Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Dramatic changes to well-known places go unnoticed.

How well do we know our city? It turns out, much more poorly than we might imagine. We used declarative memory and eye-tracking techniques to examine people's ability to detect modifications to real-world landmarks and scenes in Toronto locales with which they have had extensive experience. Participants were poor at identifying which scenes contained altered landmarks, whether the modification was to the landmarks' relative size, internal features, or relation to surrounding context. To determine whether an indirect measure would prove more sensitive, we tracked eye movements during viewing. Changes in overall visual exploration, but not to specific regions of change, were related to participants' explicit endorsement of scenes as modified. These results support the contention that very familiar landmarks are represented at a global or gist level, but not local or fine-grained, level. These findings offer a unified view of memory for gist across verbal and spatial domains, and across recent and remote memory, with implications for hippocampal-neocortical interactions.

Silicosis with Bilateral Spontaneous Pneumothorax in Rajasthan.

BACKGROUND AND AIMS: Silicosis is an occupational lung disease caused by inhalation of crystalline silica. People working in occupations like sandblasting, surface drilling, tunnelling, silica flour milling, ceramic making are predisposed to develop silicosis. Unilateral spontaneous pneumothorax is a pleural complication that can develop in such cases. Our aim is to see the prevalence of bilateral pneumothorax in silicosis in Rajasthan and associated predisposing factors. METHODS: Fifty patients of silicosis prospectively reviewed by historical, clinical evaluation, and radiological evidence with increased dyspnea and chest pain in 1 year were included in the study. In all patients, chest X-ray was done immediately. Sputum for acid fast bacilli was done in all cases. RESULTS: Cough and shortness of breath were most common symptoms and present in all cases. All cases were smokers. Chest radiograph revealed reticulonodular density with B/L pneumothorax in all patients. Tube thoracostomy was done in all cases except one in which conservative management was done. CONCLUSIONS: Cases with silicosis can develop complications like tuberculosis, lung cancer, progressive massive fibrosis, cor pulmonale, broncholithiasis, or tracheobronchial compression by lymph nodes. Pleural involvement in silicosis is rare. Spontaneous pneumothorax is a pleural complication that can develop in such cases. Usually in silicosis pneumothorax is unilateral. We report here an original article with silicosis who presented with bilateral spontaneous pneumothoraxes occurring simultaneously. The rarity of its clinical presentation in the form of bilateral simultaneous spontaneous pneumothorax combined with the typical clinical and radiological features of silicosis will make us to report this article.

Prevalence & significance of hepatitis C virus (HCV) seropositivity in blood donors.

BACKGROUND & OBJECTIVES: The clinical significance of anti HCV antibodies in healthy blood donors remains uncertain. These donors are usually asymptomatic and it is difficult to elicit risk factors of acquiring HCV infection during pre-donation questioning. Limited information on donor recall and follow up studies on anti HCV positive blood donors have been reported from India. Paucity of data which is likely to have an impact on safe blood transfusion programme has prompted us to undertake this study to assess the significance of HCV seropositivity in blood donors with respect to their clinical, biochemical and virological profile. METHODS: A total of 16,250 blood units were screened for the mandatory tests using third generation ELISA (anti HIV 1&2, anti HCV, HBsAg), VDRL and peripheral smear for malaria. Donors reactive for anti HCV were informed. Repeat anti HCV reactive donors were subjected to detailed clinical history focusing on risk factors for HCV transmission. The blood tests included liver function tests (LFT), coagulation and autoimmune profile, qualitative serum cryoglobulins and HCV RNA detection. These donors were followed at 2-3 monthly intervals for a minimum period of six months by LFT. RESULTS: An overall seropositivity of 0.44 per cent (72/16,250) was observed in our donors which was significantly lower in first time, young voluntary donors as compared to replacement donors (0.27 vs. 0.60%). In contrast to drug abuse (6.4%) we found minor percutaneous routes like sharing of shaving kits or visit to a road side barber (32%) as the major risk factor for HCV transmission. There was no prior history of blood transfusion in any of these donors; however history of some surgical procedures was present in 25.8 per cent. Raised transaminases and HCV viraemia were observed in 87 and 71 per cent donors respectively. An association was observed between HCV RNA when the ELISA ratio was >5. INTERPRETATION & CONCLUSION: Voluntary donors form a safe source of blood supply and efforts should be made to increase this precious source to 100 per cent. Abbreviated behavioural donor screening questionnaire for repeat donors is not advisable. Awareness and education of donors is required regarding modes of HCV transmission. HCV positive donors should be informed about their disease, counselled and referred to hepatologist, and permanently deferred for future donations.

Removal of toluene vapour using agro-waste as biofilter media.

Biodegradation of toluene vapour was investigated in a laboratory scale biofilter packed with cylindrical pieces of yellow-gram (Cajanus cajan) stalk. Inlet concentrations and volumetric flow rates of toluene were varied from 2.56 to 34.73 g/m3 and 0.18 to 0.24 m3/h, respectively. The steady state was achieved within seven days and the degradation of toluene followed an exponential behaviour with time. Elimination capacity increased and tended towards a constant value but removal efficiency decreased with increase in inlet toluene loading. Depending upon loading rate, the process was either mass transfer or reaction-controlled.

Study of factors influencing response and outcome of Cat-IV regimen in MDRTB patients.

BACKGROUND: CAT IV regimen or the standardized drug regimen (SDR) under the Revised National Control Program (RNTCP) uses six second-line anti-tubercular drugs in the initial intensive phase (IP). These drugs have many side effects and toxicity; they are less efficacious and have poor acceptability. The present study was conducted to evaluate the efficacy and outcome of Cat-IV regimen and the factors which influence the treatment outcome in MDR TB patients. METHODS: It was a prospective observational study, which was done in the CAT II treatment failure, LPA proven MDR TB patients, above the age of 18 years, who were referred to DOTS Plus center for treatment. The study was approved by the hospital ethics committee and patient consent was obtained before inclusion. RESULTS: We observed culture conversion in 63.04% and ADR in 96.5%, default in 15.65%, and death in11.3% cases. The factors which influenced outcome included low body weight, long duration of illness cavitatory disease and indulgence in both tobacco & alcohol. The radiological favorable response strongly and significantly correlated with the bacteriological and clinical response during the IP. CONCLUSION: We suggest that the efficacy can be further augmented by reducing default and controlling deaths which accounts for substantial numbers and occur mostly during IP.

Platelet alloimmunization in multitransfused patients with haemato-oncological disorders.

BACKGROUND: We studied the incidence of platelet alloimmunization in multitransfused patients with haemato-oncological disorders and determined the factors influencing alloimmunization. We also assessed the effect of alloimmunization on response to platelet transfusion. METHODS: Fifty patients with haemato-oncological disorders who received multiple transfusions were included. The patients were tested for antibodies before they received any transfusion and then after 3-4 weeks of transfusion. Lymphocytotoxicity and platelet immunofluorescence suspension tests were used to detect antiplatelet antibodies. Symptomatic improvement was used to assess the response to platelet transfusions. RESULTS: Thirty patients were positive by the lymphocytotoxicity test, giving an incidence of 60% for anti-HLA antibodies. The panel reactivity of the antibodies ranged from 3% to 100%. Nineteen patients were positive by the platelet immunofluorescence suspension test, 16 of whom were also positive by the lymphocytotoxicity test. The overall incidence of antiplatelet antibodies was 66%. The number of transfusions received and the underlying haemato-oncological disorder were not risk factors for the development of antibodies. Patients with a past history of transfusions and those with a positive obstetric history had a significantly higher incidence of antibodies. The response to transfusion therapy was poor in patients with antibodies, as 71.4% of patients with antibodies were nonresponsive compared to only 26.6% of antibody-negative patients. CONCLUSION: A high percentage of multitransfused patients developed antiplatelet antibodies. Previous sensitization was an important risk factor for the development of antibodies. Patients with high panel reactivity (HLA) showed non-responsiveness to platelet transfusions. Testing for the presence of antiplatelet antibodies and provision of compatible platelets should be important components in the management of patients with platelet transfusion refractoriness.

Prevalence of markers of transfusion transmissible diseases in voluntary and replacement blood donors.

BACKGROUND: Transfusion of safe blood requires a safe donor. The voluntary donor movement encompasses the concept of a donor who is free from transfusion transmissible infections. It is now mandatory to screen blood for hepatitis B surface antigen, antibodies to HIV-1 and HIV-2, antibodies to hepatitis C virus, syphilis and malarial parasites. METHODS: Between 1996 and 2002, 235 461 donors were screened for markers of hepatitis B virus, and HIV-1 and HIV-2 using commercially available ELISA kits, VDRL test for syphilis and Geimsa stain for the malarial parasite, respectively. A total of 56 476 donors were screened for hepatitis C virus antibodies from June 2001 to December 2002, using third-generation ELISA kits. RESULTS: The proportion of voluntary donors increased from 47% to 56% during the study period. The prevalence of HIV showed a steady increase from 0.16% in 1996 to 0.3% in 2002. The prevalence of hepatitis B surface antigen decreased from 1.55% to 0.99%. VDRL reactivity did not show any trend and ranged between 0.11% and 0.66%. Hepatitis C virus antibodies showed a prevalence of 0.4%. The prevalence of all markers was significantly less in voluntary donors. Among the voluntary donors, transfusion transmissible disease markers were significantly less in student donors as compared to other donors. CONCLUSION: A change-over to a voluntary donor service would considerably reduce the number of infectious donors and, among voluntary donors, student donors are the safest.

Airway obstruction in bronchiectasis and its reversibility--a study of 38 patients.

Thirty-eight patients (20 males and 18 females) with bronchiectasis were studied for the evidence of airway obstruction and its reversibility in response to subcutaneous terbutaline. There was an improvement in VC (8.56%), FEV1 (6.36%), PEFR (15%) and PEF 25-75% (18%) respectively. The difference being statistically significant in VC and highly significant in FEV1, PEFR and FEF25-75 as compared to initial values and in 6 patients the improvement in FEV1 was more than 15%. The improvement in airway obstruction was not related to the character of expectoration. It is suggested that all the patients of bronchiectasis should be assessed for the reversibility of airway obstruction and those showing a reversible pattern be treated accordingly.

A novel approach to study antibacterial properties of volatile components of selected Indian medicinal herbs.

The aromatic substances of natural origin are used medicinally in Ayurveda, and can have diverse bio-dynamic actions. The existing methods like agar-cup method or disc diffusion method are not adequate to study the exclusive antibacterial effects of the volatile components of aromatic oils due to lack of ideal diffusion and evaporation from the surface. Hence an attempt is made to develop a novel approach to assess the antibacterial activity of few aromatic herbs like Eugenia caryophyllus, Thymus vulgaris, Cinnamonum zeylanium, Cuminum cyminum; these were extracted with hexane filled in tiny sterile tubes and the volatile components were tested for their antibacterial properties using standard strains of gram +ve and gram -ve bacteria grown on agar slants. The results are expressed as a percent of inhibition of the area on the slants, from the top of the extract tube. Of the four herbs selected, volatile components of Thymus vulgaris were most effective againsts all the seven test organisms.

In vitro high frequency regeneration of plantlets of Vigna mungo and their ex vitro growth.

Of the five explants of V. mungo var. T9 used, the excised shoot tips gave best response with regard to offshoot formation followed by the embryonal axis explants. While a treatment comprising 0.5 mgL(-1) BAP, 0.5 mgL(-1) 2iP and 0.1 mgL(-1) NAA induced differentiation of an average 10 offshoots in shoot tip explants, only 3 offshoots were formed in the explants of embryonal axis in a treatment containing 0.5 mgL(-1) BAP and 0.1 mgL(-1) NAA, found optimum for them. Multiple shoots differentiated when explants with earlier regenerated and growing offshoots were first cultured in a treatment containing 0.1 mgL(-1) BAP, 0.25 mgL(-1) IAA and 5 mgL(-1) CCC and then subcultured in the same treatment but having only 1 mgL(-1) CCC. The isolated shoots rooted in 0.5 mgL(-1) IAA resulted in the formation of complete plantlets of an average height of 15 cm in 20 days. The in vitro-regenerated plants grew normally under field conditions and came to flowering as well.

Citrus tissue culture employing vegetative explants.

Citrus being a number one fruit of the world due to its high nutritional value, huge production of fruits and fruit products, the citrus industry may be considered a major fruit industry. Though citrus orchard area in India is comparable to USA, the produce is far less, while its export is nil. Biotechnology has played an outstanding role in boosting the citrus industry, e.g., in Spain, which is now the biggest exporter of citrus fruit with the application of micrografting. Amongst the fruit trees, perhaps the maximum tissue culture research has been done in citrus during the past four decades, however, the results of practical value are meagre. The shortfalls in citrus tissue culture research and some advancements made in this direction along with bright prospects are highlighted, restricting the review to vegetative explants only. Whilst utilization of nucellar embryogenesis is limited to rootstocks, the other aspects, like, regeneration and proliferation of shoot meristems measuring 200 microm in length--a global breakthrough--of two commercially important scion species, Citrus aurantifolia and C. sinensis and an important rootstock, C. limonia, improvement of micrografting technique, cloning of the same two scion species as well as some Indian rootstock species, employing nodal stem segments of mature trees, of immense practical value have been elaborated. A rare phenomenon of shift in the morphogenetic pattern of differentiation from shoot bud differentiation to embryoid formation occurred during the long-term culture of stem callus of C. grandis. Stem callus-regenerated plants of C. aurantifolia, C. sinensis and C. grandis showed variation in their ploidy levels and a somaclonal variant of C. sinensis, which produced seedless fruits was isolated. Tailoring of rooting in microshoots to a tap root-like system by changing the inorganic salt composition of the rooting medium, resulting in 100% transplant success, and germplasm preservation through normal growth culture of shoots of C grandis without loss of regeneration capacity during 31 years, observed so far, are some other significant results. Plants of C. aurantifolia and C. sinensis raised from shoot meristem and micrografting were grown in a nethouse and those from nodal stem segments in the field along with the in vitro-raised plants of rootstocks, namely, C. jambhiri, C. karna and C. limonia. All the plants showed normal healthy growth. Significantly enough, the meristem regenerated plants of C. aurantifolia attained the reproductive phase just in 1 year of transplantation to soil similar to those raised from nodal stem segments of mature trees, which also produced normal fruits in the subsequent year while growing under field conditions. Thus, a significant fundamental concept of a maturity factor, carried over through as small a shoot meristem as 200 microm in length to cloned plants has been demonstrated. The concept is of far-reaching significance in citrus industry besides production of pathogen-free orchards.

Bronchogenic carcinoma. A study of 109 cases.

The clinical profile of 109 cases of bronchogenic carcinoma has been studied. Definite histopathological typing of malignancy was possible in 61 patients, squamous cell carcinoma being the commonest tumour in 27 followed by small cell carcinoma in 16, adenocarcinoma in 11 and large cell carcinoma in 7. Another 23 patients showed changes suggestive of malignancy on histological/cytological examination. Definitive diagnosis was obtained in half of the patients by bronchial biopsy, in 16% by bronchial aspiration fluid cytology, in 13% by pleural biopsy, in 11% by lymph node biopsy and in others by pleural fluid cytology, lung biopsy and skin biopsy. Commonest radiological involvement among different cell types was hilar involvement in small cell carcinoma in 62%, evidence of bronchial obstruction (collapse/consolidation) in squamous cell carcinoma in 56%, peripheral mass in adenocarcinoma in 54% and cavitation in a mass in squamous cell carcinoma in 15% cases.

Value of serum prolactin in differentiating epilepsy from pseudoseizure.

We studied the serum prolactin levels in 35 cases with various types of seizures viz. generalized tonicolonic seizures (GTC), complex partial seizures (CPS), and simple partial seizures (SPS). We also studied 20 cases with pseudoseizure (hysteria) presenting in an epileptiform manner. Twenty two normal healthy subjects were also studied. All the cases were studied both in the postictal and interictal periods. Serum prolactin rose significantly in the postictal periods in patients with GTC and CPS, but patients with SPS or pseudoseizure did not demonstrate this rise. Thus serum prolactin estimation can be of help in differentiating true generalized seizures from pseudoseizure presenting in an epileptiform manner.

In vitro control of fasciation in proliferating nucellar embryos of Mangifera indica L. var totapari red small for cloning.

Nucellar tissue contained in ovular halves of young fruits of Mangifera indica L. totapari red small, a dwarfing rootstock, differentiated fasciated embryonal structures in presence of 6-benzylaminopurine [BAP(0.15 mg l(-1))], 6-(gamma-gamma-dimethylallylamino) purine [2iP(0.15 mg l(-1))] and indole-3-acetic acid [(IAA(0.5 mg l(-1))] incorporated in the semisolid medium during 50-60 days. Due to embryonal fasciation, hardly 2-3 well-formed embryos could be obtained per culture of proliferating embryos. Of the 3 ethylene inhibitors [L-alpha-(2-aminoethoxyvinyl)-glycine-HCl (AVG), AgNO3 and salicylic acid (SA)] used, embryonal fasciation and necrosis of intervening tissue was completely controlled by 3-4 subcultures of fasciated mass of embryos under the influence of AVG (0.05 mg l(-1)) in presence of adenine sulphate [AdS (50 mg l(-1))] incorporated in the same medium. Almost synchronized development of isolated embryos, measuring ca 2 cm in length, was observed in a different medium used in liquid stationary state and supplemented, particularly with stress-producing substances [abscisic acid (ABA, 0.01 mg l(-1)); and polyethylene glycol (PEG, 100 mg l(-1))] besides certain other modifications. About 34% convertibility of processed embryos was obtained during a period of 90 days. The plantlets had well-developed roots along with laterals which were longer than leafy shoots. In vitro raised plants survived ex vitro for about 2 months.

Occult hepatitis B virus (HBV) infection in healthy blood donors.

Blood transfusion is an important route of transmission of hepatitis B virus (HBV). Occult HBV infection can exist in the absence of HBsAg and can be detected by determining HBV DNA. To determine the occult HBV infection in healthy blood donors. One hundred adult healthy blood donors, negative for HBsAg, anti HCV, HIV-1 and other risk factors were screened for HBV DNA by PCR. All the healthy blood donors were negative for HBV DNA by PCR. Occult HBV infection does not occur in the healthy blood donors in the population studied.

Some bio-social factors for drop out of children undergoing oral polio vaccination.

PIP: This study was designed to identify biosocial factors that contribute to India's high dropout rate for completion of the oral polio vaccine series. The study sample included the 2027 children registered in 1983-84 at an immunization clinic in Agra. At the time of the 1st dose, parents were educated about the importance of completing the series. 683 of the children were not returned for the 3rd dose, for a dropout rate of 33.7%. The majority of dropouts (42.6%) were clustered in the 3-6 month age group. There was a higher but nonsignificant dropout rate in females (35.4%) than in males (32.6%). The dropout rate was lowest among children of birth order 1 (23.2%) and highest in birth order 5 (72.1%). There was a statistically significant association between dropout rates and maternal occupational status; only 3.8% of children whose mothers were engaged in service occupations failed to complete the immunization series compared with 34.6% of those whose mothers were housewives. In addition, there was a significant association with paternal occupation. The maximum number of dropouts was noted among children whose fathers were laborers (51.2%) and the lowest rate was found among children of men in service occupations (23.6%). Finally, there was a significant inverse relationship between parental education and dropout rates. This relationship was most pronounced for maternal educational status. The dropout rate was only 5% in children whose mothers were educated at the high school level and above compared with 14% in children whose father's education was at this level.^ieng