Creutzfeldt-Jakob disease: a case of 16 years' duration

A 46-year-old man with Creutzfeldt-Jakob disease confirmed postmortem had a 16-year course of very slowly progressing incoordination and mental deterioration, suggesting Alzheimer's disease. The disease course transformed abruptly into a 7-week terminal phase of florid Creutzfeldt-Jakob disease. Dementing illnesses of unknown cause were present in the patient's paternal lineage.     

Epigenetic inactivation of TRAIL decoy receptors at 8p12‐21.3 commonly deleted region confers sensitivity to Apo2L/trail‐Cisplatin combination therapy in cervical cancer

Multiple chromosomal regions are affected by deletions in cervical cancer (CC) genomes, but their consequence and target gene involvement remains unknown. Our single nucleotide polymorphism (SNP) array identified 8p copy number losses localized to an 8.4 Mb minimal deleted region (MDR) in 36% of CC. The 8p MDR was associated with tumor size, treatment outcome, and with multiple HPV infections. Genetic, epigenetic, and expression analyses of candidate genes at MDR identified promoter hypermethylation and/or inactivation of decoy receptors TNFRSF10C and TNFRSF10D in the majority of CC patients. TNFRSF10C methylation was also detected in precancerous lesions suggesting that this change is an early event in cervical tumorigenesis. We further demonstrate here that CC cell lines exhibiting downregulated expression of TNFRSF10C and/or TNFRSF10D effectively respond to TRAIL‐induced apoptosis and this affect was synergistic in combination with DNA damaging chemotherapeutic drugs. We show that the CC cell lines harboring epigenetic inactivation of TRAIL decoy receptors effectively activate downstream caspases suggesting a critical role of inactivation of these genes in efficient execution of extrinsic apoptotic pathway and therapy response. Therefore, these findings shed new light on the role of genetic/epigenetic defects in TRAIL decoy receptor genes in the pathogenesis of CC and provide an opportunity to explore strategies to test decoy receptor gene inactivation as a biomarker of response to Apo2L/TRAIL‐combination therapy. © 2015 Wiley Periodicals, Inc.     

The "metabolic syndrome" is less useful than random plasma glucose to screen for glucose intolerance

AIMS: To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. METHODS: RPG was measured and an OGTT was performed in 1155 adults. Test performance was measured by area under the receiver-operating-characteristic curve (AROC). RESULTS: Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with fasting plasma glucose (FPG) was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes--similar to RPG alone (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25. CONCLUSIONS: MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG--a more convenient and less expensive test.     

Preventing type 2 diabetes: Genes or lifestyle?

Type 2 diabetes is a complex, multi-factorial condition, caused by environment factors and an inheritance pattern that is polygenic. Preventing diabetes is a major clinical, research and public health priority. Lifestyle intervention studies, programs that promote changes in diet, activity, and behavior, have been shown to be effective ways to prevent type 2 diabetes, perhaps even in patients with genotypes that might put them at increased risk for developing the disease. Clinicians should be helping their patients to make positive lifestyle changes, and researchers must find ways to translate lifestyle interventions into real world settings in order to stop the epidemic of diabetes.     

Synthesis and antimalarial evaluation of novel pyridine quinoline hybrids

Abstract  Synthesis and evaluation of the antimalarial activity of new pyridine quinoline hybrid molecules against a chloroquine-susceptible strain of Plasmodium falciparum and as inhibitors of β-hematin formation are described. Two novel pyridine quinoline hybrid molecules and one bisquinoline molecule were synthesized and purified by column chromatography and evaluated for antimalarial and haem polymerization inhibition (HPIA) activities. The molecules were found to be very good haem polymerization inhibitors but showed poor antimalarial activity. This was attributed to their low vacuole accumulation ratio (VAR) in comparison to chloroquine. These molecules can be used as templates for designing new antimalarials targeting haem detoxification pathway of malaria parasite. Graphical Abstract   Synthesis and antimalarial evaluation of novel pyridine quinoline hybrids B.N Acharya, D. Thavaselvam^# and M.P Kaushik^* Discovery Centre, Process Technology Development Division Defence R & D Establishment, Jhansi Road, Gwalior-474002 (MP) INDIA ^#Division of Microbiology, Defence Research and Development Establishment,Gwalior-474002, India Synthesis and evaluation of antimalarial activity of new pyridine–quinoline hybrid molecules against a chloroquine-susceptible strain of Plasmodium falciparum and as inhibitors of β-hematin formation are described.