of NA dysregulation in PD as reflected by elevations of within-subjects plasma MHPG volatility during clonidine challenge. Effective selective serotonin reuptake inhibitor-antipanic treatment in this clinical sample was paralleled by normalization of dysregulated NA function.

Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions.

BACKGROUND: In an earlier study, infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations of serotonin, dopamine, and norepinephrine metabolites (5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were determined. METHODS: Second CSF taps were obtained from the previously studied cohort of 30 subjects and from 28 age-matched ad libitum-reared control subjects. Relevant assays were performed. RESULTS: All neurochemicals assayed except MHPG were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group, statistically significant positive correlations between corticotropin-releasing factor and each neurochemical was found, except for MHPG. In the non-VFD subjects, no significant correlations with corticotropin-releasing factor were observed. No effect of age was evident. CONCLUSIONS: Reducing the predictability of maternal foraging demand during early rearing was associated with elevations of cisternal somatostatin and of serotonin and dopamine metabolite concentrations in grown offspring. The corticotropin-releasing factor elevations reported previously were positively correlated with all the elevated CSF parameters of the current study. The findings support the notion that adverse early rearing experiences in primates have longstanding and complex effects on a range of neurochemicals relevant to emotional regulation. Replication in prospective age-controlled studies is warranted.

Dose-response effects of oral yohimbine in unrestrained primates.

Six unrestrained bonnet macaques were each observed after oral administration of four dosages of yohimbine hydrochloride (0.10, 0.25, 0.50, and 0.75 mg/kg) and a placebo. Yohimbine significantly increased episodes of motoric activation and affective response interspersed with intervals of behavioral enervation. Yohimbine scores correlated closely with baseline levels; there was no dose-response relationship. Response to oral yohimbine differed in several ways from subcutaneous and intravenous sodium lactate infusions, including prominent enervative symptoms and the appearance of sexual arousal. In light of the appearance of cyclic enervative episodes, this study suggests limitations to primate models of panic disorder utilizing oral yohimbine.

Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates.

It has been proposed that certain adverse early experiences may play a role in determining subsequent susceptibility to adult anxiety and affective disorders and this relationship may be the result of altered neurodevelopment of the noradrenergic and/or serotonergic systems. In this study of nonhuman primates, the predictability of foraging requirements for mothers during an early period of their infants' lives was manipulated. When the offspring were young adults, these early manipulations were related to differences in behavioral response to acute administration of two putative anxiety-provoking agents: the noradrenergic probe, yohimbine, and the serotonergic probe, mCPP. These long-term effects of the developmental environment on subsequent pharmacological responsivity suggest that both neuronal systems may be permanently altered by early experiential factors.

Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin-releasing factor concentrations in adult primates.

BACKGROUND: The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood. METHODS: Cisternal CSF samples were obtained from those unpredictably reared young adult primates who had been previously studied as juveniles and age-matched ad libitum normally reared controls. Samples were assayed for CSF CRF. RESULTS: Concentrations of CSF CRF were significantly elevated in the unpredictably reared sample in comparison to the ad libitum-reared control group. A significant positive correlation was noted between juvenile and young adult CSF CRF values within the unpredictably reared cohort. CONCLUSIONS: Disturbances of maternal-infant attachment processes have an enduring impact on primate CRF function into young adulthood. The CRF elevations following unpredictable maternal foraging conditions appear traitlike in nature.

Imipramine and alprazolam treatment of lactate-induced acute endogenous distress in nonhuman primates.

The authors studied the response of 10 macaque monkeys to administration of sodium lactate, a panicogenic agent used in human panic disorder research, after treatment with the tricyclic antidepressant imipramine, the triazolobenzodiazepine alprazolam, or placebo. Both drugs effectively blocked the lactate-induced acute endogenous distress responses that had been reliably observed in the monkeys before drug treatment. Only alprazolam significantly reduced the occurrence of conditioned situational anxiety responses observed in the home cage. The alprazolam monkeys appeared to be sedated compared to the imipramine and placebo groups, and tremor and temporary exacerbation of anxious behaviors were observed during alprazolam withdrawal.

Effects of sodium lactate infusion on cisternal lactate and carbon dioxide levels in nonhuman primates.

OBJECTIVE: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings. METHOD: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions. RESULTS: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures. CONCLUSIONS: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.

Persistence of blunted human growth hormone response to clonidine in fluoxetine-treated patients with panic disorder.

OBJECTIVE: The authors determined the effects of antipanic treatment with fluoxetine on human growth hormone (GH) response to the alpha 2 agonist clonidine. METHOD: Seventeen patients with panic disorder and 15 healthy volunteers were challenged with clonidine. Thirteen of the patients and 12 of the volunteers were given a second challenge with clonidine 12 weeks later. The patients received open fluoxetine and the healthy subjects received no treatment between challenges. Subjects with high baseline human GH levels (greater than 2 ng/ml) at the first and second challenges were excluded from further analysis. RESULTS: The patients with panic disorder (N = 13 for the first challenge and N = 9 for the second) had significantly lower human GH responses to clonidine than the healthy subjects (N = 14 during the first challenge and N = 9 for the second) during both challenges, despite clinical improvement in eight of the nine patients at the time of the second challenge. CONCLUSIONS: Blunted secretion of human GH in response to clonidine in patients with panic disorder persists despite clinical recovery.

Increasing impact of HIV infection on hospitalizations in the United States, 1983-1988.

During 1983-1988, hospitalizations of patients with a diagnosis of human immunodeficiency virus (HIV) infection increased from 1.3 to 33.7 per 100,000 persons. We used the National Hospital Discharge Survey, which is based on a representative sample of discharges from nonfederal short-stay hospitals, to describe illnesses among hospitalized patients with HIV infection. Of 222,200 such hospitalizations during 1983-1988, most occurred among persons who were 25-44 years of age (79%), white (66%), and male (90%). Among men 25-44 years of age, HIV admissions increased from 8.5 to 148.6 per 100,000 persons during 1983-1988; among black men 25-44 years of age, HIV hospitalizations increased from 43.1 to 387.4 per 100,000 persons. Among women, hospitalizations increased 3.4-fold. Frequently listed illnesses in the Centers for Disease Control (CDC) AIDS case definition were Pneumocystis carinii pneumonia (30%), candidiasis (20%), and Kaposi's sarcoma (13%). Other frequently listed illnesses included infections (39%) such as pneumonia, sepsis, and urinary tract infections; blood dyscrasias (30%) such as anemia, thrombocytopenia, and agranulocytosis; metabolic (17%), gastrointestinal (16%), and respiratory disorders (12%); and drug abuse (9%). These data provide a minimum estimate of HIV hospitalizations because for some patients HIV infection may not be specified on the discharge record. HIV hospitalizations are increasing markedly and are associated with a broad spectrum of severe morbidity.

Behavioral effects of oral yohimbine in differentially reared nonhuman primates.

Eight unrestrained macaques were observed for 2 hours following either two oral doses of yohimbine (0.2 mg/kg and 2.0 mg/kg) or placebo administration. Four of the subjects were normally reared and four subjects had early maternal and social deprivation. In the normal subjects, yohimbine, at both doses, produced increased tension and enervation and decreased species-typical "normal" behaviors. In deprivation-reared subjects, low-dose yohimbine produced reductions in tension and enervation, and increases in "normal" behaviors. High doses of yohimbine diminished behavioral score differences between groups. The prominent increases in enervation observed in normally reared subjects suggests that yohimbine is not unequivocally anxiogenic. Moreover, early social deprivation may alter the pattern of response to yohimbine, perhaps as a result of aberrant neurodevelopment. This study reflects the role of experiential factors in determining patterns of affective response to putative anxiogenic agents.

Uncoupling of the noradrenergic-hypothalamic-pituitary-adrenal axis in panic disorder patients.

In this paper the authors examine the interrelationship of both the noradrenergic (NA) system and the hypothalamic-pituitary-adrenal (HPA) axis and its implications for panic disorder (PD). Seventeen PD patients and 16 healthy volunteers were challenged orally 12 weeks apart with the alpha 2-agonist clonidine (13 healthy volunteers and 12 patients repeated the challenge). Between challenges, PD patients were treated with fluoxetine, with 10 of 12 improving at least moderately. Both during the acute phase of the illness and during the phase of pharmacological improvement, patients demonstrated a greater percentage of reductions of plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and plasma cortisol during clonidine challenge. We used correlational matrices to examine the relationship between the NA system, as reflected by plasma MHPG, and the HPA axis, as reflected by plasma cortisol measures. Healthy volunteers exhibited multiple significant "couplings" between either baseline or maximal decrease (delta max) of plasma MHPG, with either baseline or delta max plasma cortisol measures both within the first and second challenges and between the first and second challenges. In contrast, PD patients demonstrated "uncoupling" of the NA system and the HPA axis, with no significant correlations observed between either baseline and/or maximal decrease (delta max) measures of MHPG with the same cortisol measures for either the first or second challenge. The same uncoupling was observed for NA/HPA correlations between the first and second challenges. These data suggest that the hyperresponsivity to clonidine in PD patients persists during fluoxetine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Maintenance tendency in co-ordinated rhythmic movements: relative fluctuations and phase.

Evidence from the oscillatory behavior of fish fins and the crayfish swimmeret system suggests that local rhythmic-pattern generators preserve their characteristic properties over the various locomotory co-ordinations in which they participate. This maintenance tendency, as von Holst termed it, was investigated in an experiment in which human subjects swung, through motions at the wrists, hand-held pendulums of variable mass and length. In the experiment (comprising six sessions over 21 months with the same three subjects) the context for the maintenance tendency was steady-state absolute co-ordination: two rhythmic units oscillating at a single, common period and at a bounded phase relation. The experimental methodology permitted systematic control of (a) the characteristic periods of the individual rhythmic units and (b) the deviations from these periods. Relative fluctuations in periodic timing and amplitude were least when a rhythmic unit's period in absolute co-ordination approximated its characteristic period and increased with departures from the characteristic period. Rates of increase in timing fluctuations were approximately the same for deviations on either side of the characteristic period; the rate of increase in spacing fluctuations was substantially greater for the range in which periods were less than the characteristic period. The phase relation between two co-ordinated rhythmic movement units in absolute co-ordination depended on the difference between their characteristic periods. The intended phase relation of 180 degrees was attained only when the characteristic periods were identical. When the characteristic periods differed, the departure from 180 degrees increased systematically with the difference. The fluctuation results are discussed in terms of the relation between relaxation and harmonic dynamics in producing rhythmic movements, with particular emphasis on the harmonic tuning of relaxation oscillations. The phase results are discussed in terms of whether or not the very many stable phase relations in absolute co-ordination are reflective of the nervous system or of differences in response latencies in left and right muscle systems induced by different degrees of inertial compensation.