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Early B cell factor 3 (EBF3) is a transcription factor involved in brain development. Heterozygous, loss-of-function mutations in EBF3 have been reported in an autosomal dominant neurodevelopmental syndrome characterized by hypotonia, ataxia, and developmental delay (sometimes described as “HADD”s). We report 2 unrelated cases with novel de novo EBF3 mutations: c.455G>T (p.Arg152Leu) and c.962dup (p.Tyr321*) to expand the genotype/phenotype correlations of this disorder; clinical, neuropsychological, and MRI studies were used to define the phenotype. IQ was in the normal range and diffusion tensor imaging revealed asymmetric alterations of the longitudinal fasciculus in both cases. Our results demonstrate that EBF3 mutations can underlie neurodevelopmental disorders without intellectual disability. Long tract abnormalities have not been previously recognized and suggest that they may be an unrecognized and characteristic feature in this syndrome.

Background: Aflatoxin exposure has been shown to cause cell-mediated immune suppression and enhance HIV viral replication. Such immune suppression from aflatoxin can impair resistance to both infectious diseases and chronic infections. Methods: Hazard ratios (HRs) with 95% confidence intervals (CI) and a test for trend for opportunistic infections OI) among 141 HIV positive Ghanaians based on quartiles of aflatoxin B1 albumin adduct levels (AF-ALB) were calculated. Findings: HRs were significantly higher for developing symptomatic TB (HR 3.30, 95% CI 1.34–8.11) for those in the highest AF-ALB quartile compared to the lowest. Significantly higher HRs were not observed for other infections investigated. Conclusions: Those with the highest levels AF-ALB from dietary intake have an increased hazard of symptomatic TB but not malaria, HBV, or pneumonia.

Steep insect biomass declines ('insectageddon') have been widely reported, despite a lack of continuously collected biomass data from replicated long-term monitoring sites. Such severe declines are not supported by the world's longest running insect population database: annual moth biomass estimates from British fixed monitoring sites revealed increasing biomass between 1967 and 1982, followed by gradual decline from 1982 to 2017, with a 2.2-fold net gain in mean biomass between the first (1967-1976) and last decades (2008-2017) of monitoring. High between-year variability and multi-year periodicity in biomass emphasize the need for long-term data to detect trends and identify their causes robustly.

Diagnostic next generation sequencing (NGS) services for patients with inherited retinal diseases (IRD) traditionally use gene panel based approaches, which have cost and resource implications. Phenotype-based gene panels use a targeted strategy with further testing protocols, if initial results are negative. We present the molecular findings of the Oxford phenotype-based NGS panels for genetic testing in IRD.Results of 655 consecutive patients referred for phenotype-based panel testing over 54 months were analysed to assess diagnostic yield.Variants were identified in 450 patients (68.7%). The overall diagnostic yield from phenotype-based panels was 42.8%. The diagnostic yield was highest from panels representing distinct clinical phenotypes: Usher panel 90.9% and congenital stationary night blindness panel 75.0%. Retinitis pigmentosa/rod-cone dystrophy was the commonest presenting phenotype (n = 243) and Usher syndrome was the commonest presenting syndromic disease (n = 39). Patients presenting with late-onset (≥50 years) macular disease had a lower diagnostic yield (18.0%) compared with patients50 years (24.2%). Additionally, a diagnostic yield of 1.8% was attributable to copy number variants.Phenotype-based genetic testing panels provide a targeted testing approach and reduce bioinformatics demand. The overall diagnostic yield achieved in this study reflects the wide range of phenotypes that were referred. This pragmatic approach provides a high yield for early-onset and clearly defined genetically determined disorders but clinical utility is not as clear for late-onset macular disorders. This phenotype-based panel approach is clinician-referrer orientated, and can be used as a front-end virtual panel, when whole genome sequencing is introduced into diagnostic services for IRD.

The importance of establishing a genetic diagnosis in patients with a choroideremia phenotype has been underscored by the advent of gene replacement therapy for this condition. Here, we describe a complex imbalance at the CHM locus in a male patient with classical disease. At the DNA level, this imbalance consists of 2 non-contiguous duplications (exons 1-2 and 9-12). Further characterization suggests the generation of 2 independent CHM transcriptional units, one of which may produce a deleted form of the Rab escort protein 1 protein. Expression of such a type of aberrant protein in photoreceptors may have important implications when considering gene therapy for this disorder.

Spinocerebellar ataxia type 5 (SCA-5) is a predominantly slowly progressive adult onset ataxia. We describe a child with a presentation of ataxic cerebral palsy (CP) and developmental delay at 6 months of age. Genetic testing confirmed a c.812C>T p.(Thr271Ile) mutation within the SPTBN2 gene. Seven previous cases of infantile onset SCA-5 are reported in the literature, four of which had a CP presentation. Early onset of SCA-5 presents with ataxic CP and is a rare cause of cerebral palsy.

Steep insect biomass declines ('insectageddon') have been widely reported, despite a lack of continuously collected biomass data from replicated long-term monitoring sites. Such severe declines are not supported by the world's longest running insect population database: annual moth biomass estimates from British fixed monitoring sites revealed increasing biomass between 1967 and 1982, followed by gradual decline from 1982 to 2017, with a 2.2-fold net gain in mean biomass between the first (1967-1976) and last decades (2008-2017) of monitoring. High between-year variability and multi-year periodicity in biomass emphasize the need for long-term data to detect trends and identify their causes robustly.

IMPORTANCE: Gene therapy is a promising treatment for choroideremia, an X-linked retinal degeneration. The required minimum level of gene expression to ameliorate degeneration rate is unknown. This can be interrogated by exploring the association between messenger RNA (mRNA) levels and phenotype in mildly affected patients with choroideremia. OBJECTIVE: To analyze CHM mRNA splicing outcomes in 2 unrelated patients with the same c.940+3delA CHM splice site variant identified as mildly affected from a previous study of patients with choroideremia. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective observational case series, 2 patients with c.940+3delA CHM variants treated at a single tertiary referral center were studied. In addition, a third patient with a c.940+2T>A variant that disrupts the canonical dinucleotide sequence at the same donor site served as a positive control. Data were collected from October 2013 to July 2018. MAIN OUTCOMES AND MEASURES: Central area of residual fundus autofluorescence was used as a biomarker for disease progression. CHM transcript splicing was assessed by both end point and quantitative polymerase chain reaction. Rab escort protein 1 (REP1) expression was assessed by immunoblot. RESULTS: The 2 mildly affected patients with c.940+3delA variants had large areas of residual autofluorescence for their age and longer degeneration half-lives compared with the previous cohort of patients with choroideremia. The control patient with a c.940+2T>A variant had a residual autofluorescence area within the range expected for his age. Both patients with the c.940+3delA variant expressed residual levels of full-length CHM mRNA transcripts relative to the predominant truncated transcript (mean [SEM] residual level: patient 1, 2.3% [0.3]; patient 2, 4.7% [0.2]), equivalent to approximately less than 1% of the level of full-length CHM expressed in nonaffected individuals. Full-length CHM expression was undetectable in the control patient. REP1 expression was less than the threshold for detection both in patients 1 and 2 and the control patient compared with wild-type controls. CONCLUSIONS AND RELEVANCE: These results demonstrate the first genotype-phenotype association in choroideremia. A +3 deletion in intron 7 is sufficient to cause choroideremia in a milder form. If replicated with gene therapy, these findings would suggest that relatively low expression (less than 1%) of the wild-type levels of mRNA would be sufficient to slow disease progression.

Early B cell factor 3 (EBF3) is an atypical transcription factor that is thought to influence the laminar formation of the cerebral cortex. Here, we report that de novo mutations in EBF3 cause a complex neurodevelopmental syndrome. The mutations were identified in two large-scale sequencing projects: the UK Deciphering Developmental Disorders (DDD) study and the Canadian Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) study. The core phenotype includes moderate to severe intellectual disability, and many individuals exhibit cerebellar ataxia, subtle facial dysmorphism, strabismus, and vesicoureteric reflux, suggesting that EBF3 has a widespread developmental role. Pathogenic de novo variants identified in EBF3 include multiple loss-of-function and missense mutations. Structural modeling suggested that the missense mutations affect DNA binding. Functional analysis of mutant proteins with missense substitutions revealed reduced transcriptional activities and abilities to form heterodimers with wild-type EBF3. We conclude that EBF3, a transcription factor previously unknown to be associated with human disease, is important for brain and other organ development and warrants further investigation.

Aflatoxin B1 (AFB1) is immunotoxic to animals and a suspected immunosuppressant in humans. In this study, we investigated the effects of AFB1 on splenic lymphocyte phenotypes and the inflammatory cytokine expression in male F344 rats. Exposure of animals to AFB1 [5-75 µg kg(-1) body weight (BW)] for 1 week showed dose-dependent decreases in the percentage of splenic CD8(+) T cells and CD3(-) CD8a(+) NK cells. A general inhibition of the expression of interleukin (IL)-4 and interferon (IFN)-γ by CD4(+) T cells, IL-4 and IFN-γ by CD8a(+) cells, and tumor necrosis factor (TNF)-α expression by natural killer (NK) cells was also found; however, no concurrent histological changes in spleen tissue were present, suggesting acute immunosuppression without overt toxicity. Five-week exposure with AFB1 significantly increased the percentages of CD3(+) and CD8(+) T cells, especially at low doses (≤ 25 µg kg(-1)). AFB1 treatment significantly decreased the anti-inflammatory cytokine IL-4 expression by CD4(+) T cells and significantly increased the pro-inflammatory cytokine IFN-γ expression by CD4(+) T cells and TNF-α expression by NK cells. These results indicated that repeated AFB1 exposure promotes inflammatory responses by regulating cytokine expression. Our data provides novel insights into the mechanisms by which AFB1 exposure differentially modulates the cell-mediated immune responses and suggests the involvement of an inflammatory response upon repeated exposure.

In this study, male F344 rats were orally exposed to a single dose of aflatoxin B1 (AFB1) at 0, 50, 250, or 1,000 µg/kg body weight (BW) or repeated dose of 0, 5, 10, 25, or 75 µg/kg BW for up to 5 weeks. Biochemical and histological changes were assessed together with the formation of AFB1-lysine adduct (AFB-Lys) and liver foci positive for placental form glutathione S transferase (GST-P+). In single-dose protocol, serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed dose-related elevation, with maximal changes observed (>100-fold) at day 3 after treatment. Animals that received 250 µg/kg AFB1 showed concurrent bile duct proliferation, necrosis, and GST-P+ hepatocytes at 3 day, followed by liver GST-P+ foci appearance at 1 week. In repeated-dose protocol, bile duct proliferation and liver GST-P+ foci co-occurred after 3-week exposure to 75 µg/kg AFB1, followed by proliferation foci formation after 4 week and dramatic ALT, AST, and CK elevations after 5 weeks. Liver GST-P+ foci were induced temporally and in a dose-related manner. Serum AFB-Lys increased temporally at low doses (5–25 µg/kg), and reached the maximum after 2-week exposure at 75 µg/kg. This integrative study demonstrated that liver GST-P+ cells and foci are sensitive biomarkers for AFB1 toxic effect and correlated with bile duct proliferation and biochemical alterations in F344 rats.

Aflatoxin B(1)-lysine adduct (AFB-Lys) is a reliable biomarker for aflatoxin exposure; however, a systematic toxicokinetic evaluation has not been reported. In this study, male F344 rats were orally exposed to single, or repeated, doses of AFB(1) and the toxicokinetics of serum AFB-Lys that followed treatments were investigated. A single-dose of AFB(1) increased serum AFB-Lys levels rapidly peaking at 4h, followed by first-order elimination, through which the half-life was estimated to be 2.31 days. A physiologically based pharmacokinetic model showed that approximately 3.00-3.90% and 1.12-1.98% of the administered AFB(1) doses were converted to serum AFB-Lys adducts at 2h and 24h post treatment, respectively. Repeated AFB(1) exposure at 5-25 μg/kg body weight linearly increased serum AFB-Lys levels for 5 weeks in animals, resulting in a 1-1.5 times higher AFB-Lys level overall. This indicates the potential of this adduct as a reliable biomarker for repeated low dose exposure. Higher dose exposure at 75 μg/kg increased the level of AFB-Lys to a maximum at 2 weeks, followed by a gradual decrease to near plateau level up to 5 weeks. In conclusion, this study systematically evaluated the toxicokinetics of serum AFB-Lys adduct in F344 rats using a physiologically based pharmacokinetic model and robust statistical modeling analysis and provided a firm and clear understanding of the toxicokinetics of this biomarker.

Background Advanced glycation end-products (AGEs) and their receptor (RAGE) occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1) those with dementia have higher levels of neuronal and vascular AGEs and (2) if cognitive dysfunction depends on neuronal and/or vascular AGE levels. Methods Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing) cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology) were immunostained for N ε -(carboxymethyl)-lysine (CML), the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures. Results The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01) or a history of hypertension (p = 0.028). Additionally, vascular CML staining related to cognitive impairment (p = 0.02) and a history of diabetes (p = 0.007). Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002). Conclusion CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.

Objectives: Cerebral small vessel disease (SVD) is common in aged brains and causes lacunar stroke, diffuse white matter lesions (leukoaraiosis), and vascular cognitive impairment. The pathogenesis is unknown. Endothelial dysfunction is a possible causal factor, and circulating markers of endothelial activation (intercellular adhesion molecule-1, thrombomodulin) and inflammation (interleukin [IL]-6) are elevated in patients with SVD. In this case-control study, we tested whether brain endothelial ICAM1, thrombomodulin, and IL-6 are altered in SVD. Methods: We examined small penetrating cerebral arteries of pathologically diagnosed SVD cases, aged controls without SVD, young control cases with no brain pathology, and cases with early-onset hereditary SVD (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]). All tissues had minimal cerebral amyloid angiopathy or other Alzheimer pathology. Results: Thrombomodulin immunoreactivity was present in all aged SVD, aged control, and CADASIL cases, primarily in small artery endothelium. Thrombomodulin was augmented in aged SVD cases compared with aged controls (p = 0.012) and in vessels with higher sclerotic index (an indicator of SVD severity; p < 0.01). Thrombomodulin was sparse/absent in young controls. Endothelial ICAM1 and IL-6 were rarely seen, and were not related to SVD. Conclusions: Our data suggest that cerebral endothelial activation in deep penetrating arteries is not associated with SVD. Endothelial thrombomodulin increased with SVD severity, and CADASIL data suggest that this may be a cerebral response to SVD. Elevated thrombomodulin may be a protective agent in SVD. Our data confirm endothelial involvement in SVD. Copyright © 2012 by AAN Enterprises, Inc.

DAMAGED 5-HT (5-hydroxytryptamine) axons in the central nervous system have been observed to undergo vigorous sprouting1,2. Regeneration of these axons to their original termination sites has been seen several months after intraventricular administration of selective 5-HT neurotoxic drugs; and in the spinal cord this regrowth has been correlated with a return of normal 5-HT receptor function as measured by a hindlimb stretch reflex3. These findings raise two questions. First, is the pattern of re-innervation after injury dependent on some regenerative property of the damaged axons themselves, or is it primarily controlled by the denervated terminal field? And second, can re-innervation take place not only by regeneration of the original axons but also by collateral sprouting of chemically identical but anatomically separate undamaged fibres; and , if so, will function be restored? In the work reported here we have taken advantage of the fact that the hippocampus receives two separate inputs of 5-HT fibres from the median raphe nucleus, and we have shown that the unilateral removal of one input induces re-innervation of the unoccupied sites by the other. This collateral sprouting occuring in a single hippocampus is accompanied by disappearance of an asymmetrical behavioural response, suggesting that not only structural but functional recovery has occurred. Our results, therefore, suggest that the 5-HT terminal field plays a major part in the reorganisation of this system after injury to the brain.

The effects of certain GABA-modulating drugs, fornicotomy, hippocampectomy and various septal lesions were analysed in a discrete-trial fixed ratio 5 (FR5) bar-press paradigm. Chlordiazepoxide, fornicotomy, hippocampectomy, electrolytic lateral septal lesions and ibotenic acid medial septal lesions facilitate extinction of the FR5 response. Some of these treatments (chlordiazepoxide, hippocampectomy, electrolytic lateral septal lesions) have previously been found to increase resistance to extinction of alley-running after continuously reinforced (CRF) acquisition training. The treatments which facilitated extinction in the discrete-trial FR5 paradigm have been found to reduce or abolish the partial reinforcement extinction effect in the alley. These results indicate that the discrete-trial FR5 paradigm is not analogous to a runway CRF schedule, but may be analogous to a runway partial reinforcement schedule.

Healthy volunteers who received i.v. injections of either saline or haloperidol (0.5 or 1.0 mg) made visual analogue scale ratings of subjective mood, tension, shakiness and the global feeling of having received an active drug. The subjective ratings of volunteers who received haloperidol did not differ, overall, from those who received saline. In contrast, the drug caused clear objective changes in several psychological tests. I.v. administration of low doses of haloperidol may permit double-blind testing of the psychological actions of haloperidol in healthy volunteers.

Mortality resulting from diarrhea especially that occurs in children younger than 5 y of age ranks 3rd among all deaths caused by infectious diseases worldwide. Probiotics such as Lactobacillus rhamnosus GG are clinically shown to effectively reduce the incidence of diarrhea in children. A food substrate is one of the major factors regulating the colonization of microorganisms in human gastrointestinal tracts. Peanut butter is a nutritious, low-moisture food that could be a carrier for probiotics. In this study, we observed the influence of storage conditions and product matrixes on the survival of L. rhamnosus GG. Cells of L. rhamnosus GG were inoculated into full fat or reduced fat peanut butter at 10(7) CFU/g. Inoculated peanut butter was stored at 4, 25, or 37 °C for 48 wk. Samples were drawn periodically to determine the populations of L. rhamnosus GG. Results showed that there was no significant decrease in the viable counts of L. rhamnosus GG in products stored 4 °C. The survivability of L. rhamnosus GG decreased with increasing storage temperature and time. Product matrixes did not significantly affect the survival of L. rhamnosus GG except at 37 °C. Populations of L. rhamnosus GG were preserved at >6 logs in products stored at 4 °C for 48 wk and at 25 °C for 23 to 27 wk. At 37 °C, the 6-log level could not be maintained for even 6 wk. The results suggest that peanut butter stored at 4 and 25 °C could serve as vehicles to deliver probiotics.

Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB1 control, FB1 + 2% NS or absolute control group. FB1 alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day−1) or placebo (1.5 g day−1) for 3 months. Urines from weeks 8 and 10 were collected from the ...

We examined the association between certain clinical factors and aflatoxin B(1)-albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg(-1) albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17-7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03-22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression.

Aflatoxins are fungal metabolites that contaminate staple food crops in many developing countries. Up to 40% of women attending a prenatal clinic in Africa may be anemic. In a cross-sectional study of 755 pregnant women, Aflatoxin B(1)-lysine adducts (AF-ALB) levels were determined by high-performance liquid chromatography. Participants were divided into quartiles "low," "moderate," "high," and "very high." Anemia was defined as hemoglobin levels < 11 g/dL. Logistic regression was used to examine the association of anemia with AF-ALB. The mean AF-ALB level was 10.9 pg/mg (range = 0.44-268.73 pg/mg); 30.3% of participants were anemic. The odds of being anemic increased 21% (odds ratio [OR], 1.21, P = 0.01) with each quartile of AF-ALB reaching an 85% increased odds in the "very high" compared with the "low" category (OR, 1.85; confidence interval [CI], 1.16-2.95). This association was stronger among women with malaria and findings were robust when women with evidence of iron deficiency anemia were excluded. This study found a strong, consistent association between anemia in pregnancy and aflatoxins.

Context Although it is known that aflatoxins have many adverse health effects, there is no systematic summary of how it affects the reproductive system or its reproductive health effects. Objective Summarize evidence on the reproductive health effects of aflatoxins. Results The search yielded 121 potential studies, of which 25 were retained. One study found a higher concentration of aflatoxins in the semen of infertile men (40% of cases compared to 8% of controls). Six studies found significant associations or correlations between low birth weight and aflatoxins while one study did not find any correlation. One study found maternal serum aflatoxin to be a risk factor for jaundice in infants (OR, 2.68; CI, 1.18–6.10). Overall, maternal breast milk in developing countries had higher rates of aflatoxin contamination than in high income countries. Conclusions Stakeholders in developing countries need to take steps to reduce exposure of vulnerable populations to the toxic effects of aflatoxins.

Objective. The objective of the study was to assess Plasmodium/intestinal helminth infection in pregnancy and other risk factors for stillbirth in Ghana.Methods. A cross-sectional study of women presenting for delivery in two hospitals was conducted during November-December 2006. Data collected included sociodemographic information, medical and obstetric histories, and anthropometric measures. Laboratory investigations for the presence ofPlasmodium falciparumand intestinal helminths, and tests for hemoglobin levels were also performed.Results. The stillbirth rate was relatively high in this population (5%). Most of the stillbirths were fresh and 24% were macerated. When compared to women with no malaria, women with malaria had increased risk of stillbirth (OR=1.9, 95% CI=1.2–9.3). Other factors associated with stillbirth were severe anemia, low serum folate concentration, past induced abortion, and history of stillbirth.Conclusion. The fact that most of the stillbirths were fresh suggests that higher quality intrapartum care could reduce stillbirth rates.

Both malaria and intestinal helminths are endemic in sub-Saharan Africa, and their co-infection occurs commonly. This cross-sectional study assessed the prevalence of malaria and intestinal helminth co-infection in a sample of > 700 pregnant women in Ghana and identified risk factors for co-infection. The prevalence of malaria infection, intestinal helminth infection(s), and co-infection was 36.3%, 25.7%, and 16.6%, respectively. Women with intestinal helminth infection(s) were 4.8 times more likely to have malaria infection. Young age, low income, being single, and being primigravid were each associated with increased odds of co-infection. These associations were present when assessed separately for primi- and multigravid women, but the strength of associations varied considerably for the two groups of women. Young age had the strongest association among both primigravid (odds ratio = 5.2) and multigravid (odds ratio = 3.2) women. This study shows relatively high prevalence rates of malaria, intestinal helminths, and co-infection in pregnant women in Ghana.

To assess the potential interference of NovaSil (NS) clay with micronutrients in humans, vitamins A and E and minerals (15 nutrient and 15 non-nutrient minerals) were measured in serum samples from a 3-month intervention trial with NS. Participants (n = 177) were randomly divided into three groups that received 3.0 g NS day(-1) (high dose, HD), 1.5 g NS day(-1) (low dose, LD), or placebo (PL). Levels of vitamins A and E in serum were comparable among the three study groups at baseline, 1 month and 3 months of NS intervention. Gender-stratified non-parametric mixed-effect model analysis showed no significant effects of dose and dose-time interaction for levels of vitamins A and E. A significant time effect was detected; however, it was limited to an increase in vitamin E in the male participants over the course of the study. No significant differences were found in levels of the nutrient and non-nutrient minerals between the HD and PL groups at baseline and 3 months of NS intervention, except for strontium levels. Strontium was significantly increased (p0.001) in the HD group (male = 113.65 +/- 28.00 microg l(-1); female = 116.40 +/- 24.26 microg l(-1)) compared with the PL group (male = 83.55 +/- 39.90 microg l(-1); female = 90.47 +/- 25.68 microg l(-1)) following the 3-month intervention with NS. These results, combined with safety and efficacy data, confirm that NS clay is highly effective in reducing aflatoxin exposure and acts as a selective enterosorbent that does not affect the serum concentrations of important vitamins and nutrient minerals in humans.

The efficacy of NovaSil clay (NS) to reduce aflatoxin (AF) biomarkers of exposure was evaluated in 656 blood samples and 624 urine samples collected from study participants during a 3-month phase IIa clinical intervention trial in Ghana. NS was delivered before meals via capsules. Serum AFB (1)-albumin adduct was measured by radioimmunoassay and urinary AFM (1) metabolites were quantified by immunoaffinity-high-performance liquid chromatography (HPLC)-fluorescence methods. Levels of AFB (1) -albumin adduct in serum samples collected at baseline and at 1 month were similar (p = 0.2354 and p = 0.3645, respectively) among the placebo (PL), low dose (LD, 1.5 g NS day (-1)), and high dose (HD, 3.0 g NS day (-1)) groups. However, the levels of AFB (1)-albumin adduct at 3 months were significantly decreased in both the LD group (p < 0.0001) and the HD group (p < 0.0001) compared with levels in the PL group. Levels of AFM(1) in urine samples collected at baseline and at 1 month were not statistically different among the three study groups. However, a significant decrease (up to 58%) in the median level of AFM (1) in samples collected at 3 months was found in the HD group when compared with the median level in the PL group (p < 0.0391). In addition, significant effects were found for dose, time, and dose-time interaction with serum AFB(1)-albumin adduct and dose-time interaction with urinary AFM (1) metabolites. The results suggest that capsules containing NS clay can be used to reduce effectively the bioavailability of dietary AF based on a reduction of AF-specific biomarkers.

Innovative sorption strategies for the detoxification of aflatoxins have been developed. NovaSil clay (NS) has been shown to prevent aflatoxicosis in a variety of animals when included in their diet. Results have shown that NS clay binds aflatoxins with high affinity and high capacity in the gastrointestinal tract, resulting in a notable reduction in the bioavailability of these toxins without interfering with the utilization of vitamins and other micronutrients. This strategy is being evaluated as a potential remedy for acute aflatoxicosis, and as a sustainable human intervention for aflatoxins via the diet. Phase I and II clinical trials confirmed the apparent safety of NS for further study in humans. A recent study in Ghanaians at high risk for aflatoxicosis has indicated that NS (at a dose level of 0.25%) is effective in decreasing biomarkers of aflatoxin exposure and does not interfere with the levels of serum vitamins A and E, and iron and zinc. In summary, enterosorption strategies/therapies based on NS clay are promising for the management of aflatoxins and as a sustainable public health intervention. The NS clay remedy is novel, inexpensive and easily disseminated. Based on the present research, aflatoxin sequestering clays should be rigorously evaluated in vitro and in vivo, and should meet the following criteria: (1) favourable thermodynamic characteristics of mycotoxin sorption, (2) tolerable levels of priority metals, dioxins/furans and other hazardous contaminants, (3) safety and efficacy in multiple animal species, (4) safety and efficacy in long-term studies, and (5) negligible interactions with vitamins, iron and zinc and other micronutrients.

A 3-month double-blind and placebo-controlled, phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption efficacy of dietary NovaSil (NS). Volunteers (507 subjects) were clinically screened to evaluate their general health, pregnancy status and blood AFB(1)-albumin adduct levels. Of these subjects, 177 were randomly assigned to three groups: high-dose (HD), low-dose (LD) and placebo-control (PL) groups receiving 3.0, 1.5 and 0 g NS day(-1) in capsules. Trained study-monitors supervised NS capsule administration to participants and recorded side-effects daily. Physical examinations were performed monthly. Blood and urine samples were collected for laboratory analysis. Approximately 92% of the participants (162 of 177) completed the study and compliance rate was over 97%. Overall, 99.5% of person x time reported no side-effects throughout the study. Mild to moderate health events ( approximately 0.5% of person x time) were recorded in some participants. Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. These findings demonstrate that NS clay is apparently safe and practical for the protection of humans against aflatoxins in populations at high risk for aflatoxicosis.

Purpose. We examined the relationship between various health parameters and aflatoxin B1 (AFB1) albumin adduct levels in plasma.Design. A cross‐sectional field study was conducted in four villages ...

Aflatoxins are among the most potent of carcinogens found in staple foods such as groundnuts, maize and other oil seeds. This study was conducted to measure the levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1) (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming region of Ghana and to examine the association between aflatoxin levels and several socio-demographic factors and food handling and consumption practices. A cross-sectional study was conducted in four villages in the Ejura Sekyedumase district of Ghana. A socio-demographic survey was administered to 162 participants. Blood samples were collected from 140 and urine samples from 91 of the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in urine were measured. High AFB(1) albumin-adduct levels were found in the plasma (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg; median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/-2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg; median=472.67pg/mg) of most of the participants. There was a statistically significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in plasma and AFM(1) levels in urine. Several socio-demographic factors, namely, educational level, ethnic group, the village in which participants lived, number of individuals in the household, and number of children in the household attending secondary school, were found to be significantly associated with AFB(1) albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic group (p=0.04), the village in which participants live (p=0.02), and the number of individuals in the household (p=0.01), were significant predictors of high AFB(1) albumin-adducts. These findings indicate strongly that there is need for specifically targeted post-harvest and food handling and preparation interventions designed to reduce aflatoxin exposure among the different ethnic groups in this region of Ghana.

Although aflatoxins (AFs) have been shown to be immune-suppressive agents in animals, the potential role of AFs in modifying the distribution and function of leukocyte subsets in humans has never been assessed. We examined the cellular immune status of 64 Ghanaians in relation to levels of aflatoxin B1 (AFB1)-albumin adducts in plasma. The percentages of leukocyte immunophenotypes in peripheral blood, CD4+ T cell proliferative response, CD4+ T(h) and CD8+ T cell cytokine profiles and monocyte phagocytic activity were measured using flow cytometry. NK cell cytotoxic function was determined by perforin and tumor necrosis factor-alpha expression in CD3-CD56+ NK cells. AFB1-albumin adducts levels ranged from 0.3325 to 2.2703 (mean = 0.9972 +/- 0.40, median = 0.9068) pmol mg(-1) albumin. Study participants with high AFB1 levels had significantly lower percentages of CD3+ and CD19+ cells that showed the CD69+ activation marker (CD3+CD69+ and CD19+CD69+) than participants with low AFB1 levels (P = 0.002 for both). Also, the percentages of CD8+ T cells that contained perforin or both perforin and granzyme A were significantly lower in participants with high AFB1 levels compared with those with low AFB1 (P = 0.012 for both). Low levels of CD3+CD69+ (r = -0.32, P = 0.016) and CD19+CD69+ (r = -0.334, P = 0.010) cells were significantly associated with high AFB1 levels using correlation analysis. By multivariate analysis, there were strong negative correlations between the percentages of these cells (CD3+CD69+: b = -0.574, P = 0.001, and CD19+CD69+: b = -0.330, P = 0.032) and AFB1 levels. These alterations in immunological parameters in participants with high AFB1 levels could result in impairments in cellular immunity that could decrease host resistance to infections.

Background. Previous researchers have suggested that a vegetarian diet or one rich in fish may protect against Alzheimer's disease (AD). However, assessing diet is difficult in AD patients. 1 5 N: 1 4 N isotopic ratios (δ 1 5 N) of body proteins can estimate long-term dietary habits in a way that does not depend on memory. δ 1 5 N is high in people who eat a lot of fish and low in vegetarians. Methods. To choose between the vegetarian and fish hypotheses of AD, we compared dietary questionnaire reports and δ 1 5 N of hair samples from AD patients and controls. Results. Patients' cognitive scores related directly to reported frequency of eating fish and to hair δ 1 5 N A I R , but inversely to reported frequency of eating beans. Homocysteine levels related inversely to hair δ 1 5 N A I R in controls, but not in patients. Dietary questionnaire reports accounted for slightly more variance in δ 1 5 N A I R in patients than controls. Therefore, our questionnaire assessed dietary habits as reliably for individuals with AD as for cognitively unimpaired controls. Conclusions. A diet rich in fish may ameliorate AD, possibly by lowering homocysteine, but more vegetarian diets do not. In fact, eating beans correlated with worse cognition in AD patients. Further studies should test if restricting the intake of beans slows the progression of AD.

We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P . carinii , causing irreversible damage, thus indicating a different mode of action. Penetration was demonstrated by showing DFO uptake by high-pressure liquid chromatography analysis. By using calcein-AM as an indicator, exposure to DFO was shown to cause a reduction in P . carinii cytoplasmic free iron. Exposure to ≥100 μM DFO for ≥8 h in vitro caused growth to cease and cell numbers to decline over several days. This direct and irreversible damage to P . carinii led to the prediction that infrequent delivery of DFO to the lungs via an aerosol would be an effective treatment in the animal model of PCP. This prediction was confirmed by demonstrating that a once-a-week aerosol treatment of rats was 100% effective both as a prophylactic and as a curative treatment in a rat model of PCP.

Heat tolerance of groundnut (Arachis hypogaea L.) was evaluated under field conditions using physiological traits identified in a yield model [crop growth rate (C), reproductive duration (Dr) and partitioning (p)]. In 1991, 625 diverse genotypes were initially screened under irrigation during the hottest months (February to May). Subsequent tests consisted of 16 contrasting genotypes selected based on a combination of high pod yield and partitioning coefficient of >0· 50. Large variation was observed among the 625 genotypes for pod yield and physiological traits. C was a powerful factor influencing pod yield. Eight genotypes combining high pod yield and a partitioning coefficient greater than 0·6 were identified. These included two released cultivars (55–437 and 796) in the Sahel. Correlations between seasons were significant for p (r=0·84), but non-significant for pod yield (r=0·40), C (r=0·39), and Dr (0·36). Date of sowing and genotypes had significant effects on pod yield and C, but were slight on p and Dr. Pod yield of most genotypes declined by more than 50% when flowering and pod formation occurred when maximum temperatures averaged 40°C. The results revealed that estimates of p would be a more reliable selection criterion for identification of genotypes tolerant to heat than yield. Further research is suggested to maximize crop growth rate and partitioning of genotypes growing under supra-optimal temperatures.

Continuous axenic culture of Pneumocystis carinii has been achieved. A culture vessel is used that allows for frequent medium exchange without disturbance of organisms that grow attached to a collagen-coated porous membrane. The growth medium is based on Minimal Essential Medium with Earle’s salt supplemented with S -adenosyl- l -methionine, putrescine, ferric pyrophosphate, N -acetyl glucosamine, putrescine, p -aminobenzoic acid, l -cysteine and l -glutamine, and horse serum. Incubation is in room air at 31°C. The pH of the medium begins at 8.8 and rises to ≈9 as the cells grow. Doubling times calculated from growth curves obtained from cultures inoculated at moderate densities ranged from 35 to 65 hours. With a low-density inoculum, the doubling time is reduced to 19 hours. The morphology of cultured organisms in stained smears and in transmission electron micrographs is that of P. carinii , and P. carinii -specific mAbs label the cultured material. Cultured organisms are infective for immunosuppressed rats and can be stored frozen and used to reinitiate culture.

Carbon isotope discrimination (A) and specific leaf area (SLA) have been shown to be correlated with water-use efficiency (WUE) of peanut (Arachis hypogaea L.) and SLA has been proposed as an indirect selection criterion for Δ and WUE. The effect of high temperature and water deficit on WUE, A, and SLA, and relations between them, was investigated in controlled environments. Five Spanish (A. hypogaea ssp.fastigiata) and three Virginia (A. hypogaea ssp. hypogaea, botanical type) lines were grown at mean temperatures of 27 and 34°C and at 50 and 100% available soil water (ASW) from first flowering to maturity, and WUE, A and SLA measured at maturity. Virginia genotypes had higher total dry matter, water use and WUE (P < 0.01), but were more sensitive to high temperature (P < 0.01) than Spanish genotypes. Water defidt reduced water use and SLA, and increased WUE. The only water deficit × temperature interaction (P < 0.05) was for A, where water deficit reduced the value of Δ at 27° but not at 34°C. High temperature had no effect on water use, but decreased WUE and increased SLA. Across all water defidt and temperature treatments (n = 32), WUE was correlated with Δ (r = -0.78, P < 0.001) and SLA (r = - 0.70, P < 0.001), and SLA correlated with A (r = 0.75, P < 0.001) with no difference associated with botanical type. Temperature and water deficit had significant (P ≤ 0.05) effects on the intercept, but not the slope of these relations. The results support the view that SLA can be used as an indirect selection criterion for Δ and WUE in genotypic selection.

In the Sudano-Sahelian zone of West Africa there is potential for groundnut (Arachis hypogaea L.) to be grown as a dry-season crop where irrigation is available. However, there are substantial variations in the temperatures during the post-rainy season that can be expected to influence growth and yield. An experiment at the ICRISAT Sahelian Centre was done in order to study the effect of sowing date on phenology, yield and the processes of yield determination for four groundnut cultivars under irrigation in the dry seasons of 1990/91 and 1991/92. Starting on 15 November, eight sowing dates at 2-weekly intervals were tested. Sowing date significantly affected phenology (time to emergence, flowering and maturity) with groundnut sown in November/December taking the longest time to reach these phenological stages. November and December sowings gave the highest pod yield within each year, despite the lowest crop growth rates (B), and yield declined progressively as sowing occurred later (50% decrease by March) despite increasing B. The observed responses appear to have been due to the effect of temperature differences during the pod-filling phase on partitioning. Partitioning (p) to pods was optimized at c. 30 C, with some indication of cultivar differences in partitioning response to temperature. Across all the environments, cultivars displayed substantial differences in yield stability. When sown late, yields were low and lines with high partitioning were the best. When sown early in the post-rainy season, cultivars with a high B value were the better choices. Plant habit differences and B suggest that radiation interception was a limitation to yield, particularly when the crops were sown in the cool months of the year. However, haulm yield and crop growth rates were not consistently affected by sowing date across the years, and cultivars demonstrated different degrees of stability for B. It is concluded that where pod has a price advantage over fodder, irrigated groundnut for the dry season should be sown in November to allow the crop to develop under the relatively cool temperatures that maximize pod yield. Further agronomic research is suggested to maximize B for individual cultivars for given sowing dates.

Merozoites of Plasmodium falciparum placed in an erythrocyte sonicate medium under appropriate conditions have been found to develop extracellularly through a complete schizogonic cycle. Although 20–30% of the merozoites developed into rings at 14 h, only 1–2% went further to produce trophozoites and schizonts. This proportion was too small to permit extracellular maintenance through additional cycles. A series of 36-h experiments revealed a favoring effect of carnitine and of other modifications in culture medium, including a high level of magnesium. These improvements have permitted extracellular culture through three schizogonic cycles over a 6-day period with an approximately fivefold increase in parasite number at each schizogony at 48 and at 96 h and with infectivity to erythrocytes demonstrated at 144 h.

We have previously shown that 0.5 mg haloperidol (i.v.) increased latent inhibition in one of two visual tasks. The present study analysed the effects of a higher dose of haloperidol (1.0 mg, i.v.) on latent inhibition in these two visual tasks in healthy volunteers in a randomised controlled trial. In the task where 0.5 mg haloperidol had enhanced latent inhibition, 1.0 mg had the same effect, thus replicating the previous result. In the task where 0.5 mg haloperidol had been ineffective, 1.0 mg haloperidol enhanced latent inhibition in high schizotypal subjects only. This indicates that subjects with higher schizotypy scores are more sensitive to dopamine blockade. A comparison of the results from the studies at the two different doses suggests a dose dependence of haloperidol's effects on latent inhibition that parallels results from animal work.

Cultivar trials comparing nine early maturing and 14 medium maturing peanut (Arachis hypogaea L.) lines were conducted over 3 yr at five sites in Northern Benin. Trials were conducted using presently recommended agronomic practices. Pod and biomass yields, defoliation from all causes and phenology were observed. Crop growth rate (C), partitioning (p) and reproductive duration (parameters of a simple physiological model for yield) were estimated. Both C and p contributed to yield differences among lines within a maturity group. The dwarf cultivar MH2 was in all cases lower yielding due to low C. Duration was apparently not an important determinant of yield differences between early and medium maturity trial sets since (with MH2 excluded) the extra time taken by the medium maturity lines only resulted in 50 kg/ha greater yield. Partitioning of the trial entries was high suggesting that selection should focus on traits that maximize C. Across all lines there appears considerable potential for higher yields achieved by improvements of the crop growth rate, and crop management research and breeding should focus on tactics to increase this determinant of the yield. Lines selected for resistances to foliar diseases in India had, on average, lower C than West African lines, and some Southern African lines, but they had greater stability of C across environments. Stability analysis of yield and the parameters of the yield model identified lines with superior stability of p and others with superior stability of C. It is suggested that both phenotypic and physiological yield models should be used in the identification of lines with desirable adaptive attributes.

In this study, male F344 rats were orally exposed to a single dose of aflatoxin B(1) (AFB(1)) at 0, 50, 250, or 1,000 μg/kg body weight (BW) or repeated dose of 0, 5, 10, 25, or 75 μg/kg BW for up to 5 weeks. Biochemical and histological changes were assessed together with the formation of AFB(1)-lysine adduct (AFB-Lys) and liver foci positive for placental form glutathione S transferase (GST-P(+)). In single-dose protocol, serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed dose-related elevation, with maximal changes observed (>100-fold) at day 3 after treatment. Animals that received 250 μg/kg AFB(1) showed concurrent bile duct proliferation, necrosis, and GST-P(+) hepatocytes at 3 day, followed by liver GST-P(+) foci appearance at 1 week. In repeated-dose protocol, bile duct proliferation and liver GST-P(+) foci co-occurred after 3-week exposure to 75 μg/kg AFB(1), followed by proliferation foci formation after 4 week and dramatic ALT, AST, and CK elevations after 5 weeks. Liver GST-P(+) foci were induced temporally and in a dose-related manner. Serum AFB-Lys increased temporally at low doses (5–25 μg/kg), and reached the maximum after 2-week exposure at 75 μg/kg. This integrative study demonstrated that liver GST-P(+) cells and foci are sensitive biomarkers for AFB(1) toxic effect and correlated with bile duct proliferation and biochemical alterations in F344 rats.

Summary. Growth analysis presently uses destructive samples to detect temporal variations in biomass. The destructive nature of the measurements, their cost, and statistical considerations limit the application of growth studies in many domains of crop science. In contrast radiation interception data are cheap and easy to obtain without destruction of experimental material. Biomass may be modelled as the product of cumulative radiation intercepted by the crop [ΣI] and a radiation use efficiency coefficient [e]. Therefore, in theory, an alternative to destructive samples is provided by measurement of I at intervals during growth and e. The success of this approach depends on the validity of the value of e and its constancy through time. With measurement of I at intervals the mean radiation use efficiency [Σ] can be estimated from the seasonal ΣI and the final harvest data. The Σ can then be used with the time series data for ΣI to estimate the biomass for that plot for any date. To test this approach model-derived biomass data were compared with data from destructive samples at seven dates for six groundnut germplasm lines grown in water limiting and fully irrigated conditions. The model-derived data was consistently less than destructively obtained data when the plants were small. This bias was an artifact of the interception measurement technique used not being accurate for small plants. Once plants were tall enough for fractional interception to be measured without substantial error, the nondestructive method effectively described the growth of the well-watered crops. For the drought treatments, it was less effective. However, by dealing with the phases of growth separately, good correlation between the two methods was achieved. An important assumption in the method is that the final harvest biomass is a realistic reflection of the preceding growth, since the model method forces the estimates of growth to that point. In one germplasm line this assumption was not valid and the model-based method did not match the sampled biomass data.

Calcium (Ca) deficiency causes peanut pegs and pods to abort, resulting in decreased shelling percentages and yields. Environmental factors influencing calcium availability include soil Ca content and soil moisture. Genetic attributes that influence the sensitivity of cultivars to soil Ca supply include pod size, soil volume per pod (varied by plant growth habit), and pod wall attributes. Where Ca fertilization is not possible, genetic solutions to Ca deficiency are important, and breeders need information on the relative importance of these attributes. The objective of this research was to quantify the relative importance of these three sources of variation. Data from three trials were used to evaluate the relative importance of these attributes. The trials, sited on Ca-deficient alfisols, used between four and 12 germplasm lines with varied Ca sensitivity- determining attributes. Lines differed in growth habit (spreading or bunch), pod volume, pod yield, shelling percentage, and seed yield. The trial treatments and environments (sites and seasons) also varied Ca supply through soil type, fertilization, and water supply. Assuming that Ca supply has little impact on crop growth rates (CGR), a physiological model was used to set aside the contributions of CGR to yield differences between treatments. The three trials were analyzed separately and then combined for further regression analysis by defining each site and treatment combination as an environment. Within trials, variations in shelling percentage accounted for up to half the variations in seed yield between lines. In the combined analysis, easily selected attributes—pod volume (58% of germplasm sums of squares) and plant habit (8%) and their interaction (14%)—accounted for much of the variation in shelling percentage. The interaction was due to shelling percentage being less influenced by pod volume in spreading than in the bunch types. Thus, in Ca-limiting situations, the spreading growth habit allowed larger seeded peanuts to be grown than the bunch growth habit because of the greater pod dispersal of this type. Assuming that the lines tested typified peanuts for their relation between attributes and Ca deficiency-based shelling percentage variations, breeders should place the greatest emphasis on small pod size to decrease peanut sensitivity to Ca deficiency. Increased soil available to each pod by pod dispersal decreases the need for small pods to decrease sensitivity to Ca-deficient soils.

Cannabis use or high scores on self-report schizotypy questionnaires predict an increased risk of developing clinical psychosis. We tested whether cannabis use correlated with schizotypal and other personality traits in 211 healthy adults. Subjects who had used cannabis showed higher scores on schizotypy, borderline and psychoticism scales than never-users. Multivariate analysis, covarying lie scale scores, age and educational level indicated that high schizotypal traits best discriminated subjects who had used cannabis from never-users, whether or not they reported having used other recreational drugs. These results indicate that cannabis use is related to a personality dimension of psychosis-proneness in healthy people.

We tested whether hippocampal theta has frequency-specific functions related to anxiety. Male rats received chronic implants of septal and subicular electrodes to elicit and record theta. Two to six weeks later, experimental rats received thirty 3-sec trains of theta-driving septal stimulation daily for 10 days; controls were connected to the apparatus, but not stimulated. The results were as follows: 7.7-Hz or 8.3-Hz theta driving before acquisition of a fixed-ratio 5 (FR5) barpress response increased its resistance to extinction subsequently (Experiment 1). In contrast, 7.5-Hz theta driving before acquisition of the FR5 response facilitated its later extinction (Experiment 2). Finally, 8.3-Hz theta driving after acquisition of the FR5 response also facilitated its extinction (Experiment 3). Thus, theta-driving stimulation (1) has nonassociative behavioral effects, which (2) are exquisitely frequency specific (Experiments 1–2) and (3) are modified by associative processes during acquisition of an appetitive response (Experiment 3). Theta is involved in producing anxiety, but not via spatial, motor, or memorial mechanisms.

We analysed relationships between tobacco smoking and schizotypal or borderline personality traits. Three-hundred and sixty healthy adults gave information about their smoking habits and completed a computerised personality questionnaire. Schizotypal and borderline traits correlated with tobacco smoking. These correlations remained significant in analyses which covaried age, gender, educational level, neuroticism and psychoticism. The associations of tobacco smoking with schizotypal and borderline traits may illuminate the relationships of smoking and schizotypy with clinical disorders, such as schizophrenia.

Effect of temperature and photoperiod and their interaction on -plant growth and partitioning of dry matter to pods was examined in three selected groundnut genotypes viz., TMV 2, N C Ac 17090 and VA 81B. The genotypes were grown in six walk-in growth chambers which were programmed to simulate three temperature regimes (22/18°C, 26/22°C and 30/26°C day/night) each under long (12 h) and short (9 h) photoperiods. The plant growth rates and partitioning of dry matter to pods were estimated on a thermal time basis. Plant growth (PLGR) was significantly influenced by tp""1T'1P.T::.tJ toperiod and genotype, whereas pod growth rate (PLGR) was primarily by temperature and genotype. The interaction of genotype with photoperiod and with temperature was significant for both PLGR and PDGR. For example, at the 22/18°C temperature regime, VA 81B had a high PDGR, while NC Ac 17090 did not even initiate pod growth. The partitioning of dry matter to pods (Pf) was also significantly influenced by photoperiod, temperature and genotype, and significant interactions were found. Photoperiod did not significantly affect Pf under the low temperature regime, but at higher temperatures, partitioning to pods was significantly under short days. Pf of VA 81B was relatively insensitive to photoperiod compared with the other two genotypes. study provided evidence of genotypic variability for photoperiod x temperature interactions which could influence adaptation of groundnut to new environments

In field experiments in India and Niger runner and bunch groundnut cultivars were compared for their pod distribution pattern and its relevance to the calcium (Ca) supply for pod development. Bunch cultivars produced sixty to eighty percent of their pods within 5 cm of the tap root. Runner cultivars explored a radius of up to 30 cm for pod production and exploited the soil area in a more homogeneous manner than bunch types. The available soil volume per pod was 19 to 27 cm3 for bunch types and 43 to 46 cm3 for runner types, varying the potential for Ca competition between pods. Computation of the soil Ca content needed to satisfy pod Ca requirements showed that much higher concentrations were needed for the bunch cultivars than for the runners. No significant differences in Ca content of pods existed between bunch and runner cultivars. However, in the runner cultivars, the Ca content of the more widely dispersed pods in outer zones was greater than that of the more densely populated inner pod zones. Regression analysis of shelling percentage across a range of environments showed that the shelling percentage of runners declined less rapidly than did the shelling percent of bunch types, indicating that runners were more efficient in exploiting Ca at lower soil Ca availability than the bunch types.