Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

The COVID-19 pandemic's impact on worry and medical disruptions reported by individuals with chromosome 22q11.2 copy number variants and their caregivers.

BACKGROUND: The world has suffered immeasurably during the COVID-19 pandemic. Increased distress and mental and medical health concerns are collateral consequences to the disease itself. The Genes to Mental Health (G2MH) Network consortium sought to understand how individuals affected by the rare copy number variations of 22q11.2 deletion and duplication syndrome, associated with neurodevelopmental/neuropsychiatric conditions, were coping. The article focuses on worry and disruptions in medical care caused by the pandemic. METHODS: The University of Pennsylvania COVID-19 Stressor List and care disruption questions were circulated by 22 advocacy groups in English and 11 other languages. RESULTS: A total of 512 people from 23 countries completed the survey; most were caregivers of affected individuals. Worry about family members acquiring COVID-19 had the highest average endorsed worry, whilst currently having COVID-19 had the lowest rated worry. Total COVID-19 worries were higher in individuals completing the survey towards the end of the study (later pandemic wave); 36% (n = 186) of the sample reported a significant effect on health due to care interruption during the pandemic; 44% of individuals (n = 111) receiving care for their genetic syndrome in a hospital setting reported delaying appointments due to COVID-19 fears; 12% (n = 59) of the sample reported disruptions to treatments; and of those reporting no current disruptions, 59% (n = 269) worried about future disruptions if the pandemic continued. Higher levels of care disruptions were related to higher COVID-19 worries (Ps < 0.005). Minimal differences by respondent type or copy number variation type emerged. CONCLUSIONS: Widespread medical care disruptions and pandemic-related worries were reported by individuals with 22q11.2 syndrome and their family members. Reported worries were broadly consistent with research results from prior reports in the general population. The long-term effects of COVID-19 worries, interruptions to care and hospital avoidance require further study.

Association among income loss, financial strain and depressive symptoms during COVID-19: evidence from two longitudinal studies.

BACKGROUND: The COVID-19 pandemic has major ramifications for global health and the economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between COVID-19 pandemic-related income loss with financial strain and mental health trajectories over a 1-month course. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; N = 4 171) and at a 1-month follow-up (T2; N = 1 559). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. FINDINGS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). INTERPRETATION: Income loss and financial strain were uniquely associated with depressive symptoms and the exacerbation of symptoms over time, above and beyond pandemic-related anxiety. Considering the painful dilemma of lockdown versus reopening, with the tradeoff between public health and economic wellbeing, our findings provide evidence that the economic impact of COVID-19 has negative implications for mental health. FUNDING: This study was supported by grants from the National Institute of Mental Health, the US-Israel Binational Science Foundation, Foundation Dora and Kirsh Foundation.

Apnoeic oxygenation during intubation: a systematic review and meta-analysis.

Apnoeic oxygenation during intubation is used to prevent desaturation during intubation. The aim of this review was to assess whether apnoeic oxygenation during endotracheal intubation reduced the incidence of hypoxaemia. Five major databases were systematically searched for all relevant studies published up to May 2016. All study designs with a control group and a group receiving apnoeic oxygenation were included in this review. These studies were then assessed for level of evidence and risk of bias. The data were then analysed using a meta-analysis. Eleven studies (six high quality randomised controlled trials, four low quality level two studies and one low quality level three study) were found. In the meta-analysis there was strong evidence for benefit of apnoeic oxygenation in terms of improved SpO2 in elective surgical patients, obese patients and those undergoing emergency intubation without respiratory failure. However, no significant benefit was found in patients with respiratory failure. This is the first meta-analysis to be performed on apnoeic oxygenation during intubation. Apnoeic oxygenation provides significant benefit in terms of improving SpO2 for the majority of intubations, although there appears to be no benefit in patients whose indication for intubation is respiratory failure. Apnoeic oxygenation ought to be considered for integration into intubation protocols.

Modification of threat-processing in non-anxious individuals: a preliminary behavioral and ERP study.

BACKGROUND AND OBJECTIVES: Previous research suggests that attention bias toward threat contributes to the development and maintenance of anxiety. The current study extends this work by mapping the neural correlates of experimentally-induced changes in attention bias. The study examines both behavioral and psychophysiological changes associated with experimentally-induced changes in threat bias. METHODS: Thirty-four non-anxious female adults were randomly assigned to one of two conditions: training attention toward threat or placebo control. Attention bias was assessed and trained via a modified dot-probe task. Participants completed pre- and post-training assessments of attention bias and stress reactivity. As well, EEG was collected during pre- and post-test assessment of attention bias using the dot-probe task. RESULTS: Training induced significant changes in attention bias, though findings were complicated by group differences in baseline threat-bias scores. Compared to controls, those in the training group showed greater depression vulnerability to a post-training stressor and increased P2 amplitude, an ERP component associated with attention toward threat, during the dot-probe task. LIMITATIONS: Although participants were randomly assigned to groups, there were still group differences in pre-training bias scores. Also, while the use of a stress task before the initial assessment of attention bias was used to control for initial differences in stress vulnerability, this may have altered pre-bias scores since participants completed this task immediately after being stressed. CONCLUSIONS: These findings demonstrate training-induced changes in behavior and neural response patterns relevant to work on attention bias modification.

Telomerase inhibitors.

There has been a vast increase in telomerase research over the past several years, with many different pre-clinical approaches being tested for inhibiting the activity of this enzyme as a novel therapeutic modality to treat malignancy. In this review, we will provide some basic background information about telomeres and telomerase and then discuss the pros, cons and challenges of the approaches that are currently under investigation, and what we might expect in the future of this emerging field.

Intrastriatal infusions of ascorbate antagonize the behavioral response to amphetamine.

Compared to saline, bilateral infusions of ascorbate (AA) into the neostriatum of freely moving rats attenuated rearing, head bobbing, and sniffing at various times after systemic amphetamine administration. Comparable AA infusions into overlying cerebral cortex failed to alter the amphetamine behavioral response. Intrastriatal AA also enhanced the ability of haloperidol to antagonize amphetamine-induced forepaw shuffling and locomotion. Voltammetric measurements in separate animals revealed a linear increase in neostriatal AA that remained within reasonable physiological limits over the course of the AA infusion. Thus, endogenous AA may modulate behavior via mechanisms intrinsic to the neostriatum.

Identifying reinforcers for persons with profound handicaps: staff opinion versus systematic assessment of preferences.

We evaluated a systematic means of determining stimulus preferences among seven profoundly handicapped persons. Preferences were determined by observing student approach responses to individual stimuli. Results indicated that there were differential stimulus preferences across the multiply handicapped participants. However, results of the systematic assessment did not coincide with the results of a more traditional, caregiver-opinion method of assessing student preferences. A second experiment was then conducted with five participants to evaluate whether stimuli that were assessed to consistently represent preferences would function as reinforcers in skill training programs. Results indicated that stimuli that were systematically assessed to represent student preferences typically functioned as reinforcers when applied contingently. However, preferred stimuli as reflected by caregiver opinion did not function as reinforcers unless those stimuli were also preferred on the systematic assessment. Results are discussed in terms of assisting profoundly handicapped persons by (a) improving the effectiveness of training programs by increasing the likelihood of using stimuli that have reinforcing value and (b) increasing the overall quality of life by providing preferred stimuli in the routine living environment.

Ascorbate antagonizes the behavioral effects of amphetamine by a central mechanism.

The behavioral response to amphetamine was monitored in rats that received simultaneous intraventricular infusions of saline or ascorbate. Both groups of animals displayed comparable responses, although ascorbate significantly delayed the onset of amphetamine-induced locomotion and rearing. In rats pretreated with a threshold dose of haloperidol (0.025 mg/kg), virtually all aspects of the amphetamine response were attenuated, and this effect was enhanced by ascorbate. In haloperidol-pretreated rats, ascorbate significantly lowered sniffing and forepaw shuffling throughout the amphetamine response. These results suggest that ascorbate antagonizes dopaminergic transmission by a central mechanism.

Contact hole imaging characteristics from projection lithography.

Image intensity profiles (IIPs) are calculated for selected cross sections of contact hole arrays for a circular source and objective in the presence of the defocus aberration. The IIPs for selected cross sections of contact holes are compared with IlPs from correspondingly dimensioned gratings. At resolution levels equal to or greater than 0.9 lambda/N.A., the predicted contact hole image quality should be similar to that attainable from correspondingly dimensioned line-space gratings. Although the shapes of the contact holes appear to be predicted well, in some cases the experimental contact hole to grating dimensional comparison indicates significantly less than perfect imaging characteristics. Advanced lens systems with similar resolution ratios but different depth of focus characteristics are also compared for contact hole imaging. Contact hole imaging characteristics are much more sensitive to residual aberrations in the optical lens system and can provide a convenient measure of the relative magnitude of these aberrations.

Divorce and marital instability over the life course.

"This study uses a [U.S.] national sample of married persons under age 55, interviewed in 1980 and again in 1983, to estimate why divorce and marital instability vary by age and duration of marriage. Results indicate that the accumulation of assets substantially reduces the propensity to divorce. We also find that several important correlates of divorce and instability (age at marriage, health, social integration, and income) interact with age and duration. In general, these factors seem to operate almost exclusively among young people and young marriages."

Synthesis of a functional F0 sector of the Escherichia coli H+-ATPase does not require synthesis of the alpha or beta subunits of F1.

The uncB, E, F, and H genes of the Escherichia coli unc operon were cloned behind the lac promoter of plasmid pUC9, generating plasmid pBP101. These unc loci code, respectively, for the chi, omega, and psi subunits of the F0 sector and the delta subunit of the F1 sector of the H+-ATP synthase complex. Induction of expression of the four unc genes by the addition of isopropyl-beta-D-thiogalactoside resulted in inhibition of growth. During isopropyl-beta-D-thiogalactoside induction, the three subunits of F0 were integrated into the cytoplasmic membrane with a resultant increase in H+ permeability. A functional F0 was formed from plasmid pBP101 in a genetic background lacking all eight of the unc structural genes coding the F1F0 complex. In the unc deletion background, a reasonable correlation was observed between the amount of F0 incorporated into the membrane and the function measured, i.e., high-affinity binding of F1 and rate of F0-mediated H+ translocation. This correlation indicates that most or all of the F0 assembled in the membrane is active. Although the F0 assembled under these conditions binds F1, only partial restoration of NADH-dependent or ATP-dependent quenching of quinacrine fluorescence was observed with these membranes. Proteolysis of a fraction of the psi subunit may account for this partial deficiency. The experiments described demonstrate that a functional F0 can be assembled in vivo in E. coli strains lacking genes for the alpha, beta, gamma, and epsilon subunits of F1.

The transition to parenthood and marital quality.

PIP: An extensive literature demonstrates a negative correlation between the presence of children and marital quality. Few of these studies are designed to test the reasons for this relationship. This study examines 2 possible paths: that people who choose to have children differ from those who do not in ways that affect marital quality, and that having a child changes marital structure and process. This research is based on a nationwide sample interviewed 1st in 1980 and again in 1983. In 1980, telephone interviews were conducted with 2,033 married individuals. The analysis of the effects of transition to parenthood is restricted to the 220 individuals who met the following conditions: childless in 1980, wife under 35 in 1980, successfully reintterviewed in 1983, and marriage intact between 1980-3. The results of the analysis support neither hypotheses. Prior to the birth of the child, parents and nonparents do not differ in marital interaction, happiness, disagreements, problems, or traditionalism in the division of labor, though future parents are already somewhat more likely to believe that the division of household labor is unfair. In regard to the argument that a new baby causes negative changes in marital structure and process, these data give only weak support. The sharpest difference found in this analysis is in the propensity to divorce or permanently separate, a propensity substantially greater among the nonparents. The greater willingness of childless couples to divorce means that a continuing sample of childless couples is more highly selected for marital happiness than a continuing sample of parents. This selectivity in divorce rather than the direct effect of children seems to be the major reason that cross-sectional comparisons show parents to be somewhat less happy than nonparents.^ieng

Predicting divorce and permanent separation.

PIP: The ability of a scale, called the marital instability index, to predict divorce or permanent separation in the United States is examined. It is tested using data on a national sample of about 1,663 married persons under age 55 who were interviewed originally by telephone in 1980 and reinterviewed in 1983. The results show that high scorers on the scale are nine times more likely to divorce than low scorers. The process of moving from marital instability to divorce is also analyzed. The findings indicate that the marital instability index provides the basis for a comprehensive model predicting divorce, particularly if adequate information on alternative attractions to marriage and on barriers to divorce is available.^ieng

H+-ATPase of Escherichia coli. An uncE mutation impairing coupling between F1 and Fo but not Fo-mediated H+ translocation.

The uncE114 mutation from Escherichia coli strain KI1 (Nieuwenhuis, F. J. R. M., Kanner, B. I., Gutnick, D. L., Postma, P. W., and Van Dam, K. (1973) Biochim. Biophys. Acta 325, 62-71) was characterized after transfer to a new genetic background. A defective H+-ATPase complex is formed in strains carrying the mutation. Based upon the genetic complementation pattern of other unc mutants by a lambda uncE114 transducing phage, and complementation of uncE114 recipients by an uncE+ plasmid (pCP35), the mutation was concluded to lie in the uncE gene. The uncE gene codes for the omega subunit ("dicyclohexylcarbodiimide binding protein") of the H+-ATPase complex. The mutation was defined by sequencing the mutant gene. The G----C transversion found results in a substitution of Glu for Gln at position 42 of the omega subunit in the Fo sector of the H+-ATPase. The substitution did not significantly impair H+ translocation by Fo or affect inhibition of H+ translocation by dicyclohexylcarbodiimide. Wild-type F1 was bound by uncE114 Fo with near normal affinity, but the functional coupling between F1 and Fo was disrupted. The uncoupling was indicated by an H+-leaky membrane, even when saturating levels of wild-type F1 were bound. Disassociation of F1 from Fo under conditions of assay did partially contribute to the H+ leakiness, but the major contributor to the high H+ conductance was Fo with bound F1. The F1 bound to uncE114 membranes exhibited normal ATPase activity, but ATP hydrolysis was uncoupled from H+ translocation and was resistant to inhibition by dicyclohexylcarbodiimide. The F1 isolated from the uncE114 mutant was modified with partial loss of coupling function. However, this modification did not account for the uncoupled properties of the mutant Fo described above, since these properties were retained after reconstitution of mutant membrane (Fo) with wild-type F1.

Ascorbic acid and the behavioral response to haloperidol: implications for the action of antipsychotic drugs.

Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs.

Mutations altering aspartyl-61 of the omega subunit (uncE protein) of Escherichia coli H+ -ATPase differ in effect on coupled ATP hydrolysis.

Mutations in the H+-translocating ATPase complex (F1F0) of Escherichia coli have been described in which aspartyl-61 of the omega subunit ( uncE protein) is substituted by either glycine ( uncE105 ) or asparagine ( uncE107 ). Either substitution blocks the H+-translocation activity of the F0 sector of the complex. Here we report a difference in the effects of the two substitutions on the coupled ATPase activity of F1 bound to F0. Wild-type F1 was bound to the F0 of either mutant with affinities comparable to wild-type. The ATPase activity of F1 bound to uncE107 F0 was inhibited by 50%, whereas that bound to uncE105 F0 was not inhibited. Complementation studies with a pBR322-derived plasmid that carried the E gene of the unc operon only indicated that a single mutation in the host strain was responsible for the respective phenotypes. In mutants complemented by the uncE + plasmid, restoration of wild-type biochemical properties was only partial and may be attributed to a mixing of wild-type and mutant omega subunits in a hybrid F0 complex. The activity of membrane-bound F1 was less inhibited in the uncE +/ uncE107 hybrid. Paradoxically, complementation of uncE105 by the uncE + plasmid resulted in substantial inhibition of the activity of membrane-bound F1. The results indicate that a glycine-versus-asparagine substitution for aspartyl-61 must lead to altered conformations of omega and that these differences in conformation are important in the coupling between the F0 and F1 sectors of the complex.

A note on racial differences in the effect of female economic opportunity on marriage rates.

The previously observed aggregate relationship between marriage rates and female work opportunities is not found among black Americans. Alternative definitions of family formation which take illegitimacy into consideration are explored and also found to be unrelated to black females' economic opportunities. Although some of the difference may be attributed to measurement error, the significant disparity between the two populations probably reflects substantive differences.

Metal site conformational states of vanadyl(IV) human serotransferrin complexes.

This study was undertaken to investigate the conformational states of the two metal sites in the human serum transferrin molecule. The 9.2 GHz electron paramagnetic resonance spectra of frozen solutions of divanadyl(IV) transferrin consist of a superposition of two sets of resonances, A and B, due to the magnetically nonequivalent binding environments of the VO2+ ion. Examination of the intensities of the A and B resonances as a function of pH from 6.0 to 10.7 reveals that they arise from two conformational states of the metal sites in which the geometrical arrangement and/or identity of one or more ligands in the first coordination sphere are different. From pH 7.5 to 9.0, the metal sites exist in A and B conformations but above pH 9.0 the A conformation. This transformation is coupled to the ionization of an apparently noncoordinating protein functional group with a pK - 10.0 +/- 0.1. Below pH 7.0, binding in the B conformation is rapidly lost, driven in part by the protonation of a functional group, possibly the anion, with a pK - 6.6 +/- 0.1. In 90% D2O, this pK is elevated to 7.8 +/- 0.1. At pH 6.0 in H2O, essentially one VO2+ ion remains bound to the protein with the metal site in the A conformation. Experiments with mixed VO2+ -Fe3+ transferrin complexes indicate that the same may be true of Fe3+. At pH 10.7, a new set of VO2+ resonances, labeled C, are observed; they possibly arise from a third conformation of the metal site. One bicarbonate or corbonate is required per VO2+ ion bound to the protein. 2.7 H+ are released per VO2+ bound in either the A or B conformations. The above results are discussed in terms of the "equivalence" and "nonequivalence" of the metal sites.