Effects of Apremilast, an Oral Inhibitor of Phosphodiesterase 4, in a Randomized Trial of Patients With Active Ulcerative Colitis.

BACKGROUND & AIMS: New oral therapeutic agents are needed for patients with ulcerative colitis (UC) who are unresponsive or intolerant to conventional therapy. METHODS: We performed a double-blind, phase 2 trial of adults with active UC for 3 months or more who were naïve to biologic therapy or had been failed by, could not tolerate, or had contraindications to conventional therapies. The study was performed at 61 sites in 14 countries (screening from January 2015 through May 2017). Patients were randomly assigned to groups given apremilast 30 mg (n = 57), apremilast 40 mg (n = 55), or placebo (n = 58) twice daily for 12 weeks; patients were then randomly assigned to groups that received apremilast, 30 or 40 mg twice daily, for an additional 40 weeks. Endoscopies were performed and biopsies were collected during the screening phase, at week 12, and at week 52. Blood and fecal samples were also collected and analyzed throughout the study. The primary endpoint was clinical remission at week 12, defined as a total Mayo score of 2 or less, with no individual subscore above 1. RESULTS: Clinical remission was achieved at week 12 by 31.6% of patients in the 30 mg apremilast group and 12.1% of patients in the placebo group (P = .01). However, only 21.8% of patients in the 40 mg apremilast group achieved clinical remission at week 12 (P = .27 compared with placebo). Differences in clinical remission between the 30 mg and 40 mg apremilast groups were associated with differences in endoscopic improvement. Both apremilast groups had similar improvements from baseline in Mayo score components (stool frequency score, rectal bleeding score, physician's global assessment). The 30 mg and 40 mg apremilast groups had greater median percent reductions in C-reactive protein (measured by a high-sensitivity blood test) and fecal calprotectin through week 12 than the placebo group. At week 52, clinical remission was achieved by 40.4% of patients initially assigned to the apremilast 30 mg group and 32.7% of patients initially assigned to the apremilast 40 mg group. The most frequent apremilast-associated adverse events were headache and nausea. CONCLUSIONS: Although the primary endpoint of clinical remission was not met in this phase 2 trial, a greater proportion of patients with active UC who received apremilast (30 mg or 40 mg) had improvements in clinical and endoscopic features, and markers of inflammation, at 12 weeks. Clinical remission was maintained to week 52 in up to 40% of patients who continued apremilast until that time point. ClinicalTrials.gov no: NCT02289417.

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring.

BACKGROUND: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies. METHODS: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region. RESULTS: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients. CONCLUSIONS: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

Current evidence supporting obstetric fistula prevention strategies in sub Saharan Africa: a systematic review of the literature.

Obstetric fistula has been eliminated in developed countries, but remains highly prevalent in sub-Saharan Africa. The End fistula campaign is the first concerted effort to eradicate the disease. The objective of this review is to retrieve and link available evidence to obstetric fistula prevention strategies in sub-Saharan Africa, since the campaign began. We searched databases for original research on obstetric fistula prevention. Fifteen articles meeting inclusion criteria were assessed for quality, and data extraction was performed. Grey literature provided context. Evidences from the articles were linked to prevention strategies retrieved from grey literature. The strategies were classified using an innovative target-focused method. Gaps in the literature show the need for fistula prevention research to aim at systematically measuring incidence and prevalence of the disease, identify the most effective and cost-effective strategies for fistula prevention and utilise innovative tools to measure impact of strategies in order to ensure eradication of fistula.

Postnatal development of renal function in preterm and term neonates.

The study was done to determine the renal function in preterm and term newborn infants in the neonatology unit of the Department of Paediatrics and Labour Ward of the Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of February 2002 to February 2003. Sixty physiologically stable newborn infants were enrolled in this study, 40 of those were preterm and 20 were term. The gestational ages of preterm and term babies were 35.6±4.7 and 39.10±1.41 weeks respectively. Mean weight of preterm babies was 1840±410 gm and term babies was 3150±340 gm respectively. Male to female ratio was1.6:1. The concentration of serum creatinine was high during the first week of life in both the term and preterm babies. The concentration decreased in both the groups during the subsequent 3 weeks. Although creatinine values were significantly high in preterm babies than the term babies at first week (p<0.001), the values reach to almost similar at 3rd week of life. A negative correlation was found between serum creatinine and gestational age (r=0.86, p<0.001). Creatinine clearance was found low at birth, the lowest values being observed in the most premature infants (p<0.0001) and was increased in the subsequent 3 weeks of the study period. Creatinine clearance showed a positive correlation to gestational age from the first week onwards (r=0.87, p<0.001). Fifteen percent preterm babies were hyponatraemic and in all term babies serum level of sodium was within normal limit. Fractional excretion of sodium was high in preterm neonate than the term neonate especially in early weeks of life (p<0.001). The value correlated negatively to gestational age (r=0.67, p<0.001). It was evident from the present study that the renal function is significantly lower in preterm neonates than term neonates. The study also indicates that the maturation of renal function occurs earlier in the term babies than the preterm babies.

Solid waste characterization, quantification and management practices in developing countries. a case study: Nablus district - Palestine.

Solid waste management (SWM) is one of the most challenging issues faced by developing countries that suffer from serious pollution problems caused by the generation of large waste quantities. This paper presents the case study of SWM in the Nablus district - Palestine. Surveys for household residents' and SWM program operators, field investigations, on-site waste measurements and characterizations were conducted. Per capita waste generation rates varied between different localities although trends were similar. Overall, the majority of waste was organic (65.1% by weight), suggesting a strong resource recovery potential in terms of animal feed or compost. Recyclable waste (plastic, paper and card) made up 16.7% by weight the waste composition suggesting an incentive to introduce source separation. Household attitudes complemented the waste characterization study, revealing the main problems faced. SWM operators quoted on the current status, highlighting problems with disposing in unsanitary landfills, ineffective solid waste fees system, increasing solid waste quantities and lacking equipment and experienced personnel. To enhance sustainable SWM, public awareness, funding, expertise, equipment and facilities and other provisions currently lacking or inappropriate must be provided.

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP): a 13-year retrospective review at Jordan University Hospital.

OBJECTIVE: Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP) is the term to describe what was previously known as encapsulated follicular variant of papillary thyroid carcinoma. This new paradigm shift was agreed upon by experts in the field. The objective of this study is to evaluate cases previously diagnosed as follicular adenomas, follicular variant of papillary thyroid carcinoma and hyperplastic nodules to be reclassified as NIFTP according to the new criteria. Furthermore, the clinical follow-up of these NIFTP cases is evaluated. METHODS: This retrospective study reviewed potential NIFTP cases over the last 13 years, at Jordan University Hospital. RESULTS: A total of 811 thyroid surgery reports were identified and revised to identify the potential NIFTP cases. The review yielded 173 cases identified as potential NIFTP cases. Further pathological slide review resulted in a revised diagnosis of 32 cases of NIFTP according to the new criteria. The NIFTP cases comprised 4% of the total number of thyroidectomy cases and 16.1% of the total pool of previously diagnosed papillary thyroid carcinoma cases at our institution. While 111 cases retained their original diagnosis. Follow-up showed that all patients are alive and well with no evidence of disease. CONCLUSION: Patients with NIFTP are not uncommon and the diagnosis is made only after a thorough evaluation of excision. Therefore, initial conservative management of solitary thyroid nodules suspicious for NIFTP in the form of lobectomy is recommended to avoid unnecessary total thyroidectomies. Our follow-up of NIFTP cases is similar to all previous reports.

Photogravitational perturbations in the infinitesimal orbits around the libration points in the oblate RTBP.

In this paper, the infinitesimal orbits around the libration points in the photogravitational oblate restricted problem are computed. To reach this goal, the Hamiltonian of our dynamical model taking into account the considered perturbing forces is constructed. A lie operator method, as a method of solution, is outlined. The Hamiltonian is transferred to any point of the equilibruim point as an origin. The explicit first order as well as the second order solutions for the coordinates and their conjugate momenta of a test particle in an infinitesimal orbit around any equilibrium point are obtained.

Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials.

OBJECTIVES: Therapies for dysmotility-like functional dyspepsia (FD) are limited. We studied tegaserod, a selective serotonin type 4 receptor agonist, in patients with FD. METHODS: Two identical multicenter, double-blind, randomized, placebo-controlled trials enrolled women >/=18 yr with recurring mid-upper abdominal discomfort characterized by postprandial fullness, early satiety, and/or bloating. Patients were randomized to tegaserod 6 mg b.i.d. or placebo. Two patient-reported primary variables were assessed: percentage of days with satisfactory symptom relief, and symptom severity using the composite average daily severity score (CADSS). RESULTS: In total, 2,667 women were randomized with no differences between trials in terms of recruitment method, Helicobacter pylori status, heartburn, or medication use. Mean percentage of days with satisfactory symptom relief for tegaserod versus placebo in Trial 1: 32.2%versus 26.6% (95% CI of treatment difference 2.82, 9.27; P < 0.01), Trial 2: 31.9%versus 29.4% (95% CI of treatment difference -0.21, 6.53; P= 0.066). Mean CADSS in Trial 1: 3.14 versus 3.35 (95% CI of treatment difference -0.29, -0.10; P < 0.0001), Trial 2: 3.15 versus 3.23 (95% CI of treatment difference -0.18, 0.01; P= 0.094). Meta-analysis showed significant benefit for both end points: increase in days with satisfactory relief 4.6% (95% CI 2.29, 6.96); decrease in CADSS 0.14 (95% CI 0.21, 0.07). Treatment effect was greater in patients with severe baseline symptoms. Diarrhea requiring study discontinuation was more common with tegaserod than placebo (4.1%vs 0.3%). CONCLUSIONS: Some improvement in dysmotility-like FD was observed with tegaserod treatment. The clinical implication of this improvement is uncertain.

Detection of antibiotic-producing Actinobacteria in the sediment and water of Ma'in thermal springs (Jordan).

INTRODUCTION: Detection of new Actinobacteria is significant to discover new antibiotics because development of new antibiotics is connected to the characterization of novel bacterial taxa. This study has focused on the identification and isolation of antibiotic-producing Actinobacteria from the sediment and the water of Ma'in thermal springs (48-59°C) situated in the center area of Jordan. METHODS: Samples of sediment and water were transferred to glucose yeast malt agar medium and Actinobacteria were cultivated, isolated and identified according to scanning electron microscopy and 16S rRNA gene analysis. Antibacterial activities of the isolates were then tested against different test bacteria by agar well diffusion method. RESULTS: Three different species of Actinobacteria were isolated (M1-1, M2-2, M3-2) from sediment samples. Based on 16S rRNA gene analysis, isolate M1-1 was found to have only 90% identity percentage with Nocardiopsis sp., however, isolates M2-2 and M3-2 were found to be closely related Streptomyces sp. (97%) and Nocardioides luteus (99%), respectively. The antibacterial activity showed that strain M1-1 is active against P. aeruginosa ATCC 2785 (inhibition zone, 9 mm). Strain M2-2 was found to be active against S. aureus ATCC 29213 (12 mm), B. cereus ATCC 11778 (11 mm), and E. coli ATCC 25922 (9 mm). In respect to strain M3-2, it was found to be active against S. aureus ATCC 29213 (14 mm) and B. cereus ATCC 11778 (9 mm). There were no actinobacterial isolates obtained from water samples despite their significant diversity revealed by our previous metagenomic analysis, which showed the presence of 13 different species dominated by Arthrobacter (an Actinobacterium belonging to family Actinomycetales). CONCLUSION: There were 17 different Actinobacteria that could be detected in Ma'in thermal springs (13 unculturable species and 3 culturable species). The culturable Actinobacteria were found to have some antimicrobial activity. Further chemical analysis of the bioactive compounds is recommended.

The light microscopy and ultrastructural characteristics of Myxobolus naffari (Myxosporea, Myxobolidae) infecting the Nile carp Labeo niloticus (Cyprinidae) and its histological impact

During a survey of myxosporean parasites infecting freshwater fishes from the River Nile at Giza Governorates, Egypt between March and September 2016, nine out of 30 specimens of the Nile carp Labeo niloticus (Cyprinidae) were found to be naturally infected with Myxobolus naffari (Myxobolidae). Small macroscopic plasmodia appeared embedded in the host gill tissue accompanied with fusion of the gill epithelia, and atrophy was observed at the site of infection. The host reaction was manifested by the encapsulation of the plasmodia with a thick layer of connective tissue. The plasmodia appeared as white, elongated rods between gill filaments with an intensity ranging from three to eight cysts/fish. The average dimensions of plasmodia were 1.2­2.0 (1.8 ± 0.2) mm long × 0.4­0.7 (0.6 ± 0.2) mm wide. The spores were oval, reaching 9.56­11.2 (10.2 ± 0.2) µm long and 6.5­7.7 (7.0 ± 0.4) µm wide with two equal-sized polar capsules regularly arranged at the anterior pole of each spore. They were 4.51­5.5 (5.1 ± 0.4) µm in length and 1.5­2.0 (1.7 ± 0.2) µm in width. Histological, semi-thin sections were taken through parasite plasmodia and transmission electron microscopic examination of ultrathin sections was performed to describe the developmental stages of the recorded parasite within the host fish.

Exploring the microbial diversity in Jordanian hot springs by comparative metagenomic analysis.

A culture-independent approach was utilized in this study to reveal the microbial diversity in Jordanian hot springs represented by Ma'in and Afra hot springs. Water samples from Ma'in and Afra hot springs were collected in June 2015. The in situ temperature of water samples range was 38-59°C and the pH range was 7.4-8.4. The metagenome was extracted and analyzed using the next generation technology (bTEFAP® ). A total of 314,310 sequences were parsed and 288,452 were then clustered. The sequences were predominated by bacteria (>84%) and the relative abundance of archaea in each sample was <1%. Eukaryotic microorganisms were detected but with varying abundances (0.6%-15%). Because most of the detected sequences were found to belong to the domain of bacteria (196,936 sequences out 288,452), the bacterial sequences were utilized for further microbial analyses. With respect to alpha and beta diversity, samples were rarefied to 30,000 sequences and bootstrapped at 10,000 sequences. The Shannon-Wiener Index curve plot reaches a plateau at approximately 3,000 sequences indicating that sequencing depth was sufficient to capture the full scope of microbial diversity. By examining the relative abundance of phyla detected in each sample, it appears that the biota of both Jordanian hot springs sampled are compositionally similar, with over 50% of the microbial community of each sample being comprised of the phylum Proteobacteria. The second most abundant phylum was the phylum Bacteroidetes which represents more than 13% in each sample. The phylum Firmicutes was also detected with a significant abundance. However, lower abundance of Deinococcus, Verrucomicrobia, Planctomycetes, and Chloroflexi was detected. A principal coordinate analysis plot was generated based upon the weighted UniFrac distance matrix. By utilizing Monte Carlo simulations, we were able to determine that there were no significant differences in the microbial diversity between each sample.

Microbiological analysis, antimicrobial activity, and heavy-metals content of Jordanian Ma'in hot-springs water.

Ma'in hot springs are known as sites of balneotherapy. However, little is known about their microbiology and chemistry. In this study, we aim at evaluating the antimicrobial activity of Ma'in hot-springs water (MHSW), studying its microbiology, and determining its physicochemical properties including the heavy metals content. Therefore, water samples were collected from Ma'in hot springs and tested for antimicrobial activity using agar diffusion method. Water was then cultivated on nutrient agar to isolate and identify the dominant bacteria by chemical and molecular methods. The identified strains were tested by cross streak method to evaluate their antimicrobial activity against different clinical and standard strains. Finally, water samples were chemically analyzed and the heavy-metals content was assessed. Results revealed that MHSW was not active against any of the clinical isolates. Nevertheless, MHSW was found to be active against five standard bacterial strains, namely, Staphylococcus epidermidis ATCC 12228 (inhibition zone: 20mm), Staphylococcus aureus ATCC 29213 (inhibition zone: 19mm), Micrococcus luteus ATCC 9341 (inhibition zone: 15.3mm), and Bacillus cereus ATCC 11778 (inhibition zone: 12.3mm). After cultivation of MHSW, five bacterial isolates were obtained and identified based on 16S rRNA gene analysis as new strains of Anoxybacillus flavithermus (identity percentage ranges between 96-99%). Physicochemical analysis revealed that the in situ temperature was 59°C, pH was 7.8, salinity was 1.6ppt, and dissolved oxygen was 3.8mgl-1. In respect to heavy-metals content in MHSW, the following metals were present in the order: Cr (0.571ppm)>Mn(0.169ppm)>Fe (0.124ppm)>Zn (0.095)>Cu(0.070ppm)>Ni(0.058ppm)>Cd (0.023ppm)>Pb (0ppm). Cd, Cr, Ni and Mn were found to be higher than permissible levels set by international organizations and countries. This study highlights new chemical and microbiological data about Ma'in hot springs.

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

OBJECTIVES: A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. METHODS: Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). RESULTS: Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). CONCLUSION: Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Age-related structural modulation of T lymphocyte-associated CD45 isoforms.

A monoclonal antibody, specific to all conventional CD45 isoforms, was employed in two-dimensional (2D) sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting to investigate possible age-related differential expression of these isoforms among immature and mature thymocytes as well as CD4+ and CD8+ T cell subpopulations in the periphery of newly-born, young and aged BALB/c mice. In young mice, and to a lesser degree in newly-born mice, intra-thymic maturation seemed to be paralleled by the capacity of thymocytes to synthesize distinct CD45 isoforms constituted by extensively heterogeneous acidic charge entities. Thymocyte maturation in aged mice, on the other hand, was characterized by minimal heterogeneity, as the observed pattern was essentially similar to the immature population in 2D blots. As inferred from comparisons of 2D blots of sialylated and desialylated forms of the CD45 complex, age-related differences in isoforms expressed by the CD4+ and the CD8+ T cell subpopulations in the periphery resided mainly in the degree of sialylation of the constituent isoforms. Given the potential of the differential sialylation state of CD45 in altering the recognition properties of lymphocytes, regulation of CD45 sialylation with age may add another level of complexity to the lymphocyte surface phenotype, which in turn may be implicated in cell-cell interaction mechanisms during lymphocyte maturation and senescence.

Effect of dietary fat on toad liver tumor induced by DMBA: ultrastructural studies.

Toads injected with 2 mg 7,12-dimethyl-benza(a)anthracene (DMBA)/toad, 3 times/week for 12 weeks induced liver tumors in 12 out of 50 cases. The electron micrograph of toad liver tumor showed disorganization of the rough endoplasmic reticulum which encircles or partially surrounds the mitochondria. Cristae mitochondrialis are rare in comparison with control. Enhancement of liver tumor incidences (29 out of 50 cases) by DMBA at the same dose level plus 2cc corn oil/toad, 3 times/week for 12 weeks was detected. Electronicrograph of this group showed the same criteria of malignancy as in the first group. No tumor incidences were detected in toads fed corn oil only. The electronmicrograph of liver cells showed a high increase in glycogen and lipid droplets.

Identification and localization of a schistosome-associated fucosyllactose determinant expressed by Fasciola hepatica.

A Biomphalaria alexandrina-derived lectin (BaSII), of proven specificity to a Schistosoma mansoni-associated fucosyllactose [(Fuc alpha1-2) Gal beta1-4 Glc] determinant, was employed to investigate the putative antigenic cross-reactivity between Schistosoma mansoni and Fasciola hepatica in terms of this structurally-defined oligosaccharide sequence. BaSII affinity column chromatography of extracts of adult worms metabolically radiolabelled with 35S-methionine and analysis by two-dimensional gels established the expression of the fucosyllactose determinant in multiple copies among heterogeneous, acidic glycoproteins synthesized by adult Fasciola hepatica. Direct fluorescence microscopy revealed that determinant-bearing glycoproteins were localized to the external glycocalyx and perikarya of the tegument as well as the epithelial lining of the intestinal caeca and vitelline ducts and glands. Determinant expression was also evident in embryonated cells of eggs and miracidia as well as the intermediate cellular wall of encysted metacercariae, suggesting its conservation during the course of development of the parasite. Based on the structural relatedness of the cross-reactive fucosyllactose determinant to the antigenic mammalian blood group H trisaccharide, our observations may have implications in serodiagnosis and immunoprophylaxis of schistosomiasis/fascioliasis.

Scanning probe microscopy with landmark referenced control for direct biological investigations.

We report the successful use of continuous wavelet transforms applied to atomic force microscope data sets for landmark recognition of biological features. The data sets were images of mixed red and white blood cells. Contrast enhancement followed by continuous wavelet transform of the data was used to successfully distinguish erythrocytes from neutrophil and monocyte leukocytes within the mixed cell images. All of the above are spherical objects between 6 and 8 microns in diameter, which demonstrates the ability to sort similar biological objects into distinct classes. The implications for development of on-line scanning probe recognition microscopy are discussed.

A new feedback neural network with supervised learning.

A model is introduced for continuous-time dynamic feedback neural networks with supervised learning ability. Modifications are introduced to conventional models to guarantee precisely that a given desired vector, and its negative, are indeed stored in the network as asymptotically stable equilibrium points. The modifications entail that the output signal of a neuron is multiplied by the square of its associated weight to supply the signal to an input of another neuron. A simulation of the complete dynamics is then presented for a prototype one neuron with self-feedback and supervised learning; the simulation illustrates the (supervised) learning capability of the network.

A real-time experiment using a 50-neuron CMOS analog silicon chip with on-chip digital learning.

The authors present initial results of a pattern/character recognition and association experiment using a newly fabricated 50-neuron CMOS analog silicon chip with digital on-chip learning. Attention is given to the circuit architecture, the VLSI chips, and the interface circuitry.

Chemopreventive effects of cabbage on 7,12-dimethylbenz(a)-anthracene-induced hepatocarcinogenesis in toads (Bufo viridis).

Hepatocellular carcinoma was induced in the toad, Bufo viridis, in 29 out of 100 cases by the administration of 0.5 mg of 7,12-dimethylbenz(a)anthracene (DMBA)/toad, 3 times/week for 12 weeks. In contrast, toads treated with DMBA and cabbage diet 1 or 2 ml (3 h prior to the carcinogen)/toad, every day for 12 weeks showed a lower incidence of liver tumors: 15 and 12 cases out of 100. However, cabbage diet (2 ml/toad, every day for 12 weeks) was ineffective when administered 3 h after the carcinogen (DMBA) in 27 out of 100 cases. Neither tumor growth nor neoplastic changes were observed in toads treated with olive oil alone or with cabbage diet. It is concluded that a cabbage diet during initiation has an inhibitory effect on hepatocarcinogenesis in toads.