Specificity of the effect of a nicotinic receptor polymorphism on individual differences in visuospatial attention

Cortical neurotransmitter availability is known to exert domain-specific effects on cognitive performance. Hence, normal variation in genes with a role in neurotransmission may also have specific effects on cognition. We tested this hypothesis by examining associations between polymorphisms in genes affecting cholinergic and noradrenergic neurotransmission and individual differences in visuospatial attention. Healthy individuals were administered a cued visual search task which varied the size of precues to the location of a target letter embedded in a 15-letter array. Cues encompassed 1, 3, 9, or 15 letters. Search speed increased linearly with precue size, indicative of a spatial attentional scaling mechanism. The strength of attentional scaling increased progressively with the number of C alleles (0, 1, or 2) of the alpha-4 nicotinic receptor gene C1545T polymorphism (n = 104). No association was found for the dopamine beta hydroxylase gene G444A polymorphism (n = 135). These findings point to the specificity of genetic neuromodulation. Whereas variation in a gene linked to cholinergic transmission systematically modulated the ability to scale the focus of visuospatial attention, variation in a gene governing dopamine availability did not. The results show that normal variation in a gene controlling a nicotinic receptor makes a selective contribution to individual differences in visuospatial attention.     

Pediatric asthma: improving management to reduce cost of care

BACKGROUND: The economic burden of pediatric asthma is substantial, with national annual health care costs of $3 billion. Successful clinical management of asthma in children has the potential to decrease this burden by lowering the disproportionate costs of hospitalization and acute care for pediatric asthma patients. RESULTS: Based on increased understanding of the pathogenesis of asthma, revised guidelines were published by the National Institutes of Health in 1997 (with an update in 2002) and by the American Academy of Allergy, Asthma, and Immunology in 1999 to assist in the diagnosis and management of pediatric asthma. These guidelines emphasize the role of inflammation in asthma and recommend treatment of the underlying inflammatory process. Despite increased knowledge regarding the pathogenesis of the disease and the availability of effective anti-inflammatory agents, particularly inhaled corticosteroids, the prevalence of asthma and disease-related morbidity continues to remain high in children. CONCLUSION: Asthma interventions that include the use of guideline-recommended inhaled corticosteroid therapy and patient and caregiver education in asthma management may help to reduce asthma morbidity in children and decrease the substantial costs of pediatric asthma.     

Scaling of visuospatial attention undergoes differential longitudinal change as a function of APOE genotype prior to old age: results from the NIMH BIOCARD study

The effect of apolipoprotein E (APOE) genotype on longitudinal cognitive decline in midlife was investigated with attentional scaling. Healthy individuals (mean age 59.6 years) genotyped for APOE were tested at 3 12-month intervals on a cued visual search task. A random effects model revealed significant interaction in effect of precue size on search speed between APOE-epsilon4 gene dose and assessment, with longitudinal increases in noncarriers and heterozygotes but longitudinal decreases in homozygotes. Association of APOE-epsilon4 with cognitive decline in midlife is consistent with an Alzheimer's disease (AD) prodrome, albeit a decade or more before average age of AD diagnosis. However, cognitive decline in midlife associated with a gene modulating neuronal response to insult argues that the concept of an AD prodrome includes factors that allow as well as cause AD.     

Career involvement and family involvement as moderators of relationships between work-family conflict and withdrawal from a profession

This study extended prior analyses by J. H. Greenhaus, K. M. Collins, R. Singh, and S. Parasuraman (1997) by examining relationships between 2 directions of work-family conflict (work-to-family conflict and family-to-work conflict) and withdrawal from public accounting. The sample consisted of 199 members of the American Institute of Certified Public Accountants (135 men and 64 women) who were married or in a long-term relationship and who had 1 or more children. It was found that work-to-family conflict (but not family-to-work conflict) was positively related to withdrawal intentions. In addition, relationships of work-to-family conflict with withdrawal intentions and withdrawal behavior were stronger for individuals who were relatively uninvolved in their careers than for those who were highly involved in their careers. The implications of the findings for future research are discussed.     

The unspoken benefit of participation in a clinical trial

BackgroundPublicly funded trials do not usually offer financial incentives to volunteers. An intensive level of medical care could act as an additional motivator for participation. Our aim was to establish whether patients may draw any clinical benefit from volunteering in a clinical trial.MethodsWe analysed the recruitment process of a phase II randomised controlled trial, the Inorganic Nitrate in Angina Study.ResultsTwo-hundred and thirteen patients with a history of stable angina and who had been under at least annual primary care review were screened for participation by history taking, examination, 12-lead electrocardiography, treadmill test and echocardiography. Thirty-five (16.4%) patients were found to have significant unstable or new clinical pathology, requiring urgent clinical attention. We identified 17 (7.9%) patients with unstable angina. Furthermore, we found new undiagnosed pathologies: amyloidosis in two (0.9%), hypertrophic cardiomyopathy in two (0.9%), left ventricular systolic dysfunction (ejection fraction <45%) in three (1.4%), left ventricular thrombus in one (0.4%), significant valvular disease in five (2.4%) and arrhythmias in six (2.8%).ConclusionCompared with routine care, patients screened for a clinical trial may come under an increased level of scrutiny that may affect their clinical management. This may act as additional motivator to attract patients to future studies.KEYWORDS: clinical research, recruitment     

A comparative assessment of in vitro cytotoxic activity and phytochemical profiling of Andrographis nallamalayana J.L.Ellis and Andrographis paniculata (Burm. f.) Nees using UPLC-QTOF-MS/MS approach

Andrographis paniculata (Burm. f.) Nees and Andrographis nallamalayana J.L.Ellis have traditionally been used to treat various ailments such as mouth ulcers, intermittent fever, inflammation, snake bite. This study compares the comparative in vitro cytotoxic activity, and phytochemical profiling of methanol extract of A. nallamalayana (ANM) and A. paniculata (APM). UPLC-ESI-QTOF-MS/MS analysis has been performed. The cytotoxic activity of crude methanol extracts were evaluated against three different cancer cell lines (HCT 116, HepG2, and A549 cell line). Both plants'' extract exhibited significant cytotoxic activity against tested cell lines in a dose-dependent manner. IC₅₀ of ANM and APM in HCT 116 cell was 11.71 ± 2.48 μg ml⁻¹ and 45.32 ± 0.86 μg ml⁻¹ and in HepG2 cell line was 15.65 ± 2.25 μg ml⁻¹ and 60.32 ± 1.05 μg ml⁻¹ respectively. Cytotoxicity of these two extracts was comparatively similar in A549 cells. ANM induced cytotoxicity involved programmed cell death, externalisation of phosphatidylserine, ROS generation, up-regulation and down-regulation of major apoptotic markers. HRMS analysis of ANM and APM resulted in the identification of 59 and 42 compounds, respectively. Further, using the MS/MS fragmentation approach, 20 compounds, of which 18 compounds were identified for the first time from ANM, which belongs to phenolic acids, flavonoids, and their glycosides. Three known compounds, echioidinin, skullcapflavone I and 5,2′,6′-trihydroxy-7-methoxyflavone 2′-O-β-d-glucopyranoside, were isolated from A. nallamalayana and their crystal structures were reported for the first time. Subsequently, seven major compounds were identified in A. nallamalayana by direct comparison (retention time and UV-spectra) with authentic commercial standards and isolated compounds using HPLC-UV analysis. The cytotoxicity of phytochemicals from both the plants using in silico tools also justify their in vitro cytotoxic activity. It is the first report on the comparative characterisation of phytochemicals present in the methanolic extract of both the species of Andrographis, along with the cytotoxic activity of A. nallamalayana.

A comparative study of two Andrographis species have been done, and it was found that Andrographis nallamalayana J.L.Ellis is phytochemically and biologically different from Andrographis paniculata (Burm. f.) Nees.     

Brain metastases in pediatric Ewing sarcoma and rhabdomyosarcoma: the St. Jude Children's Research Hospital experience.

PURPOSE: Although brain metastases rarely occur in children with solid tumors, pediatric Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) are among those most likely to metastasize to the brain. The authors review their institution's experience of brain metastases of ES and RMS. PATIENTS AND METHODS: The clinical characteristics, therapy, and outcome of all patients treated at St. Jude Children's Research Hospital over a 36-year period who had ES or RMS with brain metastases were reviewed. RESULTS: Of 419 patients with RMS, 10 (2.4%) had brain metastases. Of 335 patients with ES, 11 (3.3%) had brain metastases. The median age of the 21 patients was 10.4 years (range, 0.4-18.0 years) at the time of primary diagnosis. All had clinical signs of central nervous system (CNS) involvement. Outcome was dismal: The median duration of survival after diagnosis of brain metastasis was 2.7 months. The estimated survival 1 year after detection of brain involvement was 23.8%+/-8.5% (mean +/- standard error). One patient, who underwent chemotherapy, surgical resection, and radiotherapy, at the time of this writing is a long-term survivor. CONCLUSIONS: Brain metastases are rare in children with ES and RMS, but carry a grave prognosis. Because most brain metastases are accompanied by signs of neurologic involvement, routine imaging studies of asymptomatic children are not necessary. Combined-modality treatment offers the best chance of long-term survival.     

Phytochemical composition,therapeutical and pharmacological potential of Nigellasativa:a review

Plants naturally produce chemical compounds, which are used to endorse health and fight against diseases and have been used traditionally. Nigella sativa (N. sativa) has a broad spectrum of usage in traditional folk medicines and it's a well-known medicinal herb in ancient Ayurveda, Siddha, Chinese, Arab and Unani Tibb. N. sativa stimulates the body with its natural vitalizing process and cures the disease. Phytochemically, N. sativa seed contains a wide range of fixed oils, proteins, alkaloids, saponin and essential oils. Most of the medicinal properties of N. sativa are due to the presence of the quinone constituent. Among the constituents of N. sativa, thymoquinone is one of the predominant bioactive compounds. The aim of this review is to explore the phytochemical, therapeutical and pharmacological potentials of N. sativa. N. sativa reported to have many therapeutical and pharmacological actions which includes antioxidant, antimicrobial, antidiabetic, anticancer, anti-inflammatory, immunomodulator, cardioprotective, antihyperlipidemic, pulmonary protective, hepatoprotective, nephroprotective, gastroprotective, diuretics, anti-osteoporotic, dermatologic, neuroprotective effects and also has stimulative action on the reproductive system. N. sativa seeds and its derivatives have to be isolated and further investigations should be done using animal models and clinical trials to understand its novel molecular mechanism of action. So, N. sativa and the plant derived constituents can be used in the production of new drug and to treat several diseases.     

Comparison of long-term actual renal allograft survival in mycophenolate mofetil and azathioprine-based triple drug immunosuppression protocols

INTRODUCTION: The use of mycophenolate mofetil (MMF) in renal transplantation results in a 50% lower incidence of acute rejection compared to azathioprine (AZA). However, the graft survival reports are conflicting: the European trial and US database analysis suggest better survival with MMF, an observation that was not seen in the US and tricontinental studies. METHODS: We retrospectively reviewed our single-center experience (60% African-Americans) comparing the serum creatinine (SCr) values and 3-year actual graft survival with MMF versus AZA-based immunosuppression. Group I included patients transplanted between January 1990 and December 1992 on cyclosporine (CSA), AZA, and steroids; group II subjects, from January 1996 to December 1998 on CSA, MMF, and steroids. We analyzed SCr and all causes of graft losses at 3, 6, 12, 18, 24, and 36 months posttransplantation. RESULTS: The patient demographics were similar in both groups as was the mean SCr values at different times. The time-group interaction for SCr, the Kruskal-Wallis test for SCr for different categories (<1.5, 1.5 to 2.0, 2.0 to 2.5, and >2.5 mg/dL) and the all-cause graft loss between the two groups were not significantly different. CONCLUSION: Our results failed to show better long-term actual graft survival despite the 6-year interval between the two groups. These findings agree with the results of the United States and the tricontinental studies. A lower incidence of acute rejection early after transplantation observed with MMF may not always translate into a long-term benefit, possibly due to the influence of nonimmunological factors, such as hypertension, calcineurin inhibitor toxicity, more frequent cytomegalovirus infections, and increased attempts to withdraw steroids using MMF-based protocols.     

Quality of life and psychosocial factors in renal transplant recipients

An ideal method for quality of life (QOL) assessment in renal transplant recipients (RTR) has not yet been determined. Present assessments of QOL in RTR are lengthy, cumbersome to administer, and difficult to interpret. We used a previously validated single question QOL scale score (QLS) that directly asks about the patients' overall assessment of their QOL; "Considering all parts of my life-physical, emotional, social, spiritual, and financial--over the past 2 days the quality of my life has been ... ". The QLS ranges from 0 ("very bad") to 10 ("excellent"). Patients were contacted prior to their routine office visit when they were free of acute medical problems. Fifty RTR participated. Psychosocial and medical variables included the Beck Depression Inventory, Illness Effects Questionnaire, Multidimensional Scale of Perceived Social Support, time since transplant, age, creatinine, hemoglobin, and albumin levels. Of the patients, 64% were African-American and 48% were women; 94% of patients had a score>5. Mean QLS was 7.5+/-2.3. Perception of a better QOL correlated with less perception of depression and illness effects and with perception of greater social support and satisfaction with life (all P<.05). Perception of QOL did not correlate with age, time since transplantation, creatinine, hemoglobin or albumin levels. We concluded that QLS is a quick tool to measure subjective QOL in RTR for correlation with psychosocial factors of interest in this group. These studies should be replicated in larger multiethnic populations.