Risk of adolescent offspring's completed suicide increases with prior history of their same-sex parents' death by suicide.

BACKGROUND: To investigate the risk of completed suicide in offspring during adolescence in relation to prior history of the same-sex parent's death by suicide and other causes. METHOD: A total of 500 adolescents who died by suicide at age 15-19 years between 1997 and 2007 were identified from the Taiwan Mortality Registration (TMR). For each case, 30 age- and time-matched controls were selected randomly from all adolescents registered in the Taiwan Birth Registry (TBR). A multivariate conditional logistic regression model was used to assess the risk of adolescent completed suicide in relation to their same-sex parent. RESULTS: Adolescent suicide risk was positively associated with both paternal [odds ratio (OR) 5.38, 95% confidence interval (CI) 2.17-13.33] and maternal suicide (OR 6.59, 95% CI 1.82-23.91). The corresponding risk estimates associated with paternal and maternal deaths from non-suicidal causes were much lower, at 1.88 and 1.94 respectively. The risk of suicide in male adolescents was significantly associated with prior history of paternal death by suicide (OR 8.23, 95% CI 2.96-22.90) but not of maternal death by suicide (OR 3.50, 95% CI 0.41-30.13). On the other contrary, the risk of suicidal death in female adolescents was significantly associated with prior history of maternal suicide (OR 9.71, 95% CI 1.89-49.94) but not of paternal suicide (OR 2.42, 95% CI 0.30-19.57). However, these differences did not reach statistical significance. CONCLUSIONS: Although limited by sample size, our study indicates that adolescent offspring suicidal death is associated with prior history of their same-sex parent's death by suicide.

Characterization of amine donor and acceptor sites for tissue type transglutaminase using a sequence from the C-terminus of human fibrillin-1 and the N-terminus of osteonectin.

Transglutaminase (TGase)-modified proteins are commonly observed in a wide range of biological systems. Therefore, the identification of TGase substrates and respective consensus sites may contribute to a better understanding of the physiological role of TGase. In this study, we identified enzyme-specific properties of two peptide sequences, EDGFFKI, derived from human fibrillin-1, and the previously characterized APQQEA, derived from human osteonectin. EDGFFKI was identified in a previous publication as an amine donor substrate for tissue TGase; APQ(3)Q(4)EA is an amine acceptor for this enzyme. A widely-used lysine donor mimic, monodansylcadaverine (MDC), was used as a control. EDGFFKI crosslinked specifically only to Q(3) of the acceptor probe. The EDGFFKI sequence also showed enzyme specificity for tissue TGase while no reaction was observed with plasma TGase (Factor XIIIa), consistent with its natural occurrence in vivo. Using this substrate in biotinylated form we demonstrate its value as a tracer probe to detect endogenous TGase activity in human tissues as well as to target potential amine acceptor substrates via an enzyme-directed site-specific labeling. The results of this study show natively derived EDGFFKI and APQQEA are better and more specific indicators of endogenous tissue TGase activity as compared to a small molecule probe; this may be important in diagnostic applications. The specificity with which matrix sequences APQQEA and EDGFFKI interact with tissue TGase but not plasma TGase may also be crucial for understanding and controlling the function of these TGases in vivo and in tissue engineering.

Implementation of graphic user interface screen capture solution for workflow assessment of abdominal MR examinations valuable tool to analyze discrepancies in expected and experienced MR table time.

RATIONALE AND OBJECTIVES: The aim of this study was to assess if graphical user interface screen-capture software applied to a magnetic resonance (MR) hardware console could nonintrusively allow the analysis of discrepancies between expected and experienced MR table time. MATERIALS AND METHODS: Individual MR examination acquisition processes were captured in audio-video interleave streams for 10 patients who underwent comprehensive liver MR imaging. These audio-video streams were dissected into periods of true image data acquisition, scanner activity without direct image data acquisition, and scanner inactivity. RESULTS: Total expected time required for standardized liver MR image acquisition was estimated at 15 minutes. Experienced table times varied highly, ranging from 19:00 to 58:08 minutes. Image data acquisition occurred during approximately 58% (range, 43.3%-73.7%) of overall table time. Image data were obtained approximately 77% (range, 65.6%-87.0%) of the time the scanner spent active. CONCLUSION: Graphical user interface screen-capture software installed on an MR console nonintrusively revealed significant periods of table time spent not obtaining true image data and explained discrepancies between expected and experienced MR table times. Table-time calculations using Digital Imaging and Communications in Medicine image headers and scanner-logged time stamps are underestimations of true table time because they do not take into account some scanner activities not directly leading to image formation.

Subnanosecond mJ eye-safe laser with an intracavity optical parametric oscillator in a shared resonator.

We theoretically verify that the threshold of an intracavity optical parametric oscillator pumped by a passively Q-switched laser is entirely controlled by the bleach of the saturable absorber not by the signal output reflectivity. We use a series of different output couplers to optimize the output performance. With a signal output reflectivity of 15%, we experimentally achieve an efficient subnanosecond eye-safe laser with 3.3 mJ pulse energy and 1.5 MW peak power.

Electro-spinning of pure collagen nano-fibres - just an expensive way to make gelatin?

Scaffolds manufactured from biological materials promise better clinical functionality, providing that characteristic features are preserved. Collagen, a prominent biopolymer, is used extensively for tissue engineering applications, because its signature biological and physico-chemical properties are retained in in vitro preparations. We show here for the first time that the very properties that have established collagen as the leading natural biomaterial are lost when it is electro-spun into nano-fibres out of fluoroalcohols such as 1,1,1,3,3,3-hexafluoro-2-propanol or 2,2,2-trifluoroethanol. We further identify the use of fluoroalcohols as the major culprit in the process. The resultant nano-scaffolds lack the unique ultra-structural axial periodicity that confirms quarter-staggered supramolecular assemblies and the capacity to generate second harmonic signals, representing the typical crystalline triple-helical structure. They were also characterised by low denaturation temperatures, similar to those obtained from gelatin preparations (p>0.05). Likewise, circular dichroism spectra revealed extensive denaturation of the electro-spun collagen. Using pepsin digestion in combination with quantitative SDS-PAGE, we corroborate great losses of up to 99% of triple-helical collagen. In conclusion, electro-spinning of collagen out of fluoroalcohols effectively denatures this biopolymer, and thus appears to defeat its purpose, namely to create biomimetic scaffolds emulating the collagen structure and function of the extracellular matrix.

Validation of the Chinese version Scale of Needs (SON) for caregivers of mentally ill patients.

The purpose of this study was to develop the Chinese version Scale of Needs (SON) for Caregivers of Mentally Ill Patients. There were 23 items designed for the initial scale, and 250 Taiwanese caregivers of mentally ill patients were recruited in the study. Exploratory factor analysis and principle component analysis were conducted. The 23 items of the SON for Caregivers of Mentally Ill Patients were classified into four factors and accounted for 66.12% of the variance. Factor I was assigned as Information need, Factor II was named Supportive need, Factor III was named Break need and Factor IV was called Emotional Releasing Service.

Compact efficient eye-safe intracavity optical parametric oscillator with a shared cavity configuration.

We present a compact efficient eye-safe intracavity optical parametric oscillator pumped by a passively Q-switched Nd:YAG laser in a shared cavity configuration. A signal pulse of 3.3 mJ energy at a 1573 nm wavelength with a peak power of 150 kW was achieved. The effective conversion efficiency with respective to the optimized 1064 nm Q-switched pulse energy was as high as 51%.

A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours.

The present study determined the influence of a retinoid X receptor agonist bexarotene on angiogenesis and metastasis in solid tumours. In the experimental lung metastasis xenograft models, treatment with bexarotene inhibited the development of the lung tumour nodule formation compared to control. In vivo angiogenesis assay utilising gelfoam sponges, bexarotene reduced angiogenesis in sponges containing vascular endothelial growth factor, epidermal growth factor and basic fibroblast growth factor to various extent. To determine the basis of these observations, human breast and non-small-cell lung cancer cells were subjected to migration and invasion assays in the presence of bexarotene. Our data showed that bexarotene decrease migration and invasiveness of tumour cells in a dose-dependent manner. Furthermore, bexarotene inhibited angiogenesis by directly inhibiting human umbilical vein endothelial cell growth and indirectly inhibiting tumour cell-mediated migration of human umbilical vein endothelial cells through Matrigel matrix. Analysis of tumour-conditioned medium indicated that bexarotene decreased the secretion of angiogenic factors and matrix metalloproteinases and increased the tissue inhibitor of matrix metalloproteinases. The ability of bexarotene to inhibit angiogenesis and metastasis was dependent on activation of its heterodimerisation partner peroxisome proliferator-activated receptor gamma. Collectively, our results suggest a role of bexarotene in treatment of angiogenesis and metastasis in solid tumours.

Contra-directional two-beam coupling by use of a single input beam in an iron-doped lithium niobate multimode fiber.

Experimental results are presented for 1,800 contra-directional two-beam coupling (TBC) measurements in a single crystal fiber of LiNbO8:Fe using a single incident beam and its Fresnel reflection off the back surface of the fiber. To our knowledge, this is the first time that volume gratings have been written in a fiber using this beam coupling geometry. At small f-numbers, the TBC efficiency has been predicted to decrease in bulk LiNbO3:Fe due to the erasure of the weak gratings by the dark conductivity. We present experimental results validating the published theory and show experimentally that confinement of the interfering beams in a fiber geometry overcomes this limitation.

Antioxidant effects of water extracts from barley (Hordeum vulgare L.) prepared under different roasting temperatures.

The antioxidant effects of water extracts of roasted barley (WERB) were investigated under different roasting temperatures and compared with those of the water extracts of unroasted barley (WEUB). It was found that the Maillard reaction products increased upon increasing the roasting temperatures. Both WERB and WEUB exhibited significant antioxidant activities in linoleic acid and liposome model systems. Although WERB and WEUB afforded considerable protection against the damage of deoxyribose and proteins, the antioxidant efficiency of roasted samples was weaker than that of unroasted samples because of the reduction of antioxidant components (catechin, tocopherol, and lutein) with increasing roasting temperature. Unroasted samples were more effective in reducing power, quenching free radical, hydroxyl radical, and chelating iron than the roasted samples. The different antioxidant activity among roasted and unroasted barley samples may be partly attributed to the changes in catechin, tocopherol, and lutein contents.

Complications of liner locking system in Micro-structured Omnifit acetabular components: a radiographic evaluation of 887 hips followed for 5-10 years.

We evaluated 887 hips in 672 patients with uncemented MicroStructured Omnifit acetabular components for liner locking complications. We found 2 types of radiographic signs of liner locking system complications in 7 hips, developing between 2 and 4 years postoperatively. The incidence of liner locking system complications was 0.8% using this modular acetabular component. We recommend that a patient who has received a total hip arthroplasty including a MicroStructured Omnifit acetabular component should be monitored frequently for radiographic signs of liner locking system complications, especially with a polyethylene thickness of less than 8 mm.

Human granulocytic ehrlichiosis agent infection in a pony vaccinated with a Borrelia burgdorferi recombinant OspA vaccine and challenged by exposure to naturally infected ticks.

A pony was vaccinated with recombinant OspA vaccine (rOspA) and then exposed 3 months later to Borrelia burgdorferi-infected ticks (Ixodes scapularis) collected in Westchester County, N.Y. At 2 weeks after tick exposure, the pony developed a high fever (105 degrees F). Buffy coat smears showed that 20% of neutrophils contained ehrlichial inclusion bodies (morulae). Flunixin Meglumine (1 g daily) was given for 2 days, and the body temperature returned to normal. PCR for ehrlichial DNA was performed on blood samples for 10 consecutive days beginning when the pony was first febrile. This pony was monitored for another 3.5 months but developed no further clinical signs. The 44-kDa immunodominant human granulocytic ehrlichiosis antigen gene was amplified by PCR and cloned into a pCR2.1 vector. DNA sequence analysis of this gene showed it was only 8 bp different (99% identity) from the results reported by others (J. W. Ijdo et al., Infect. Immun. 66:3264-3269, 1998). Western blot analysis, growth inhibition assays, and repeated attempts to isolate B. burgdorferi all demonstrated the pony was protected against B. burgdorferi infection. These results highlight the potential for ticks to harbor and transmit several pathogens simultaneously, which further complicates the diagnosis and vaccination of these emerging tick-borne diseases.

Reproductive isolation in Caenorhabditis: terminal phenotypes of hybrid embryos.

Several interspecific combinations of the "elegans" group of Caenorhabditis species are cross-fertile. Most F1 hybrids from these crosses arrest during embryogenesis. Developmental defects observed in hybrid embryos include defects in gastrulation initiation, defects in embryonic compaction, and defects in embryonic elongation. These reproductive barriers have arisen multiple times in the evolution of Caenorhabditis.

MicroStructured Omnifit acetabular components: concerns with locking system complications and excessive polyethylene wear.

BACKGROUND: We began to use cementless MicroStructured Omnifit acetabular components in November 1988. Liner dislodging and excessive polyethylene wear later occurred in some of our patients. This finding prompted us to review our experience with the use of such modular acetabular components. METHODS: A total of 887 hips in 672 patients, which had been fitted with cementless MicroStructured Omnifit acetabular components, were evaluated for locking system complications using radiographic examinations. Of the cases, 240 hips which had received a 26-mm femoral head (group 1) and 110 hips which had received a 32-mm femoral head (group 2) were compared using a digitiser to determine the influence of femoral head size on polyethylene wear. RESULTS: There were two types of radiographic signs of locking system complications in 7 hips, at a mean time of 2.9 years after implantation. The incidence of liner locking system complications using this modular acetabular component was 0.8%. The mean liner wear rate per year was 0.15 mm in group 1 and 0.20 mm in group 2 (p <0.005). The initial polyethylene thickness ranged from 5.9 to 13.6 mm in group 1, compared with 3.9 to 10.6 mm in group 2 (p < 0.005). CONCLUSION: A patient who has received a total hip arthroplasty that includes a MicroStructured Omnifit acetabular component should be monitored frequently for radiographic signs of locking system complications. In this study, the mean liner wear rate was significantly higher in group 2. Inadequate polyethylene thickness in this group was implicated as the major cause of excessive polyethylene wear.

Identification of a novel peroxisome proliferator responsive cDNA isolated from rat hepatocytes as the zinc-finger protein ZFP-37.

The implementation of a rat hepatocyte model system and differential display-polymerase chain reaction resulted in the isolation of ZFP-37 as a peroxisome proliferator-responsive gene. In addition to being responsive to peroxisome proliferators, rat ZFP-37 (rZFP-37) mRNA accumulates rapidly after treating cells with several other hepatic tumor promoters, serum, and cycloheximide, indicating that this gene belongs to the immediate-early growth responsive gene family. Although rZFP-37 and mouse ZFP-37 (mZFP-37) are both members of the Krüppel-associated box and C2H2 zinc finger superfamily of proteins, there are several features that distinguish the two proteins. The primary protein sequences of rat and mouse ZFP-37 are highly conserved, especially within the region encoding the 12 C2H2 zinc finger motifs; however, a region believed to be involved in DNA binding in mZFP-37 is divergent in rZFP-37. Mouse ZFP-37 mRNA is expressed almost exclusively in testes and brain, whereas rZFP-37 mRNA is expressed in testes, brain, kidney, spleen, thymus, lung, and at low levels in liver. A major difference between regulation of ZFP-37 in the two species exists as rZFP-37 is induced, while mZFP-37 is repressed, in liver by the administration of the potent peroxisome proliferator Wy 14,643. Despite the fact that mZFP-37 is believed to be important in cell growth and differentiation in testes and brain, the pronounced differences in regulation of this gene in two closely related species preclude an extrapolation to rZFP-37's biological role. Nonetheless, the effects of tumor promoters and mitogens on its expression and the inclusion of rZFP-37 into the immediate-early growth gene families raise the possibility that this gene plays a role in hepatocyte proliferation and/or differentiation.

Quality of life effects of alprostadil therapy for erectile dysfunction: results of a trial in Europe and South Africa.

OBJECTIVES: Quality of life (QOL) data were used to evaluate the effects of self-administered intracavernosal injection of alprostadil for erectile dysfunction, when used for up to 18 months during a 13 country Phase III clinical trial. METHODS: The Duke Health Profile was used to measure patients' physical and psychosocial QOL at baseline, 3, 6, 12 and 18 months. Changes from baseline were measured using paired t-tests, with additional analyses by cause of dysfunction, starting dosage, and prior treatment. RESULTS: Patients displayed significant improvements in mental and social health and self-esteem at six months (P < 0.01, n = 570), with greater improvements at 12 and 18 months. Anxiety and depression measures also improved significantly at 12 and 18 months, as did the summary general health score. Worse pain scores were observed in the first year but not at 18 months. Those with a starting dosage of 10-20 micrograms, those with psychogenic causes of dysfunction, and those with no prior treatment for erectile dysfunction generally showed the greatest improvements. CONCLUSION: In this study, the clinical improvements in erectile function due to intracavernosal alprostadil therapy were complemented by QOL improvements, particularly in the mental health, of many patients.

Different pH dependency of mitomycin C activity in monolayer and three-dimensional cultures.

PURPOSE: Previous studies by other investigators have shown an enhancement of mitomycin C (MMC) activity at acidic extracellular pH (pHe) in monolayer cultures of human cells. The goal of the present study was to determine if the efficacy of intravesical MMC therapy in patients treated for superficial bladder cancer can be enhanced by using acidified dosing solutions. We evaluated (a) the effect of pHe on MMC activity in patient bladder tumors in vitro, and (b) the pH dependency of MMC activity in 2-dimensional monolayer and 3-dimensional multilayer cultures of human bladder RT4 tumor cells. METHODS: Patient bladder tumors were maintained as 3-dimensional histocultures. RT4 cells were harvested and maintained as monolayer cultures or as 3-dimensional cell pellets on a collagen gel matrix. The cell pellets were 300-450 cell layers and 4,000-5,000 microns in diameter. Tumors or cells were incubated for 2 hr with MMC-containing media at pHe of 5, 6, and 7.4. The drug effect was measured by the inhibition of DNA precursor (thymidine) incorporation. The stability of MMC as a function of pHe was determined. About 24% of MMC was degraded following 2 hr exposure at pHe 5 and < or = 2% at pHe 6 and 7.4. RESULTS: The drug concentrations required to inhibit thymidine incorporation by 50% (IC50) were corrected for the degraded MMC at acidic pHe. The results showed no pH-dependent MMC activity in human patient bladder tumors nor in RT4 multilayer cultures; the IC50 values were about 10 micrograms/ml at all three pHe. In contrast, the monolayer RT4 cultures showed a pH-dependent MMC cytotoxicity; the IC50 were 0.1, 0.8 and 1.2 micrograms/ ml at pHe 5, 6 and 7.4, respectively (p < 0.05). Pre-incubation of multilayered RT4 cultures in acidic pH medium for 8 hr enhanced the MMC activity; the IC50 was reduced by about 5 fold at pHe about 3 fold at pHe 6. Similar pH-dependent MMC activity was found when multilayers were pre-treated for 1 hr with 0.5 microgram/ml nigericin, a proton ionophore known to cause the intracellular pH (pHi) to equilibrate with pHe. CONCLUSIONS: These data suggest that the difference in the pH dependency of MMC activity in the monolayer and multilayer systems was due to the different experimental conditions. The time lag for pHi to equilibrate with pHe in the multilayer systems and the instability of MMC at low pHe imply that the efficacy of intravesical MMC therapy is unlikely to be enhanced by using acidic dosing solution.

Differential effect of taxol in rat primary and metastatic prostate tumors: site-dependent pharmacodynamics.

PURPOSE: This study compared the sensitivity of rat prostate MAT-LyLu primary and lymph node metastatic tumors to taxol. METHODS: Tumors were established by subcutaneous implantation of tumor cells in a hind leg (primary site) of male Copenhagen rats. Lymph node metastases were used for serial transplantation. Eleven pairs of primary and metastatic tumors between the sixth and twentieth generations were harvested and maintained as 3-dimensional histocultures. The effects of taxol (24 hr treatment at 1 nM to 10 microM) were measured by the appearance of apoptotic cells, and by the inhibition of DNA precursor (thymidine) incorporation. To determine the basis of differential sensitivity of primary and metastatic tumors to the DNA inhibition, we examined the expression of multidrug resistance pglycoprotein (Pgp) and the accumulation of 3H-taxol after 24 hr exposure and the retention after a 48 hr washout period. RESULTS: The fraction of apoptotic cells increased linearly with the logarithm of taxol concentration to a maximal value of 25%; the concentration-response curves for primary and metastatic tumors were superimposable. Taxol produced a sigmoidal, concentration-dependent inhibition of thymidine incorporation; the maximal inhibition of approximately 40% was reached at 0.1 and 1 microM for primary and metastatic tumors, respectively. Within the primary or metastatic subgroups, the IC30 (drug concentration that produced a 30% inhibition of DNA synthesis) among consecutive generations varied by < 5 fold, but the primary tumor consistently showed a lower IC30 than the daughter or the parent metastatic tumor (mean, 20-fold; median, 15-fold; range, 6- to 56-fold). The finding that the lower drug sensitivity in metastatic tumors was not exhibited in its daughter primary tumor but was regained in its daughter metastatic tumors suggests that the chemoresistant phenotype is maintained only in lymph nodes and not in the primary site. There were no differences in the Pgp status (neither tumor expressed Pgp), accumulation and retention of taxol in primary and metastatic tumors. CONCLUSIONS: Taxol induced apoptosis and inhibited DNA synthesis in the rat MAT-LyLu primary and lymph node metastatic tumors. The apoptotic effect was not different among the two tumors, whereas the primary tumor was more sensitive to the inhibition of DNA synthesis. The differential sensitivity of the two tumors to the DNA effect is not associated with a difference in Pgp expression, drug accumulation nor drug retention, and appears to be associated with changes that are linked to lymph node metastasis.

Role of Na+ in the asymmetric paracellular transport of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg across rabbit colonic segments and Caco-2 cell monolayers.

This study was conducted to demonstrate that Na+ played a role in the paracellular transport of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (Pz-peptide), a hydrophilic proline-containing pentapeptide, across the rabbit colonic mucosa and Caco-2 cell monolayers. Over the 1 to 5 mM concentration range, Pz-peptide transport was 25 to 180 times greater from the mucosal-to-serosal than from the opposite direction. This asymmetry in transport was consistent with the ability of Pz-peptide to lower the transepithelial electrical resistance of Caco-2 cell monolayers only from the mucosal side. Blockade of Na+ access to the apically located amiloride-sensitive Na+ channel in the lower intestinal segments by mucosal 10 microM amiloride, serosal 100 microM ouabain or removal of Na+ ions in the mucosal fluid dramatically reduced Pz-peptide transport to 5% of the control. Moreover, Pz-peptide transport across Caco-2 cell monolayers could be titrated against mucosal Na+ concentration. There was a small mucosal-to-serosal solvent drag effect induced by transepithelial Na+ flux stimulated by Pz-peptide in the colon, contributing in part to enhanced paracellular solute transport. Overall, the above findings are consistent with a scenario whereby Pz-peptide stimulates transepithelial Na+ flux across the colonic segments at the level of the amiloride-sensitive Na+ channel, thereby triggering yet to be identified intracellular biochemical changes that ultimately result in tight junctional opening and enhanced paracellular solute transport.