Four cases of acute comitant esotropia associated with diffuse intrinsic pontine glioma in children.

BACKGROUND: Acute acquired concomitant esotropia (AACE) is usually a benign form of strabismus that infrequently is associated with intracranial pathology. Clinicians have noted an increase in its incidence and theorize that it may be related to public health "lockdown" measures taken in response to the COVID-19 pandemic. With an increased incidence of AACE clinicians must firstly differentiate AACE from common accommodative esotropia and secondly recognize AACE as a possible sign of serious neuropathology.Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating diagnosis for affected families. Children typically present at age 6-7 years with cranial nerve palsies, long tract signs, and/or cerebellar signs. Diagnosis is made from characteristic findings on magnetic resonance brain imaging (MRI brain) and treatment includes radiotherapy and palliative care. Two years from diagnosis, 90% of affected children will have died from their disease. CASE SERIES: We present four cases that attended our pediatric ophthalmology clinic with AACE either as a presenting sign of DIPG or as a clinical finding following a DIPG diagnosis. Patient A (age 5 years) presented to the emergency eye clinic with sudden onset diplopia and intermittent esotropia. Suppression later developed, they had 0.00 logMAR visual acuity either eye, and bilateral physiological hypermetropia. MRI brain imaging requested as a result of the unusual presentation led to the DIPG diagnosis. The other 3 cases (ages 11, 5 & 5 years) were assessed post DIPG diagnosis and found to have an esotropia measuring bigger on 1/3-meter fixation than 6-meter fixation, full ocular motility, physiological hypermetropia or emmetropia, and visual acuity normal for age. Other than patient B (age 11 years), who had papilledema and gaze evoked nystagmus when they were assessed 2 weeks prior to death, no patient had any other clinical eye findings. CONCLUSIONS: This small series of 4 patients attending our clinic within a 12-month period supports the notion that children presenting with AACE should routinely be offered brain MRI. Not all children with DIPG-associated AACE have significant ophthalmic findings indicative of intracranial pathology. With the potential for increased incidence of AACE related to lockdowns, clinicians should be reminded of the infrequent possibility their patient has a more serious condition.

Temporal Changes in Innate and Adaptive Immunity During Sepsis as Determined by ELISpot.

Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The ELISpot assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. Herein, we tested the hypothesis on whether the ELISpot assay can detect dynamic changes in both innate and adaptive immunity as they often occur during sepsis. We also tested whether ELISpot could detect the effect of immune drug therapies to modulate innate and adaptive immunity. Methods: Mice were made septic using sublethal cecal ligation and puncture (CLP). Blood and spleens were harvested serially and ex vivo IFN-γ and TNF-α production were compared by ELISpot and ELISA. The capability of ELISpot to detect changes in innate and adaptive immunity due to in vivo immune therapy with dexamethasone, IL-7, and arginine was also evaluated. Results: ELISpot confirmed a decreased innate and adaptive immunity responsiveness during sepsis progression. More importantly, ELISpot was also able to detect changes in adaptive and innate immunity in response to immune-modulatory reagents, for example dexamethasone, arginine, and IL-7 in a readily quantifiable manner, as predicted by the reagents known mechanisms of action. ELISpot and ELISA results tended to parallel one another although some differences were noted. Conclusion: ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.

Evaluating the impact of information and support for people with nystagmus in the digital age: A patient and carer questionnaire study.

Background: Nystagmus is a disorder of rhythmic, involuntary oscillations of the eyes and can be classified as either infantile or acquired. Whether it occurs in isolation or as a part of other visual or neurological disorders, it causes significant visual dysfunction and problems with social functioning. In this study, we seek to understand ways in which people with nystagmus are currently supported across the UK and identify any geographical variations or disconnects between current practice and best practice, as judged by patients and their carers.Methods: A nationwide, qualitative, cross-sectional, questionnaire study of people with nystagmus and their carers. Recruitment was achieved through specialist clinics, charity events, online advertisements and social media calls. Data was gathered using five, age-appropriate questionnaires which were completed and returned to the research team between November 2016 and August 2018.Results: 184 respondents were included (89 carers, 47 patients aged 4-10 years, 5 aged 11-14 years, 4 aged 15-17 years and 39 > 18 years). Notably, respondents rated social media as the best source of information they have received, even compared with face-to-face consultation with medical professionals. Additionally, only 33% of the respondents had been offered visual impairment support. Notably, patterns of clinical practice and patient experience emerged according to geographical location, particularly provision of initial information and ongoing VI support.Conclusions: This study highlights a significant variation in the support and information received by people in the UK with nystagmus. It also supports the role of charities and increasingly, social media in the provision of patient information. The study also highlights the need for standardized guidelines for the management of patients with nystagmus, particularly with regard to support and information.

Supranuclear eye movements and nystagmus in children: A review of the literature and guide to clinical examination, interpretation of findings and age-appropriate norms.

Abnormal eye movements in children, including nystagmus, present a significant challenge to ophthalmologists and other healthcare professionals. Similarly, examination of supranuclear eye movements and nystagmus in children and interpretation of any resulting clinical signs can seem very complex. A structured assessment is often lacking although in many cases, simple clinical observations, combined with a basic understanding of the underlying neurology, can hold the key to clinical diagnosis. As the range of underlying diagnoses for children with abnormal eye movements is broad, recognising clinical patterns and understanding their neurological basis is also imperative for ongoing management. Here, we present a review and best practice guide for a structured, methodical clinical examination of supranuclear eye movements and nystagmus in children, a guide to clinical interpretation and age-appropriate norms. We also detail the more common specific clinical findings and how they should be interpreted and used to guide further management. In summary, this review will encourage clinicians to combine a structured assessment and a logical interpretation of the resulting clinical signs, in order to recognise patterns of presentation and avoid unnecessary investigations and protracted delays in diagnosis and clinical care.

Developmental role of adenosine kinase for the expression of sex-dependent neuropsychiatric behavior.

Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are associated with deficits in various cognitive domains. To distinguish between developmental and adult functions of ADK, we used two transgenic mouse lines with widespread disruption of ADK expression in the adult brain, but differences in the onset of ADK deletion. Specifically, we compared Nestin-Cre+/-:ADK-floxfl/fl (ADKΔBrain) mice with global loss of ADK in the whole brain, beginning in mid-gestation and persisting for life, with Gfa2-Cre+/-:ADK-floxfl/fl (ADKΔAstro) mice that have normal ADK expression throughout development, but lose astrocyte-specific ADK-expression in young adulthood. Because ADK-expression in adulthood is generally confined to astrocytes, adult ADKΔAstro mice show a similar expression profile of ADK in key areas of the brain related to neuropsychiatric behavior, compared to adult ADKΔBrain mice. We sought to determine a neurodevelopmental role of ADK on the expression of psychiatric behaviors in adult male and female mice. Adult ADKΔBrain mice showed significant deficits in social memory in males, significant contextual learning impairments in both sexes, and a hyper-responsiveness to amphetamine in males. In contrast, ADKΔAstro mice showed normal social memory and contextual learning but hypo-responsiveness to amphetamine in males. Our results demonstrate a key developmental role of ADK in mediating behaviors in adulthood related to neuropsychiatric disease and support the greater prevalence of these disorders among males.

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.

The impact of prostate cancer on partners: a qualitative exploration.

OBJECTIVE: Prostate cancer and its treatment can result in numerous physical and psychological morbidities for the patient as well as his partner. This qualitative study aimed to explore the experiences of intimate spouses or partners of men diagnosed and/or treated for prostate cancer to better understand the personal impact of prostate cancer on the partner. METHODS: Twenty-seven partners participated in this study. Six focus groups were convened, and one in-depth interview was undertaken to explore the practical impact of prostate cancer on the intimate spouse/partner. All discussions were audio-recorded and transcribed and then coded using a thematic approach. RESULTS: Six themes emerged: (a) The influence of the man's response to prostate cancer on the partner, (b) The need to be involved in treatment and medical decision making, (c) Supporting a man who is experiencing a loss of masculinity, (d) Degree of congruence between each partner's coping responses, (e) Constrained communication, and (f) Changed roles and increased practical management. CONCLUSIONS: It is clear that prostate cancer impacts substantially on many areas of partner well-being. An effective intervention provided to this population seems warranted and may lead to improvements in partner well-being, assist the couple in lessening the impact of prostate cancer and its treatment on their relationship, and assist in the man's recovery.

A review of the volatiles from the healthy human body.

A compendium of all the volatile organic compounds (VOCs) emanating from the human body (the volatolome) is for the first time reported. 1840 VOCs have been assigned from breath (872), saliva (359), blood (154), milk (256), skin secretions (532) urine (279), and faeces (381) in apparently healthy individuals. Compounds were assigned CAS registry numbers and named according to a common convention where possible. The compounds have been grouped into tables according to their chemical class or functionality to permit easy comparison. Some clear differences are observed, for instance, a lack of esters in urine with a high number in faeces. Careful use of the database is needed. The numbers may not be a true reflection of the actual VOCs present from each bodily excretion. The lack of a compound could be due to the techniques used or reflect the intensity of effort e.g. there are few publications on VOCs from blood compared to a large number on VOCs in breath. The large number of volatiles reported from skin is partly due to the methodologies used, e.g. collecting excretions on glass beads and then heating to desorb VOCs. All compounds have been included as reported (unless there was a clear discrepancy between name and chemical structure), but there may be some mistaken assignations arising from the original publications, particularly for isomers. It is the authors' intention that this database will not only be a useful database of VOCs listed in the literature, but will stimulate further study of VOCs from healthy individuals. Establishing a list of volatiles emanating from healthy individuals and increased understanding of VOC metabolic pathways is an important step for differentiating between diseases using VOCs.

Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic, and white early adolescent girls living in the U.S.

UNLABELLED: Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. METHODS: Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9-14 years) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. RESULTS: Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. CONCLUSION: Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups.

Gastrointestinal symptomatology as a predictor of severe outcomes of invasive group A streptococcal infections.

Invasive group A streptococcal (GAS) disease is a condition of clinical and public health significance. We conducted epidemiological analyses to determine if the presence of gastrointestinal (GI) complaints (diarrhea and/or vomiting) early in the course of invasive GAS disease is associated with either of two severe outcomes: GAS necrotizing fasciitis, or hospital mortality. Subjects were hospitalized for invasive GAS disease throughout the state of Florida, USA, during a 4-year period. Multiple imputation using the Markov chain Monte Carlo method was used to replace missing values with plausible values. Excluding cases with missing data resulted in a sample size of 138 invasive GAS patients (the complete subject analysis) while the imputed datasets contained 257 records. GI symptomatology within 48 h of hospital admission was not associated with hospital mortality in either the complete subject analysis [adjusted odds ratio (aOR) 0.86, 95% confidence interval (CI) 0.31-2.39] or in the imputed datasets. GI symptoms were significantly associated with GAS necrotizing fasciitis in the complete subject analysis (aOR 4.64, 95% CI 1.18-18.23) and in the imputed datasets but only in patients aged <55 years. The common cause of GI symptoms and necrotizing fasciitis may be streptococcal exotoxins. Clinicians who are treating young individuals presumed to be in the early stages of invasive GAS disease should take note of GI symptoms and remain vigilant for the development of a GAS necrotizing soft-tissue infection.

Maintaining control over illness: a model of partner activity in prostate cancer.

Prostate cancer demonstrates particular characteristics and potential stresses for both patient and partner, yet its consequences for the couple are often inadequately addressed in the clinical setting. One-to-one interviews have shown areas of partner need but do not address the dynamic of the couple which itself holds implications for clinical practice. The participation of nine out of a possible 15 women in interviews with men taking part in a study of information needs suggested the extent of involvement by partners in prostate cancer. Secondary analysis of the verbal interaction and thematic content of the interviews authenticated the representation by members of the couple of the struggle against cancer as a shared experience. The women were shown to exercise authority, accepted by men in relation to illness-related issues and assumed responsibility for the management of information, care and the continuation of normal day-to-day life. Findings suggest a model of partner activity in prostate cancer conceptualized as 'maintaining control over illness'. In the clinical setting, attention to the interaction between partners may facilitate appropriate communication strategies by health professionals, leading to more effective information exchange. Encouragement of the attendance and involvement of partners in the planning of care would support their contribution.

Adaptation and impairment of DNA repair function in pollen of Betula verrucosa and seeds of Oenothera biennis from differently radionuclide-contaminated sites of Chernobyl.

BACKGROUND AND AIMS: The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. METHODS: Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. KEY RESULTS: Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. CONCLUSIONS: Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

Fundamentals of pair diffusion in kinematic simulations of turbulence.

We demonstrate that kinematic simulation (KS) of three-dimensional homogeneous turbulence produces fluid element pair statistics in agreement with the predictions of L F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)] even though KS lacks explicit modeling of turbulent sweeping of small eddies by large ones. This scaling is most clearly evident in the turbulent diffusivity's dependence on rms pair separation and, to a lesser extent, on the pair's travel time statistics. It is also shown that kinematic simulation generates a probability density function of pair separation which is in good agreement with recent theory [S. Goto and J. C. Vassilicos, New J. Phys. 6, 65 (2004)] and with the scaling of the rms pair separation predicted by L. F. Richardson [Proc. R. Soc. London, Ser. A 110, 709 (1926)]. Finally, the statistical persistence hypothesis (SPH) is formulated mathematically and its validity tested in KS. This formulation introduces the concept of stagnation point velocities and relates these to fluid accelerations. The scaling of accelerations found in kinematic simulation supports the SPH, even though KS does not generate a Kolmogorov scaling for the acceleration variance (except for a specific case and a limited range of outer to inner length-scale ratios). An argument is then presented that suggests that the stagnation points in homogeneous isotropic turbulence are on average long-lived.

Elevated levels of WT1 transcripts in bone marrow harvests are associated with a high relapse risk in patients autografted for acute myeloid leukaemia.

Relapse postautograft in acute myeloid leukaemia (AML), may in part arise from leukaemia cells present in the bone marrow (BM) inoculum, and the level of minimal residual disease (MRD) in BM harvests used for autografting may therefore be clinically important. We have used the WT1 transcript as a marker of MRD, which was quantitated by RQ-PCR, in the BM harvests of 24 patients receiving an ABMT for AML. ABL was used as a control gene with WT1 level being normalised to 10(5) copies of ABL per sample. Median WT1 level was 651 copies (range=113-32 700) for the 13 patients with relapse-free survival (RFS) of less than 5 years, and 174 (range=0-1900) for patients with RFS of over 5 years postautograft (P<0.04). The RFS was 10.5 months for patients with WT1 level of >2000 copies (n=5), and has not yet been reached for patients with WT1 level<2000 (n=21), at a median follow-up of 92 months (P<0.05). We show that elevated levels of MRD in BM harvests are associated with a higher relapse risk in patients autografted for AML.

Acceleration statistics as measures of statistical persistence of streamlines in isotropic turbulence.

We introduce the velocity Vs of stagnation points as a means to characterize and measure statistical persistence of streamlines. Using theoretical arguments, direct numerical simulations (DNS), and kinematic simulations (KS) of three-dimensional isotropic turbulence for different ratios of inner to outer length scales L/eta of the self-similar range, we show that a frame exists where the average Vs = 0 , that the rms values of acceleration, turbulent fluid velocity, and Vs are related by La'/u'2 approximately (V's/u')(L/eta)(2/3+q) , and that V's/u' approximately (L/eta)q with q = -1/3 in Kolmogorov turbulence, q = -1/6 in current DNS, and q = 0 in our KS. The statistical persistence hypothesis is closely related to the Tennekes sweeping hypothesis.

Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.

OBJECTIVE: To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE. METHODS: Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (+/-6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests. RESULTS: Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function. CONCLUSIONS: Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.

Falls: a comparison of trends in community, hospital and mortality data in older Australians.

BACKGROUND AND AIMS: Falls are major contributors to disability, morbidity and death for older people. Frequently, falls-related data for each of these areas is viewed in isolation. The aim of this study was to establish trends in incidence of falls-related events including: community reporting of falls and falls-related injuries, hospitalizations as a result of accidental falls, and mortality related to accidental falls for older people in two states of Australia (Victoria and South Australia). METHODS: We analysed data sets for falls hospitalizations and mortality rates for the period 1988 to 1997, and from two longitudinal population-based proportional samples during the same time period. RESULTS: Age-standardised falls mortality rates have steadily declined in Victoria, and remained unchanged between 1988 and 1997 in South Australia. In both states, age-standardised falls hospitalization rates have increased significantly (in Victoria, RR=1.32, 95% CI: 1.30-1.34; and South Australia, RR=1.05, 95% CI: 1.03-1.06). In both states, there was a clear age-related effect, with those in the 85-year and older age group having a falls-related mortality rate approximately 40 times that of those aged 65-69 years, and a hospitalization rate 9 times that of those in the 65-69 age group. The community studies indicated that falls rates remain high among older Australians, and that injurious falls occurred in 10% in the first wave of data collection in each of these studies. CONCLUSIONS: The results highlight that various indicators related to falls trends taken in isolation may yield differing conclusions. For a true reflection of the effectiveness of falls prevention programs, falls-related mortality, hospitalization and community data need to be integrated. Increased focus on falls prevention activity in Australia during the 1990's has not reduced the magnitude of this major public health problem.

Failed expression of an endo-beta-1,4-glucanhydrolase (cellulase) in a non-abscinding mutant of Lupinus angustifolius cv Danja.

Cellulase expressions in a normal shedding wild-type and a non-abscinding single gene mutant of Lupinus angustifolius have been studied during ethylene treatments of leaf abscission zone explants. Of the range of different glycohydrolases investigated only the abscission cell-specific beta-1,4-glucanhydrolase (cellulase) was not produced in the non-abscinding mutant. An endo-polygalacturonase was induced equally in both wild-type and mutant and other glycohydrolases were equally up-regulated. The abscission cell-specific cellulase induced at shedding of wild-type is antigenically similar to the Phaseolus vulgaris induced leaf abscission pI 9.5 cellulase but with a higher molecular mass (50 kD compared with 48 kD) and like the bean abscission-specific cellulase that of lupin is not glycosylated. Causes of the loss of function of cellulase expression in the non-shedding mutant are discussed.

Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.

Does increasing ovum donor compensation lead to differences in donor characteristics?

OBJECTIVE: To evaluate the effects of a compensation increase for anonymous ovum donors on demographic and social characteristics. DESIGN: Retrospective analysis. SETTING: The Mount Sinai Medical Center Ovum Donation Program. PATIENT(S): All program applicants for 2 years preceding (group I, n = 2,934) and 1 year following an increase in donor compensation (group II, n = 1,114; total N = 4,048). INTERVENTION(S): Compensation was increased from $2,500 to $5,000 per cycle. MAIN OUTCOME MEASURE(S): Demographic and social characteristics of applicants and donors. RESULT(S): More group II applicants (65.7%) than group I applicants (49.2%) returned an initial biographical questionnaire. Compensation level did not affect the percentage rejected at any stage in the application process or ultimately selected. There were no differences in donors in age, marital status, education, race, religion, or psychological profile. Group II donors had more previous pregnancies (group II mean = 1.2, group I mean = 0.6) and previous abortions (group II mean = 0.8, group I mean = 0.4). CONCLUSION(S): Increasing compensation may result in a higher percentage of potential donors completing an initial questionnaire but does not alter the demographic and social characteristics of selected donors. Adherence to a rigorous applicant screening ensures that donor characteristics remain independent from compensation.