Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

A simplified ELISA for anti-receptor antibodies in myasthenia gravis

Nicotinic acetylcholine receptor (nAchR) from triton extracts of muscle adsorbed specifically and optimally to microtitration plates at pH 7.4 rather than at pH 9.6. An ELISA for anti-receptor antibodies in myasthenia gravis based on direct adsorption of the receptor at pH 7.4 is described (direct assay). The direct assay compares very well in sensitivity and specificity with an indirect assay, in which the receptor was attached through alpha-bungarotoxin adsorbed on the solid phase (correlation coefficient 0.94).     

Predicting protein complex membership using probabilistic network reliability

Evidence for specific protein-protein interactions is increasingly available from both small- and large-scale studies, and can be viewed as a network. It has previously been noted that errors are frequent among large-scale studies, and that error frequency depends on the large-scale method used. Despite knowledge of the error-prone nature of interaction evidence, edges (connections) in this network are typically viewed as either present or absent. However, use of a probabilistic network that considers quantity and quality of supporting evidence should improve inference derived from protein networks. Here we demonstrate inference of membership in a partially known protein complex by using a probabilistic network model and an algorithm previously used to evaluate reliability in communication networks.     

Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose

BACKGROUND: Increasing plasma glucose levels improves memory in patients with Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improvement is due to changes in insulin, independent of hyperglycemia. We address this question by examining memory and counterregulatory hormone response during hyperglycemia when endogenous insulin was suppressed by concomitant infusion of the somatostatin analogue octreotide (Sandostatin). METHODS: Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsulinemia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [225 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somatostatin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium chloride solution (saline) infusion (fasting insulin and glucose); and (4) an active control condition in which somatostatin alone was infused (150 mg/h). Declarative memory (story recall) and selective attention (Stroop interference test) were measured during steady metabolic states. RESULTS: Patients with AD showed improved memory during hyperinsulinemia relative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatostatin analogue infusion alone also improved memory for patients with AD (P<.05). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. CONCLUSIONS: These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD.     

AIDS-related policies, legislation and programme implementation in India

This paper traces the evolution of AIDS-related policy and legislation in India from an initial response characterized by conservatism and discrimination to the development of a coherent national programme which aims to prevent the transmission of HIV and to develop support structures for people with HIV and AIDS. Examining the strategies, achievements and problems of specific components of the National AIDS Control Programme (NACP), the paper finds that the very progressive approach of national-level policy makers has been countered by conservative forces at the state and local levels. Little progress has been made, moreover, in incorporating HIV/AIDS prevention efforts into broader development and empowerment strategies. The paper concludes by considering the wider social context of AIDS in India and the role of more far-reaching policy measures.     

Molecular composition of the alveolar lining fluid in the aging lung

As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.     

Heart failure education in the emergency department markedly reduces readmissions in un- and under-insured patients

Background

Heart failure (HF) readmissions are a longstanding national healthcare issue for both hospitals and patients. Our purpose was to evaluate the efficacy of a structured, educational intervention targeted towards un- and under-insured emergency department (ED) HF patients.

Relative percentage signal intensity recovery of perfusion metrics—an efficient tool for differentiating grades of glioma

Objective:

Glioma classification and characterization may be facilitated by a multiparametric approach of perfusion metrics, which could not be achieved by conventional MRI alone. Our aim is to explore the potential of relative percentage signal intensity recovery (rPSR) values, in addition to relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) of first-pass T₂* dynamic susceptibility contrast (DSC) perfusion MRI, in differentiating high- and low-grade glioma.

Methods:

This prospective study included 39 patients with low-grade and 25 patients with high-grade glioma. rPSR, rCBV and rCBF were calculated from the first-pass T₂* DSC perfusion MRI. rPSR was calculated using standard software and validated with dedicated perfusion metrics analysis software. The statistical analysis was performed using analysis of variance and receiver operating characteristic (ROC) curves.

Results:

Variation in rPSR, rCBV and rCBF values between low- and high-grade gliomas were statistically significant (p < 0.005). The ROC curve analysis for each of them yielded 96% sensitivity and 71.8% specificity; 88% sensitivity and 69.2% specificity; and 72% sensitivity and 66.7% specificity. The area under the curve (AUC) from the ROC curve analysis yielded 0.893, 0.852 and 0.702 for rPSR, rCBV and rCBF, respectively. The rPSR calculation with the validation software yielded 92.3% sensitivity and 72% specificity with an AUC of 0.864.

Conclusion:

rPSR inversely correlates while rCBV and rCBF values directly correlate with the tumour grade. Furthermore, the overall diagnostic performance of rPSR is better than rCBV and rCBF values.

Advances in knowledge:

rPSR of T₂* DSC perfusion is an indicator of blood–brain barrier status and lesion leakiness, which has not been explored yet compared with the usual haemodynamic parameters, rCBV and rCBF.Gliomas, the most common primary brain tumour of the brain, are heterogeneous, showing highly varied histopathological features during malignant transformation of the tumour reflecting alterations in the tumour vasculature.¹ The broad category of glioma represents approximately 30% of all the tumours. Low-grade astrocytomas (60–70%) and oligodendrogliomas (10–30%) are two common subtypes of low-grade gliomas. Among them, glioblastoma and astrocytoma account for 75% of gliomas.² With the advent of advanced imaging technologies, heterogeneity in gliomas such as neovascularization, angiogenesis, loss of blood–brain barrier (BBB) integrity, tortuousness, disorganized and highly permeable vessels may be non-invasively measured with the help of perfusion imaging.^3–5 Dynamic susceptibility contrast (DSC) perfusion MRI is a widely accepted tool for evaluating the haemodynamic characteristics of the brain, which are of great interest since it helps in assessing the malignancy of the tumour. The common haemodynamic parameters assessed using perfusion MRI are relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF).^6–8 In this study, we use a comparatively newer parameter, relative percentage signal intensity recovery (rPSR), whose potential has not been exploited to its best for haemodynamic calculations, even though this parameter has shown promise in the differentiation of brain tumours.^9–11 PSR is the percentage of the signal intensity recovered at the end of the first pass of the contrast agent with respect to the pre-contrast baseline signal intensity. After the administration of the contrast agent, there is a sudden decrease in the signal intensity owing to the variation in the local magnetic field leading to T₂* decay, which is seen as a dip in the mean signal intensity–time curve, and then the signal returns towards the baseline.^9–11The tumour rCBV provides information about the tumour blood levels and degree of angiogenesis but fails to provide information regarding capillary permeability. This drawback of DSC-MR perfusion imaging can be addressed by evaluating the rPSR obtained from the signal intensity–time curve formed at the end of the first pass of contrast agent in DSC-MR perfusion imaging.^9,10 Previous studies have observed that the contrast agent leakage, size of the extravascular space and the rate of blood flow that reflects the alterations in capillary permeability are related to rPSR.^10,11 There are reports which state that information regarding capillary permeability and lesion leakiness can be gathered from the signal intensity–time curve obtained from the first-pass T₂* DSC perfusion. Usually, this is performed using dynamic contrast-enhanced perfusion MRI, which involves additional scan time and also post-processing assumptions and extrapolations.^9–11Lupo et al⁴ was the first to report the characterization of high-grade gliomas using the PSR and peak height. rPSR is the only parameter among the different perfusion metrics which takes into account the leakage factor for the characterization of heterogeneity of brain tissues, compared with the other two parameters rCBV and rCBF where the leakage is neglected during the evaluation. The rPSR values of lower grade gliomas have not been explored, and hence an effort to differentiate between high- and low-grade gliomas using this new parameter will be advantageous. Hence, in the present study, we have evaluated all the parameters rPSR, rCBV and rCBF of low- and high-grade gliomas to find the potential of rPSR to differentiate different grades of glioma over the other two conventionally used parameters rCBV and rCBF. rPSR values were evaluated using two different standard software programs. Furthermore, we have performed a test for correlation between these parameters.     

Childhood cancer incidence in India: A review of population-based cancer registries

Objectives

To summarize and provide an overview of the childhood cancer incidence reported in 25 population-based cancer registries of India.

Methods

Secondary data on age-adjusted rates of cancer incidence for children (0–14 years) were collected from the report of the National Cancer Registry Programme in the year 2013. range of age-adjusted-rates per million children were tabulated for six regions of the country.

Results

Age-adjusted cancer incidence rates ranged from 18.6 per million to 159.6 per million for boys and 11.3 to 112.4 for girls. The highest incidence was observed for males (159.6) in Southern region of the country and the lowest in North-east in both boys (18.6) and girls (11.3). Leukemia and lymphoma were the commonest malignancies in boys whereas leukemia and brain tumors were commonest in girls.

Conclusion

Childhood cancer indicidence appears to be increasing in India.