title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Proliferation and differentiation of human osteoblasts within 3D printed poly-lactic-co-glycolic acid scaffolds. | Bone repair and regeneration can be enhanced through implantation of biocompatible and biodegradable scaffolds, which serve primarily as osteoconductive moieties. In this study, the mechanical properties and microenviroment of 3D printed poly-lactic-co-glycolic acid (PLGA) scaffolds are examined. Additionally, the proliferation and differentiation of human fetal osteoblasts are evaluated after 3 weeks of in vitro culture on the scaffolds. The results showed that the PLGA scaffolds examined had mechanical properties similar to that of trabecular bone, but was still much weaker compared to cortical bone. In addition to general porosity, the PLGA scaffolds also had micropores within macropore walls. Cultured human osteoblasts could proliferate upon seeding on the PLGA scaffolds. Alkaline phosphatase activity and osteonectin expression of the osteoblasts cultured on the PLGA scaffolds remained stable over three weeks, whilst expression of collagen type I and osteopontin decreased. The alkaline phosphatase activity of osteoblasts cultured on PLGA scaffolds is comparable with that from two commercially-available scaffolds - OPLA and collagen scaffolds (Becton-Dickinson (BD) Inc., Franklin Lakes, NJ, USA). Hence, the results suggested that the PLGA scaffolds examined are conducive for promoting osteogenesis. | 18,757,495 |
The clinical time-course of experimental autoimmune uveoretinitis using topical endoscopic fundal imaging with histologic and cellular infiltrate correlation. | EAU is an established preclinical model for assessment of immunotherapeutic efficacy toward translation of therapy for posterior uveitis. Reliable screening of clinical features that correlate with underlying retinal changes and damage has not been possible to date. This study was undertaken to describe, validate, and correlate topical endoscopic fundus imaging (TEFI) with histologic features of murine experimental autoimmune uveoretinitis (EAU), with the intent of generating a rapid noninvasive panretinal assessment of ocular inflammation. EAU was induced in B10.RIII mice by immunization with the peptide RBP-3(161-180). The clinical disease course (days 0-63) was monitored and documented using TEFI. Disease severity and pathology were confirmed at various time points by histologic assessment. The composition of the cell infiltrate was also examined and enumerated by flow cytometry. TEFI demonstrated the hallmark features of EAU, paralleling many of the clinical features of human uveitis, and closely aligned with underlying histologic changes, the severity of which correlated significantly with the number of infiltrating retinal leukocytes. Leukocytic infiltration occurred before manifestation of clinical disease and clinically fulminant disease, as well as cell infiltrate, resolved faster than histologic scores. During the resolution phase, neither the clinical appearance nor number of infiltrating retinal leukocytes returned to predisease levels. In EAU, there is a strong correlation between histologic severity and the number of infiltrating leukocytes into the retina. TEFI enhances the monitoring of clinical disease in a rapid and noninvasive fashion. Full assessment of preclinical immunotherapeutic efficacy requires the use of all three parameters: TEFI, histologic assessment, and flow cytometric analysis of retinal infiltrate. | 18,757,507 |
Role of cell and matrix-bound VEGF isoforms in lens development. | To determine the role of vascular endothelial growth factor (VEGF) in embryonic eye development and lens differentiation. Expression of components of the VEGF signaling pathway during lens development and in adults was characterized by beta-galactosidase staining of VEGF-LacZ mice, immunohistochemistry, and real-time (q) PCR. Embryonic eyes from wild-type mice and VEGF120/120 mice were analyzed by light microscopy and immunohistochemistry. VEGF function during lens development was analyzed using eye explants treated with VEGF-neutralizing antibody. Direct function of VEGF was demonstrated on the human lens epithelial cell line, HLE-B3. Embryonic lens epithelium and posterior lens fibers expressed VEGF and VEGFR2. qPCR revealed VEGF164 as the major isoform in embryonic lens. Transgenic mice expressing only VEGF120 (VEGF120/120 mice) showed major defects in eye development, including microphthalmia, failed lens differentiation, and hyperplastic hyaloid vessels. The lens displayed abnormal cell patterning and differentiation associated with altered c-Maf, Prox1, and p57 expression pattern in the anterior epithelium. The number of proliferating epithelial cells was drastically reduced in VEGF120/120 lenses. Altered MIP26 cellular localization and reduced E-cadherin expression in the lens epithelium were observed. VEGF-neutralization led to reduced fiber elongation of eye explants. Exogenous VEGF increased survival and proliferation of HLE-B3 cell in a dose-dependent manner. Abnormalities in ocular development in VEGF120/120 mice suggest a role for VEGF not only in the formation of ocular vascular beds but also in the differentiation of the lens itself. | 18,757,513 |
Adsorption of human tear lipocalin to human meibomian lipid films. | Tear lipocalin (Tlc) is a major lipid binding protein in tears and is thought to have an important role in stabilizing the Meibomian lipid layer by transferring lipids to it from the aqueous layer or ocular surface, or by adsorbing to it directly. These possible roles have been investigated in vitro using human Tlc. Tlc was purified from human tears by size exclusion chromatography followed by ion exchange chromatography. Three additional samples of the Tlc were prepared by lipidation, delipidation, and relipidation. The lipids extracted from the purified Tlc were analyzed by HPLC-MS followed by fragmentation. Adsorption of these different forms of Tlc to a human Meibomian lipid film spread on the surface of an artificial tear buffer in a Langmuir trough were observed by recording changes in the pressure with time (Pi-T profile) and monitoring the appearance of the film microscopically. These results were compared with similar experiments using a bovine Meibomian lipid film. The results indicated that Tlc binds slowly to a human Meibomian lipid film compared with lysozyme or lactoferrin, even at 37 degrees C. The adsorption of Tlc to a human Meibomian lipid film was very different from its adsorption to a bovine Meibomian lipid film, indicating the nature of the lipids in the film is critical to the adsorption process. Similarly, the different forms of Tlc had quite distinct adsorption patterns, as indicated both by changes in Pi-T profiles and the microscopic appearance of the films. It was concluded that human Tlc was capable of adsorbing to and penetrating into a Meibomian lipid layer, but this process is very complex and depends on both the types of lipids bound to Tlc and the lipid complement comprising the Meibomian lipid film. | 18,757,516 |
Fixation stability, fixation location, and visual acuity after successful macular hole surgery. | This study examined whether changes in fixation stability and fixation location are good predictors of visual acuity after successful macular hole surgery. Ten patients with macular hole were tested before surgery and at 1 and 3 months after surgery. Visual acuity was measured with the ETDRS; fixation stability and fixation location were assessed with the MP-1 Microperimeter (Nidek Technologies Srl., Vigonza, PD, Italy). The quantitative measure of fixation stability was calculated with a bivariate contour ellipse area (BCEA). Fixation location shift was evaluated using the differential map analysis feature of the MP-1 Microperimeter. There was a significant improvement in visual acuity after macular hole closure. Fixation location shifted an average of 0.55 deg and 0.87 deg at 1 month and 3 months after surgery, respectively. The fixation shift was not a good predictor of visual outcome. Fixation stability improved from an average of 0.35 deg(2) before surgery to 0.29 deg(2) at 3 months after surgery. The change in fixation stability (DeltaBCEA = BCEA before - BCEA after surgery) correlated highly with visual outcome. The regression model showed that DeltaBCEA accounted for a significant proportion of the variance in visual acuity both 1 and 3 months after surgery. Some changes in ocular motor function explain the visual outcome after the anatomic success of macular hole surgery. Fixation location shift has no influence on visual acuity post-operatively; however, change in fixation stability is a strong predictor of visual outcome after successful closure of the macular hole. | 18,757,517 |
Aromatic amino acid-dependent expression of indole-3-pyruvate decarboxylase is regulated by TyrR in Enterobacter cloacae UW5. | The plant growth-promoting rhizobacterium Enterobacter cloacae UW5 synthesizes the plant growth hormone indole-3-acetic acid (IAA) via the indole-3-pyruvate pathway utilizing the enzyme indole-3-pyruvate decarboxylase that is encoded by ipdC. In this bacterium, ipdC expression and IAA production occur in stationary phase and are induced by an exogenous source of tryptophan, conditions that are present in the rhizosphere. The aim of this study was to identify the regulatory protein that controls the expression of ipdC. We identified a sequence in the promoter region of ipdC that is highly similar to the recognition sequence for the Escherichia coli regulatory protein TyrR that regulates genes involved in aromatic amino acid transport and metabolism. Using a tyrR insertional mutant, we demonstrate that TyrR is required for IAA production and for induction of ipdC transcription. TyrR directly induces ipdC expression, as was determined by real-time quantitative reverse transcription-PCR, by ipdC promoter-driven reporter gene activity, and by electrophoretic mobility shift assays. Expression increases in response to tryptophan, phenylalanine, and tyrosine. This suggests that, in addition to its function in plant growth promotion, indolepyruvate decarboxylase may be important for aromatic amino acid uptake and/or metabolism. | 18,757,531 |
The Mycobacterium tuberculosis phoPR operon is positively autoregulated in the virulent strain H37Rv. | The attenuated Mycobacterium tuberculosis H37Ra strain is an isogenic counterpart of the virulent paradigm strain H37Rv. Recently, a link between a point mutation in the PhoP transcriptional regulator and avirulence of H37Ra was established. Remarkably, a previous study demonstrated negative autoregulation of the phoP gene in H37Ra. These findings led us to study the transcriptional autoregulation of PhoP in the virulent H37Rv strain. In contrast to the negative autoregulation of PhoP previously published for H37Ra, our experiments using a phoP promoter-lacZ fusion showed that PhoP is positively autoregulated in both H37Rv and H37Ra compared with an H37Rv phoP deletion mutant constructed in this study. Using quantitative reverse transcription-PCR (RT-PCR) analysis, we showed that the phoP gene is transcribed at similar levels in H37Rv and H37Ra. Gel mobility shift and DNase I footprinting assays allowed us to identify the precise binding region of PhoP from H37Rv to the phoP promoter. We also carried out RT-PCR studies to demonstrate that phoP is transcribed together with the adjacent gene phoR, which codes for the cognate histidine kinase of the phoPR two-component system. In addition, quantitative RT-PCR studies showed that phoR is independently transcribed from a promoter possibly regulated by PhoP. Finally, we discuss the possible role in virulence of a single point mutation found in the phoP gene from the attenuated H37Ra strain but not in virulent members of the M. tuberculosis complex. | 18,757,548 |
Molecular remodeling of photosystem II during state transitions in Chlamydomonas reinhardtii. | State transitions, or the redistribution of light-harvesting complex II (LHCII) proteins between photosystem I (PSI) and photosystem II (PSII), balance the light-harvesting capacity of the two photosystems to optimize the efficiency of photosynthesis. Studies on the migration of LHCII proteins have focused primarily on their reassociation with PSI, but the molecular details on their dissociation from PSII have not been clear. Here, we compare the polypeptide composition, supramolecular organization, and phosphorylation of PSII complexes under PSI- and PSII-favoring conditions (State 1 and State 2, respectively). Three PSII fractions, a PSII core complex, a PSII supercomplex, and a multimer of PSII supercomplex or PSII megacomplex, were obtained from a transformant of the green alga Chlamydomonas reinhardtii carrying a His-tagged CP47. Gel filtration and single particles on electron micrographs showed that the megacomplex was predominant in State 1, whereas the core complex was predominant in State 2, indicating that LHCIIs are dissociated from PSII upon state transition. Moreover, in State 2, strongly phosphorylated LHCII type I was found in the supercomplex but not in the megacomplex. Phosphorylated minor LHCIIs (CP26 and CP29) were found only in the unbound form. The PSII subunits were most phosphorylated in the core complex. Based on these observations, we propose a model for PSII remodeling during state transitions, which involves division of the megacomplex into supercomplexes, triggered by phosphorylation of LHCII type I, followed by LHCII undocking from the supercomplex, triggered by phosphorylation of minor LHCIIs and PSII core subunits. | 18,757,554 |
The cold-inducible CBF1 factor-dependent signaling pathway modulates the accumulation of the growth-repressing DELLA proteins via its effect on gibberellin metabolism. | Plants have evolved robust mechanisms to respond and adapt to unfavorable environmental conditions, such as low temperature. The C-repeat/drought-responsive element binding factor CBF1/DREB1b gene encodes a transcriptional activator transiently induced by cold that controls the expression of a set of genes responding to low temperature (the CBF regulon). Constitutive expression of CBF1 confers freezing tolerance but also slows growth. Here, we propose that low temperature-induced CBF1 expression restrains growth at least in part by allowing the accumulation of DELLAs, a family of nuclear growth-repressing proteins, the degradation of which is stimulated by gibberellin (GA). We show that cold/CBF1 enhances the accumulation of a green fluorescent protein (GFP)-tagged DELLA protein (GFP-RGA) by reducing GA content through stimulating expression of GA-inactivating GA 2-oxidase genes. Accordingly, transgenic plants that constitutively express CBF1 accumulate less bioactive GA and as a consequence exhibit dwarfism and late flowering. Both phenotypes are suppressed when CBF1 is expressed in a line lacking two DELLA proteins, GA-INSENSITIVE and REPRESSOR OF GA1-3. In addition, we show that DELLAs contribute significantly to CBF1-induced cold acclimation and freezing tolerance by a mechanism that is distinct from the CBF regulon. We conclude that DELLAs are components of the CBF1-mediated cold stress response. | 18,757,556 |
Specific DNA binding of a potential transcriptional regulator, inosine 5'-monophosphate dehydrogenase-related protein VII, to the promoter region of a methyl coenzyme m reductase I-encoding operon retrieved from Methanothermobacter thermautotrophicus strain DeltaH. | Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus DeltaH are expressed in response to H(2) availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cultures restricted them to 46- and 41-bp-long mcr and mrt upstream regions, respectively. Affinity particle purification of DNA-binding proteins conjugated with putative operator regions resulted in the retrieval of a protein attributed to IMP dehydrogenase-related protein VII (IMPDH VII). IMPDH VII is predicted to have a winged helix-turn-helix DNA-binding motif and two cystathionine beta-synthase domains, and it has been suspected to be an energy-sensing module. EMSA with oligonucleotide probes with unusual sequences showed that the binding site of IMPDH VII mostly overlaps the factor B-responsible element-TATA box of the mcr operon. The results presented here suggest that IMPDH VII encoded by MTH126 is a plausible candidate for the transcriptional regulator of the mcr operon in this methanogen. | 18,757,575 |
Comparative molecular analysis of endoevaporitic microbial communities. | A phylogenetic comparison of microbial communities in hypersaline evaporites was conducted on crusts from Guerrero Negro, Mexico, and Lindsey Lake, New Mexico, using culture-independent rRNA gene sequence analysis. Many sequences were shared between evaporites, which suggests that similar environments select for specific microbial lineages from a global metacommunity. | 18,757,573 |
Current status of salivary hormone analysis. | Saliva, which offers a noninvasive and stress-free alternative to plasma and serum, is a widely accepted sample source for analysis of steroids and also of certain amines and peptides. In recent years, numerous publications have described the use of salivary hormone analysis in many fields of clinical and basic research. This review provides an overview of the current applications of salivary hormone analysis. A description of the different modes of hormone entry into saliva is followed by a detailed description of analytical methods and approaches for reliable collection of saliva, including several interesting applications in diverse fields including psychiatry, stress research, clinical endocrinology, sports medicine, and veterinary medicine. Although saliva has not yet become a mainstream sample source for hormone analysis, it has proven to be reliable and, in some cases, even superior to other body fluids. Nevertheless much effort will be required for this approach to receive acceptance over the long term, especially by clinicians. Such effort includes the development of specific and standardized analytical tools, the establishment of defined reference intervals, and implementation of round-robin trials. One major problem, the lack of compliance sometimes seen in outpatient saliva donors, requires strict standardization of both collection and analysis methods to achieve better comparability and assessment of published salivary hormone data. | 18,757,583 |
Impact of the seeking safety program on clinical outcomes among homeless female veterans with psychiatric disorders. | Seeking Safety is a manualized cognitive-behavioral therapy intervention that is designed to treat clients with comorbid substance abuse and trauma histories. This study examined its effectiveness when used with homeless women veterans with psychiatric or substance abuse problems at 11 Department of Veterans Affairs medical centers that had Homeless Women Veterans Programs. The intervention consists of 25 sessions that cover topics to help build safety in clients' lives and is present-focused, offering psychoeducation and coping skills. A cohort of homeless women veterans (N=359) was recruited before Seeking Safety was implemented (phase I). After clinicians were trained and certified in Seeking Safety, a postimplementation cohort was recruited and offered Seeking Safety treatment (phase II, N=91). Phase I lasted from January 2000 to June 2003. Phase II lasted from June 2003 to December 2005. The intervention lasted for six months. All participants were interviewed every three months for one year and received intensive case management and other services during the study. Mixed models were used to compare one-year clinical outcomes across phases. There were few differences across groups at baseline. All women entering the Homeless Women Veterans Programs showed significant improvement on most clinical outcome measures over one year. The Seeking Safety cohort reported significantly better outcomes over one year in employment, social support, general symptoms of psychiatric distress, and symptoms of posttraumatic stress disorder, particularly in the avoidance and arousal clusters. However, the Seeking Safety cohort was significantly more likely to have used drugs in the past 30 days. Seeking Safety appears to have had a moderately beneficial impact on several clinical outcomes. Although the nonequivalent comparison groups and low follow-up rates limit the internal validity of these results, availability of Seeking Safety may be of benefit for homeless female veterans. It is noteworthy that it could be delivered and implemented by case managers with little or no prior counseling experience. | 18,757,592 |
Factors related to knowledge retention after crisis intervention team training for police officers. | This study examined whether knowledge scores of Crisis Intervention Team (CIT) officers would decline in the months following CIT training and whether shorter time since training would be a significant predictor of mental health knowledge retention. This study also examined whether sociodemographic and work-related characteristics would predict knowledge retention. Eighty-eight CIT officers trained within the past three years completed an online survey containing sociodemographic and work-related questions and 17 of the 40 items used on the knowledge test that is administered at the end of training. Officers' posttraining and follow-up exam scores were matched. As expected, knowledge scores decreased significantly in the months after CIT training. Less experienced officers had lower follow-up scores. However, time elapsed since training did not predict knowledge retention. The findings indicate that CIT officers would benefit from continuing education about mental illnesses and that more seasoned officers may be better candidates for CIT training, at least in terms of knowledge retention. | 18,757,600 |
Reproductive cloning in humans and therapeutic cloning in primates: is the ethical debate catching up with the recent scientific advances? | After years of failure, in November 2007 primate embryonic stem cells were derived by somatic cellular nuclear transfer, also known as therapeutic cloning. The first embryo transfer for human reproductive cloning purposes was also attempted in 2006, albeit with negative results. These two events force us to think carefully about the possibility of human cloning which is now much closer to becoming a reality. In this paper we tackle this issue from two sides, first summarising what scientists have achieved so far, then discussing some of the ethical arguments in favour and against human cloning which are debated in the context of policy making and public consultation. Therapeutic cloning as a means to improve and save lives has uncontroversial moral value. As to human reproductive cloning, we consider and assess some common objections and failing to see them as conclusive. We do recognise, though, that there will be problems at the level of policy and regulation that might either impair the implementation of human reproductive cloning or make its accessibility restricted in a way that could become difficult to justify on moral grounds. We suggest using the time still available before human reproductive cloning is attempted successfully to create policies and institutions that can offer clear directives on its legitimate applications on the basis of solid arguments, coherent moral principles, and extensive public consultation. | 18,757,615 |
Challenges of informed choice in organised screening. | Despite much research on informed choice and the individuals' autonomy in organised medical screening, little is known about the individuals' decision-making process as expressed in their own words. To explore the decision-making process among women invited to a mammography screening programme. Women living in the counties of Sør- and Nord-Trøndelag, Norway, invited to the first round of the Norwegian Breast Cancer Screening Program (NBCSP) in 2003. Qualitative methods based on eight semistructured focus-group interviews with a total of 69 women aged 50-69 years. The decision to attend mammography screening was not based on the information in the invitation letter and leaflet provided by the NBCSP. They perceived the invitation letter with a prescheduled appointment as if a decision for mammography had already been made. This was experienced as an aid in overcoming the postponements that easily occur in daily lives. The invitation to mammography screening was embraced as an indication of a responsible welfare state, "like a mother taking care." In a welfare state where governmental institutions are trusted, mass screening for disease is acknowledged by screening participants as a valued expression of paternalism. Trust, gratitude, and convenience were more important factors than information about benefits, harms, and risks when the women made their decisions to attend screening. These elements should be included in the ethical debates on informed choice in preventive medicine. | 18,757,624 |
The do-not-resuscitate order: associations with advance directives, physician specialty and documentation of discussion 15 years after the Patient Self-Determination Act. | Since the passage of the Patient Self-Determination Act, numerous policy mandates and institutional measures have been implemented. It is unknown to what extent those measures have affected end-of-life care, particularly with regard to the do-not-resuscitate (DNR) order. Retrospective cohort study to assess associations of the frequency and timing of DNR orders with advance directive status, patient demographics, physician's specialty and extent of documentation of discussion on end-of-life care. DNR orders were more frequent for patients on a medical service than on a surgical service (77.34% vs 64.20%, p = 0.02) and were made earlier in the hospital stay for medicine than for surgical patients (adjusted mean ratio of time from DNR orders to death versus total length of stay 0.30 for internists vs 0.21 for surgeons, p = 0.04). 22.18% of all patients had some form of an advance directive in their chart, yet this variable had no impact on the frequency or timing of DNR ordering. Documentation of DNR discussion was significantly associated with the frequency of DNR orders and the time from DNR to death (2.1 days with no or minimal discussion vs 2.8 days with extensive discussion, p<0.01). The physician's specialty continues to have a significant impact on the frequency and timing of DNR orders, while advance directive status still has no measurable impact. Additionally, documentation of end-of-life discussions is significantly associated with varying DNR ordering rates and timing. | 18,757,631 |
What reasons do those with practical experience use in deciding on priorities for healthcare resources? A qualitative study. | Priority setting is necessary in current healthcare services. Discussion of fair process has highlighted the value of developing reasons for allocation decisions on the basis of experience gained from real cases. To identify the reasons that those with experience of real decision-making concerning resource allocation think relevant in deciding on the priority of a new but expensive drug treatment. Semistructured interviews with members of committees with responsibility for making resource allocation decisions at a local level in the British National Health Service, analysed using modified grounded theory. 22 interviews were carried out. 14 reasons were identified. Four reasons were almost universally considered most important: cost effectiveness; clinical effectiveness; equality and gross cost. No one reason was considered dominant. Some considerations, such as political directives and fear of litigation, were thought by many participants to distort decision-making. There was a substantial lack of agreement over the relevance of some reasons, such as the absence of alternative treatment for the condition. There is a clear consensus on the importance and role of a limited number of reasons in allocation decisions among participants. A focus on the process of decision-making, however, does not obviate the need for those involved in the process to engage with problematical ethical issues, nor for the importance of further ethical analysis. | 18,757,635 |
Estimating recurrence of spontaneous preterm delivery. | To identify factors associated with spontaneous preterm birth and to estimate the risk of its recurrence for the second through fourth births among women in Utah who had a first and any subsequent birth between 1989 and 2001, using a retrospective cohort study design. Utah state birth records were reviewed to identify women with a first live birth and at least one subsequent live birth from 1989 to 2001. Recurrence risks for spontaneous preterm birth were calculated for first through fourth births. Then all parties (1-12) and multiple maternal risk factors were used to estimate recurrence risks for pre-term birth outcomes by multinomial regression. Recurrence risks for early and late spontaneous preterm birth were calculated. Recurrence also was evaluated as the fraction attributable to previous spontaneous preterm birth. Using the identified factors, the sample was divided and the model was estimated for a subset of births (1989-1999); its predictive value was tested on the remaining births (2000-2001). Women who experienced a spontaneous preterm birth before 34 weeks of gestation in their first or second live birth had the highest rate of recurrence. Spontaneous preterm birth before 34 weeks was the highest risk factor for recurrence of early spontaneous preterm birth (relative risk 13.56, 95% confidence interval 11.5-16.0), and, in general, risks were highest for recurrences of same gestational age outcomes. A history of a live spontaneous birth before 34 weeks of gestation is a strong predictor of subsequent spontaneous preterm birth. A model of clinical risk factors may be used to identify women at increased risk for recurrent spontaneous preterm birth. | 18,757,647 |
High-concentration supplemental perioperative oxygen to reduce the incidence of postcesarean surgical site infection: a randomized controlled trial. | Most postcesarean infections are caused by anaerobic bacteria. Oxidative killing, an important defense against surgical infections, depends on the oxygen level in contaminated tissue. Among patients undergoing colorectal surgery, perioperative supplemental oxygen decreased infection rates by 50%. We tested the hypothesis that high-concentration inspired oxygen decreases the incidence of surgical site infection in women undergoing cesarean delivery. Using a double blind technique, 143 women undergoing cesarean delivery under regional anesthesia after the onset of labor were randomly assigned to receive low- or high-concentration inspired oxygen via nonrebreathing mask during the operation and for 2 hours after. Surgical site infection was defined clinically as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery. Interim statistical analysis was performed after 25% of the planned sample size (143 of 550) accrued using intention-to-treat principle. The stopping rule P value for futility was P>.11 with two planned interim analyses. Postcesarean infection occurred in 17 (25%, 95% confidence interval [CI] 15-35%) of 69 women assigned to high-concentration oxygen compared with 10 (14%, 95% CI 6-22%) of 74 women assigned to low-concentration inspired oxygen (relative risk 1.8, 95% CI 0.9-3.7, P=.13). The P value exceeded the P value for futility, suggesting these differences were unlikely to reach statistical significance with continued recruitment. High-concentration perioperative oxygen delivered through a nonrebreathing mask did not decrease the risk of postcesarean surgical site infection. | 18,757,651 |
Correlation of catheterized and clean catch urine protein/creatinine ratios in preeclampsia evaluation. | To examine whether clean catch urine specimens correlate with catheterized specimens for determination of protein/creatinine ratios in pregnant women being evaluated for preeclampsia. Sixty pregnant women who were at least at 20 weeks of gestation were enrolled. Patients with ruptured membranes, vaginal bleeding, or urinary tract infections were excluded. Midstream clean catch urine specimens were collected. Catheterized specimens were then collected and used for clinical management. The specimens were analyzed for protein, creatinine, urinalysis, and culture. Based on sample size calculations, 60 participants were needed to detect a correlation of 0.90 with 80% power and alpha=0.05. Mean gestational age at enrollment was 35.9 weeks (range 23.1-41.7 weeks). Median (range) clean catch and catheterized protein/creatinine ratios were 0.204 (0.089-3.465) and 0.181 (0.067-3.335), respectively, with a correlation coefficient of 0.897 (P<.001). When results were categorized by degree of proteinuria using a cutoff of 0.3, sensitivity and specificity of the clean catch protein/creatinine ratios were 95.2% and 97.4%. When using a more conservative cutoff of 0.19, sensitivity and specificity of the clean catch protein/creatinine ratios were 96.4% and 75.0%. Clean catch and catheterized urine specimens correlate well in women with suspected preeclampsia. Routine catheterization of pregnant women is not necessary in the evaluation of preeclampsia. | 18,757,659 |
Retinal waves in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor. | The structural and functional properties of the visual system are disrupted in mutant animals lacking the beta2 subunit of the nicotinic acetylcholine receptor. In particular, eye-specific retinogeniculate projections do not develop normally in these mutants. It is widely thought that the developing retinas of beta2(-/-) mutants do not manifest correlated activity, leading to the notion that retinal waves play an instructional role in the formation of eye-specific retinogeniculate projections. By multielectrode array recordings, we show here that the beta2(-/-) mutants have robust retinal waves during the formation of eye-specific projections. Unlike in WT animals, however, the mutant retinal waves are propagated by gap junctions rather than cholinergic circuitry. These results indicate that lack of retinal waves cannot account for the abnormalities that have been documented in the retinogeniculate pathway of the beta2(-/-) mutants and suggest that other factors must contribute to the deficits in the visual system that have been noted in these animals. | 18,757,739 |
Toxoplasma gondii Tic20 is essential for apicoplast protein import. | Apicomplexan parasites harbor a secondary plastid that has lost the ability to photosynthesize yet is essential for the parasite to multiply and cause disease. Bioinformatic analyses predict that 5-10% of all proteins encoded in the parasite genome function within this organelle. However, the mechanisms and molecules that mediate import of such large numbers of cargo proteins across the four membranes surrounding the plastid remain elusive. In this work, we identify a highly diverged member of the Tic20 protein family in Apicomplexa. We demonstrate that Tic20 of Toxoplasma gondii is an integral protein of the innermost plastid membrane. We engineer a conditional null-mutant and show that TgTic20 is essential for parasite growth. To characterize this mutant functionally, we develop several independent biochemical import assays to reveal that loss of TgTic20 leads to severe impairment of apicoplast protein import followed by organelle loss and parasite death. TgTic20 is the first experimentally validated protein import factor identified in apicoplasts. Our studies provide experimental evidence for a common evolutionary origin of import mechanisms across the innermost membranes of primary and secondary plastids. | 18,757,752 |
Structural basis for the catalytic mechanism of human phosphodiesterase 9. | The phosphodiesterases (PDEs) are metal ion-dependent enzymes that regulate cellular signaling by metabolic inactivation of the ubiquitous second messengers cAMP and cGMP. In this role, the PDEs are involved in many biological and metabolic processes and are proven targets of successful drugs for the treatments of a wide range of diseases. However, because of the rapidity of the hydrolysis reaction, an experimental knowledge of the enzymatic mechanisms of the PDEs at the atomic level is still lacking. Here, we report the structures of reaction intermediates accumulated at the reaction steady state in PDE9/crystal and preserved by freeze-trapping. These structures reveal the catalytic process of a PDE and explain the substrate specificity of PDE9 in an actual reaction and the cation requirements of PDEs in general. | 18,757,755 |
Mechano-regulated tenascin-C orchestrates muscle repair. | Tenascin-C (TNC) is a mechano-regulated, morphogenic, extracellular matrix protein that is associated with tissue remodeling. The physiological role of TNC remains unclear because transgenic mice engineered for a TNC deficiency, via a defect in TNC secretion, show no major pathologies. We hypothesized that TNC-deficient mice would demonstrate defects in the repair of damaged leg muscles, which would be of functional significance because this tissue is subjected to frequent cycles of mechanical damage and regeneration. TNC-deficient mice demonstrated a blunted expression of the large TNC isoform and a selective atrophy of fast-muscle fibers associated with a defective, fast myogenic expression response to a damaging mechanical challenge. Transcript profiling mapped a set of de-adhesion, angiogenesis, and wound healing regulators as TNC expression targets in striated muscle. Expression of these regulators correlated with the residual expression of a damage-related 200-kDa protein, which resembled the small TNC isoform. Somatic knockin of TNC in fast-muscle fibers confirmed the activation of a complex expression program of interstitial and slow myofiber repair by myofiber-derived TNC. The results presented here show that a TNC-orchestrated molecular pathway integrates muscle repair into the load-dependent control of the striated muscle phenotype. | 18,757,758 |
High-dose methotrexate for elderly patients with primary CNS lymphoma. | The introduction of methotrexate (MTX)-based chemotherapy has improved median survival for patients with primary CNS lymphoma (PCNSL). Older age is a negative prognostic marker in patients with PCNSL and may increase the likelihood of MTX toxicity. We studied the response and adverse effects of intravenous high-dose MTX in patients who were 70 or more years of age at the time of diagnosis. We identified 31 patients at our institution diagnosed with PCNSL at age > or =70 years (median, 74 years) who were treated with high-dose MTX (3.5-8 g/m(2)) as initial therapy from 1992 through 2006. The best response to MTX was determined by contrast-enhanced MRI. Toxicity was analyzed by chart review. These 31 patients received a total of 303 cycles of MTX (median, eight cycles per patient). Overall, 87.9% of the cycles required dose reduction because of impaired creatinine clearance. In 30 evaluable patients, the overall radiographic response rate was 96.7%, with 18 complete responses (60%) and 11 partial responses (36.7%). Progression-free survival and overall survival were 7.1 months and 37 months, respectively. Grade I-IV toxicities were observed in 27 of 31 patients and included gastrointestinal disturbances in 58% (3.2% grade III), hematological complications in 80.6% (6.5% grade III), and renal toxicity in 29% (0% grade III/IV). High-dose MTX is associated with a high proportion of radiographic responses and a low proportion of grade III/IV toxicity in patients 70 or more years of age. High-dose MTX should be considered as a feasible treatment option in elderly patients with PCNSL. | 18,757,775 |
Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. | The role of gender on the disposition of drugs metabolized by cytochrome P4503A (CYP3A) remains controversial. Some sources suggest that CYP3A activity in women exceeds that in men, but evidence to support this position is inconsistent at best. We evaluated 38 data sets in which clearance of CYP3A substrate drugs was studied in healthy young male and young female subjects. None of these drugs was a substrate for transport by P-glycoprotein (P-gp). The overall mean (+/-SE) for the female/male ratio of weight-normalized clearance was 1.26 (+/-0.07) for parenteral dosage and 1.17 (+/-0.07) for oral dosage. Both ratios were significantly different (P < .05) from 1.0. For oral dosage studies, the female/male clearance ratio was unrelated to the drug's absolute oral bioavailability. Thus gender has a small and statistically significant, although most likely clinically unimportant, influence on CYP3A phenotype for substrates not transported by P-gp. | 18,757,784 |
Effect of single and repeated doses of ketoconazole on the pharmacokinetics of roflumilast and roflumilast N-oxide. | Effects of single and multiple doses of oral ketoconazole on roflumilast and its active metabolite, roflumilast N-oxide, were investigated in healthy subjects. In study 1, subjects (n = 26) received oral roflumilast 500 microg once daily for 11 days and a concomitant 200-mg single dose of ketoconazole on day 11. In study 2, subjects (n = 16) received oral roflumilast 500 microg on days 1 and 11 and a repeated dose of ketoconazole 200 mg twice daily from days 8 to 20. Coadministration of single-dose ketoconazole with steady-state roflumilast increased the AUC of roflumilast by 34%; C(max) was unchanged. For roflumilast N-oxide, AUC and C(max) decreased by 12% and 20%, respectively. Repeated doses of ketoconazole increased the AUC and C(max) of roflumilast by 99% and 23%, respectively; for roflumilast N-oxide, AUC was unchanged, and C(max) decreased by 38%. No clinically relevant adverse events were observed. Coadministration of ketoconazole and roflumilast does not require dose adjustment of roflumilast. | 18,757,786 |
Production of curcuminoids by Escherichia coli carrying an artificial biosynthesis pathway. | Curcuminoids, which are produced specifically by plants of the order Zingiberales, have long been used as food additives because of their aromatic, stimulant and colouring properties and as traditional Asian medicines because of their anti-tumour, antioxidant and hepatoprotective activities. Curcuminoids are therefore attractive targets for metabolic engineering. An artificial curcuminoid biosynthetic pathway, including reactions of phenylalanine ammonia-lyase (PAL) from the yeast Rhodotorula rubra, 4-coumarate : CoA ligase (4CL) from Lithospermum erythrorhizon and curcuminoid synthase (CUS) from rice (Oryza sativa), a type III polyketide synthase, was constructed in Escherichia coli for the production of curcuminoids. Cultivation of the recombinant E. coli cells in the presence of tyrosine or phenylalanine, or both, led to production of bisdemethoxycurcumin, dicinnamoylmethane and cinnamoyl-p-coumaroylmethane. Another E. coli system carrying 4CL and CUS genes was also used for high-yield production of curcuminoids from exogenously supplemented phenylpropanoid acids: p-coumaric acid, cinnamic acid and ferulic acid. The yields of curucminoids were up to approximately 100 mg l(-1). Furthermore, this system gave approximately 60 mg curcumin l(-1) from 10 g rice bran pitch, an industrial waste discharged during rice edible oil production, as a source of ferulic acid. | 18,757,796 |
Lactobacillus plantarum response to inorganic carbon concentrations: PyrR2-dependent and -independent transcription regulation of genes involved in arginine and nucleotide metabolism. | Lactobacillus plantarum susbp. plantarum is a capnophilic Gram-positive heterotroph with optimal growth in 4 % CO(2)-enriched air. At low inorganic carbon (C(i)) concentrations, the pyr genes encoding the enzymes of the pyrimidine biosynthetic pathway were overexpressed, in agreement with a previous study showing that these genes are regulated at the transcription level in response to C(i) via a PyrR(2)-mediated mechanism. A previous study of high-CO(2)-requiring (HCR) mutants revealed an unknown genetic link between arginine regulation and C(i)-dependent nutritional needs. To better understand L. plantarum's adaptation to C(i) availability, additional C(i)-responsive genes were sought in the arginine biosynthetic pathway (arg and car genes) using slot-blot hybridization and a proteomic differential 2D gel electrophoresis (DIGE) global approach. Besides the nine pyr-encoded proteins, 16 new Icr (inorganic-carbon-regulated) proteins accumulated differentially in response to C(i) availability, suggesting that the C(i) response involves several metabolic pathways and adaptation processes. Among these Icr proteins only argininosuccinate lyase, encoded by argH, was involved in arginine biosynthesis. Three proteins involved in the purine biosynthetic pathway and nucleotide conversion, adenylate kinase (Adk), GMP synthase (GuaA), and IMP dehydrogenase (GuaB), accumulated differentially in response to changes in C(i) levels. Expression of the Icr protein-encoding genes argH and guaB was regulated at the transcription level or by RNA stability in response to C(i) availability, as previously demonstrated for the pyr genes. However, PyrR(2) was not essential for the C(i)-regulated transcription of argH and guaB, demonstrating that PyrR(2) modulates only a subset of C(i)-regulated genes. These results suggest that the C(i) response may involve at least two regulatory mechanisms in L. plantarum. | 18,757,797 |
Transcriptional interplay among the regulators Rrp2, RpoN and RpoS in Borrelia burgdorferi. | The RpoN-RpoS alternative sigma factor pathway is essential for key adaptive responses by Borrelia burgdorferi, particularly those involved in the infection of a mammalian host. A putative response regulator, Rrp2, is ostensibly required for activation of the RpoN-dependent transcription of rpoS. However, questions remain regarding the extent to which the three major constituents of this pathway (Rrp2, RpoN and RpoS) act interdependently. To assess the functional interplay between Rrp2, RpoN and RpoS, we employed microarray analyses to compare gene expression levels in rrp2, rpoN and rpoS mutants of parental strain 297. We identified 98 genes that were similarly regulated by Rrp2, RpoN and RpoS, and an additional 47 genes were determined to be likely regulated by this pathway. The substantial overlap between genes regulated by RpoS and RpoN provides compelling evidence that these two alternative sigma factors form a congruous pathway and that RpoN regulates B. burgdorferi gene expression through RpoS. Although several known B. burgdorferi virulence determinants were regulated by the RpoN-RpoS pathway, a defined function has yet to be ascribed to most of the genes substantially regulated by Rrp2, RpoN and RpoS. | 18,757,798 |
Mitochondrial involvement in aspirin-induced apoptosis in yeast. | We have previously reported that aspirin induces apoptosis in manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae cells when cultivated on the non-fermentable carbon source ethanol. Here, we investigated the role of mitochondria in aspirin-induced apoptosis. We report that aspirin had an inhibitory effect on cellular respiration, and caused the release of most of the mitochondrial cytochrome c and a dramatic drop in the mitochondrial membrane potential (DeltaPsi(m)). Also, aspirin reduced the intracellular cytosolic pH in the MnSOD-deficient cells growing in ethanol medium, but this did not seem to be the initial trigger that committed these cells to aspirin-induced apoptosis. Furthermore, loss of DeltaPsi(m) was not required for aspirin-induced release of cytochrome c, since the initial release of cytochrome c occurred prior to the disruption of the DeltaPsi(m). It is thus possible that cytochrome c release does not involve the early onset of the mitochondrial permeability transition, but only an alteration of the permeability of the outer mitochondrial membrane. | 18,757,807 |
The impact of childhood ADHD on dropping out of high school in urban adolescents/ young adults. | To examine cognitive and psychosocial factors associated with high school dropout in urban adolescents with and without childhood ADHD. In a longitudinal study, 49 adolescents/young adults with childhood ADHD and 44 controls who either dropped out or graduated from high school are included. Risk factors examined as potential correlates of dropout were intelligence, reading skills, socioeconomic status, marijuana use, and paternal contact. Lower IQ, reading ability, socioeconomic status, frequent marijuana use, and limited paternal contact significantly differentiated dropouts from graduates, irrespective of childhood ADHD. Follow-up analyses determined that IQ, marijuana use, and paternal contact independently contribute to the likelihood of dropout. Selected cognitive and psychosocial factors appear independently associated with the likelihood of high school dropout irrespective of ADHD. Notably, childhood ADHD did not increase this risk, suggesting that previous reports of increased dropout because of ADHD may become negated in urban areas when matched with similar community controls. | 18,757,845 |
A common inferior pulmonary trunk detected by computed tomography affects atrial fibrillation ablation strategy. | Pulmonary veins (PV) display a variety of anomalies with a common trunk of the inferior pulmonary veins being the most infrequent. We report on a 65-year-old man who underwent an ablation procedure for atrial fibrillation (AF) exclusively based on electro-anatomical mapping. After recurrence of AF, a common trunk of the inferior PV was detected by computed tomography imaging resulting in a modified ablation approach. Due to a possible role of the common inferior trunk for the initiation of AF, a repeat procedure was performed by en bloc isolation of the common inferior trunk with the left superior PV. The right superior PV was ablated separately. Off antiarrhythmic medication, the patient has remained free of any arrhythmia during a 14 month follow-up. | 18,757,868 |
SNAP predicts effect of mutations on protein function. | Many non-synonymous single nucleotide polymorphisms (nsSNPs) in humans are suspected to impact protein function. Here, we present a publicly available server implementation of the method SNAP (screening for non-acceptable polymorphisms) that predicts the functional effects of single amino acid substitutions. SNAP identifies over 80% of the non-neutral mutations at 77% accuracy and over 76% of the neutral mutations at 80% accuracy at its default threshold. Each prediction is associated with a reliability index that correlates with accuracy and thereby enables experimentalists to zoom into the most promising predictions. | 18,757,876 |
Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects. | Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, most often caused by mutations in the MLC1 gene. MLC1 is an oligomeric plasma membrane (PM) protein of unknown function expressed mainly in glial cells and neurons. Most disease-causing missense mutations dramatically reduced the total and PM MLC1 expression levels in Xenopus oocytes and mammalian cells. The impaired expression of the mutants was verified in primary cultures of rat astrocytes, as well as human monocytes, cell types that endogenously express MLC1, demonstrating the relevance of the tissue culture models. Using a combination of biochemical, pharmacological and imaging methods, we also demonstrated that increased endoplasmatic reticulum-associated degradation and endo-lysosomal-associated degradation can contribute to the cell surface expression defect of the mutants. Based on these results, we suggest that MLC1 mutations reduce protein levels in vivo. Since the expression defect of the mutants could be rescued by exposing the mutant-protein expressing cells to low temperature and glycerol, a chemical chaperone, we propose that MLC belongs to the class of conformational diseases. Therefore, we suggest the use of pharmacological strategies that improve MLC1 expression to treat MLC patients. | 18,757,878 |
Patient dose in neonatal units. | Lung disease represents one of the most life-threatening conditions in prematurely born children. In the evaluation of the neonatal chest, the primary and most important diagnostic study is therefore the chest radiograph. Since prematurely born children are very sensitive to radiation, those radiographs may lead to a significant radiation detriment. Hence, knowledge of the patient dose is necessary to justify the exposures. A study to assess the patient doses was started at the neonatal intensive care unit (NICU) of the University Hospital in Leuven. Between September 2004 and September 2005, prematurely born babies underwent on average 10 X-ray examinations in the NICU. In this sample, the maximum was 78 X-ray examinations. For chest radiographs, the median entrance skin dose was 34 microGy and the median dose area product was 7.1 mGy.cm(2). By means of conversion coefficients, the measured values were converted to organ doses. Organ doses were calculated for three different weight classes: extremely low birth weight infants (<1000 g), low birth weight infants (1000-2500 g) and normal birth weight infants (>2500 g). The doses to the lungs for a single chest radiograph for infants with extremely low birth weights, low birth weights and normal birth weights were 24, 25 and 32 microGy, respectively. | 18,757,900 |
Transmission dynamics of heritable silencing induced by double-stranded RNA in Caenorhabditis elegans. | Heritable silencing effects are gene suppression phenomena that can persist for generations after induction. In the majority of RNAi experiments conducted in Caenorhabditis elegans, the silencing response results in a hypomorphic phenotype where the effects recede after the F1 generation. F2 and subsequent generations revert to the original phenotype. Specific examples of transgenerational RNAi in which effects persist to the F2 generation and beyond have been described. In this study, we describe a systematic pedigree-based analysis of heritable silencing processes resulting from initiation of interference targeted at the C. elegans oocyte maturation factor oma-1. Heritable silencing of oma-1 is a dose-dependent process where the inheritance of the silencing factor is unequally distributed among the population. Heritability is not constant over generational time, with silenced populations appearing to undergo a bottleneck three to four generations following microinjection of RNA. Transmission of silencing through these generations can be through either maternal or paternal gamete lines and is surprisingly more effective through the male gametic line. Genetic linkage tests reveal that silencing in the early generations is transmitted independently of the original targeted locus, in a manner indicative of a diffusible epigenetic element. | 18,757,930 |
Inducing segmental aneuploid mosaicism in the mouse through targeted asymmetric sister chromatid event of recombination. | Loss or gain of whole chromosomes, or parts of chromosomes, is found in various pathological conditions, such as cancer and aneuploidy, and results from the missegregation of chromosomes during cellular division or abnormal mitotic recombination. We introduce a novel strategy for determining the consequences of segmental aneuploid mosaicism, called targeted asymmetric sister chromatin event of recombination (TASCER). We took advantage of the Cre/loxP system, used extensively in embryonic stem cells for generating deletions and duplications of regions of interest, to induce recombination during the G2 phase. Using two loxP sites in a Cis configuration, we generated in vivo cells harboring microdeletions and microduplications for regions of interest covering up to 2.2 Mb. Using this approach in the mouse provides insight into the consequences of segmental aneuploidy for homologous regions of the human chromosome 21 on cell survival. Furthermore, TASCER shows that Cre-induced recombination is more efficient after DNA replication in vivo and provides an opportunity to evaluate, through genetic mosaics, the outcome of copy number variation and segmental aneuploidy in the mouse. | 18,757,940 |
A simple performance test for quantifying the severity of cervical myelopathy. | We evaluated 30 patients with cervical myelopathy before and after decompressive surgery and compared them with 42 healthy controls. All were asked to grip and release their fingers as rapidly as possible for 15 seconds. Films recorded with a digital camera were divided into three files of five seconds each. Three doctors independently counted the number of grip and release cycles in a blinded manner (N1 represents the number of cycles for the first five-second segment, N2 for the second and N3 for the third). N1 [corrected] N2 and N3 of the pre-operative group were significantly fewer than those of the control group, and the post-operative [corrected] group's results were significantly fewer [corrected] than those of the pre-operative group. In the control group, the numbers decreased significantly with each succeeding five-second interval (fatigue phenomenon). In the pre-operative myelopathy group there was no significant difference between N1 and N2 (freezing phenomenon). The 15-second test is shown to be reliable in the quantitative evaluation of cervical myelopathy. Although it requires a camera and animation files, it can detect small changes in neurological status because of its precise and objective nature. | 18,757,962 |
The viability and proliferation of human chondrocytes following cryopreservation. | Human articular cartilage samples were retrieved from the resected material of patients undergoing total knee replacement. Samples underwent automated controlled freezing at various stages of preparation: as intact articular cartilage discs, as minced articular cartilage, and as chondrocytes immediately after enzymatic isolation from fresh articular cartilage. Cell viability was examined using a LIVE/DEAD assay which provided fluorescent staining. Isolated chondrocytes were then cultured and Alamar blue assay was used for estimation of cell proliferation at days zero, four, seven, 14, 21 and 28 after seeding. The mean percentage viabilities of chondrocytes isolated from group A (fresh, intact articular cartilage disc samples), group B (following cryopreservation and then thawing, after initial isolation from articular cartilage), group C (from minced cryopreserved articular cartilage samples), and group D (from cryopreserved intact articular cartilage disc samples) were 74.7% (95% confidence interval (CI) 73.1 to 76.3), 47.0% (95% CI 43 to 51), 32.0% (95% CI 30.3 to 33.7) and 23.3% (95% CI 22.1 to 24.5), respectively. Isolated chondrocytes from all groups were expanded by the following mean proportions after 28 days of culturing: group A ten times, group B 18 times, group C 106 times, and group D 154 times. This experiment demonstrated that it is possible to isolate viable chondrocytes from cryopreserved intact human articular cartilage which can then be successfully cultured. | 18,757,968 |
Grey matter abnormalities in trichotillomania: morphometric magnetic resonance imaging study. | Trichotillomania (repetitive hair-pulling) is an Axis I psychiatric disorder whose neurobiological basis is incompletely understood. Whole-brain trichotillomania neuroimaging studies are lacking. To investigate grey and white matter abnormalities over the whole brain in patients with trichotillomania. Eighteen patients with DSM-IV trichotillomania and 19 healthy controls undertook structural magnetic resonance imaging after providing written informed consent. Differences in grey and white matter were investigated using computational morphometry. Patients with trichotillomania showed increased grey matter densities in the left striatum, left amygdalo-hippocampal formation, and multiple (including cingulate, supplementary motor, and frontal) cortical regions bilaterally. Trichotillomania was associated with structural grey matter changes in neural circuitry implicated in habit learning, cognition and affect regulation. These findings inform animal models of the disorder and highlight key regions of interest for future translational research. | 18,757,980 |
[Mechanism underlying osteoarthritis induced by mechanical stress on joint cartilage]. | Osteoarthritis (OA) , one of the most common skeletal disorders characterized by cartilage degradation and osteophyte formation in joints, is induced by accumulated mechanical stress ; however, little is known about the underlying molecular mechanism. Several experimental OA models in mice by producing instability in the knee joints have been developed to apply approaches from mouse genetics. Our mouse genetic approaches found that the induction of a transcriptional activator Runx2 in chondrocytes under mechanical stress contributes to the pathogenesis of OA through chondrocyte hypertrophy. In addition, chondrocyte apoptosis has recently been identified as being involved in OA progression. We hereby propose that these endochondral ossification signals may be important for the OA progression, suggesting that the related molecules can clinically be therapeutic targets of this disease. | 18,758,033 |
[Osteocytes and mechanical stress]. | A number of fascinating studies suggest that osteocytes play an important role in bone metabolism, especially in its regulation by mechanical stimuli. However, it has been still discussed how the osteocytes were activated by mechanical stimuli. For example, direct mechanical load applied to cells at levels measured to occur in humans in vivo do not affect bone cells in vitro . In order to solve the contradiction, theories based on fluid flow-induced shear stress stimulation around osteocytes in bone have appeared with the most prominence. In addition, I would like to introduce recent hypothesis to mechanically stimulate osteocyte, such as strain amplification by radial hoop strains, flow induced integrin mediated signaling, and osteocyte lacuna strain. To validate the availability of these hypothesis, it is important to observe 3-dimensional osteocyte morphology as well as its interaction with pericellular matrix. | 18,758,034 |
[TRP channels and mechanical stress]. | Transient receptor potential (TRP) channels respond to diverse external stimuli and convert them into intracellular calcium signals. Recent evidence shows that TRPV4, one of the vanilloid subfamily, plays a key role in mechanosensation in bone. Here I summarize the current knowledge on possible functions of TRP channels. | 18,758,036 |
[PTH and mechanical stress]. | Intermittent administration of PTH increases bone mass by enhancing bone formation. Several mechanisms have been demonstrated for this effect of PTH on bone formation such as the enhancement of Wnt signaling as well as the stimulation of differentiation and the inhibition of apoptosis of cells in the osteoblast lineage. Because mechanical loading to bone also enhances bone formation at least in part through the stimulation of Wnt signaling, it has been anticipated that the intermittent PTH is useful for the prevention of bone loss by mechanical unloading. However, results so far obtained in animal models have indicated that PTH can not completely abolish the deleterious effect of unloading on bone mass. It is necessary to search new drugs that show more potent effect on bone formation and also to investigate the mechanism of action of mechanical loading on bone. | 18,758,039 |
[Supracondylar and condylar fracture of the humerus]. | Fractures of the distal humerus around the elbow joint are most often in supracondylar or condylar lesion. This article described the diagnosis, classification, treatment, progress, side-effect, after-treatment and rehabilitation of fractures of supracondylar, lateral condyle and medial epicondyle of the humerus in child, and also described these of supracondylar, epicondylar fractures of the humerus in adult. Physical therapy should include active and active-assisted exercises for joint mobilization as soon as soft tissue healing permits. To prevent the contracture and the loss of motion of the elbow, rehabilitation of the patient and upper extremity should begin immediately, depending on the fracture and soft tissue stability in these fractures. | 18,758,040 |
Dipyridamole therapy improves long-term survival after complete revascularization in patients with impaired cardiac function: a propensity analysis. | Although dipyridamole is no longer used as a mainstream medication for coronary artery disease because of the coronary steal phenomenon, recent studies have shown that the elevation of serum adenosine levels caused by dipyridamole improves cardiac function in heart failure patients. In the present study it was investigated whether use of dipyridamole at the time of complete revascularization affects long-term mortality in patients with impaired left ventricular (LV) function. The 1,836 consecutive patients who underwent complete revascularization between 1984 and 1992 were assessed; 254 patients with impaired LV function (ejection fraction < 50%) were enrolled. Cox proportional hazards regression adjusted for baseline covariates and the propensity score were used to compare the risks for mortality between patients who did and did not take dipyridamole. The mean follow-up period was 12 years; 178 patients (70.1%) took dipyridamole and there were 66 (37.1%) all-cause and 22 (12.4%) cardiac deaths in that group. In the multivariate analysis, the dipyridamole group had a lower risk for both all-cause (hazard ratio (HR) 0.54; p = 0.005) and cardiac mortality (HR 0.42; p = 0.010). The use of dipyridamole reduced both all-cause and cardiac mortality in patients with impaired LV function. | 18,758,087 |
Sustained release of prostaglandin E1 potentiates the impaired therapeutic angiogenesis by basic fibroblast growth factor in diabetic murine hindlimb ischemia. | Basic fibroblast growth factor (bFGF) is a potent mitogen; however, diabetes mellitus might impair its angiogenic property. Prostaglandin E1 (PGE1) is a potent vasodilator and improves endothelial function. Thus, PGE1 could potentiate the angiogenic properties of bFGF in patients with diabetes mellitus. Streptozotocin-induced diabetic mice with unilateral hindlimb ischemia were randomly treated as follows: no treatment, 0.2 microg of PGE1, 10 microg of bFGF, and combined administration of PGE1 and bFGF. Blood perfusion was evaluated by the ratio of ischemic-to normal-limb blood perfusion. Four weeks after the treatment, the combined administration of bFGF and PGE1 increased the blood perfusion ratio as compared with single bFGF or PGE1 (77+/-10% vs 56+/-10% and 58+/-10%; p < 0.05, respectively). A histological evaluation showed that vascular density in the combined therapy was higher than single bFGF or PGE1 (418+/-59 vs 306+/-69 and 283+/-71 vessels/mm2; p < 0.01, respectively); the maturity in combined therapy was also higher than single bFGF or PGE1 (46+/-14 vs 30+/-14 and 28+/-6 vessels/mm2; p < 0.01, respectively). PGE1 potentiated the impaired angiogenic properties of bFGF in diabetic murine hindlimb ischemia. This new strategy might contribute to more effective therapeutic angiogenesis for ischemic limb in patients with diabetes. | 18,758,090 |
Coumarins from campylotropis hirtella (FRANCH.) SCHINDL. and their inhibitory activity on prostate specific antigen secreted from LNCaP cells. | Campylotropis hirtella (FRANCH.) SCHINDL. was used as a folk medicine for the treatment of benign prostate hyperplasia (BPH) in China. In this study, two new coumarins, 7,2',4'-trihydroxy-5-methoxy-3-arylcoumarin (1), 6-[(1S,2S)-2-angeloyloxy-1,3-dihydroxy-3-methylbutyl]-7-methoxycoumarin, named angelol M (2), together with eleven known related compounds (3-13) were isolated from this plant under the bioassay guided fractionation. All the compounds showed activity with different levels in inhibiting prostate specific antigen (PSA) secreted from androgen dependent prostate cancer cell line, LNCaP cells, using ELISA method. | 18,758,115 |
8'-Hydroxyzearalanone and 2'-hydroxyzearalanol: resorcyclic acid lactone derivatives from the marine-derived fungus Penicillium sp. | Two new 14-membered resorcyclic acid lactone derivatives, 8'-hydroxyzearalanone (1) and 2'-hydroxyzearalanol (2), and four known zearalanone derivatives (3-6) were isolated from the marine-derived fungus Penicillium sp. The structures of compounds 1-6 were elucidated by spectroscopic methods. | 18,758,119 |
Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells. | Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells. | 18,758,152 |
First prenatally detected small supernumerary neocentromeric derivative chromosome 13 resulting in a non-mosaic partial tetrasomy 13q. | Neocentromeres are functional centromeres located in non-centromeric euchromatic regions of chromosomes. The formation of neocentromeres results in conferring mitotic stability to chromosome fragments that do not contain centromeric alpha satellite DNA. We present a report of a prenatal diagnosis referred to cytogenetic studies due to ultrasound malformations such as large cisterna magna, no renal differentiation, hypotelorism and ventriculomegaly. Cytogenetic analysis of GTG-banded chromosomes from amniotic fluid cells and fetal blood cells revealed a de novo small supernumerary marker chromosome. Molecular cytogenetic studies using fluorescence in situ hybridization and comparative genomic hybridization showed this marker to be an inverted duplication of the distal portion of chromosome 13q which did not contain detectable alpha satellite DNA. The neocentromeric constriction was located at band 13q31. The presence of a functional neocentromere on this marker chromosome was confirmed by immunofluorescence with antibodies to centromere protein-C. The anatomopathologic study revealed a female fetus with facial dysmorphisms, low set ears and renal dysplasia. Ten small supernumerary neocentromeric chromosomes originating from the distal region of chromosome 13q have been reported to date. There are only three additional cases described with the location of the neocentromere in band 13q31. This is the first reported case detected prenatally. | 18,758,175 |
Pattern of pain management practices of Filipino surgeons. | Among all the fields of specialization in medicine, the surgeons probably encounter the highest number of pain patients, aside from 'causing' many painful conditions due to surgical procedures. It was widely presumed that surgeons in general do not pay much attention to pain management of their patients, often passing on the responsibility to other specialists. A survey was conducted among general surgeons from all the regions in the Philippines. There were 167 respondents of 200 questionnaires sent. An 18-item, multiple-choice questionnaire was developed to assess their prevailing pain management practices preoperatively, postoperatively and when the patients are recovering, as well as their preferences in medications. The majority of the respondents (58%) claim that they personally manage their patients' postoperative pain. Almost half use a combination of a nonsteroidal anti-inflammatory drug (NSAID) and a weak opioid, and only 13% use a combination of a strong opioid and an NSAID. Only 17% of the respondents start oral medications in the recovery room. The majority (90%) claim that they personally attend to their patients' pain in the wards. Almost all the respondents (98.8%) started oral medications as soon as possible. Only 20% of the respondents always use the Visual Analog Scale in pain assessment. The majority of the respondents (55%) have no narcotic license (S2). Although the majority of the respondents claim to be involved in the management of perioperative pain of their patients, an objective assessment of the patients' pain is not usually done. The use of opioids alone or in combination is still low among Filipino surgeons; the main reason could be the regulatory provisions of the government on opioid use. | 18,758,196 |
Postmarketing surveillance study of OxyContin tablets for relieving moderate to severe cancer pain. | To evaluatethe efficacy and safety of OxyContin tablets (controlled-release oxycodone hydrochloride: 5, 10, 20, and 40 mg) in relieving moderate to severe cancer pain. A multicenter, open-label, prospective, self-controlled clinical trial was used. Pain was relieved in 89.1% of patients within 1 h after drug administration. OxyContin tablets showed good clinical efficacy in relieving both moderate and severe cancer pain. Compared with baseline average pain scores of 6.9 +/- 1.4, subjects had lower average pain scores after administration of OxyContin tablets: 2.7 +/- 1.8 after 1 week and 2.1 +/- 1.5 after 2 weeks. Response rate reached 75.0% at the end of the 1st week and was maintained at approximately 90% from the 3rd to the 8th week. The most common adverse drug reactions (ADRs) caused by OxyContintablets were, in descending order of incidence rate: constipation (25.5%), nausea (13.3%), vomiting (6.2%), lethargy (3.7%), and dysuria (2.1%). All these ADRs could be decreased by preventive medications. OxyContin tablets demonstrated fast onset of cancer pain control, superior efficacy in relieving both moderate and severe cancer pain and a good safety profile. | 18,758,197 |
Urodynamic evaluation of patients with lower urinary tract symptoms and small prostate volume. | The relevance of prostate size in the pathophysiology of lower urinary tract symptoms (LUTS) is controversial. We evaluated the urodynamic findings in patients with LUTS and small prostate volumes. 84 patients aged >or=50 years with LUTS and prostates <40 ml were evaluated. All had an International Prostate Symptom Score (IPSS) >or=8. Average age was 62.0 +/- 8.1 years. We evaluated the impact of bladder outlet obstruction (BOO) and detrusor overactivity (DO) on the voiding symptoms and urodynamic findings. Mean prostate volume was 29.2 +/- 7.2 ml and mean IPSS was 13.5 +/- 4.6. BOO was the main finding, affecting 42 (50.0%) patients, followed by detrusor underactivity (DU) in 41 (48.8%) and DO in 28 (33.3%) patients. Patients without BOO were significantly older than the obstructed (64.0 +/- 8.8 and 60.1 +/- 6.9 years, respectively; p = 0.026) and had an increased prevalence of DU (76.2 and 21.4%, respectively; p < 0.001). Comparison of patients with and without DO showed reduced bladder capacity and compliance in the DO group (p < 0.001). No other comparisons were significant. Half of the patients with LUTS and small prostates are not obstructed and may have DO or decreased detrusor contractility as the basis for their voiding symptoms. Our results emphasize the value of urodynamics in this population, especially when invasive treatments are being considered. | 18,758,208 |
A-to-I RNA editing and cancer: from pathology to basic science. | In eukaryotes mRNA transcripts are extensively processed by different post-transcriptional events such as alternative splicing and RNA editing in order to generate many different mRNAs from the same gene, increasing the transcriptome and then the proteome. The most frequent RNA editing mechanism in mammals involves the conversion of specific adenosines into inosines by the ADAR family of enzymes. This editing event can change both the sequence and the secondary structure of RNA molecules, with important consequences on both the final proteins and regulatory RNAs. Alteration in RNA editing has been connected to numerous human pathologies and recent studies have demonstrated its importance in tumor progression. | 18,758,244 |
Percutaneous plating of periarticular tibial fractures: a reliable, reproducible technique for controlling plate passage and positioning. | This article describes percutaneous plating of periarticular tibial fractures, in which a suture, tied to the proximal pole of a precontoured plate, is used to guide the plate through a submuscular tunnel. The technique enables the surgeon to manipulate both poles of the plate during its passage and to accurately position the plate. Percutaneous techniques continue to evolve, providing the advantage of fracture fixation while preserving the integrity of the soft tissue envelope. Various clinicians have described impressive results in percutaneous fixation of fractures of the distal tibia. These techniques reduce soft tissue stripping while preserving the vascularity of the fracture site. However, because percutaneous plating can present challenges for the surgeon, meeting these challenges is essential to ensuring the reproducibility of this technique. Manipulation of both poles of the plate can be difficult, and malalignment can result if the plate is not correctly positioned. The technique described below allows the surgeon to easily manipulate both poles of the plate to achieve accurate anatomic positioning and to avoid soft tissue stripping. | 18,758,289 |
Oral vinorelbine and cisplatin as induction chemotherapy and concomitant chemo-radiotherapy in stage III non-small cell lung cancer: final results of an international phase II trial. | Cisplatin in combination with vinorelbine has reported an optimal activity/tolerance ratio when used in combination with radiotherapy in locally advanced unresectable non-small cell lung cancer. The currently available oral formulation of vinorelbine should be easier to use assuming a similar activity profile. An international phase II trial with vinorelbine oral and cisplatin as induction followed by oral vinorelbine and cisplatin with concomitant radiotherapy was implemented to evaluate the efficacy in terms of objective response (OR) following this combination as primary end point and duration or response, progression-free survival, overall survival, and safety as secondary endpoints. The study included patients between 18 and 75 years, with histologically proven untreated locally advanced inoperable stage IIIA/IIIB (supraclavicular lymph nodes and pleural effusion excluded) non-small cell lung cancer, adequate bone marrow, hepatic and renal function, Karnofsky performance status >/=80%. Patients were treated with oral vinorelbine 60 mg/m day 1,8 cycle 1 and 80 mg/m day 1,8 cycle 2 (if no grade 3-4 toxicity) and cisplatin 80 mg/m day 1 every 3 weeks for 2 cycles as induction. Patients without progression received oral vinorelbine 40 mg/m day 1, 8 and cisplatin 80 mg/m day 1 every 3 weeks for 2 more cycles with radiotherapy 66 Gy in 6.5 weeks. Patient and disease characteristics (n = 54) included: median age 57 years; female sex 24%; stage IIIA 48% and IIIB 52%; Squamous carcinoma 59%, Karnofsky performance status 100% (range, 80-100%) 50%, patients >/=5% weight loss at baseline 7%. Relative dose intensities of oral vinorelbine/cisplatin were 86%/93% and 97%/98% at induction and in combination with radiotherapy, respectively. Forty-one patients (76%) increased oral vinorelbine from 60 to 80 mg/m day during induction (reasons for nonescalation: hematological 7 patients, nonhematological 2 patients, error 4 patients). After two cycles of chemotherapy induction, the OR intent-to-treat in the 54 patients was 37%. Toxicities during induction were as follows: Neutropenia G3-4 (28%), Febrile Neutropenia (7%), nausea G3 (11%), vomiting G3-4 (9%), anorexia G3 (4%), diarrhea G4 (2%), constipation G3 (2%). Forty-seven out of 54 (87%) patients received concomitant chemo-radiotherapy.Median radiotherapy delivered dose was 66 Gy. Tolerance: 9% G3 Neutropenia; 4% G3 dysphagia/radiation; 2% G3 radiation dermatitis. Late pulmonary fibrosis was reported in one patient (1.8%). One month after completion of chemo-radiotherapy, the overall OR intent-to-treat in the 54 patients was 54% (95% CI: 40-67%). With a median follow-up of 37 months (95% CI: 34-41) the median progression-free survival and overall survival were: 12.5 (95% CI: 9.6-16.4) and 23.4 (95% CI: 17.6-29.8) months, respectively. Oral vinorelbine in combination with cisplatin is an effective combination in stage IIIA/IIIB patients. The excellent tolerance profile allowed to complete concomitant chemo-radiotherapy in 87% of patients. Oral vinorelbine in combination with cisplatin is a new and promising option that facilitates the administration of concomitant chemo-radiotherapy with high rates of treatment completion. | 18,758,302 |
Tracheal glomus tumor successfully resected with rigid bronchoscopy: a case report. | Glomus tumor of the trachea is a rare disease. A glomus tumor of the trachea in a 70-year-old man is described. The tumor was successfully excised with rigid bronchoscopy. Twenty-four months after treatment there remains no evidence of endobronchial regrowth at bronchoscopy or imaging studies. Histologic features and treatment are discussed. | 18,758,313 |
Occlusive endobronchial stent placement as a novel management approach to massive hemoptysis from lung cancer. | Massive hemoptysis in patients with advanced thoracic malignancies can be difficult to manage. Frequently, the bleeding source is not amenable to either bronchial artery embolization or surgical resection. Isolation of the bleeding source by endobronchial tamponade is an alternative management option. This is commonly achieved by the use of double-lumen endotracheal tubes or the placement of endobronchial balloons. Although effective, these approaches are not permanent solutions and may require prolonged intubation. We describe here an alternative, novel approach to endobronchial tamponade that does not require prolonged mechanical ventilation. We present a case in which massive hemoptysis from a left lower lobe cavitary lung cancer was successfully tamponaded and ultimately stopped by the placement of 2 covered self-expanding bronchial stents, allowing the patient to be extubated and to undergo further palliative therapy. No recurrent episodes of hemoptysis occurred throughout the patient's lifetime. | 18,758,315 |
Another cause for conductive hearing loss with present acoustic reflexes. | There are numerous potential causes of conductive hearing loss (HL). It is important to obtain a thorough history and perform a complete examination, including audiometric testing and radiographic evaluation when necessary. In this report, we present a patient with an intact tympanic membrane, no history of ear disease or trauma who as an adult developed progressive, conductive HL because of an anomalous course of a dehiscent facial nerve. In the patient with a conductive HL and at least partially intact reflexes, superior semicircular canal dehiscence, fracture of the stapes superstructure proximal to the tendon, other third window phenomena, and now dehiscence of the facial nerve resulting in decreased mobility of the ossicular chain must be considered. | 18,758,374 |
Cortical sensorimotor control in vocalization: a functional magnetic resonance imaging study. | Verbal communication is a human feature and volitional vocalization is its basis. However, little is known regarding the cortical areas involved in human vocalization. Therefore, functional magnetic resonance imaging at 3 Tesla was performed in 16 healthy adults to evaluate brain activations related to voice production. The main experiments included tasks involving motor control of laryngeal muscles with and without intonation. In addition, reference mappings of the sensorimotor hand area and the auditory cortices were performed. Related to vocalization, in addition to activation of the most lateral aspect of the primary sensorimotor cortex close to the Sylvian fissure (M1c), we found activations medially (M1a) and laterally (M1b) of the well-known sensorimotor hand area. Moreover, the supplementary motor area and the anterior cingulate cortex were activated. Although M1a could be ascribed to motor control of breathing, M1b has been associated with laryngeal motor control. Consequently, even though M1c represents a laryngeal sensorimotor area, its exclusiveness as suggested previously could not be confirmed. Activations in the supplementary motor area and anterior cingulate cortex were ascribed to "vocal-motor planning." The present data provide the basis for further functional magnetic resonance imaging studies in patients with neurological laryngeal disorders. | 18,758,379 |
Activation of signal transducers and activators of transcription 3 and overexpression of its target gene CyclinD1 in laryngeal carcinomas. | Constitutive activation of signal transducers and activators of transcription (STAT) 3 has been observed in many solid tumors including head and neck squamous cell carcinoma. Expression and activation of STAT3 in laryngeal carcinoma have not been fully understood. The study aims to investigate the expression and activation of STAT3 in laryngeal carcinoma, the relationship between activated STAT3 and its downstream target gene CyclinD1 and the related clinicopathological factors of activated STAT3. Prospective. Sixty-four samples of laryngeal squamous cell carcinoma and 12 samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and reverse transcriptase-polymerase chain reaction. Statistical analysis was performed using SPSS. The overexpression of both STAT3 and CyclinD1 mRNA was observed in all samples of laryngeal squamous cell carcinoma. The mRNA levels of STAT3 and CyclinD1 in carcinoma tissue were 2.1- and 2.3-fold higher than those in control mucosa, respectively; the differences were statistically significant (P < .01). The overexpression of STAT3, p-STAT3, and CyclinD1 protein was also observed in all tumor samples. The protein levels of STAT3, p-STAT3, and CyclinD1 in carcinoma tissue were 1.6-, 4.5-, and 2.0-fold higher than those in control mucosa respectively; the differences were statistically significant (P < .01). There was a positive correlation between p-STAT3 protein and CyclinD1 mRNA (Pearson correlation coefficient = 0.827, P < .01). There were significant correlations between the overexpression of p-STAT3 protein and clinical T stage (P < .01), and tumor size (P < .05). The p-STAT3 protein level of patients in T1, T2 was higher than that of patients in T3, T4. The p-STAT3 protein level of patients with tumor size within 20 mm was higher than that of patients with tumor size more than 20 mm. High expression and activation of STAT3 exist in laryngeal carcinomas. Activated STAT3 may take effect on promoting transcription of its downstream target gene CyclinD1. The role of activation of STAT3 in laryngeal carcinogenesis needs further research. | 18,758,380 |
Sleep apnea and mandibular advancement device. Revision of the literature. | Sleep apnea and hypopnea syndrome (SAHS) is a disorder characterized by intermittent and repetitive obstruction of the upper airway provoking pharyngeal collapse. It is characterized clinically by a triad of daytime hypersomnia, snoring and pauses in breathing during sleep that are normally reported by the partner. Polysomnography is the chosen method for diagnosing this pathology. Patients with this disorder tend to have the following dental and orofacial signs: a retrognathic jaw, a narrow palate, a wide neck, deviation of the nasal septum and relative macroglossia, among others. Dentists should be ready to evaluate the risk-benefit of certain dental treatment options for this public health problem. The treatment of this problem will depend on its severity, with one of the options being the Mandibular Advancement Device (MAD) that is used especially in the treatment of slight or moderate SAHS and in the treatment of snoring, with results that are occasionally very successful. The objective of this study is to carry out an up-to-date literature review of SAHS and to evaluate the role of the dentist when faced with this pathology. | 18,758,397 |
Treatment of condylar fractures: A retrospective cohort study. | Evaluate routine alterations in patients submitted to treatment of unilateral fractures of the mandibular condyle. The sample consisted of 30 patients of both sexes submitted to surgical and nonsurgical treatment. All patients answered an evaluation questionnaire on perception of the Oral Impact on Daily Performances (OIDP) and underwent physical and imaging examination. The following aspects were evaluated in temporo mandibular join (TMJ) physical examination: maximum mouth opening, left/right lateral movements and protrusive movements. Vertical height measurements of right and left mandibular branches were evaluated by means of orthopantomography. Lateromedial and anteroposterior displacements were measured using Hirtz's axial radiography. Evaluation of diameter of the mandibular fossa and height of the glenoid fossa were measured by hypocycloidal tomography. A minority (13.3%) answered the questions on OIDP positively, with a similar rate for both treatments. With regard to the vertical height variable, average vertical height was similar for both treatments. However, comparing fractured and nonfractured sides, the difference observed was statistically significant for both treatments. On the basis of the statistical results of this study, for both treatments there were no significant alterations in the maximum mouth opening variable, with an average of 43.35 mm for open treatment and 44 mm for closed treatment. In the present study there were no significant differences between open and closed treatment of unilateral fractures of the mandibular condyle. | 18,758,405 |
Treatment of bilateral hyperplasia of the coronoid process of the mandible. Presentation of a case and review of the literature. | Bilateral hyperplasia of the coronoid process is infrequent. It consists of an elongation of the coronoid process of the mandible and is, accordingly, a mechanical problem, limiting mouth opening. This article looks at the case of a 28 year-old male with significant limitation on opening his mouth, secondary to bilateral hyperplasia of the coronoid process. We reviewed the literature and analysed the diagnostic and therapeutic procedures used, paying special attention to the surgical approaches to the coronoid process and emphasising the importance of early post-operative rehabilitation, describing our experience with the TheraBite (Atos Medical AB, PO Box 183, 242 22 Hörby, Sweden). The satisfactory result of the procedure is marked by the stable recovery of the mouth opening, achieved by a good combination of surgical and physiotherapeutic techniques. | 18,758,406 |
Behavioral and psychological symptoms in the preclinical stage of Alzheimer's disease. | AD is preceded by a lengthy preclinical period. Neural degeneration may lead to the appearance of behavioral and psychological symptoms, even before other clinical symptoms are manifest. We attempted to evaluate this symptomatology in preclinical AD. We recruited 291 care center residents who did not demonstrate dementia symptoms according to DSM-IV, whose MMSE score was at least 24, and who reached the first or second stage on the Global Deterioration Scale. Psychopathology was assessed using the AMDP, while the ADAS-cog was used to assess cognitive dysfunctions. Seven years later, 155 patients participated in the follow-up study (MMSE and ADAS-cog). If the MMSE was less than 24, a psychiatric workup was done to verify dementia. The AD group consisted of persons properly diagnosed with AD (n=25), while the control group consisted of persons in whom dementia had not developed. The AD and control groups differed in the level of psychopathological symptoms at baseline. The disparities related both to the global AMDP score and to every particular symptom category. The analysis did not disclose a pathognomonic symptom for preclinical AD, but there were many symptoms whose intensity differentiated AD patients from the controls. The degree of cognitive dysfunction seems to correlate with the clinical manifestation of some psychopathological symptoms in preclinical AD. The degeneration process before the clinical manifestation of dementia leads not only to the impairment of several cognitive functions, but also the intensification of behavioral and psychological symptoms. | 18,758,418 |
Growth inhibition of an established A431 xenograft tumor by a full-length anti-EGFR antibody following gene delivery by AAV. | Therapeutic monoclonal antibodies continue to achieve clinical success for the treatment of many different diseases, particularly cancer. However, the production and purification of antibodies continues to be a time and labor-intensive process with considerable technical challenges. Gene-based delivery of antibodies may address this, via direct production within the host that achieves therapeutic levels. In this report, we validate the feasibility that gene-based delivery is a viable approach for efficacious delivery of antibodies in the preclinical and, presumably, clinical setting. We demonstrate high and sustained in vivo expression of the murine antihuman epidermal growth factor receptor antibody 14E1 following intramuscular delivery by adeno-associated virus (AAV) 2/1. Incorporating the Furin/2A technology for monocistronic expression of both heavy and light chains, we achieved sustained serum levels of full-length 14E1 peaking over 1 mg ml(-1) in athymic nude mice. In the A431 xenograft tumor model, 14E1 was capable of significantly inhibiting tumor growth and prolonging survival when AAV was administered prior to tumor challenge. Furthermore, 14E1 demonstrated significant antitumor efficacy against well-established tumors (approximately 400 mm(3)) when AAV was administered up to 20 days after tumor challenge. Here we demonstrate for the first time growth inhibition of a well-established tumor by a full-length antibody following delivery by AAV. | 18,758,433 |
Novel function of the class I bHLH protein Daughterless in the negative regulation of proneural gene expression in the Drosophila eye. | Two types of basic helix-loop-helix (bHLH) family transcription factor have functions in neurogenesis. Class II bHLH proteins are expressed in tissue-specific patterns, whereas class I proteins are broadly expressed as general cofactors for class II proteins. Here, we show that the Drosophila class I factor Daughterless (Da) is upregulated by Hedgehog (Hh) and Decapentaplegic (Dpp) signalling during retinal neurogenesis. Our data suggest that Da is accumulated in the cells surrounding the neuronal precursor cells to repress the proneural gene atonal (ato), thereby generating a single R8 neuron from each proneural cluster. Upregulation of Da depends on Notch signalling, and, in turn, induces the expression of the Enhancer-of-split proteins for the repression of ato. We propose that the dual functions of Da--as a proneural and as an anti-proneural factor--are crucial for initial neural patterning in the eye. | 18,758,436 |
The Creb1 coactivator Crtc1 is required for energy balance and fertility. | The adipocyte-derived hormone leptin maintains energy balance by acting on hypothalamic leptin receptors (Leprs) that act on the signal transducer and activator of transcription 3 (Stat3). Although disruption of Lepr-Stat3 signaling promotes obesity in mice, other features of Lepr function, such as fertility, seem normal, pointing to the involvement of additional regulators. Here we show that the cyclic AMP responsive element-binding protein-1 (Creb1)-regulated transcription coactivator-1 (Crtc1) is required for energy balance and reproduction-Crtc1(-/-) mice are hyperphagic, obese and infertile. Hypothalamic Crtc1 was phosphorylated and inactive in leptin-deficient ob/ob mice, while leptin administration increased amounts of dephosphorylated nuclear Crtc1. Dephosphorylated Crtc1 stimulated expression of the Cartpt and Kiss1 genes, which encode hypothalamic neuropeptides that mediate leptin's effects on satiety and fertility. Crtc1 overexpression in hypothalamic cells increased Cartpt and Kiss1 gene expression, whereas Crtc1 depletion decreased it. Indeed, leptin enhanced Crtc1 activity over the Cartpt and Kiss1 promoters in cells overexpressing Lepr, and these effects were disrupted by expression of a dominant-negative Creb1 polypeptide. As leptin administration increased recruitment of hypothalamic Crtc1 to Cartpt and Kiss1 promoters, our results indicate that the Creb1-Crtc1 pathway mediates the central effects of hormones and nutrients on energy balance and fertility. | 18,758,446 |
Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. | Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity. | 18,758,451 |
Notch signaling regulates tumor angiogenesis by diverse mechanisms. | The Notch signaling pathway is fundamental to proper cardiovascular development and is now recognized as an important player in tumor angiogenesis. Two key Notch ligands have been implicated in tumor angiogenesis, Delta-like 4 and Jagged1. We introduce the proteins and how they work in normal developing vasculature and then discuss differing models describing the action of these Notch ligands in tumor angiogenesis. Endothelial Dll4 expression activates Notch resulting in restriction of new sprout development; for instance, in growing retinal vessels. In agreement with this activity, inhibition of Dll4-mediated Notch signaling in tumors results in hypersprouting of nonfunctional vasculature. This Dll4 inhibition may paradoxically lead to increased angiogenesis but poor tumor growth because the newly growing vessels are not functional. In contrast, Jagged1 has been described as a Notch ligand expressed in tumor cells that can have a positive influence on tumor angiogenesis, possibly by activating Notch on tumor endothelium. A novel Notch inhibitor, the Notch1 decoy, which blocks both Dll4 and Jagged1 has been recently shown to restrict tumor vessel growth. We discuss these models and speculate on therapeutic approaches. | 18,758,482 |
Inhalation of an endothelin receptor A antagonist attenuates pulmonary inflammation in experimental acute lung injury. | We recently demonstrated that inhalation of the endothelin receptor A (ETA) antagonist LU 135252 improved arterial oxygenation and reduced pulmonary artery pressure in experimental acute lung injury (ALI). In this study we analyzed potential immune modulatory effects of inhaled LU 135252 in experimental ALI. ALI was induced by repeated lung lavage in intubated (100% O2) and anesthetized piglets. Animals were randomly assigned to inhale either nebulized LU 135252 (0.3 mg.kg(-1), ALI + LU group, n = 8) or saline buffer (ALI control group, n = 16), both for 30 min. Surviving animals were sacrificed 6 h after induction of ALI, and lung tissue specimens were obtained from all animals for histology and immunhistochemistry. Induction of ALI significantly decreased arterial oxygenation in all animals. Inhalation of LU 135252 significantly reduced mortality and induced significant and sustained increase in PaO2 (316 +/- 47 mm Hg vs. control 53 +/- 3 mm Hg, p < 0.001). We measured a significant reduction in the number of pulmonary leukocyte L1 antigen-positive cells in ALI + LU animals (8% +/- 1% positive cells vs. control 12% +/- 2% positive cells, p < 0.05). The number of CD3-positive cells was not altered by treatment with LU 135252. Pulmonary tissue concentration of IL-6 was significantly suppressed by LU 135252 inhalation (4 +/- 1 pg.100 mg-1 wet weight vs. control 7 +/- 1 pg.100 mg(-1) wet weight, p < 0.05). Concentrations of TNF-alpha, IL-1beta, and ET-1 in pulmonary tissue were not influenced by inhalation of LU 135252. In conclusion, we demonstrated that inhalation of LU 135252 not only improves mortality and gas exchange, but also blunts the local immune response in experimental ALI. | 18,758,498 |
Hybrid digital holographic imaging system for three-dimensional dense particle field measurement. | To apply digital holography to the measurement of three-dimensional dense particle fields in large facilities, we have developed a hybrid digital holographic particle-imaging system. The technique combines the advantages of off-axis (side) scattering in suppressing speckle noise and on-axis (in-line) recording in lowering the digital sensor resolution requirement. A camera lens is attached to the digital sensor to compensate for the weak object wave from side scattering over a large recording distance. A simple numerical reconstruction algorithm is developed for holograms recorded with a lens without requiring complex and impractical mathematical corrections. We analyze the effect of image sensor resolution and off-axis angle on system performance and quantify the particle positioning accuracy of the system. The holographic system is successfully applied to the study of inertial particle clustering in isotropic turbulence. | 18,758,519 |
Applications of the theory of fluctuation in the regular transmittance through a dispersion of large cylindrical particles to concentration and size measurements. | Four measurement principles based on the theory of fluctuation in the regular transmittance through a dispersion of large cylindrical particles are presented. The principles concern the measurement of particle concentration, particle length classes, particle length, and particle width. In previous publications, the measurement principles were briefly presented. A more complete description, experimental demonstrations, and a number of considerations needed to understand the region of validity of the different principles, as well as their uncertainty, are presented. A recently published simulation model [Appl. Opt.47, 993 (2008)] is used. The basic ideas of the measurement principles within their respective regions of validity are supported. | 18,758,520 |
Two-dimensional integration of a vertical-cavity surface-emitting laser and photodetectors for position sensing. | Noncontact long-range position sensing is desirable for a number of applications. We have designed and fabricated a monolithically integrated vertical-cavity surface-emitting laser (VCSEL) and p-type/intrinsic/n-type (PIN) photodetectors for optical position sensing. Calculations using the reflection from a periodic metallic corrugation as a position gauge indicate resolution in the submicron regime. High device uniformity is obtained using novel fabrication techniques. We observe a threshold current of 0.52 mA for the VCSELs and a detector responsivity of 0.38 A/W at 840 nm. The optical cross talk between VCSELs and detectors is also quantified. | 18,758,525 |
Time-averaged electronic speckle pattern interferometry in the presence of ambient motion. Part I. Theory and experiments. | An electronic speckle pattern interferometer is introduced that can produce time-averaged interferograms of harmonically vibrating objects in instances where it is impractical to isolate the object from ambient vibrations. By subtracting two images of the oscillating object, rather than the more common technique of subtracting an image of the oscillating object from one of the static objects, interferograms are produced with excellent visibility even when the object is moving relative to the interferometer. This interferometer is analyzed theoretically and the theory is validated experimentally. | 18,758,536 |
Analysis of surface modes in photonic crystals by a plane-wave transfer-matrix method. | We have developed a plane-wave transfer-matrix method (PWTMM) with the aid of the interpolation technique to analyze the dispersion relation of surface modes in photonic crystal or photonic crystal surface waveguide. The proposed approach has been applied to several surface structures in two-dimensional photonic crystals. The calculated dispersion relation of the surface modes is in good agreement with the result obtained by the conventional plane-wave expansion method in combination with the supercell technique. The developed PWTMM needs to handle only a single unit-cell layer domain and is therefore numerically friendly. The proposed approach can become an efficient and accurate numerical tool to understand and design surface modes in different two-dimensional and three-dimensional photonic crystals with complex geometries. | 18,758,543 |
Coherence and polarization of electromagnetic beams modulated by random phase screens and their changes through complex ABCD optical systems. | The change of coherence and polarization of an electromagnetic beam modulated by a random anisotropic phase screen passing through any optical system is found within the framework of complex ABCD-matrix theory This means that the formalism can treat imaging and Fourier transform and free-space optical systems, as well as fractional Fourier transform systems, with finite-size limiting apertures of Gaussian transmission shape. Thus, the current paper shall be considered as a continuation, extension, and generalization of a previous work by Shirai and Wolf [J. Opt. Soc. Am. A21, 1907 (2004)]. It will be shown that the inclusion of apertures in the optical system strongly influences not only the propagation of spatial coherence but also the degree of polarization of a propagating field. Analytical expressions of coherence and polarization propagation will be given in terms of the matrix elements for any complex optical system. | 18,758,562 |
Accurate calculation of reflectance spectra for thick one-dimensional inhomogeneous optical structures and media: stable propagation matrix method. | Numerical instability is usually observed when the propagation matrix method is used to calculate the reflectance and transmittance spectra for the thick one-dimensional inhomogeneous optical structures and media. To remove this numerical instability we applied two procedures, the normalization and the singular-value decomposition, for the propagation matrix and the matrix involved in calculating the matrix of reflection coefficients, respectively. Examples of a cholesteric liquid crystal and a helical structure of ferroelectric liquid crystals with a twist defect show that the modified propagation matrix method is able to accurately calculate the reflectance spectra for thick structures. | 18,758,574 |
Fiber-array-based detection scheme for single-shot pulse contrast characterization. | We propose and demonstrate a fiber-array-based detection scheme for single-shot pulse contrast characterization. The parallel to serial mapping using the fiber array allows the use of a high-sensitivity photomultiplier tube and eliminates the external neutral density filter, both resulting in significantly improved dynamic range. The proof-of-principle experiments show a dynamic range of 2x10(7):1. The demonstrated technique can be readily applied to existing instruments for single-shot pulse characterization. | 18,758,581 |
Fluorescent or not? Size-dependent fluorescence switching for polymer-stabilized gold clusters in the 1.1-1.7 nm size range. | The synthesis of fluorescent water-soluble gold nanoparticles by the reduction of a gold salt in the presence of a designed polymer ligand is described, the size and fluorescence of the particles being controlled by the polymer to gold ratio; the most fluorescent nanomaterial has a 3% quantum yield, a 1.1 nm gold core and a 6.9 nm hydrodynamic radius. | 18,758,601 |
Direct, facile synthesis of N-acyl-alpha-amino amides from alpha-keto esters and ammonia. | N-acyl-alpha-amino amides were prepared, without the necessity of chromatographic purification, in a single step by heating the corresponding alpha-keto ester in methanolic ammonia. | 18,758,623 |
Structures of two haptotropic isomers generated by the sliding of 1,3,5-triene ligands on a Pd-Pd-Pd chain. | Two haptotropic isomers of [Pd3(micro3-DMVC)2(CH3CN)2][BF4]2 (DMVC=1,2-di-(E)-carbomethoxyvinylcyclopentene) were structurally determined by X-ray crystallographic analyses; a monoclinic crystal contained a symmetric sandwich complex (micro3-eta2:eta2:eta2-coordination of DMVC ligands) and a triclinic crystal contained an unsymmetric sandwich complex (micro3-eta2:eta3:eta1-coordination of DMVC ligands), where the latter are connected to each other by C-HO hydrogen bonds. | 18,758,626 |
Cellular and molecular mechanisms underlying neurorehabilitation after stroke in aged subjects. | Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are uncertain. Therefore studying the basic mechanism underlying functional recovery after brain ischemia in aged subjected it is of considerable clinical interest. Potential mechanisms include neuroinflammation, changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differences in the generation of scar tissue that impedes the formation of new axons and blood vessels in the infarcted region. Available data indicate that behaviorally, aged rats were more severely impaired by ischemia than were young rats, and they also showed diminished functional recovery. Further, as compared to young rats, aged rats develop a larger infarct area, as well as a necrotic zone characterized by a higher rate of cellular degeneration, and a larger number of apoptotic cells. In both old and young rats, the early intense proliferative activity following stroke leads to a precipitous formation of growth-inhibiting scar tissue, a phenomenon amplified by the persistent expression of neurotoxic factors. Reduced transcriptional activity in the healthy, contralateral hemisphere in conjunction with an early upregulation of DNA damage related genes and the early induction of proapoptotic genes in the periinfarct area of aged rats are likely to account for poor neurorehabilitation after stroke in aged rats. Finally, the regenerative potential of the rat brain is largely preserved up to 20 months of age but gene expression is temporally displaced, has lower amplitude, and is sometimes of relatively short duration. Most interestingly, it has recently been shown that the human brain can respond to stroke with increased progenitor proliferation in aged patients opening the possibilities to utilize this intrinsic attempt for neuroregeneration of the human brain as a potential therapy for stroke. Given the heterogeneity of stroke, a universal anti-inflammatory solution may be a distant prospect, but probably neuroprotective drug cocktails targeting inflammatory pathways in combination with thrombolysis may be a possibility for acute stroke treatment in the future. | 18,758,632 |
Histopathological factors as predictors for survival in colon and rectal cancers. | Colorectal cancer is one of the most frequent malignant diseases with a raising incidence in Romania. Survival at 5-years even was improved in the last decade, remains low especially because of delayed diagnosis. Many clinical-biological and pathological factors have demonstrate a good prognostic value over the time but there are not a wide consensus in this field. The aim of our study is to evaluate the accepted pathological prognostic factors of survival for colorectal cancer in relation to management adopted in a general surgical clinic. We included in our study 273 patients with colon and rectal cancers admitted in Surgical Clinic of Military Hospital of Craiova in which we evaluate the clinical-pathological features, location of the distant metastasis, postoperative staging, curability and survival. We established correlations, inside of a same stage of the disease, for pathological features (characters of the tumors, differentiation grade and location) and survival rate. Our results showed that curative resection is one of the most important factors that could improve survival. Tumor differentiation is correlated with survival only for the patients with stage II and III of the disease, perineural invasion and pathologic N stage representing important predicting factors for a shorter survival. Peritoneal washing for cytology prior to surgery is correlated with the stage of the disease and not with tumor differentiation. | 18,758,642 |
Study of the correlation between newborn and fetus ages and some morphometric cervical vertebral arches indices. | Establishing the newborn and fetus age by taking into account of cervical vertebral bony parts dimensions is useful in anthropology and anthropometry as well. In the present study, we tried to determine some morphometric indices of fifth bony part's cervical vertebral arch in both fetus and newborn. We analyzed their correlation with the age of the subjects studied. We used a set of five newborn and five fetuses of six-seven months. We removed the fifth right cervical vertebral hemiarch from each subject. Images of vertebral bony parts hemiarches were acquisitioned, processed and measured by a morphometric Lucia M specialized soft. We measured the bony parts surface area, we traced the hemiarch frame triangle, and we measured the angles, the sides and the frame-triangle surface area, for each hemiarch. By analyzing the data we succeeded in revealing that the ratio between the anteromedial angle value and the opposite side length of that angle correlates to the fetus and newborn ages. Therefore, we consider this ratio as being an anthropometric index useful in deciding upon the fetus and newborn age. | 18,758,645 |
Acid rain phenomenon in niger delta region of Nigeria: economic, biodiversity, and public health concern. | Rain samples were collected from Warri and Port Harcourt, two major oil-producing cities of Nigeria in April-June, July-August, and September-October 2005 and 2006. Awka, a "non-oil" city was used as control. Samples were collected from three points, using clean plastic basins fastened to a table, 2 m above ground level and 115 m away from tall buildings and trees. Water samples were filtered and acidity determined using digital pH meter. The results show that the rain samples were acidic. The pH values for the 2 years under study show that the rainfall in Warri was more acidic than that of Port Harcourt. Oil exploration and other anthropogenic sources may be responsible for the acid rain in the Niger Delta region of Nigeria. | 18,758,657 |
The physiotherapy clinical outcome variables scale predicts length of hospital stay, discharge destination and future home facility in the acute comprehensive stroke unit. | The aims of this study were: to follow the course of recovery of motor function following acute stroke, as assessed by the Physiotherapy Clinical Outcome Variables Scale (COVS), and; to investigate the ability of this instrument to predict length of hospital stay, discharge destination and future home facility. In this prospective longitudinal study, COVS was registered at admission and discharge from an acute stroke unit and at 3 months post-stroke onset. Sixty subjects were recruited consecutively from a sample of patients after first-ever acute stroke, and of these, 50 received follow-up assessment. Length of hospital stay, discharge destination and home facility 3 months post-stroke. The overall COVS scores increased significantly during the 3-month follow-up. The admission COVS score correlated negatively with length of stay. A cut-off at 50 points and 41 points could predict discharge destination and future home facility, respectively. COVS measures improvements and can predict length of hospital stay, discharge destination and future home facility. Thus, it could be used in early prediction for effective planning of the acute stroke unit services and efficient discharge planning. | 18,758,668 |
A randomized controlled trial of acupuncture added to usual treatment for fibromyalgia. | To evaluate the effectiveness of acupuncture for fibromyalgia. Fifty-eight women with fibromyalgia were allocated randomly to receive either acupuncture together with tricyclic antidepressants and exercise (n=34), or tricyclic antidepressants and exercise only (n=24). Patients rated their pain on a visual analogue scale. A blinded assessor evaluated both the mean pressure pain threshold value over all 18 fibromyalgia points and quality of life using SF-36. At the end of 20 sessions, patients who received acupuncture were significantly better than the control group in all measures of pain and in 5 of the SF-36 subscales. After 6 months, the acupuncture group was significantly better than the control group in numbers of tender points, mean pressure pain threshold at the 18 tender points and 3 subscales of SF-36. After one year, the acupuncture group showed significance in one subscale of the SF-36; at 2 years there were no significant differences in any outcome measures. Addition of acupuncture to usual treatments for fibromyalgia may be beneficial for pain and quality of life for 3 months after the end of treatment. Future research is needed to evaluate the specific effects of acupuncture for fibromyalgia. | 18,758,677 |
Mobility of heavy metals from soil into hot pepper fruits: a field study. | Capsaicin and dihydrocapsaicin contribute to pungency as well as having health-promoting properties, in peppers. Twenty-three genotypes (four spp.) of hot pepper from the USDA germplasm collection were grown in the field to identify accessions having increased concentrations of these two compounds and determine the concentrations of heavy metals, in mature fruits. Concentrations and relative proportions of capsaicin, dihydrocapsaicin, and seven heavy metals varied between and within pepper species. Plant Introduction 547069 (C. annuum) contained the greatest concentrations of the two pungent compounds. Fruits of PI-439381 and PI-267729 (C. baccatum) accumulated the greatest concentrations of Pb, while PI-246331 (C. annuum) accumulated the greatest concentration of Cd among accessions tested. | 18,758,679 |
High number of striatal dopaminergic neurons during early postnatal development: correlation analysis with dopaminergic fibers. | Dopamine (DA) axons in the developing striatum cluster in discrete areas called "DA islands". During the third postnatal week, most DA islands are no-longer detectable and the DA innervation becomes uniform. In this study we explored the relationship between the pattern of DA innervation and the number of striatal tyrosine hydroxylase positive (TH+) cells during early postnatal development. By using dedicated stereology we found that the newborn striatum contains striatal TH+ cells, which cluster around newly sprouted DA axons. The number of these cells decreases when DA axons develop a full pattern of striatal innervation. This condition suggests a causal relationship between the amount of striatal DA innervation and the presence of striatal DA neurons. A better knowledge of the mechanisms regulating the ontogenesis of the nigrostriatal DA system may pave the way to strategies of neurorescue of the DA system. | 18,758,687 |
Analysis of the downstream region of nodD3 P1 promoter by deletion and complementation tests in Sinorhizobium meliloti. | In Sinorhizobium meliloti, the nodD3 gene is transcriptionally controlled by two promoters, P1 and P2. Under P1, there is a 660 bp sequence including a small open reading frame, ORF2, followed by the nodD3 coding region. Genetic analysis using the different deletions on the 3' ends of P1 downstream sequence showed that the downstream sequence +1-+125nt is essential for P1 expression. Complementation, mutations and nodulation tests demonstrated that the ORF2 auto-represses P1 expression, while the P1 downstream sequence +1-+125nt counteracts it. | 18,758,707 |
A study of gene transfer and expression of human clotting factor IX in hemophilia B mice mediated by mini-adenoviral vector. | Vector Gti'IX containing human clotting factor IX cDNAwith intron 1 (hFIX mini-gene or Fi'IX) driven by CMV promoter was constructed based on the mini-adenoviral vector GT2073 (mini-Ad vector) with all viral protein coding sequences deleted. Mini-Ad packaging cell 293Cre4 was first transduced with GTi'IX, and then was transfected with helper-adenovirus AdLC8, thus mini-Ad virions AdGTi'IX were obtained. At the same time, previous normal adenoviral vector pAdSPi'IX containing viral genome and hFIX mini-gene was constructed, and then previous adenovirus (pre-Ad) AdSPi'IX was obtained as control. The ratio of helper-adenovirus among purified virons AdGTi'IX was less than 0.8%. 3T3 cells were transfected with AdGTi'IX and AdSPi'IX at a MOI of 50 per cell and ELISA result showed that transient expression level in vitro was 1.4 +/-0.2 mug /10(6) . 24 h and 1.6 +/-0.3 mug/10(6) . 24 h respectively. Each hemophilia B (FIX knock-out) mouse received celiac injection of 1x10(10) pfu AdGTi'IX or AdSPi'IX. The highest expression level of hFIX in mouse plasma was 590 ng/mL and 690 ng/mL respectively, and the expression time lasted for 16 weeks and 9 weeks respectively. The bleeding time reduced from over 30 min to 7.5 min, and 5-min blood lost reduced from 430 muL to 60 muL. The results of anti-Ad IgG assays indicated that immune response triggered by AdGTi'IX was obviously weaker than that triggered by AdSPi'IX. These results indicated that, compared with previous adenovirus (pre-Ad), the mini-Ad vector system prolonged the expression time of hFIX and reduced immune response, thus offering a promising result for further pre-clinical study. | 18,758,720 |
Map-based cloning of the ALK gene, which controls the gelatinization temperature of rice. | Gelatinization temperature (GT) is an important parameter for evaluating the cooking and eating quality of rice besides amylose content (AC). The inheritance of the genes affecting GT has been widely studied and is considered to be controlled by a major gene. Here, we report the map-based cloning of rice ALK that encodes the soluble starch synthase II (SSSII). Comparison between the DNA sequences from different rice varieties, together with the results obtained with digestion of the rice seeds in alkali solution, indicates that the base substitutions in coding sequence of ALK may cause the alteration in GT. | 18,758,723 |
Soft tissue tension in extension in total knee arthroplasty affects postoperative knee extension and stability. | The purpose of this study was to assess correlation of soft tissue tension in extension with postoperative extension deficit and valgus/varus instability. Sixty-four osteoarthritic knees that underwent primary total knee arthroplasty were investigated. Soft tissue tension in extension was measured during operation with a balancer/tensor device. Extension deficit was measured, and valgus/varus laxity was assessed by stress radiographs in extension and 30 degrees -flexion 1 year after operation. The extension deficit became larger with an increase of soft tissue tension a year after operation. (P < 0.05) The varus laxity in extension and 30 degrees -flexion and valgus laxity in 30 degrees -flexion became smaller with an increase of soft tissue tension (P < 0.05). Our results demonstrated that soft tissue tension during operation affects postoperative knee extension and stability. | 18,758,749 |
Individual differences in acute alcohol impairment of inhibitory control predict ad libitum alcohol consumption. | Research has begun to examine how acute cognitive impairment from alcohol could contribute to alcohol abuse. Specifically, alcohol-induced impairment of inhibitory control could compromise the drinker's ability to stop the self-administration of alcohol, increasing the risk of binge drinking. The present study was designed to test this hypothesis by examining the relation between acute alcohol impairment of inhibitory control and alcohol consumption during a single drinking episode. Twenty-six healthy adults performed a cued go/no-go task that measured inhibitory control. The study tested the degree to which their inhibitory control was impaired by a moderate dose of alcohol (0.65 g/kg) versus a placebo and the extent to which individual differences in this impairment predicted levels of alcohol consumption as assessed by ad lib drinking in the laboratory. In accord with the hypothesis, greater impairment of inhibitory control from alcohol was associated with increased ad lib consumption. Acute impairment of inhibitory control might be an important cognitive effect that contributes to abuse in addition to the positive rewarding effects of the drug. | 18,758,758 |
Drug discrimination and neurochemical studies in alpha7 null mutant mice: tests for the role of nicotinic alpha7 receptors in dopamine release. | The nicotine discriminative stimulus has been linked to beta2-containing (beta2*) nicotinic receptors, with little evidence of a role for alpha7 nicotinic receptors, because nicotine discrimination was very weak in beta2 null mutant mice but normal in alpha7 mutants. As both alpha7 and beta2* nicotinic receptors have been implicated in nicotine-stimulated dopamine overflow, this study focused on the dopamine-mediated element in the nicotine stimulus by examining cross-generalisation between amphetamine and nicotine. Male alpha7 nicotinic receptor null mutant mice and wild-type controls were bred in-house and trained to discriminate nicotine (0.8 mg/kg) or (+)-amphetamine (0.6 mg/kg) from saline in a two-lever procedure with a tandem VI-30 FR-10 schedule of food reinforcement. Dopamine release from striatal slices was determined in parallel experiments. An alpha7 nicotinic receptor-mediated component of dopamine release was demonstrated in tissue from wild-type mice using choline as a selective agonist. This response was absent in tissue from null mutant animals. The mutation did not influence acquisition of drug discriminations but subtly affected the results of cross-generalisation tests. In mice trained to discriminate nicotine or amphetamine, there was partial cross-generalisation in wild-type mice and, at certain doses, these effects were attenuated in mutants. Further support for an alpha7 nicotinic receptor-mediated component was provided by the ability of the alpha7 nicotinic receptor antagonist methyllycaconitine to attenuate responses to nicotine and amphetamine in wild-type mice. These findings support the concept of an alpha7 nicotinic receptor-mediated dopaminergic element in nicotine discrimination, warranting further tests with selective dopamine agonists. | 18,758,759 |
High variability in the MHC class II DA beta chain of the brushtail possum (Trichosurus vulpecula). | The diversity of class II major histocompatibility complex (MHC) loci was investigated in the brushtail possum, an important marsupial pest species in New Zealand. Immunocontraception, a form of fertility control that generates an autoimmune response, is being developed as a population control method for the possum. Because the immune response is partly under genetic control, an understanding of immunogenetics in possum will be crucial to the development of immunocontraceptive vaccines. MHC molecules are critical in the vertebrate immune response. Class II MHC molecules bind and present exogenously derived peptides to T lymphocytes and may be important in the presentation of immunocontraceptives. We used polymerase chain reaction primers designed to amplify the peptide binding region of possum class II MHC genes to isolate sequences from 49 animals. We have previously described 19 novel alleles from the DAB locus in the possum (Holland et al., Immunogenetics 60:449-460, 2008). Here, we report on another 11 novel alleles isolated from possum DAB, making this the most diverse marsupial locus described so far. This high level of diversity indicates that DAB is an important MHC locus in the possum and will need to be taken into account in the design of immunocontraceptive vaccines. | 18,758,765 |
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