Serum antibody levels to SARS-CoV-2 receptor-binding domain (RBD) in convalescent patients and vaccinated individuals of northern Nevada.

Antibodies reactive with the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein are associated with viral neutralization, however low antibody titers, specifically against SARS-CoV-2 variants, may result in reduced viral immunity post naturally acquired infection. A cohort study comprised of 121 convalescent individuals from northern Nevada was conducted looking at anti-RBD antibody levels by enzyme-linked immunosorbent assay. Serum was collected from volunteers by staff at the University of Nevada, Reno School of Medicine Clinical Research Center and assessed for antibodies reactive to various SARS-CoV-2 RBD domains relevant to the time of the study (2020-2021). A nonpaired group of vaccinated individuals were assessed in parallel. The goal of the study was to identify antibody levels against the RBD subunit in convalescent and vaccinated individuals from northern Nevada.

Comparison of a Prototype SARS-CoV-2 Lateral Flow IMMUNOASSAY with the BinaxNOWTM COVID-19 Antigen CARD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. From the onset of the pandemic, rapid antigen tests have quickly proved themselves to be an accurate and accessible diagnostic platform. The initial (and still most commonly used antigen tests) for COVID-19 diagnosis were constructed using monoclonal antibodies (mAbs) specific to severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (NP). These mAbs are able to bind SARS-CoV-2 NP due to high homology between the two viruses. However, since first being identified in 2019, SARS-CoV-2 has continuously mutated, and a multitude of variants have appeared. These mutations have an elevated risk of leading to possible diagnostic escape when using tests produced with SARS-CoV-derived mAbs. Here, we established a library of 18 mAbs specific to SARS-CoV-2 NP and used two of these mAbs (1CV7 and 1CV14) to generate a prototype antigen-detection lateral flow immunoassay (LFI). A side-by-side analysis of the 1CV7/1CV14 LFI and the commercially available BinaxNOWTM COVID-19 Antigen CARD was performed. Results indicated the 1CV7/1CV14 LFI outperformed the BinaxNOWTM test in the detection of BA.2, BA.2.12.1, and BA.5 Omicron sub-variants when testing remnant RT-PCR positive patient nasopharyngeal swabs diluted in viral transport media.

The maternal CCAAT box transcription factor which controls GATA-2 expression is novel and developmentally regulated and contains a double-stranded-RNA-binding subunit.

The transcription factor GATA-2 is expressed at high levels in the nonneural ectoderm of the Xenopus embryo at neurula stages, with lower amounts of RNA present in the ventral mesoderm and endoderm. The promoter of the GATA-2 gene contains an inverted CCAAT box conserved among Xenopus laevis, humans, chickens, and mice. We have shown that this sequence is essential for GATA-2 transcription during early development and that the factor binding it is maternal. The DNA-binding activity of this factor is detectable in nuclei and chromatin bound only when zygotic GATA-2 transcription starts. Here we report the characterization of this factor, which we call CBTF (CCAAT box transcription factor). CBTF activity mainly appears late in oogenesis, when it is nuclear, and the complex has multiple subunits. We have identified one subunit of the factor as p122, a Xenopus double-stranded-RNA-binding protein. The p122 protein is perinuclear during early embryonic development but moves from the cytoplasm into the nuclei of embryonic cells at stage 9, prior to the detection of CBTF activity in the nucleus. Thus, the accumulation of CBTF activity in the nucleus is a multistep process. We show that the p122 protein is expressed mainly in the ectoderm. Expression of p122 mRNA is more restricted, mainly to the anterior ectoderm and mesoderm and to the neural tube. Two properties of CBTF, its dual role and its cytoplasm-to-nucleus translocation, are shared with other vertebrate maternal transcription factors and may be general properties of these proteins.

Injection of a neuroleptic produces changes in caregiver-infant interactions in marmosets.

The effects of injecting a low dose of the neuroleptic fluphenazine decanoate (MODECATE) on the responsiveness of family members (fathers and siblings) to infant common marmosets (Callithrix jacchus ) are described. Tentative conclusions are that the overall effect of the injection is to make fathers and siblings more 'passive' and unresponsive, though the detailed effects are complex and not all interactions with infants are affected. Drugged fathers spend less time grooming infants, pick them up more infrequently, and approach and leave them less often than undrugged fathers. Drugged siblings spend less time playing with infants, ignore them more often, and approach and leave them less often than undrugged siblings. These results indicate the need for studies of the effects of drugs on normal behaviours as well as studies of their side-effects or therapeutic efficacy.

Predictive diagnosis of familial adenomatous polyposis with linked DNA markers: population based study.

OBJECTIVES: To evaluate the use of polymorphic DNA probes linked to the APC gene in the presymptomatic diagnosis of familial adenomatous polyposis. DESIGN: Four DNA probes were tested on an unselected population of patients at risk of familial adenomatous polyposis. SUBJECTS: The first 47 families notified to the West Midlands familial adenomatous polyposis register. Plus five families sent to our hospital as part of the West of Britain DNA consortium. MAIN OUTCOME MEASURES: The proportion of families and family members in whom DNA testing could be used to adjust the estimate of risk. RESULTS: Only 17 families on the register (containing 46% (74/162) of the population at risk) had a suitable pedigree structure for DNA analysis. DNA was analysed in 12 of these families plus the five families from the West of Britain consortium. At least one probe was informative in 27 of the 33 subjects born with 50% risk, but the most informative probe (pi 227) was the one with the highest recombination rate (10%). Flanking markers were informative in only four of the 33 subjects. CONCLUSIONS: These findings confirm the potential for accurate predictive diagnosis of familial adenomatous polyposis with polymorphic DNA probes, but such an approach is currently limited to about one third of affected families. A combined approach to presymptomatic diagnosis, which includes DNA testing and indirect ophthalmoscopy, is advocated.

Effects on the behavior of infant common marmosets (Callithrix jacchus) of separation from caregivers and of drug-induced reduction in caregiver responsiveness.

The effects of separating 4-week-old twin marmosets for 8 days from their families are compared with the effects of leaving 4-week-old infants with their families, but reducing the responsiveness of their caregivers for 8 days by administration of the tranquilizer fluphenazine decanoate. Both treatments reduce infant mobility, abolish play, and increase the time that infants spend with each other. During the period after the termination of the treatment, both treatment groups continue to play and move less than controls, and try to climb onto the mothers more frequently. These results are consistent with the hypothesis that the principal factor precipitating disturbed behaviors in infant monkeys subjected to long-term separation is disruption of the infant-caregiver relationship rather than the separation itself. Some post-treatment differences occur between separated and tranquilized groups. Notably, reunion after separation appears to involve a marked readjustment of the behavior of all family members to the return of the infants, whereas withdrawal of the tranquilizer does not.

Correlations among measures of playfulness and skillfulness in captive common marmosets (Callithrix jacchus jacchus).

Infant sensorimotor and social skills, playfulness, and nonplayful behaviors were measured in common marmosets from 6 to 22 weeks old. Different measures of skill showed a low concordance, implying that skill is a multiple rather than unitary attribute. Significant correlations were found between the amount of social play infants performed from 11 to 13 weeks of age and their performance at 14 weeks in (1) competitive food tests with their mothers, and in (2) their ability to negotiate an obstacle for a food reward. Significant correlations were also found between these skills and nonplayful behaviors, however. Comparable analyses at other ages revealed few significant correlations, suggesting that the association between social play and skills is restricted to the age when infants are rapidly becoming independent of their caregivers both for locomotion and food. Age-specific correlations occurred between changes in levels of skills and both playful and nonplay behaviors. Our results are consistent with the hypothesis that social play promotes the development of skills, but alternative explanations are possible.

A SCUBA-diving fatality.

An investigation by a Naval Board of Inquiry into the circumstances of a fatal naval diving accident is presented. Although drowning contributed to the fatal outcome, massive arterial gas embolism is thought to have been the principal cause of death, and the value of post-mortem computed tomography scanning for its detection is demonstrated. The possibility is discussed of diver error due to unfamiliarity with equipment and procedures, compounded by nitrogen narcosis. The shortfall in expertise of coronial inquiries into diving deaths is emphasized against a background of increasing popularity of sports diving around Australia. The implications for the offshore industry are obvious and suggest the need for a federal diving inspectorate.

Screening practice for familial adenomatous polyposis: the potential for regional registers.

Existing screening practice for familial adenomatous polyposis (FAP) was evaluated in 47 families with FAP notified to the West Midlands Polyposis Register between February 1988 and July 1990. Of these 269 individuals, 107 were known to be affected and 162 were at 50 per cent prior risk of developing FAP; 35 decreased affected individuals from living generations were included in the analysis. Of 105 individuals in the at-risk group aged between 12 and 40 years, only 55 (52 per cent) were under follow-up by bowel examination. Thirty-seven affected individuals had developed colorectal carcinoma before diagnosis; the incidence was three of 51 (6 per cent) in those diagnosed through screening compared with 34 of 53 (64 per cent) in the unscreened group (P < 0.001). A total of 28 individuals (26 per cent of the FAP population) died from advanced colorectal carcinoma; all were from the unscreened population. In 22 (59 per cent) of the cases of colorectal carcinoma and 17 (61 per cent) of the deaths from advanced colorectal cancer there was a positive family history of FAP; these tumours were therefore potentially preventable through screening and prophylactic surgery. Since establishing the register the median age at diagnosis of the affected patients has been reduced from 32 to 23 years (P = 0.0004) and the incidence of colorectal cancer has fallen from 35 to 14 per cent (P < 0.05). It is concluded that by providing more comprehensive case ascertainment a regional register can have a dramatic effect on this largely preventable form of colorectal cancer. Regional registers are recommended as an essential component of screening for this disease.

Role of congenital hypertrophy of the retinal pigment epithelium in the predictive diagnosis of familial adenomatous polyposis.

A study was carried out to evaluate congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a disease marker in a defined population with familial adenomatous polyposis (FAP). Indirect ophthalmoscopy was performed on 75 individuals from 25 known families with FAP, of whom 32 were known to be affected and 43 were at a 50 per cent prior risk of developing the disease. A further ten individuals from five families with hereditary non-polyposis colorectal cancer (HNPCC) were also tested. CHRPE was seen in 28 of the 32 affected individuals, 27 of whom met the criteria for a positive examination. Three individuals at risk of FAP also had positive examinations. Five individuals from the families with HNPCC also had CHRPE, although none met the criteria for a positive examination. Of four types of CHRPE analysed, one (small pigmented dots) was found to be more frequent in older family members (P = 0.012), suggesting that this type of lesion may proliferate with age. Compliance with ophthalmic screening was 97 per cent in families with FAP. Using a combined set of diagnostic criteria, CHRPE identified affected individuals with a specificity of at least 94 per cent and a sensitivity of 84 per cent. Results argue for a combined screening programme for FAP of DNA analysis, indirect ophthalmoscopy and bowel examination.

Effect of concomitant food intake on absorption kinetics of fenoldopam (SK&F 82526) in healthy volunteers.

Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.

Ibopamine (SK&F 100168) pharmacokinetics in relation to the timing of meals.

The effect of the timing of a standard meal relative to a single oral dose of 200 mg ibopamine, on the appearance of its pharmacologically active metabolite, epinine, in plasma was investigated in a randomised crossover study in 12 healthy volunteers. After a 12 h fast, ibopamine was administered either in the fasting state (no meal), or 1 h before, 0.5 h before, immediately after, 2 h after or 3 h after a standardised meal. Blood samples taken immediately before and at intervals for 3 h after dosing were analysed for free epinine. Maximum concentration (Cmax), time to Cmax(tmax), and area under the concentration-time curve (AUC) for free epinine in plasma were calculated. When compared with the fasting state, Cmax and AUC0-3h were significantly reduced when ibopamine was given immediately after or 2 h after a meal. AUC was also reduced for ibopamine given 0.5 h before a meal. tmax was significantly delayed when ibopamine was given immediately after, or 2 or 3 h after a meal. Thus, administration of ibopamine with or shortly after a meal reduced the rate and extent of appearance of free epinine in plasma. The clinical significance of reduced epinine levels on acute dosing in the presence of food is unknown.