Evaluation of pulse polio and routine immunisation coverage: Alwar district, Rajasthan

During the last decade, India achieved 88% reduction in reported poliomyelitis incidence. However, absolute number of reported cases still remains high. As an added effort to eradicate the disease, the country observed its first National Immunisation Days (NIDs) on 9.12.95 and 20.1.96. The present study evaluates the performance of Alwar district, Rajasthan. Modified 30 cluster technique was used to collect information. Overall coverage in rural and urban areas was 89% and 91% respectively. Main source of information was television in urban and health staff in rural areas. Most of the respondents knew about the usefulness of such special activity and had favourable opinion about the facilities provided. Urban Alwar had 80% OPV3 coverage but, in rural area it was almost half. The reported coverage of NIDs and UIP was found to be conflicting with the study results. The existing “dose enumeration method” of calculating reported coverage was attributed to be the cause. The study emphasises the need to incorporate an in-built community-based evaluation of future NIDs and utilisation of such results for planning.     

Postcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation

The contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.     

Na+-mediated coupling between AMPA receptors and KNa channels shapes synaptic transmission

Na⁺-activated K⁺ (K_Na) channels are expressed in neurons and are activated by Na⁺ influx through voltage-dependent channels or ionotropic receptors, yet their function remains unclear. Here we show that K_Na channels are associated with AMPA receptors and that their activation depresses synaptic responses. Synaptic activation of K_Na channels by Na⁺ transients via AMPA receptors shapes the decay of AMPA-mediated current as well as the amplitude of the synaptic potential. Thus, the coupling between K_Na channels and AMPA receptors by synaptically induced Na⁺ transients represents an inherent negative feedback mechanism that scales down the magnitude of excitatory synaptic responses.     

Sodium-dependent potassium channels of a Slack-like subtype contribute to the slow afterhyperpolarization in lamprey spinal neurons

Synaptic vesicles aggregate at the presynaptic terminal during synapse formation via mechanisms that are poorly understood. Here we have investigated the role of the putative calcium sensor synaptotagmin I in vesicle aggregation during the formation of soma–soma synapses between identified partner cells using a simple in vitro synapse model in the mollusc Lymnaea stagnalis . Immunocytochemistry, optical imaging and electrophysiological recording techniques were used to monitor synapse formation and vesicle localization. Within 6 h, contact between appropriate synaptic partner cells up-regulated global synaptotagmin I expression, and induced a localized aggregation of synaptotagmin I at the contact site. Cell contacts between non-synaptic partner cells did not affect synaptotagmin I expression. Application of an human immunodeficiency virus type-1 transactivator (HIV-1 TAT)-tagged peptide corresponding to loop 3 of the synaptotagmin I C2A domain prevented synaptic vesicle aggregation and synapse formation. By contrast, a TAT-tagged peptide containing the calcium-binding motif of the C2B domain did not affect synaptic vesicle aggregation or synapse formation. Calcium imaging with Fura-2 demonstrated that TAT–C2 peptides did not alter either basal or evoked intracellular calcium levels. These results demonstrate that contact with an appropriate target cell is necessary to initiate synaptic vesicle aggregation during nascent synapse formation and that the initial aggregation of synaptic vesicles is dependent on loop 3 of the C2A domain of synaptotagmin I.     

Singular value based characterization and analysis of thermal patches for early breast abnormality detection

The purpose of this study is to develop a novel breast abnormality detection system by utilizing the potential of infrared breast thermography (IBT) in early breast abnormality detection. Since the temperature distributions are different in normal and abnormal thermograms and hot thermal patches are visible in abnormal thermograms, the abnormal thermograms possess more complex information than the normal thermograms. Here, the proposed method exploits the presence of hot thermal patches and vascular changes by using the power law transformation for pre-processing and singular value decomposition to characterize the thermal patches. The extracted singular values are found to be statistically significant (p?<?0.001) in breast abnormality detection. The discriminability of the singular values is evaluated by using seven different classifiers incorporating tenfold cross-validations, where the thermograms of the Department of Biotechnology-Tripura University-Jadavpur University (DBT-TU-JU) and Database of Mastology Research (DMR) databases are used. In DMR database, the highest classification accuracy of 98.00% with the area under the ROC curve (AUC) of 0.9862 is achieved with the support vector machine using polynomial kernel. The same for the DBT-TU-JU database is 92.50% with AUC of 0.9680 using the same classifier. The comparison of the proposed method with the other reported methods concludes that the proposed method outperforms the other existing methods as well as other traditional feature sets used in IBT based breast abnormality detection. Moreover, by using Rank1 and Rank2 singular values, a breast abnormality grading (BAG) index has also been developed for grading the thermograms based on their degree of abnormality.     

The elusive goal of pedigree weights

Non-parametric linkage analysis methods generally involve calculating an allele-sharing statistic for each pedigree in a data set, then standardizing and summing the statistics over pedigrees. Pedigrees of different sizes can be weighted differently in the sum, though it is perhaps most common to weight all standardized pedigree statistics equally. Most other common weighting schemes are based on the number of affected individuals in the pedigree. It is also possible to derive optimal weights, which maximize power to detect linkage under particular trait models. We started by investigating three different analytical and simulation-based methods to calculate power and derive optimal weights. We found that simulation methods produce noticeably more accurate power calculations than the other methods. However, although the different calculation methods give different "optimal" weights, the power at those weights is very similar. That is, the analytical calculation methods are sufficient for finding good weights even though the simulation methods are most appropriate for calculating power. In comparing optimal weights for different trait models, we found that the weights vary quite a bit with the model, such that optimal weights for one model are not necessarily powerful at all for other models. Finally, we studied the power of a number of general weighting schemes, and of some new ones that incorporate information on how closely the affected individuals are related. We were able to find some schemes that performed well in the sense of giving reasonably powerful weights for most of the trait models and pedigree types we considered.     

Can homeopathic arsenic remedy combat arsenic poisoning in humans exposed to groundwater arsenic contamination?: a preliminary report on first human trial

Groundwater arsenic (As) has affected millions of people globally distributed over 20 countries. In parts of West Bengal (India) and Bangladesh alone, over 100 million people are at risk, but supply of As-free water is grossly inadequate. Attempts to remove As by using orthodox medicines have mostly been unsuccessful. A potentized homeopathic remedy, Arsenicum Album-30, was administered to a group of As affected people and thereafter the As contents in their urine and blood were periodically determined. The activities of various toxicity marker enzymes and compounds in the blood, namely aspartate amino transferase, alanine amino transferase, acid phosphatase, alkaline phosphatase, lipid peroxidation and reduced glutathione, were also periodically monitored up to 3 months. The results are highly encouraging and suggest that the drug can alleviate As poisoning in humans.     

Covalent Polymyxin B Conjugate with Human Immunoglobulin G as an Antiendotoxin Reagent

Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 μg of bound functional PMB per 100 μg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 μg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.