Focal epilepsy of probable temporal lobe origin in a Gypsy family showing linkage to a novel locus on 7p21.3

We aimed to characterise the phenotype and perform genetic studies in a family of Roma/Gypsy ethnicity, affected by epilepsy. The mean age at onset of epilepsy was 9 years and seizures persisted into adulthood. Antecedent febrile convulsions were rare. Seizure semiology and EEG findings suggested mesial temporal lobe origin with no evidence of hippocampal sclerosis. Seizures frequently generalised. Family structure suggested autosomal-dominant inheritance with incomplete penetrance. Linkage analysis identified a single novel locus on 7p21.3, corresponding to the expected maximum in the family. Previously reported temporal lobe epilepsy (TLE) loci were definitely excluded. The minimal shared haplotype of 2.4cM (1.3Mb) was not observed in other affected families or controls from the same population. Three brain-expressed validated genes in the critical region represent potential candidates. We have identified an epilepsy syndrome with temporal lobe seizures commonly evolving to generalised convulsions. Linkage to 7p21.3 adds up to a total of five currently known FTLE loci.     

Ag2O nanoparticle-catalyzed substrate-controlled regioselectivities: direct access to 3-ylidenephthalides and isocoumarins

Herein, we disclose the first example of an efficient, silver oxide nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides 11–16 and isocoumarins 17–20via sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively. This one pot coupling involves reaction of substituted 2-halobenzoic acid with meta/para-substituted and ortho-substituted terminal alkynes, which proceeded in a regioselective manner resulting in the formation of 3-ylidenephthalides or isocoumarins, respectively, in excellent yields (up to 95%) with complete Z-selectivity. This protocol features relatively broad substrate scope, mild conditions, operational simplicity, and is favourable with aromatic/alicyclic terminal alkynes. The competition experiments and gram-scale synthesis further highlight the importance and versatility of the methodology. The proposed mechanistic pathways illustrate that the regioselectivity is substantially being controlled by the substituent(s) present on the acetylenic phenyl ring.

We report the first example of an efficient, Ag₂O nanoparticle-catalyzed, direct regioselective synthesis of 3-ylidenephthalides and isocoumarins via Sonogashira type coupling followed by substrate-controlled 5-exo-dig or 6-endo-dig cyclization reaction, respectively.     

Mitochondrial DNA variation and substructure among the tribal populations of Andhra Pradesh,India

We analyzed mtDNA HVR‐I variation among six tribal populations—Andh, Pardan, Gond, Naikpod, Kolam and Chenchu—from Andhra Pradesh. These tribes belong to the Dravidian and Indo‐European linguistic group. Except for Chenchu, the rest of the tribal samples were collected from two or more than two locations. The analysis of molecular variance (AMOVA) of the sequences yields a significant F_ST value (0.045), suggesting a fair degree of genetic differentiation among these tribes. When the tribal samples collected from different locations were considered as subpopulations in AMOVA, it is found that the variation among the subunits within the tribal groups is smaller than among the tribes. However, when Chenchu is removed from the analysis, the magnitude of within and between groups diversity becomes similar. In the multidimensional scaling plot based on F_ST distances the Chenchu is found to be the extreme outlier. Exclusion of Chenchu from AMOVA analysis and multidimensional scaling plot does not result in any specific pattern of population clustering. Mismatch distribution suggest that Chenchu might have undergone a bottleneck effect and does not show evidence of past demographic expansion as shown by the other five tribal groups. A comparison of AP tribes with some other caste and tribal populations of India suggests common maternal genetic heritage. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

The Role of Paraoxonase 1 Activity in Cardiovascular Disease

The antioxidant activity of high density lipoprotein (HDL) is largely due to the paraoxonase (PON) 1 located on it. Experiments with transgenic PON1 knockout mice indicate the potential for PON1 to protect against atherogenesis. This effect of HDL in decreasing low density lipoprotein (LDL) lipid peroxidation is maintained for longer than that of antioxidant vitamins and could therefore be more protective. Several important advances in the field of PON research have occurred recently, not least the discovery that two other members of the PON gene family -PON2 and PON3 - may also have important antioxidant properties. Significant advances have been made in understanding the basic biochemical function of PON1 and the discovery of possible modulators of its activity. Case-control studies of PON1 activity and coronary heart disease (CHD) have shown a clear association between CHD and low serum PON1 activity. This relationship has been further strengthened by the publication of the first prospective study showing low serum PON1 activity to be an independent predictor of new CHD events. Furthermore, decreased CHD risk has been revealed by meta-analysis to be associated with the polymorphisms of PON1, which are most active in lipid peroxide hydrolysis. Although this is likely to be an underestimate of the true contribution of PON1 to CHD (because these polymorphisms explain only a small component of the variation in PON1 activity), it is important because genetic influences are unlikely to be confounded by other factors linked with both CHD and diminished PON1 activity. PON1 is being extensively researched and it is hoped that therapeutic approaches will emerge to increase its activity. Clinical trials of these, if successful, will not only provide a novel means of preventing atherosclerosis, but also provide a more satisfactory means of testing the oxidant hypothesis of atherosclerosis than antioxidant vitamin supplementation has proved to be.     

Color postprocessing of conventional CT images: preliminary results in assessment of nondisplaced proximal femoral fractures

Purpose

The purpose of this study was to demonstrate the diagnostic performance and effect on reader confidence of a custom computed tomography (CT) color postprocessing algorithm for assessment of nondisplaced proximal femoral fractures.

Materials and methods

Four radiologists, including two PGY-3 radiology residents and two emergency radiologists, independently interpreted 30 CT examinations of the hip and/or pelvis performed for trauma, consisting of a total of 15 cases positive for nondisplaced hip fracture and 15 age and sex-matched controls. Images were reviewed first with conventional CT images and after at least 8 weeks, all images were reviewed again with the addition of coronal color postprocessed images. Sensitivity and specificity were compared with McNemar’s test, and diagnostic confidence was compared with paired t tests.

Results

There was no significant difference in diagnostic performance between conventional and postprocessed images, although there was nominally increased sensitivity and decreased specificity with the postprocessed images: for all readers, the sensitivity and specificity for conventional images was 88.3 and 95.0%, compared to 93.3% (p?=?0.25) and 88.3% (p?=?0.14) for postprocessed images. Three of four readers (including both attending radiologists) reported an increase in confidence with postprocessed images for cases negative for fracture (10-point confidence scale of 7.25 for conventional images, compared to 8.2 for postprocessed images for all readers, p?=?0.0053). There was no difference in diagnostic confidence for cases positive for fracture.

Conclusions

A custom color CT postprocessing algorithm did not demonstrate a significant difference in diagnostic performance for assessment of nondisplaced proximal femoral fractures within the limitations of a relatively small sample size; however, postprocessing increases confidence of experienced readers in cases negative for fracture.

     

Synthesis and characterization of a novel series of 1,4‐dihydropyridine analogues for larvicidal activity against Anopheles arabiensis

The new‐fangled bis(4‐substituted benzyl) 4‐(4‐substitued phenyl)‐2,6‐dimethyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate derivatives were synthesized by the union of substituted aryl aldehyde, tert‐butyl acetoacetate, ammonium carbonate with 4‐substituted benzyl alcohol via Hantzsch ester synthesis in aqueous medium under catalyst‐free conditions. The newly synthesized compounds were characterized by spectroscopic techniques such as IR, NMR (¹H and ¹³C), ESI mass, elemental analysis, and single‐crystal X‐ray diffraction. The characterized title compounds were evaluated for the larvicidal activity against Anopheles arabiensis by standard WHO larvicidal assay method using Temephos as standard at 4 μg/ml. The title compounds bis(4‐methoxybenzyl) 2,6‐dimethyl‐4‐(4‐nitrophenyl)‐1,4‐dihydropyridine‐3,5‐dicarboxylate and bis(4‐chlorobenzyl) 2,6‐dimethyl‐4‐(4‐nitrophenyl)‐1,4‐dihydropyridine‐3,5‐dicarboxylate exhibited promising larvicidal activity at 65.6% and 72.2%, respectively, when compared with the standard compound at 98.9%.