Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth.

Cerebral organoids co-cultured with patient derived glioma stem cells (GLICOs) are an experimentally tractable research tool useful for investigating the role of the human brain tumor microenvironment in glioblastoma. Here we describe long-term GLICOs, a novel model in which COs are grown from embryonic stem cell cultures containing low levels of GSCs and tumor development is monitored over extended durations (ltGLICOs). Single-cell profiling of ltGLICOs revealed an unexpectedly long latency period prior to GSC expansion, and that normal organoid development was unimpaired by the presence of low numbers of GSCs. However, as organoids age they experience chronic hypoxia and oxidative stress which remodels the tumor microenvironment to promote GSC expansion. Receptor-ligand modelling identified astrocytes, which secreted various pro-tumorigenic ligands including FGF1, as the primary cell type for GSC crosstalk and single-cell multi-omic analysis revealed these astrocytes were under the control of ischemic regulatory networks. Functional validation confirmed hypoxia as a driver of pro-tumorigenic astrocytic ligand secretion and that GSC expansion was accelerated by pharmacological induction of oxidative stress. When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.

Fed-batch anaerobic valorization of slaughterhouse by-products with mesophilic microbial consortia without methane production.

This work aimed at setting up a fully instrumented, laboratory-scale bioreactor enabling anaerobic valorization of solid substrates through hydrogen and/or volatile fatty acid (VFA) production using mixed microbial populations (consortia). The substrate used was made of meat-based wastes, especially from slaughterhouses, which are becoming available in large amounts as a consequence of the growing constraints for waste disposal from meat industry. A reconstituted microbial mesophilic consortium without Archaebacteria (methanogens), named PBr, was cultivated in a 5-L anaerobic bioreactor on slaughterhouse wastes. The experiments were carried out with sequential fed-batch operations, including liquid medium removal from the bioreactor and addition of fresh substrate. VFAs and nitrogen were the main metabolites observed, while hydrogen accumulation was very low and no methane production was evidenced. After 1,300 h of culture, yields obtained for VFAs reached 0.38 g/g dry matter. Strain composition of the microbial consortium was also characterized using molecular tools (temporal temperature gradient gel electrophoresis and gene sequencing).

Measurement of ventricular size in term and preterm infants.

Real time ultrasonography was done in neonates to establish the norms for ventricular size and to see if there is a correlation between ventricle size and gestational age. A total of 153 normal infants admitted to our nursery after September, 1989 were taken up for the study. First ultrasound was performed within six days of birth. Sonography was done with 3.5 MHz transducer through anterior and lateral fontanelle. Results revealed that there is a significant difference in the mean value of falx to lateral wall of the cortex, ventricular index and ratio (VI/FC) of preterm and term infants. The ventricular size of small for gestational age infants is significantly different from appropriate gestational age infant of corresponding gestational ages. The percentile chart of VI for Indian infants is comparable to that of western infants.

Development in severely visually handicapped children and visual therapy remediation.

The motor and cognitive development of a visually handicapped child is delayed due to various constraints placed on learning by the handicap. The child requires a functional visual assessment, and assessment of mental & motor development. Based on these findings a total remediation programme needs to be worked out. This is individualised, integrated & includes stimulation of residual vision, optional use of residual vision and special measures to promote general development.

Infant feeding practices in educated mothers from upper socio-economic status.

One hundred and twenty mothers from upper socio-economic status and education up to graduation level were assessed for infant feeding practices using a pre-tested questionnaire. Prelacteal feed of honey was administered by 51.7% and initiation of breast feeding delayed by more than 24 hours by 68.3% of mothers. Colostrum was discarded by 53% mothers; 83% introduced bottle feeding in the first month of life; and poor bottle hygiene was seen in 54% cases. Addition of semisolids was delayed by almost 50% of mothers, the reason given being fear of liver disorders. These observations highlight ignorance about basic infant feeding practices in the educated elite section of our country. Health education in schools, colleges, non formal gatherings and during the antenatal period are suggested as means to remove this ignorance.

PIP: 120 mothers from upper socioeconomic status and education to the graduate level were assessed for infant feeding practices using a pretested questionnaire. Prelacteal feed of honey was administered by 51.7% and initiation of breastfeeding was delayed by more than 24 hours in 68.3% of the mothers. Colostrum was discarded by 53% of the mothers, 83% introduced bottlefeeding in the 1st month of life, and poor bottle hygiene was seen in 54% of the cases. The addition of semisolids was delayed by almost 50% of the mothers, the reason being fear of liver disorders. These observations highlight ignorance about infant feeding practices among the educated elite in India. Health education in schools, colleges, nonformal gatherings, and during the antenatal period are suggested as means to change this situation.

Fortified high calorie human milk for optimal growth of low birth weight babies.

This study was undertaken with the aim of providing adequate calories for optimal growth in low birth weight (LBW) by fortifying human milk with medium chain triglycerides and sugar. Twenty-one LBW babies with birth weight between 1.0 and 1.75 kg and gestational age 28-36 weeks constituted the study material. They were administered expressed human milk, initially with gavage and then by spoon. Coconut oil and sugar were added to increase the caloric density to (0.8 cal/ml). The aim was to achieve a caloric intake of 200 cal/kg. This was achieved between 6 and 11 days of birth. Additionally, vitamin C (50 mg) and vitamin E (25 IU/kg/day) were administered. Weight was recorded daily to the nearest 50 g. Head circumference was measured weekly using a non-stretch tape measure. Blood urea nitrogen was measured once the neonate started taking high calorie feeds. Stools were examined daily for the presence of fat globules and reducing substances and for the pH. All but one neonate tolerated the feeds well and there were no complications, such as vomiting, diarrhoea, abdominal distension, or necrotizing enterocolitis. The weight gain recorded was 17.29 +/- 5.30 g/day or 13.95 +/- 5.52 g/kg/day. The study demonstrates that optimal growth can be achieved within the metabolic tolerance of low birth weight infants by administering fortified high calorie breast milk.

Gastroesophageal reflux in infants and children.

Seventy-five infants and children presenting during the period December 1984 to December, 1987 with the clinical features of vomiting, failure to thrive, chronic cough, recurrent pneumonia and atypical asthma were evaluated for gastroesophageal reflux by standard barium esophagram. Fifty six cases (74.7%) and as many as 80% of the infants studied had gastroesophageal reflux; Grade II reflux was seen in 12 cases, Grade III in 30 and Grade IV in 14 cases. The patients with gastroesophageal reflux were put on medical treatment. All the patients had subjective improvement after 6 weeks to 6 months of conservative treatment and none of them developed further complications of gastroesophageal reflux during a follow-up period varying from two months to fifteen months. Anti-reflux surgery was not considered owing to the subjective improvement in all the patients on conservative treatment. We conclude that gastroesophageal reflux is very common in infants and children and urge the need to evaluate the patients presenting with the symptoms suggesting gastroesophageal reflux by barium esophagram; conservative treatment is the mainstay in the management of these children.