No abstract

BACKGROUND Vascular endothelial growth factor (VEGF) and its kinase insert domain receptor (KDR) play an important role in angiogenesis, and their gene expression patterns also suggest a close relationship with early pregnancy. However, limited information is available regarding the role of the VEGF system, especially its KDR receptor, in recurrent pregnancy loss (RPL). This study was conducted to investigate a genetic association between VEGF and its receptor gene (KDR) with idiopathic RPL. METHODS In this case-control study, 115 women who had experienced at least two consecutive spontaneous miscarriages (n= 62 women with two miscarriages, n= 53 with three or more) and 170 controls were included. A total of 14 tag single-nucleotide polymorphisms (SNPs) of VEGF and KDR were selected from the HapMap Web site and three functional SNPs [rs1570360 (-1154G/A) of VEGF; rs2305948 (V297I) and rs1870377 (Q472H) of the KDR gene] were genotyped using primer extension analysis. We further used multifactor dimensionality reduction analysis to evaluate gene-gene interactions. RESULTS One tag SNP (rs6838752) and the functional SNP (Q472H) of the KDR gene were in complete linkage and showed significant differences between patients and controls (P< 0.05). The frequencies of haplotypes of VEGF (A-T-G haplotype) and KDR (A-C-A-T-G haplotype) showed significant differences in patients versus controls (P< 0.05). All comparisons with controls remained significant when the subgroup of women with three or more miscarriages was analyzed. CONCLUSIONS VEGF and its receptor gene (KDR) are associated with idiopathic RPL. The VEGF/KDR system jointly contributes to recurrent miscarriage in Taiwanese Han women.

Though a reduced flush response to niacin has been found in schizophrenic patients, whether it is a vulnerability indicator to schizophrenia remains little known. We aimed to examine the familial aggregation in niacin flush response among schizophrenic patients and their nonpsychotic relatives. In a sample of 153 schizophrenia probands, 217 parents, 70 siblings, and 94 normal subjects, 3 concentrations (0.001 M, 0.01 M, and 0.1 M) of niacin were applied to the forearm skin and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. Both the heritability for continuous flush scores and the recurrence risk ratios for binary non-flush response in the nonpsychotic relatives of schizophrenic patients were estimated, and ordinal logistic regression analyses of relatives' niacin response on probands' were further conducted to adjust for potential confounders. The greatest heritabilities ranged from 47% (0.01 M at 10 minutes) to 54% (0.1 M at 5 minutes). The risk ratios of 0.01 M at 10 minutes (ranging from 2.60 for using score 1 or less to 5.06 for using score 0 as non-flush) and 5 minutes (1.66 for using score 0 as non-flush) were significantly greater than one. Multiple ordinal logistic regression analyses further revealed that the association between probands and relatives in niacin flush response remained after adjustment for potential confounders, including age, sex, allergy, tobacco smoking, and coffee drinking. These findings provide support for the potential of niacin flush response as a vulnerability indicator to schizophrenia.

This work demonstrates a quantitative interpretation of ion desorption in matrix-assisted laser desorption/ionization (MALDI). The theoretical modeling incorporates transition state theory for the desorption of surface ions, assuming chemical and thermal equilibrium in the solid state prior to desorption. It is distinct from conventional models that assume chemical equilibrium in the gas phase. This solid-state thermodynamic interpretation was used to examine the desorption of pure 2,4,6-trihydroxyacetophenone (THAP) and of angiotensin I mixed with THAP. It successfully described the changes in ion yield with the effective temperature under various laser fluence and initial temperature conditions. The analysis also revealed the key role played by ion concentration in the modeling to provide the best fit of the model to observations. On the other hand, divergence of the ion beam with laser fluence was examined using an imaging detection method, and the signal saturation normally seen at high fluence was appropriately reduced by ion focusing. Simplified but deceptive theoretical interpretations were obtained when the analysis was conducted without adequate calibration of the instrument bias.

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia.

No abstract

In contrast to bacteraemic pneumococcal community-acquired pneumonia (CAP), there is a paucity of data on the clinical characteristics and outcomes of non-bacteraemic pneumococcal CAP. This retrospective study compared the outcome of hospitalized patients with bacteraemic and non-bacteraemic pneumococcal CAP treated at a medical centre from 2004 to 2008. Data on clinical outcomes including all-cause mortality, length of hospital stay, need for intensive-care unit admission and extrapulmonary involvement were analysed. In all, 221 patients with pneumococcal pneumonia (87 bacteraemic, 134 non-bacteraemic) were included. Patients with bacteraemic pneumococcal pneumonia (BPP) were older than those with non-BPP (46·2 ± 30·7 years vs. 21·7 ± 30·8 years, P<0·001) and were more likely to have underlying medical diseases (66·7% vs. 33·6%, P<0·001). The overall mortality rates at 7, 14, and 30 days were significantly higher in BPP than non-BPP patients (12·6% vs. 2·2%, 14·9% vs. 3·7%, 19·5% vs. 5·1%, all P<0·01). Multivariate logistic regression analysis showed that pneumococcal bacteraemia was correlated with extrapulmonary involvement (odds ratio 5·46, 95% confidence interval 1·97-15·16, P=0·001). In conclusion, S. pneumoniae bacteraemia increased the risk of mortality and extrapulmonary involvement in patients with pneumococcal CAP.

Epidemiologic studies have shown that increased concentrations of ambient particles are associated with cardiovascular morbidity and mortality (1,2). However, the mechanisms of such associations have not been clearly defined. Recent epidemiologic studies have found associations of increased air particles with increased heart rate and blood pressure and decreased heart rate variability (3-6). It has been speculated that particles cause the activation of autonomic nervous system, leading to changes in heart rates (7). To clarify the relationship of particles with mortality and morbidity, animal models have been used to investigate the effects of particles (8,9). Preliminary studies revealed increased heart rates and arrhythmia in pulmonary hypertensive rats after exposure to concentrated ambient particles (8,10,11). However, a recent study revealed a decreased heart rate when residual oil fly ash was instilled into the rats (12). To investigate further the mechanisms of particleinduced cardiotoxicity, we used heart rate and blood pressure as outcome indicators to assess their association with concentrated ambient particles in pulmonary hypertensive rats. Studies have also indicated that particles with aerodynamic diameter < 2.5 µm (PM 2.5 ) exert greater adverse health effects than coarse particles (1,13). To investigate the effects of PM 2.5 on cardiovascular diseases, we used an ambient particle concentrator, which generated PM 2.5 , to test our hypothesis (14).It is a common practice to divide experimental animals into exposure and control groups to study the effects of air particles. Because of the wide variation among diseased animals, this method requires large numbers of animals to delineate the true effect of air particles (9). Furthermore, variation in circadian cycle for individual rats also makes comparisons of heart rate or blood pressure difficult. To overcome this problem, we used each animal as its own control by exposing the individual animals repeatedly to concentrated air and filtered air and successfully detected the effects of particles on heart rate and mean blood pressure in three rats. Materials and MethodsAnimals and development of pulmonary hypertension. Male Sprague-Dawley rats 60 days old were obtained from the National Laboratory Animal Breeding and Research Center, housed in plastic cages on Aspen chip bedding, and provided with Lab Diet 5001(PMI Lab, Montville, NJ, USA) and water ad libitum except during exposure.Animals were maintained on a 12-hr light/ dark cycle at 22 ± 1°C and 55 ± 10 % relative humidity. We injected rats with monocrotaline intraperitoneally at 60 mg/kg body weight to cause them to develop pulmonary hypertension. Fourteen days after monocrotaline injection, animals were ready for experimentation (15).Experimental design. Ambient particles from the Chung-Li area, a suburb of Taipei, were concentrated through a modified ultrafine particle concentrator developed by Sioutas et al. (14). Briefly, the particle concentrator used virtual impactor technology in which 110 L...