Superior outcomes of total hip arthroplasty without prior lumbar arthrodesis: a systematic review and meta-analysis.
The number of patients undergoing total hip arthroplasty (THA) surgery after previous lumbar arthrodesis (LA) is rising. Literature suggests that LA may significantly impact pelvic biomechanics and potentially compromise the success of prosthetic hip replacement. This study aims to evaluate complication rates, dislocation rates, and revision rates in patients with prior LA undergoing THA surgery compared to those undergoing THA surgery without prior LA. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. The search for relevant studies was performed across five databases, including Pubmed, Scopus, Embase, Medline, and Cochrane. The selected articles were evaluated based on the Levels of Evidence (LoE) criteria. The Coleman Methodology Score (mCMS) was employed to analyze the retrospective studies. This systematic review and meta-analysis were registered in the International Prospective Register of Systematic Reviews (PROSPERO). For the outcomes that allowed for a meta-analysis performed using R software, a p < 0.05 was considered statistically significant. The final analysis included seventeen studies comprising a total of 3,139,164 cases of THA. Among these cases, 3,081,137 underwent THA surgery alone, while 58,027 patients underwent THA with a previous LA. The study investigated various factors, including dislocation rates, revision rates, and complication, as well as the surgical approach and type of implant used, for both the THA-only group and the group of patients who underwent THA with prior LA. The analysis revealed a statistically significant difference (p < 0.05) for all variables studied, favoring the group of patients who underwent THA alone without prior LA. This systematic review and meta-analysis demonstrated a statistically significant superiority in all analyzed outcomes for patients who underwent THA-only without prior LA. Specifically, patients with isolated THA implants experienced significantly lower incidences of THA dislocation, wound complications, periprosthetic joint infection, revision, and mechanical complications. Level IV.


2-[4-(Diethyl-amino)-benzyl-idene]malono-nitrile.
In the title compound, C(14)H(15)N(3), the diethyl-amino N atom, benzene ring, olefinic bond and cyano groups form an extended conjugated system, making the mol-ecule nearly planar: the dihedral angle between the benzene ring and the best plane throught the cyano groups is 4.93 (10)°, while the dihedral angle between the benzene ring and the plane through the diethyl-amino N atom and the two attached ethyl C atoms is 9.51 (14)°. In the crystal, inter-molecular C-H⋯π inter-actions stabilize the packing.


Puzzle resolved: CFTR mediates chloride homeostasis by segregating absorption and secretion to different cell types.
In the lungs, the cystic fibrosis transmembrane conductance regulator (CFTR) regulates ion transport in surface-airway epithelia and submucosal glands, thus determining airway surface liquid (ASL) volume and mucus hydration. In this issue of the JCI, Lei Lei and colleagues report that the CFTR-rich and barttin/Cl- channel-expressing ionocytes mediate chloride absorption across airway epithelia, whereas the more abundant basal cells and secretory cells mediate chloride secretion. Thus, CFTR-mediated secretion and absorption of chloride ions in the lung are segregated by cell type, which has implications for future molecular therapies for cystic fibrosis lung disease.


Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in vitro and in vivo growth of lung cancer cells.
The ras mutation, which is observed in 20-30% of human nonsmall cell lung cancers (NSCLCs), is one of common genetic alterations and has been proposed to be a prognostic factor in lung cancer. Oncogene ras appears to be essential for tumor progression and maintenance. Several therapeutic agents have been developed to inhibit ras, such as FTIs and antisense oligonucleotides. A new tool for blocking oncogenes in cancer cells has emerged with the discovery that RNA interference can specifically silence expression of endogenous human genes. In the current study, we used small interfering RNA (siRNA) directed against mutant K-ras to determine the anti-tumor effects of decreasing the levels of this protein in lung cancer cell lines. Adenovirus-mediated siRNA (AdH1/siK-ras(V12)) against K-ras(V12) markedly decreased K-ras(V12) gene expression and inhibited cellular proliferation of NSCLC H441 cells that express the relevant mutation (K-ras codon 12 GGT --> GTT), but produced minimal growth inhibition on NSCLC H1650 cells that lack the relevant mutation. Pretreatment with AdH1/siK-ras(V12) completely abrogated subcutaneous engraftment of H441 cells, as compared with a 100% tumor take in animals that received control vector-treated tumor cells. The in vivo effect of AdH1/siK-ras(V12) treatment was further examined by intratumoral injections after tumor induction. Pre-existing tumor growth was reduced by 45% by a single intratumoral injection. Three or five repeat injections resulted in complete tumor regression in eight of ten nude mice. Further, 23.12% of AdH1/siK-ras(V12) treated H441 cells underwent apoptosis, as compared with 6.13%, and 8.27% in untreated and control vector-treated cells, respectively. These results indicate that adenovirus-mediated siRNA can specifically and efficiently target factors whose expression is altered in malignancy and may have the potential as a therapeutic modality to treat human lung cancer.


Microbial Transformations of Selenium Species of Relevance to Bioremediation.
Selenium species, particularly the oxyanions selenite (SeO3 (2-)) and selenate (SeO4 (2-)), are significant pollutants in the environment that leach from rocks and are released by anthropogenic activities. Selenium is also an essential micronutrient for organisms across the tree of life, including microorganisms and human beings, particularly because of its presence in the 21st genetically encoded amino acid, selenocysteine. Environmental microorganisms are known to be capable of a range of transformations of selenium species, including reduction, methylation, oxidation, and demethylation. Assimilatory reduction of selenium species is necessary for the synthesis of selenoproteins. Dissimilatory reduction of selenate is known to support the anaerobic respiration of a number of microorganisms, and the dissimilatory reduction of soluble selenate and selenite to nanoparticulate elemental selenium greatly reduces the toxicity and bioavailability of selenium and has a major role in bioremediation and potentially in the production of selenium nanospheres for technological applications. Also, microbial methylation after reduction of Se oxyanions is another potentially effective detoxification process if limitations with low reaction rates and capture of the volatile methylated selenium species can be overcome. This review discusses microbial transformations of different forms of Se in an environmental context, with special emphasis on bioremediation of Se pollution.


Abdominal adiposity and metabolic alterations in hypertension -a case control study.
Indians are particularly susceptible to chronic diseases like hypertension, diabetes and coronary heart disease. Several Western studies have documented the role of obesity, especially the role of regional adiposity, and associated metabolic aberrations in the aetiopathogenesis of these chronic diseases. However, there is a paucity of information on the Indian sub-continent. This study was therefore undertaken to investigate the role of regional adiposity and metabolic abnormalities in hypertension. Subjects, aged between 30-50 years, attending the out-patient department of Osmania General Hospital {1000 beds), which caters to middle and low income group of people located at Hyderabad City in India, were screened for hypertension. A total of 158 newly diagnosed subjects were selected along with 172 age and gender matched controls. Body mass index (BMI), waist hip ratio (WHR), total body fat and percentage of body fat were calculated from the anthropometric parameters. Biochemical parameters like serum lipids and plasma glucose and insulin (at fasting as well as 2 h post load glucose) were determined in a subsample of 78 hypertensives and 74 controls. Hypertensives had significantly higher body weight, body fat, BMI and WHR as compared to controls in both men and women. No differences were observed in lipid profile. Plasma glucose, fasting as well as 2 h post load, was significantly higher in both hypertensive men and women. Though there were no differences in plasma insulin at fasting, insulin level at 2 h post-load was elevated in hypertensive women. Higher glucose levels, despite elevated insulin levels, suggested insulin resistance. The calculated odds ratios revealed that increased BMI, WHR, plasma triglycerides, and 2 h post load glucose increased the risk for hypertension in both women and men. Insulin was identified as a risk factor only in women. These results suggest a role for regional adiposity and insulin resistance 1000 in the development of hypertension in the Indian sub-continent.


Analysis of microRNA from archived formalin-fixed paraffin-embedded specimens of amyotrophic lateral sclerosis.
MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression. This study investigated whether formalin-fixed paraffin-embedded (FFPE) specimens from postmortem cases of neurodegenerative disorders would be suitable for miRNA profiling. Ten FFPE samples from 6 cases of amyotrophic lateral sclerosis (ALS) and 4 neurologically normal controls were selected for miRNA analysis on the basis of the following criteria for RNA quality: (i) a postmortem interval of less than 6 hours, (ii) a formalin fixation time of less than 4 weeks, (iii) an RNA yield per sample of more than 500 ng, and (iv) sufficient quality of the RNA agarose gel image. An overall RNA extraction success rate was 46.2%. For ALS, a total of 364 miRNAs were identified in the motor cortex, 91 being up-regulated and 233 down-regulated. Target genes were predicted using miRNA bioinformatics software, and the data applied to ontology analysis. This indicated that one of the miRNAs up-regulated in ALS (miR-338-3p) had already been identified in leukocytes, serum, cerebrospinal fluid and frozen spinal cord from ALS patients. Although analysis was possible for just under half of the specimens examined, we were able to show that informative miRNA data can be derived from archived FFPE samples from postmortem cases of neurodegenerative disorders.


Modulated growth of nanoparticles. Application for sensing nerve gases.
Hydrolysis of acetylthiocholine mediated by acetylcholine esterase yields the thiol-bearing compound thiocholine. At trace concentrations, thiocholine modulates the growth of Au-Ag nanoparticles on seeding gold nanoparticles in the presence of ascorbic acid. Inhibition of the enzyme by 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284c51) or by diethyl p-nitrophenyl phosphate (paraoxon) produces lower yields of thiocholine, promoting the catalytic growth of Au-Ag nanoparticles. Here, we describe the development of a simple and sensitive colorimetric assay for the detection of AChE inhibitors.


Machine Learning Improves Risk Stratification in Myelodysplastic Neoplasms: An Analysis of the Spanish Group of Myelodysplastic Syndromes.
Myelodysplastic neoplasms (MDS) are a heterogeneous group of hematological stem cell disorders characterized by dysplasia, cytopenias, and increased risk of acute leukemia. As prognosis differs widely between patients, and treatment options vary from observation to allogeneic stem cell transplantation, accurate and precise disease risk prognostication is critical for decision making. With this aim, we retrieved registry data from MDS patients from 90 Spanish institutions. A total of 7202 patients were included, which were divided into a training (80%) and a test (20%) set. A machine learning technique (random survival forests) was used to model overall survival (OS) and leukemia-free survival (LFS). The optimal model was based on 8 variables (age, gender, hemoglobin, leukocyte count, platelet count, neutrophil percentage, bone marrow blast, and cytogenetic risk group). This model achieved high accuracy in predicting OS (c-indexes; 0.759 and 0.776) and LFS (c-indexes; 0.812 and 0.845). Importantly, the model was superior to the revised International Prognostic Scoring System (IPSS-R) and the age-adjusted IPSS-R. This difference persisted in different age ranges and in all evaluated disease subgroups. Finally, we validated our results in an external cohort, confirming the superiority of the Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS) over the IPSS-R, and achieving a similar performance as the molecular IPSS. In conclusion, the AIPSS-MDS score is a new prognostic model based exclusively on traditional clinical, hematological, and cytogenetic variables. AIPSS-MDS has a high prognostic accuracy in predicting survival in MDS patients, outperforming other well-established risk-scoring systems.


Academic integrity in the online learning environment for health sciences students.
The online learning environment not only affords accessibility to education for health sciences students, but also poses challenges to academic integrity. Technological advances contribute to new modes of academic dishonesty, although there may be a lack of clarity regarding behaviors that constitute academic dishonesty in the online learning environment. To evaluate an educational intervention aimed at increasing knowledge and improving attitudes about academic integrity in the online learning environment among health sciences students. A quasi-experimental study was conducted using a survey of online learning knowledge and attitudes with strong reliability that was developed based on a modified version of a previously developed information technology attitudes rating tool with an added knowledge section based on the academic integrity statement. Blended-learning courses in a university health sciences center. 355 health sciences students from various disciplines, including nursing, pre-medical, and exercise physiology students, 161 in the control group and 194 in the intervention group. The survey of online learning knowledge and attitudes (SOLKA) was used in a pre-post test study to evaluate the differences in scores between the control group who received the standard course introduction and the intervention group who received an enhanced educational intervention about academic integrity during the course introduction. Post-intervention attitude scores were significantly improved compared to baseline scores for the control and intervention groups, indicating a positive relationship with exposure to the information, with a greater improvement among intervention group participants (p<0.001). There was a significant improvement in the mean post-intervention knowledge score of the intervention group compared to the control group (p=0.001). Recommendations are provided for instructors in promoting academic integrity in the online environment. Emphasis should be made about the importance of academic integrity in the online learning environment in preparation for professional behavior in the technologically advancing health sciences arena.


Heschl's gyrus, posterior superior temporal gyrus, and mid-ventrolateral prefrontal cortex have different roles in the detection of acoustic changes.
A part of the auditory system automatically detects changes in the acoustic environment. This preattentional process has been studied extensively, yet its cerebral origins have not been determined with sufficient accuracy to allow comparison to established anatomical and functional parcellations. Here we used event-related functional MRI and EEG in a parametric experimental design to determine the cortical areas in individual brains that participate in the detection of acoustic changes. Our results suggest that automatic change processing consists of at least three stages: initial detection in the primary auditory cortex, detailed analysis in the posterior superior temporal gyrus and planum temporale, and judgment of sufficient novelty for the allocation of attentional resources in the mid-ventrolateral prefrontal cortex.


Gender differences in the effects of antenatal betamethasone exposure on renal function in adult sheep.
Exposure to clinically relevant doses of glucocorticoids during fetal life increases blood pressure in adult male and female sheep. The purpose of this study was to evaluate the effects of prenatal exposure to betamethasone at 80-81 days of gestation on renal function in ewes and rams at 1.5 yr of age. In prenatal betamethasone-exposed males, compared with the vehicle-exposed animals, basal glomerular filtration rate (GFR) (1.93 +/- 0.08 vs. 2.27 +/- 0.10 ml.min(-1).kg body wt(-1)) and the ability to excrete an acute Na+ load (37.1 +/- 4.4 vs. 53.7 +/- 9.7%) were reduced. (P < 0.03 and P = 0.03, respectively). In contrast, prenatal betamethasone exposure had no effect on basal GFR, Na+ excretion, or the percentage of the Na+ load excreted during the experiment in females. Systemic infusions of ANG-(1-7) at 9 ng.min(-1).kg(-1) for 2 h had minimal effects on basal GFR, renal plasma flow, and Na+ excretion in males but increased Na+ excretion in females. However, the percentage of Na+ load excreted during ANG-(1-7) infusion did not change in prenatal betamethasone-exposed females (113.1 +/- 14.2 vs. 98.1 +/- 12.2%) compared with the significant increase in vehicle females (139.2 +/- 22.3 vs. 92.2 +/- 7.5%) (P = 0.01). The data indicate that antenatal betamethasone exposure produces gender-specific alternations in renal function and thus suggest that different mechanisms underlie the antenatal steroid-induced elevations in blood pressure in male and female offspring.


[Giving care to immigrants living with HIV in France: stakes and specificities].
Representing 40% of the new infections, immigrants living in France appear as a target population for prevention. Care givers have to adapt their practice in taking into account their specificities which are not restricted to cultural differences but include socio-economic determinants playing a major role. In addition to trainings on the foreigners rights and socio- cultural basic knowledge, care-givers (especially clinicians) have to give more time (especially at the beginning of the relationship) and to accept sharing the "medical power" with other people, including mediators, having the possibility of taking into account the other aspects of the patients' life in addition to the medical one. Assuming the fact there is no evidence for any difference regarding adherence between migrants and the other patients, this is probably the price to pay to insure long term therapeutic success.


Return to Professional Australian Rules Football After Surgery for Traumatic Anterior Shoulder Instability.
The treatment of traumatic anterior shoulder instability in professional Australian Football League (AFL) players is challenging, with an emphasis on early return to play and avoidance of instability recurrence. To investigate return-to-sport (RTS) outcomes and complications after 2 different procedures for traumatic anterior shoulder instability in professional AFL players. Cohort study; Level of evidence, 3. We retrospectively reviewed our surgical database for professional AFL players who underwent capsulolabral stabilization or open Latarjet procedure by a single surgeon between 2006 and 2017. Outcomes included RTS, on-field performance, and complications. Between-group analyses for RTS and complications were estimated using Kaplan-Meier survival analyses. Within-group analyses for on-field performance data were performed using paired t tests with significance set at .05. A total of 58 capsulolabral stabilization procedures in 54 players and 32 Latarjet procedures in 29 players were included in the analysis; 93.1% of capsulolabral patients and 96.9% of Latarjet patients returned to professional AFL. The median RTS time was 6.8 months for the capsulolabral group and 7.3 months for the Latarjet group. There was no significant difference in RTS rates between the 2 groups (P = .270). Of those undergoing surgery early in the season, 75% of the capsulolabral and 71% of Latarjet group were able to RTS within the same season, at a mean time of 16.9 weeks and 18.8 weeks, respectively. There was a significant difference in instability recurrence, with 19% for the capsulolabral group and no recurrence in the Latarjet group (P = .017). There was no significant reduction in player on-field performance in either group (P < .05). In this study, the median RTS in AFL players was approximately 7 months after capsulolabral and Latarjet surgery with no compromise to on-field performance. Instability-related complications occurred only in the capsulolabral group, and the incidence increased with time.


All-Optical Sensing of the Components of the Internal Local Electric Field in Proteins.
Here, we present a new all-optical method of interrogation of the internal electric field vector inside proteins. The method is based on experimental evaluation of the permanent dipole moment change upon excitation and the pure electronic transition frequency of a fluorophore embedded in a protein matrix. The permanent dipole moment change can be obtained from two-photon absorption measurements. In addition, permanent dipole moment change, tensor of polarizability change, and transition frequency for the free chromophore should be calculated quantum-mechanically. This allows obtaining the components of the electric field by considering the second-order Stark shift. We use the fluorescent protein mCherry as an example to demonstrate the applicability of the method.


A comparison of Framingham and SCORE-based cardiovascular risk estimates in participants of the German National Health Interview and Examination Survey 1998.
Overestimation of risk by Framingham risk functions not only in southern but also in northern European populations including Germany, has led to the development of the SCORE risk estimation model. Data of the German National Health Interview and Examination Survey 1998 was used to determine whether SCORE leads to lower estimates of the 10-year absolute risk of fatal cardiovascular disease and fatal coronary heart disease than a Framingham model. Predicted numbers of events were compared with approximations based on national mortality statistics. Inclusion criteria followed the recommendations for the use of SCORE: age 30 to 69 years, no previous history of cardiovascular disease and no markedly raised levels of single risk factors (leaving 1811 men and 1955 women for analysis). The SCORE model for high-risk regions (SCORE-HIGH, which is recommended for Germany pending calibration with national data) predicted the highest number of events, followed by the estimations with mortality statistics, the Framingham model and SCORE-LOW (87 fatal cardiovascular disease events versus 77, 62 and 47; fatal coronary heart disease events 62 versus 46, 46 and 30). Agreement on high-risk status, defined as the 10-year risk of fatal cardiovascular disease of 5% or higher now or if extrapolated to age 60, was moderate for both men and women (kappa 0.52 and 0.42 for Framingham and SCORE-HIGH). Our results suggest that SCORE-HIGH may overestimate absolute risk of fatal coronary heart disease and cardiovascular disease in Germany and may need calibration. Furthermore, the limitations of current risk prediction tools emphasize the ongoing need for comprehensive, high-quality and timely European cohort data.


High-dose cladribine therapy for chronic myelogenous leukemia in the accelerated or blast phase.
A phase II clinical trial was performed to evaluate the effectiveness of high-dose cladribine (2CDA) for treatment of chronic myelogenous leukemia (CML) in the accelerated or blast phase. Nineteen patients were treated. The median age was 55 years (range, 30 to 73). Six were older than 60 years. Eight had progressed after intensive combination chemotherapy and three after allogeneic or autologous transplantation. For the first course, 16 patients received 2CDA at 15 mg/m2/d intravenously (i.v.) over 1 hour for 5 days. Two received 18 mg/m2 and one received 21.5 mg/m2 daily. The second course was escalated to 20 mg/m2/d in five patients. Rapid cytoreduction of leukemia occurred in the blood, with the nadir at 10 to 12 days. The median WBC count decreased from 36,900/microL before treatment to 500/microL at the nadir and recovered to 5,200/microL at day 30. The median platelet count changed from 113,000/microL to 24,000/microL at the nadir and 71,000/microL at day 30. The complete remission (CR) plus partial remission (PR) rate was 47% (95% confidence interval [CI], 23% to 72%). One 64-year-old man with lymphoid blast phase of CML had a morphologic and cytogenetic CR that lasted 9 months. The median survival for all patients was 34 weeks, and the median survival for the eight responders was 56 weeks (range, 11 to 167). The median number of days spent in hospital over the entire treatment period was 19 (range, 4 to 60). High-dose 2CDA therapy provides effective palliation for CML in accelerated or blast phases, even for heavily pretreated patients.


Acute thrombotic thrombocytopenic purpura following orthopedic surgery: case report and review of the literature.
Thrombotic thrombocytopenic purpura (TTP) is an uncommon cause of hematological and renal abnormalities in the postoperative period. An association between TTP and orthopedic surgery, a rare entity, has been reported in the literature. It has the strong possibility of being fatal and therefore should be treated immediately, mostly by plasmapheresis. We report a 15-year-old girl of TTP following a high tibial valgus osteotomy (HTO).


Acute effects of five Ghanaian carbohydrate diets on serum glucose, triglyceride and insulin in NIDDM.
Glycemic indices have been used to predict useful carbohydrate sources of food for patients with non-insulin-dependent diabeties mellitus (NIDDM) on dietary management programs. The present study has revealed that glycemic indices alone are not adequate predictors of useful carbohydrate meal sources. We observed for the first time that glycemic indexes inversely correlate with triglyceride indices. In our test mixed meals varying in five Ghanaian carbohydrate food types for nine non-insulin dependent diabetics, the correlation between glycemic and triglyceride indices was (r = -0.63; P = 0.005). The atherogenic potential of triglyceride makes a critical review of the sole use of glycemic indices as useful carbohydrate predictors necessary. We also observed that unripened big plantains (a staple Ghanaian food) could be a useful carbohydrate source for NIDDM patients.


[Twenty years in the 21st century: research approaches and techniques in modern system biology for mechanisms of Chinese medicinal processing].
Clarifying the mechanisms of Chinese medicinal processing is pivotal to the modernization of Chinese medicine. Research on Chinese medicinal processing gives priority to the mechanisms of the processing in enhancing efficacy, reducing toxicity, and repurposing medicinals. During the past 20 years, scholars have carried out in-depth studies on the mechanisms of Chinese medicinal processing via modern system biology. They mainly focused on the changes of medicinal properties and efficacy caused by processing using techniques of modern pharmacology and molecular biology, spectrum-efficacy correlation, and biophoton emission. However, these techniques fail to reflect the holistic view of traditional Chinese medicine. With the introduction of system biology, multi-omics techno-logies(genomics, transcriptomics, proteomics, and metabolomics) have surged, which have been applied to the research on the mec-hanisms of Chinese medicinal processing. These multi-omics technologies have advantages in the research on holism. This study aims to summarize the research techniques and approaches in system biology for mechanisms of Chinese medicinal processing in the past 20 years and analyze the limitations and advantages of them. It is concluded that the multi-omics techniques of system biology can reconstruct the mechanisms of Chinese medicinal processing. This study provides a new direction for further research on the mechanisms of Chinese medicinal processing.


Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.
Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.


Biomimetic hybrid porous scaffolds immobilized with platelet derived growth factor-BB promote cellularization and vascularization in tissue engineering.
Development of hybrid scaffolds with synergistic combination of growth factor is a promising approach to promote early in vivo wound repair and tissue regeneration. Here, we show the rapid wound healing in Wistar albino rats using biomimetic collagen-poly(dialdehyde) guar gum based hybrid porous scaffolds covalently immobilized with platelet derived growth factor-BB. The immobilized platelet derived growth factor in the hybrid scaffolds not only enhance the total protein, collagen, hexosamine, and uronic acid contents in the granulation tissue but also provide stronger tissues. The wound closure analysis reveal that the complete epithelialization period is 15.4 ± 0.9 days for collagen-poly(dialdehyde) guar gum-platelet derived growth factor hybrid scaffolds, whereas it is significantly higher for control, collagen, collagen- poly(dialdehyde) guar gum and povidine-iodine treated groups. Further, the histological evaluation shows that the immobilized platelet derived growth factor in the hybrid scaffolds induced a more robust cellular and vascular response in the implanted site. Hence, we demonstrate that the collagen-poly(dialdehyde) guar gum hybrid scaffolds loaded with platelet derived growth factor stimulates chemotactic effects in the implanted site to promote rapid tissue regeneration and wound repair without the assistance of antibacterial agents.


Monoblepharidomycetes diversity includes new parasitic and saprotrophic species with highly intronized rDNA.
The Monoblepharidomycetes is the sister class to the Chytridiomycetes in the phylum Chytridiomycota. The six known genera have thalli that are either monocentric and without rhizoids or produce hyphae with an independent evolutionary origin from the hyphae of higher fungi. On the basis of morphological characters and phylogenetic evidence from the small and large subunits of nuclear ribosomal RNA, we established two new genera, Sanchytrium and Telasphaerula, each with a single species. We re-analyzed intergeneric relationships within the monoblephs, and established two new families. The new genera significantly expand the known morphological and ecological diversity of the Monoblepharidomycetes by adding a monocentric, epibiotic, algal parasitic species and a rhizomycelial, saprotrophic species. Based on the presence of environmental sequences related to Sanchytrium strains, the Monoblepharidomycetes contain previously unsuspected diversity. The ribosomal DNA of the new genera contains an unusually high density of group I introns. We found 20 intron insertion positions including six that are new for rRNA genes (S1053, L803, L829, L961, L1844, and L2281).


Volunteers at risk.
An experiment is described in which three male volunteers, who fully understood the nature of the project, were given doses of heroin which could have led to addiction if the subjects had proved to be physiologically or psychologically vulnerable to developing a state of addiction. The experiment was discussed most carefully by the Ethics Committee of the unit where it was conducted, and the subjects were themselves the investigators. The objective was to learn about the initial stages of the adaptation to heroin, of which nothing was known as heroin addicts usually come to the doctor when the habit is firmly established. A physician, who has studied the subject of drug addiction in a special clinic, is the first commentator, the second a lawyer and the third an associate professor of social ethics. These three experts are not discussing the results or the methodology of the experiment but whether the decision of the Ethics Committe was the right one.


A rare case of pediatric primary cardiac tumor in a patient with Down syndrome.
Although hematological malignancies are a known complication of Down syndrome, few reports have described cases involving solid tumors. We describe the case of a 3-year-old Down syndrome girl with a primary solid cardiac tumor. Outpatient echocardiography after intracardiac repair of a ventricular septal defect at 6 months of age revealed a highly mobile pedunculated mass (8 × 9 mm) on the free wall of the right atrium. Due to potential incarceration of the mass in the tricuspid orifice, it was excised under extracorporeal circulation and cardiac arrest. Macroscopically, the tumor closely resembled a papillary fibroelastoma, although histopathological tests were inconclusive.


Pharmaceutical marketing practices: balancing public health and law enforcement interests; moving beyond regulation-through-litigation.
Fraudulent or abusive sales and marketing practices by pharmaceutical companies can result in costly overutilization of products that are increasingly paid for by government healthcare programs and may result in adverse health and safety consequences to the patient-beneficiaries of those programs. Federal enforcement efforts in this area are largely modeled on those used to combat white-collar crime, with cases taking years to reach conclusion. This approach overlooks the impact on patients who receive unnecessary care or are denied access to appropriate care during the course of the investigation. Many states are beginning to regulate certain pharmaceutical sales and marketing practices, but state-by-state regulation ignores the importance of a uniform federal regulatory and enforcement approach in an area already occupied by federal law. This Article explores current federal and state efforts to limit overutilization, fraud, and abuse in the sale and marketing of prescription drugs, and illustrates the merits of an expanded role for the U.S. Food and Drug Administration (FDA) to regulate pharmaceutical sales and marketing practices. This approach borrows lessons learned from the FDA's efficient and effective regulatory and enforcement methods and maintains a careful balance between the interests of patient-beneficiaries, the government and industry.


The Rorschach in contemporary forensic psychology.
Recent empirical data attest to the fact that the Rorschach is frequently used in expert witness testimony. Popularity of the Rorschach in forensic psychology is evident in the Psychological Abstracts database.


Analysis of Multiple Manding Topographies during Functional Communication Training.
We evaluated the effects of reinforcing multiple manding topographies during functional communication training (FCT) to decrease problem behavior for three preschool-age children. During Phase 1, a functional analysis identified conditions that maintained problem behavior for each child. During Phase 2, the children's parents taught them to request positive reinforcers (attention or toys) via vocal manding, manual signing, or touching a picture/word card with or without a microswitch recording device. A non-concurrent multiple-baseline design across children was used to evaluate FCT outcomes. Results showed that problem behavior decreased for all three children. Results also indicated that the children initially used multiple manding topographies but displayed a preference for vocal manding over time.


Revelation of Viral - Bacterial Interrelationship in Aggressive Periodontitis via Polymerase Chain Reaction: A Microbiological Study.
Periodontal disease is one of the most common and complex disease affecting mankind. Being multifactorial in etiology it encompasses a variety of infectious entities with various unique microbial constellations and immune responses. A bacteriologic cause alone seems insufficient in explaining several clinical features of the periodontal disease. Recent studies suggest that periodontal herpes viruses comprise an important source of triggering periodontal tissue destruction. The following study aims to assess human cytomegalovirus (HCMV), Epstein-Barr virus (EBV-I) interaction with the established periodontopathic bacteriae, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) in pathogenesis of aggressive periodontitis (AgP) using Hotstart polymerase chain reaction (PCR). A total of 30 subjects, 15 with AgP and 15 healthy controls contributed random subgingival plaque samples. PCR methodology was used to identify the subgingival herpesviruses, Pg, and Aa. Yates corrected Chi-square test was employed to identify a statistical association between herpesviruses and periodontopathic bacteriae. Findings suggested that viruses may be pertinent to disease progression. The prevalence of the periodontopathic bacteria Aa was found in 53.33% (P = 0.0168, S) and Pg in 40% (P = 0.2155, NS) of the AgP patients. Herpesviruses, HCMV and EBV-I were found to have a prevalence of 46.67% (P = 0.039, S) and 40% (P = 0.084, NS). The viral and bacterial co-infection was found to be 77.78% (P = 0.0002, S) with Aa and HCMV. The present data reveals, viruses may exert periodontopathic effect by causing local immunosupression which may set a stage for the subgingival colonization and multiplication of periodontal bacteriae. Further studies are needed to develop an understanding into the significance of herpesviruses in human periodontitis which, may allow for improved diagnosis, more specific therapy and ultimately disease prevention.


Differential effects of the persistent DDT metabolite methylsulfonyl-DDE in nonstimulated and LH-stimulated neonatal porcine Leydig cells.
3-Methylsulfonyl-DDE (MeSO₂-DDE) is a potent adrenal toxicant formed from the persistent insecticide DDT. MeSO₂-DDE is widely present in human plasma, milk and fat, and in tissues of marine mammals. In the present study, we investigated endocrine-disrupting properties of MeSO₂-DDE in primary neonatal porcine Leydig cells. Unstimulated and LH-stimulated cells were exposed to MeSO₂-DDE at concentrations ranging from 0.6 to 20 μM for 48 h. Cell viability, hormone secretion and expression of steroidogenesis related genes were recorded. Secretion of testosterone and estradiol was increased in a concentration-dependent fashion in unstimulated Leydig cells, while in LH-stimulated cells, secretion of testosterone, estradiol and progesterone was decreased. The expression of important steroidogenic genes was down-regulated both in unstimulated and LH-stimulated cells. Notably, no significant impairment of cell viability occurred at any exposure except the highest concentration (20 μM) in LH-stimulated cells. This indicated that the effects on hormone secretion and gene expression were not caused by cytotoxicity. We conclude that the adrenal toxicant MeSO₂-DDE disrupts hormone secretion in a complex fashion in neonatal porcine Leydig cells. The different endocrine responses in unstimulated and LH-stimulated cells imply that the endocrine disruptive activity of MeSO₂-DDE is determined by the physiological status of the Leydig cells.


Soluble CD14: An Independent Biomarker for the Risk of Mother-to-Child Transmission of HIV in a Setting of Preexposure and Postexposure Antiretroviral Prophylaxis.
Elevated soluble CD14 (sCD14) concentrations, a marker of monocyte activation, predicts adverse outcomes in human immunodeficiency virus (HIV)-infected adults. To examine the association of sCD14 concentrations with the risk of mother-to-child transmission (MTCT) of HIV, we nested a case-control study (49 pairs of infants and their HIV-infected mothers) within the Six-Week Extended-Dose Nevirapine trial. Median peripartum maternal log2 sCD14 concentration was higher among transmitters (defined as pairs in which maternally transmitted HIV infection occurred by 12 months of age) than nontransmitters (20.29 pg/mL vs 19.41 pg/mL; P = .005). There was an increased odds of MTCT for every log2 increase in maternal sCD14 concentration, after adjustment for maternal HIV load, CD4 count and cART exposure (adjusted odds ratio, 3.51; 95% confidence interval, 1.21-10.21). Maternal monocyte activation may adversely influence the risk of MTCT of HIV.


Silencing ZmPP2C-A10 with a foxtail mosaic virus (FoMV) derived vector benefits maize growth and development following water limitation.
Global climate change is causing more frequent and severe droughts, which can have negative impacts on plant growth and crop productivity. Under drought conditions, plants produce the hormone ABA (abscisic acid), which regulates adaptive responses, such as stomatal closure and root elongation. Plant viruses have been used in the lab to convey new traits to plants and could also be used to increase production of ABA or to enhance downstream plant drought resistance responses. In this study, foxtail mosaic virus (FoMV) was used to silence ZmPP2C-A10, a negative regulator of ABA signalling, in maize (Zea mays L.). Both silenced and control plants were exposed to an 8-day drought treatment, followed by a 30-day period of rewatering, after which indicators of drought resistance were measured. After drought treatment, we observed a nearly twofold increase in expression of a stress-mitigation gene, ZmRAB17, reduced chlorophyll fluorescence changes (indicator of stress), and increased plant biomass and development in the ZmPP2C-A10-silenced maize compared to controls. These results demonstrate that the FoMV system can be used to silence endogenous expression of ZmPP2C-A10 and increase maize tolerance to drought. This could offer a useful tool to improve crop traits and reduce yield loss during the growing season.


The role of medical libraries in undergraduate education: a case study in genetics.
Between 1996 and 2001, the Health Science Center Libraries and Department of Zoology at the University of Florida partnered to provide a cohesive and comprehensive learning experience to undergraduate students in PCB3063, "Genetics." During one semester each year, a librarian worked with up to 120 undergraduates, providing bibliographic and database instruction in the tools that practicing geneticists use (MEDLINE, GenBank, BLAST, etc.). Students learned to evaluate and synthesize the information that they retrieved, coupling it with information provided in classroom lectures, thus resulting in well-researched short papers on an assigned genetics topic. Exit surveys of students indicated that the majority found the library sessions and librarian's instruction to be useful. Responses also indicated that the project facilitated increased understanding of genetics concepts and appreciation for the scientific research process and the relevance of genetics to the real world. The library benefited from this partnership on a variety of fronts, including the development of skilled library users, pretrained future clientele, and increased visibility among campus research laboratories. The course and associated information instruction and assigned projects can be considered models for course-integrated instruction and the role of medical libraries in undergraduate education.


Butane-1,4-diammonium bis(perchlorate).
The butane-1,4-diammonium cation of the title compound, C(4)H(14)N(2) (2+)·2ClO(4) (-), lies on a special position of site symmetry 2/m, whereas the perchlorate anion is located on a crystallographic mirror plane. An intricate three-dimensional hydrogen-bonding network exists in the crystal structure with each H atom of the ammonium group exhibiting bifurcated inter-actions to the perchlorate anion. Complex hydrogen-bonded ring and chain motifs are also evident, in particular a 50-membered ring with graph-set notation R(10) (10)(50) is identified.


Water fluoridation: time to reexamine the issue.
Water fluoridation was instituted as a public health measure more than 50 years ago to help limit dental caries. However, with the advent of fluoridated dentifrices, fluoridated infant formulas, and commercially prepared beverages with fluoridated water, the incidence of dental fluorosis is increasing. Health care professionals need to understand the history of water fluoridation, examine the benefits and complications of fluoride, and, if need be, take an informed political stance on an issue that is affecting large numbers among our pediatric population.


Mapping of surface structures of electrophorus acetylcholine receptor using monoclonal antibodies.
Forty monoclonal antibodies to acetylcholine receptor from the electric organs of Electrophorus electricus have been characterized by immunoglobulin isotype, affinity for receptor, and specificity for species, subunit, and determinants within subunits. Using these antibodies, nine immunogenic regions on the receptor molecule were distinguished. Most of these are species specific, and are located on various subunits of the acetylcholine receptor. The least species-specific region forms the "main immunogenic region" (MIR). Most monoclonal antibodies and most antibodies in conventional antisera are directed at this region. The MIR is located on the extracellular surface of the alpha subunits and is homologous to the MIR which we previously described on Torpedo californica receptor. An homologous MIR is also a characteristic feature of receptor from mammalian muscle. The possible immunological and structural significance of the MIR is discussed.


[Plant-specific type III polyketide synthases superfamily: crystal structures and functions].
Plant type III polyketide synthase (PKS) generates backbones of a variety of plant secondary metabolites with diverse functions, and has long been models to elucidate the relationship between the three-dimensional structure and function. More than 80 type IIII PKS crystal structures with different functions have been reported in Protein Data Bank, including the crystal structures of the well-studied Chalcone Synthase of plant type III PKS, as well as the 6 other kinds of PKSs in the family, which are critical for understanding the structural basis for diverse starter molecule selectivity, polyketide chain length and the cyclization reaction. Structure-based analysis and site-directed mutagenesis are foundation for the investigation of enzyme engineering, genetic and metabolic engineering. This review summarized 7 plant-specific type III PKS in the aspects of their crystal structures and functions.


Ultrafast laser ablation of trapped gold nanoparticles.
We investigate the interaction of femtosecond (fs) laser pulses with single gold nanoparticles, trapped in a linear Paul trap. We study the scattering response of the particles as a function of the polarization angle of a cw laser at three different wavelengths. These measurements provide a value of the visibility that we compare with Mie theory calculations in order to obtain an estimate of the particle radius. We monitor the particle size during ultrafast laser ablation, obtaining an accurate figure for the mass loss as a function of the fs-laser dose. We discuss the particle mass loss induced by a single fs-laser shot and its relation with the number of absorbed photons.


Methionine toxicity in the chick: nutritional and metabolic implications.
Several assays with young chicks fed crystalline amino acid diets were conducted to investigate the effects of supplemental glycine, serine, threonine, arginine, or adenine on the growth depression resulting from consumption of excess methionine. Glycine was partially effective in alleviating the growth depression caused by excess methionine. The addition of threonine together with glycine improved performance still further. Efficiency of food utilization for weight gain was greater in birds fed the methionine-imbalanced diet supplemented with glycine and threonine than in those fed the control diet. Supplemental glycine, threonine, or adenine, but not arginine, was effective in ameliorating the hypoglycemia resulting from consumption of excess methionine. The rate of oxidation of a tracer dose of threonine was increased markedly by feeding 1.25% excess methionine. This was reflected in a 20% depression in threonine utilization for weight gain as measured by slope ratio. The data suggest that both threonine and glycine are antagonized by consumption of excess methionine.


[Determination of 64 veterinary drug residues in aquatic products by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry].
A method has been developed for the simultaneous determination of 64 veterinary drugs in aquatic products using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry. The samples were extracted with an acetonitrile/water mixture (80/20, v/v), cleaned up by normal hexane saturated with acetonitrile and primary secondary amine (PSA) adsorbent, quantified with external standard method. The drugs were analyzed in full scan/data dependent mass spectrum 2 (Full MS/ddMS2) Top 1 mode. The calibration curves of the 64 drugs were linear with the correlation coefficients more than 0. 9967. The average recoveries of the 64 analytes ranged from 56.2% to 124.6%, and the relative standard deviations (RSDs) were 1.3%-29.8% in the three kinds of matrixes (fish, shrimp and shell) at three levels. The limits of quantification were 0.2-10 μg/kg. The method is simple, rapid, sensitive, reliable and suitable for the screening of residues in aquatic products.


The Chinese and Korean American immigrant experience: a mixed-methods examination of facilitators and barriers of colorectal cancer screening.
Among Asian Americans, colorectal cancer (CRC) is the second leading cause of cancer deaths. Despite strong evidence that screening can reduce CRC-related mortality, fewer Chinese and Koreans receive screening as compared to non-Hispanic whites and blacks. The objective of this study was to examine facilitators and barriers as well as strategies to promote CRC screening in this population. This study employed a mixed-methods design. We conducted 17 key informant interviews and 12 focus groups in the Washington, D.C. metropolitan area. 120 Chinese and Korean focus group participants, aged 50 to 85, also provided quantitative data through self-administered surveys. All participants were asked to discuss facilitators and barriers of CRC screening, including in relation to culture. Participants who had a regular physician and doctor's recommendation for CRC screening were more likely to ever receive a colonoscopy (adjusted odds ratio (aOR) = 3.51; 95% confidence interval (CI): 1.26, 9.79 and aOR = 6.61; 95% CI: 2.63, 16.65, respectively). A doctor's recommendation was also significantly associated with receipt of a fecal occult blood test (FOBT) (aOR = 4.00; 95% CI: 1.43, 11.15). In terms of barriers, those who reported having no time and not having symptoms were less likely to have a colonoscopy (aOR = 0.15; 95% CI: 0.03, 0.82 and aOR = 0.02; 95% CI: 0.002, 0.23, respectively) than those who had time and symptoms. Preventive healthcare was often not viewed as a priority, particularly for those living the'immigrant life,' who gave precedence to work. Cultural barriers to CRC screening included language (e.g. limited English proficiency and low health literacy); fear of finding CRC and burdening the family especially children; fatalism; and stigma towards cancer. Future interventions and programs aiming to increase CRC screening among Chinese and Korean Americans should address both cultural and non-cultural factors that influence CRC screening uptake.


[Involvement of striatal serotonin in fluoxetine effects on adrenocortical function and behaviour].
Treatment of the adult rats with selective serotonin (5-HT) reuptake inhibitor: fluoxetine and its complexes with glycyrrizhinic acid during 2 weeks (25 mg/kg/day) significantly increased plasma corticosterone levels that were measured after 5-min plus-maze. All the drugs decreased the content of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the striatum as well as 5-HT in the hippocampus. There was a significant negative correlation between 5-HT in the striatum and corticosterone levels. These data suggest that fluoxetine induces serotoninergic changes in the striatum that might be related to neuroendocrine and behavioural effects of the drug.


Patients' Perspectives on Stigma of Mental Illness (an Egyptian Study in a Private Hospital).
The present study is concerned with the stigma of mental illness. It examines the subjective element of the experience of stigma among a sample of in-patients with different mental disorders. The sample was taken from consecutive admissions of in-patients meeting International Classification of Diseases, 10th revision (ICD-10) criteria for mental disorders who had capacity to decide on participation in the study and were willing to respond to the structured interview. The study was undertaken in an Egyptian private psychiatric hospital. The structured clinical interview included aspects of the emotional, behavioral, and cognitive effects of having a psychiatric diagnosis on in-patients with various diagnostic labels in an Egyptian psychiatric hospital. It also studied whether this effect changes with specific disorders, total duration of illness, or sociodemographic variables as gender, age, or educational level. The study illustrated the core items of stigmatization attached to the diagnosis of mental illness (1), which more than half of the participants responded affirmatively. The study aimed to explore the most prevailing aspects of stigma or social disadvantage; hoping that this may offer a preliminary guide for clinicians to address these issues in their practice.


Impact of Qi-invigorating traditional Chinese medicines on intestinal flora: A basis for rational choice of prebiotics.
According to the theory of traditional Chinese medicine (TCM), Qi (vital energy) is regarded as a driving force of biological activities in human body, including both nutrient substances and organ functions. Qi-invigorating TCMs are widely used to treat various symptoms and disorders, such as fatigue, obesity, immunosuppression, intestinal flora imbalance, and gastrointestinal diseases, in which Qi is considered to be reduced or depleted. Interestingly, abundant clinical evidences suggest that these disorders are associated with the alternation of intestinal flora, which directly affects disease status. Herein we review the interaction between gut microbiota and Qi-invigorating TCMs under healthy and disease conditions and discuss the mechanisms of action and applications of Qi-invigorating TCMs in enhancing health status through microbial alternation. A better understanding of the role of Qi-invigorating TCMs in modulating microbial composition and the association between intestinal microbiota and diseases would help reveal the clinical consequences of microbiota alteration and explore opportunities to harness this symbiotic relationship to improve public health.


The in vitro production of alpha--fetoprotein variants by human fetal organs.
We have demonstrated the immunological identity of alpha-fetoprotein (AFP) produced in vitro by various fetal organs such as the yolk sac, liver, intestine and kidney. AFP produced in vitro by these organs, present in fetal serum and in samples of amniotic fluid was, however, heterogeneous when studied by lectin affinity immunoelectrophoresis. Results obtained with Concanavalin A were comparable to those obtained with Lentil agglutinin, but Concanavalin A separated AFP into two variants only, while Lentil agglutinin recognised three AFP variants. AFP produced by the yolk sac, intestine and kidney was similar in their proportions of variants and differed clearly from liver AFP. The ratios of AFP variants present in fetal serum were dissimilar to those of yolk sac AFP and of liver AFP. Relative amounts of AFP variants in fetal serum were similar in the first and last trimester of gestation. The proportions of AFP variants present in amniotic fluid in the first trimester of gestation were different from fetal serum, but, at the end of pregnancy, they become identical to those observed in fetal serum. Application of AFP variants for prenatal and cancer diagnosis is discussed.


Regions and residues of an asymmetric operator DNA interacting with the monomeric repressor of temperate mycobacteriophage L1.
Previously, the repressor protein of mycobacteriophage L1 bound to two operator DNAs with dissimilar affinity. Surprisingly, the putative operator consensus sequence, 5'GGTGGa/cTGTCAAG, lacks the dyad symmetry reported for the repressor binding operators of lambda and related phages. To gain insight into the structure of the L1 repressor-asymmetric operator DNA complex, we have performed various in vitro experiments. A dimethyl sulfate protection assay revealed that five guanine bases, mostly distributed in the two adjacent major grooves of the 13 bp operator DNA helix, participate in repressor binding. Hydroxyl radical footprinting demonstrated that interaction between the repressor and operator DNA is asymmetric in nature and occurs primarily through one face of the DNA helix. Genetic studies not only confirmed the results of the dimethyl sulfate protection assay but also indicated that other bases in the 13 bp operator DNA are critical for repressor binding. Interestingly, repressor that weakly induced bending in the asymmetric operator DNA interacted with this operator as a monomer. The tertiary structure of the L1 repressor-operator DNA complex therefore appears to be distinct from those of the lambdoid phages even though the number of repressor molecules per operator site closely matched that of the lambda phage system.


Molecular cloning and characterization of a 1-deoxy-D-xylulose 5-phosphate reductoisomerase gene from Ginkgo biloba.
1-deoxy-D-xylulose 5-phosphate (DXP) reductoisomerase (DXR, EC: 126.96.36.1997) is the second enzyme of the non-mevalonate terpenoid pathway for isopentenyl diphosphate biosynthesis and actually catalyzes a committed step of the methylerythritol phosphate (MEP) pathway for ginkgolide biosynthesis. The full-length DXR cDNA sequence (GenBank accession number: AY443101) was cloned and characterized for the first time from gymnosperm plant species, Ginkgo biloba, using rapid amplification of cDNA ends (RACE) technique. The full-length cDNA of GbDXR was 1720 bp containing a 1431 bp open reading frame (ORF) encoding a peptide of 477 amino acids with a calculated molecular mass of 52 kDa and an isoelectric point of 6.58. Comparative and bioinformatic analyses revealed that GbDXR showed extensive homology with DXRs from other plant species and contained a conserved transit peptide for plastids, an extended Pro-rich region and a highly conserved NADPH binding motif in its N-terminal region owned by all plant DXRs. Phylogenetic analysis indicated that GbDXR was more ancient than other plant DXRs. Tissue expression pattern analysis indicated that GbDXR expressed in all tissues including roots, stems, leaves, pericarps and seeds and lower transcription level was observed in leaves of G. biloba than that of other tissues. The cloning and characterization of GbDXR will be helpful to understand more about the role of DXR involved in the ginkgolides biosynthesis at the molecular level.


[MINI-ENDOSCOPY OF THE BILIOPANCREATIC SYSTEM 1998]
Pancreaticoscopy is a method that is still in the midst of its development. The instruments available to date only allow inspection of proximally dilatated and extended ductal sections. Thanks to pancreaticoscopy, gastroenterological endoscopy has left the intestinal tract and achieved access to a glandular system with a unique histological wall structure. The extensive pathological anatomy of the pancreas makes intensive diagnostics desirable. Pancreaticoscopy should therefore be included in the diagnostic spectrum. However, this technique should always be performed with special circumspection, in particular with regard to the possible complications (acute pancreatitis) Ductal endoscopy of the bile duct and pancreatic duct are technically feasible and provide detailed evidence required for the diagnosis of diseases of the biliary and pancreatic system. The indications for cholangioscopy have, for the most part, been established, specifically therapeutic access to difficult gall stones. Pancreaticoscopy opens up new terrain in medical optics, although the relevance of this method, in conjunction with the outlay and technique required for its use, still have to find justification. The first prototypes for endoluminal sound have become available although this method is not expected to become a routine procedure in the near future.


Reversal of Adriamycin-impaired wound healing by transforming growth factor-beta.
Impaired wound healing remains an important clinical problem. Treatment with systemic Adriamycin (doxorubicin) is known to impair wound healing in patients, and it has been used to produce animal models of impaired healing. The results of previous studies have shown that local treatment of incisions in normal rats with transforming growth factor beta (TGF-beta) or epidermal growth factor (EGF) stimulated early increases in tensile strength of surgical incisions in normal rats. We investigated the effects of locally applied, biosynthetic TGF-beta or EGF on the tensile strength of standardized incisions in rats treated with Adriamycin. Systemic Adriamycin treatment (8 milligrams per kilogram) produced significant decreases in wound tear strength (WTS) and wound tear energy (WTE) when compared with that of normal rats at seven and ten days (p less than 0.01). A single dose of TGF-beta (2 micrograms) in a collagen vehicle stimulated a reversal of this wound healing impairment at ten days (p less than 0.05), returning the WTS and WTE to near normal levels. A single dose of EGF (50 micrograms) in hyaluronic acid failed to increase tensile strength, probably because of formulation of EGF in a vehicle that does not prolong its release in incisions. These results suggest that exogenous growth factors may be clinically useful in stimulating healing in incisions in healing impaired conditions.


[The contamination of human milk with chlororganic pesticides (author's transl)].
A survey on the situation concerning the residues on pesticides in human milk in West Germany is given, based on own investigations. Nearly the whole pattern of chlororganic pesticides - DDT with its metabolites DDE and DDD, hexachlorobenzene (HCB), the different isomeres (alpha-, beta-, gamma-) of benzenehexachloride (BHC) as well as dieldrin and heptachloroepoxid - together with polychlorinated biphenyls (PCB) coming from the environment - were found in all samples of human milk, though in different concentrations. PCB, HCB and beta-BHC had been discovered in human milk only about ten years ago. The residues have decreased in the past years. The concentrations are still so high that the amounts consumed by the suckling exceed the ADI values for the contaminants in question. But in the opinion of the experts the advantages connected with the alimentation with human milk weigh more than the eventual risk by the contamination.


Immunity provided by haemorrhagic septicaemia-subunit vaccine in ruminants.
A subunit vaccine against haemorrhagic septicaemia (HS), the principal killer disease in ruminants, especially cattle and carabao, in the Philippines, has been developed. Using capsules of Pasteurella multocida Group B as an active component of the vaccine, it gave solid protection against challenge with live organism in mice. An active calf protection test showed that in 24 hours, animals vaccinated with plain saline died after challenge compared to those given the subunit vaccine which survive the challenge dose. Using 104 cattle from a farm, the field trial of the HS subunit vaccine showed that the antibody titre was high for up to 14 months. A high titer is an indication of protection.


A New Adult Diet Formulation for Sterile Males of Anastrepha ludens and Anastrepha obliqua (Diptera: Tephritidae).
A new adult diet formulation was evaluated for sterile Anastrepha ludens (Loew) and Anastrepha obliqua (Macquart) males at the emergence and release facility of fruit flies in Mexico. The formulation consists of hydrolyzed protein, sugar, juvenile hormone analogue methoprene, and water. The proportion of the ingredients between the solute (4% hydrolyzed protein and 96% sugar) and solvent (10% methoprene and 90% water) was 5:1. This new formulation was called the 1:24 formulation. The main objectives of this study were to develop a simple way to supply the 1:24 formulation to adults and to compare the sexual performance of these flies with the performance of flies fed a standard diet (called the Mubarqui formulation) used at the emergence and release facility of fruit flies in Mexico. The preparation, time, and cost also were evaluated. The results showed no significant differences in the sexual behaviors of the males (number of males mating, number of males calling, mating latency, and mating duration) between the 1:24 formulation and the Mubarqui formulation. However, the cost and the required preparation time are much lower for the 1:24 formulation process than for the Mubarqui formulation process. Based on these results, we recommend the 1:24 formulation as an additional adult diet option in the handling of sterile flies. Its application is practical and does not require changes in packaging systems. The contribution of our findings and their potential application to the improvement of the sterile insect technique are discussed.


Parser for protein folding units.
General patterns of protein structural organization have emerged from studies of hundreds of structures elucidated by X-ray crystallography and nuclear magnetic resonance. Structural units are commonly identified by visual inspection of molecular models using qualitative criteria. Here, we propose an algorithm for identification of structural units by objective, quantitative criteria based on atomic interactions. The underlying physical concept is maximal interactions within each unit and minimal interaction between units (domains). In a simple harmonic approximation, interdomain dynamics is determined by the strength of the interface and the distribution of masses. The most likely domain decomposition involves units with the most correlated motion, or largest interdomain fluctuation time. The decomposition of a convoluted 3-D structure is complicated by the possibility that the chain can cross over several times between units. Grouping the residues by solving an eigenvalue problem for the contact matrix reduces the problem to a one-dimensional search for all reasonable trial bisections. Recursive bisection yields a tree of putative folding units. Simple physical criteria are used to identify units that could exist by themselves. The units so defined closely correspond to crystallographers' notion of structural domains. The results are useful for the analysis of folding principles, for modular protein design and for protein engineering.


The additional value of a home physical therapy regimen versus patient education only for the treatment of myofascial pain of the jaw muscles: short-term results of a randomized clinical trial.
To compare the short-term efficacy of patient education only versus the combination of patient education and home exercises for the treatment of myofascial pain of the jaw muscles. Seventy myogenous temporomandibular disorder patients were assigned to 2 treatment groups. One group received patient education supplemented by general information about self-care of the jaw musculature. The other group received both education and a home physical therapy program. Treatment contrast, calculated from the mean normalized relative changes in anamnestic and clinical scores, was used to determine treatment success. Clinical outcome measures included pressure pain threshold (PPT) of the masseter, anterior temporalis, and Achilles tendon; pain-free maximal jaw opening; and pain on chewing, spontaneous muscle pain, and headache as rated on visual analog scales. After 3 months the success rate was 57% for the group that received education only and 77% for the group that received both education and home physical therapy (P = .157). The patients were then redivided into 2 groups: successfully treated patients and unsuccessfully treated patients. In the unsuccessfully treated group, pain-free maximal jaw opening increased significantly more among those who had been in the education and physical therapy group than among those who had been in the education-only group (P = .019). The change in PPT was significantly greater in successfully treated patients than in unsuccessfully treated patients (.009 < P < .039), independent of the treatment modality, with higher PPTs among successful patients. There were no significant differences between the successfully and unsuccessfully treated groups or between treatment modalities for any other variable. Over a period of 3 months, the combination of education and a home physical therapy regimen, as used in this protocol, is slightly more clinically effective than education alone for the treatment of myofascial pain of the jaw muscles.


Estimation of the relationship between body mass index and EQ-5D health utilities in individuals with type 2 diabetes: evidence from the population-based KORA studies.
Obesity is known to be an important risk factor for type 2 diabetes and its related comorbid conditions; however, its specific impact on generic health-related quality of life (HRQL) is less clear. The objective of this study was to estimate the association between body mass index (BMI) and HRQL in individuals with type 2 diabetes. The EQ-5D quality of life questionnaire was administered in a follow-up of 10,385 participants aged 33-94 of the population-based German MONICA/KORA surveys. 1033 participants with type 2 diabetes were identified by self-report combined with validated physician diagnoses. Semiparametric additive regression models were used to estimate the effect of BMI on EQ-5D health utilities adjusted for age, sex, education and comorbidities. BMI was significantly associated with EQ-5D health utilities even after adjustment for macro- and microvascular complications. The functional relationship between BMI and utilities was nonlinear, reflecting optimal health around 26 kg/m² and significantly decreasing health utilities with increasing levels of overweight and obesity (-0.09 points between BMI values 26 and 40). Among the diabetic complications, the history of a stroke (-0.13) and neuropathy (-0.10) were the strongest predictors of reduced health utility scores. BMI is strongly associated with health utilities in persons with type 2 diabetes. This suggests that lifestyle measures to reduce obesity can markedly improve patients' health-related quality of life and that the negative effect of potential weight gain should be taken into account when determining patient preferences for different type 2 diabetes treatment options.


Effects of a forced-air warming system and warmed intravenous fluids on hemodynamic parameters, shivering, and time to awakening in elderly patients undergoing open cardiac surgery.
As one of the most common postoperative complications, hypothermia is the main cause of numerous problems during treatment, especially in elderly patients with decreased cardiac reserves. The aim of the present study was to compare the effects of forced-air warming system (FAWS), warmed intravenous fluids (WIVFs) and routine method on hemodynamic parameters, arterial blood gases (ABGs), shivering, and time to awakening in elderly patients undergoing open cardiac surgery (OCS). This clinical randomized controlled trial was conducted on 94 elderly patients who underwent OCS at Ayatollah Rouhani Hospital, Babol, Iran. They were divided into three groups, namely FAWS (n=31), WIVFs (n=31) and routine rewarming method (RRWM, with a blanket) (n=32). The data were then recorded in a checklist. Descriptive and inferential statistics were performed using SPSS 26 at a significance level of less than 0.05. The findings demonstrated that the degree of hypothermia had a significant decreasing trend in the groups receiving FAWS and WIVFs (P=0.002). Additionally, increased respiratory rate (P=0.013), higher bicarbonate (HCO3-) levels on arrival up to 4 hours after surgery (P=0.045), reduced lactate level (P=0.005), normal base excess (BE) and accelerated time to awakening (P=0.004) were observed in patients receiving FAWS. There was no significant difference in the study groups regarding shivering. The results revealed that FAWS could mitigate the degree of hypothermia, increase body temperature and decrease the postoperative serum lactate levels. Moreover, BE as one of the most important parameters for ABGs, could remain at a normal level. Besides, the use of FAWS could lead to early awakening, and thus facilitate weaning and extubation of these patients.


Diagnostic performance of ID screen MVV-CAEV Indirect Screening ELISA in identifying small ruminant lentiviruses-infected goats.
Diagnostic performance of ID Screen MVV-CAEV Indirect Screening ELISA in identifying goats infected with small ruminant lentiviruses (SRLV) was evaluated. In total 299 serum samples from the collection of the Laboratory of Veterinary Epidemiology and Economics--109 truly positive and 190 truly negative--were used. To be enrolled in the study a serum sample had to come from at least 2 year-old goat which had reacted identically in two serological surveys preceding sample collection and was kept in a herd of stable serological status confirmed at least twice during preceding 5 years. Moreover, in seropositive herds at least 20% of goats had to be serologically positive at the moment when the serum sample was collected for the study. The test proved to have high accuracy. Area under curve was 98.8% (95% CI: 97.5%, 100%). Diagnostic performance of the test was almost identical (Youlden's index of 90%, sensitivity > 90% and specificity > 95%) within a fairly wide range of cut-off values--between 20% and 60%. At manufacturer's cut-off of 50% sensitivity and specificity were 91.7% (95% CI: 85.0%, 95.6%) and 98.9% (95% CI: 96.2%, 99.7%), respectively. For this cut-off positive likelihood ratio was 87 (95% CI: 22, 346) and negative likelihood ratio was 0.08 (95% CI: 0.04, 0.16). In conclusion, the results of this study indicate that ID Screen MVV-CAEV Indirect Screening ELISA is a highly accurate diagnostic test for SRLV infection.


Gastrointestinal bleeding and blood transfusion in the elderly in Japan.
The incidence of gastrointestinal bleeding (GIB) increases with age and blood transfusion is frequently given for the management of GIB. In this report, we summarized our data of the patients with GIB and discussed the relationship between blood transfusion and age in patients with GIB. The patients were divided into two groups according to age, following elderly (≥75 years old) and younger (<75 years old) group. The causes and clinical outcome (blood transfusions, management) of each group were compared. One-hundred and twenty patients with GIB were hospitalized (59 men, 61 women) with a mean age of 72.0±15.8 years (range 16-96 years old). Thirty-one patients (25.8%) received blood transfusion. The mean pre-transfusion hemoglobin was 6.4±1.2g/dL (elderly 6.3±1.4, younger 6.6±1.0g/dL) and the mean amount of blood transfusion was 2.8±1.6U (elderly 3.2±1.8, younger 2.3±0.9U). The elderly patients using antithrombotic drugs need greater amounts of blood transfusion than younger patients using antithrombotic drugs. The hemoglobin level of the elder patients without antithrombotic drugs was significantly lower than that of younger patients without antithrombotic drugs. Our data suggest that our blood transfusion strategy seems to be in tolerance level with restrictive blood transfusion strategy.


Rebamipide and mosapride enhance pilocarpine-induced salivation.
During esophageal acid clearance, salivation plays an important role in defending the esophageal mucosa. Mosapride, an agent used in chronic, long-term therapy of gastro-esophageal reflux disease (GERD) was regarded as mediating its efficacy through prokinetic properties. Rebamipide is also widely used as an anti-gastritis and anti-ulcer agent in GERD patients with chronic gastritis. The aim of this study is to investigate the effects of rebamipide, mosapride, and risperidone on the salivation induced by pilocarpine. The experiments were conducted on 4-week male SD rats (120-150g). The salivation was induced by intraperitoneally administrated pilocarpine and saliva was collected using preweighted small cotton balls inserted into the animal's mouth every 30 min for 180 min. Thirteen minutes before intraperitoneal administration of pilocarpine, rebamipide, mosapride, and risperidone were administered intraduodenally. Control rats were conducted by intraperitoneal administration of saline and intraduodenal administration of 0.5% methylcellulose solution. The saliva weight at 0-30 min was significantly (p<0.01) increased after administration of pilocarpine, compared to control rats. An additional administration of mosapride and rebamipide increased the saliva weight at 0-30 min. The total volume of saliva for 150 min after administration of pilocarpine was the highest after preadministration of rebamipide, followed by mosapride, and risperidone. Increase in salivation produced by i.p. pilocarpine was enhanced by preadministration of rebamipide and mosapride.


DNA cleavage by UVA irradiation of NADH with dioxygen via radical chain processes.
Efficient DNA cleaving-activity is observed by UVA irradiation of an O(2)-saturated aqueous solution of NADH (beta-nicotinamide adenine dinucleotide, reduced form). No DNA cleavage has been observed without NADH under otherwise the same experimental conditions. In the presence of NADH, energy transfer from the triplet excited state of NADH ((3)NADH*) to O(2) occurs to produce singlet oxygen ((1)O(2)) that is detected by the phosphorescence emission at 1270 nm. No quenching of (1)O(2) by NADH was observed as indicated by no change in the intensity of phosphorescence emission of (1)O(2) at 1270 nm in the presence of various concentrations of NADH. In addition to the energy transfer, photoinduced electron transfer from (3)NADH* to O(2) occurs to produce NADH(*+) and O(2)(*-), both of which was observed by ESR. The quantum yield of the photochemical oxidation of NADH with O(2) increases linearly with increasing concentration of NADH but decreases with increasing the light intensity absorbed by NADH. Such unusual dependence of the quantum yield on concentration of NADH and the light intensity absorbed by NADH indicates that the photochemical oxidation of NADH with O(2) proceeds via radical chain processes. The O(2)(*-) produced in the photoinduced electron transfer is in the protonation equilibrium with HO(2)(*), which acts as a chain carrier for the radical chain oxidation of NADH with O(2) to produce NAD(+) and H(2)O(2), leading to the DNA cleavage.


Emergence of extensively drug-resistant Aeromonas hydrophila complex isolated from wild Mugil cephalus (striped mullet) and Mediterranean seawater.
Antibiotic resistance has been a progressively documented problem, resulting in treatment failure in humans and animals. This study aimed to investigate the antimicrobial susceptibility and virulence of extensively drug-resistant (XDR) Aeromonas spp. in wild Mugil cephalus and its surrounding seawater along the coastal road of Port Said, Egypt. Specimens were examined bacteriologically, confirmed biochemically, and tested for their sensitivity against 11 antimicrobial agents. Molecular confirmation of the obtained isolates by 16S rRNA was performed, followed by the detection of antimicrobial resistance and virulence genes. Aeromonas spp. was recovered from fish (44%) and water samples (36%). A. hydrophila was the most prevalent identified strain, followed by Aeromonas sobria, Aeromonas caviae, and Aeromonas schubertii. Moreover, 90% of the tested isolates were multidrug-resistant (MDR), while 26.67% were XDR. Tested isolates were resistant to b-lactams and sulfonamides (100%), oxytetracycline (90%), and streptomycin (62.22%) but completely susceptible to cefotaxime. XDR isolates successfully amplified resistance genes (blaTEM , sul1, and tetA(A)) but not the (aadA1) gene, although there was phenotypic resistance to streptomycin on plates. All XDR isolates carry the cytotoxic enterotoxin gene (act), but alt gene was detected in only one isolate (12.5%). Data in this study provide a recent update and highlight the role of wild mullet and seawater as reservoirs for MDR and XDR Aeromonas spp. that may pose a risk to humans as food-borne infection or following direct contact.


Fast Growth of GaN Epilayers via Laser-Assisted Metal-Organic Chemical Vapor Deposition for Ultraviolet Photodetector Applications.
In this study, we successfully developed a carbon dioxide (CO2)-laser-assisted metal-organic chemical vapor deposition (LMOCVD) approach to fast synthesis of high-quality gallium nitride (GaN) epilayers on Al2O3 [sapphire(0001)] substrates. By employing a two-step growth procedure, high crystallinity and smooth GaN epilayers with a fast growth rate of 25.8 μm/h were obtained. The high crystallinity was confirmed by a combination of techniques, including X-ray diffraction, Raman spectroscopy, transmission electron microscopy, and atomic force microscopy. By optimizing growth parameters, the ∼4.3-μm-thick GaN films grown at 990 °C for 10 min showed a smooth surface with a root-mean-square surface roughness of ∼1.9 nm and excellent thickness uniformity with sharp GaN/substrate interfaces. The full-width at half-maximum values of the GaN(0002) X-ray rocking curve of 313 arcsec and the GaN(101̅2) X-ray rocking curve of 390 arcsec further confirmed the high crystallinity of the GaN epilayers. We also fabricated ultraviolet (UV) photodetectors based on the as-grown GaN layers, which exhibited a high responsivity of 0.108 A W-1 at 367 nm and a fast response time of ∼125 ns, demonstrating its high optical quality with potential in optoelectronic applications. Our strategy thus provides a simple and cost-effective means toward fast and high-quality GaN heteroepitaxy growth suitable for fabricating high-performance GaN-based UV detectors.


Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction.
A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E-05, pcombined = 1.8E-05, and pcombined = 6.5E-06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54-2.46, pcombined = 2.5E-08 versus OR = 1.46, 95% CI = 1.23-1.73, pcombined = 1.5E-05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span.


[Clinical study of baoyuan dahuang decoction in the treatment of chronic renal failure].
The quality of life of 56 chronic renal failure (CRF) patients using two kinds of treatment has been observed. 36 of them were taken as Group A with BUN 21.62 +/- 5.96 mmol/L, Cr 528.63 +/- 176.3 mumol/L and Hb 65 +/- 13 g/L were treated with Baoyuan Dahuang Decoction consisted of Panax ginseng, Astragalus membranaceus, Cassia cinnamomi, Glycyrrhiza uralensis and Rheum palmatum. Six symptoms were observed, that were: fatigue, lassitude in loin and legs, aversion of cold, anorexia, sexual dysfunction and mental depression. Five of them improved markedly, from 12.5 +/- 2.91 before treatment to 5.58 +/- 4.68 after treatment in terms of symptom scores, P < 0.001. Furthermore, dihydrothelin (E2), testosterone (T) and pregnendione (P) were regulated significantly, the elevated level of creatine phosphokinase (CPK) before treatment lowered to near normal. The other 20 patients, BUN 20.24 +/- 6.57 mmol/L, Cr 487.08 +/- 238.68 mumol/L and Hb 68 +/- 13g/L formed Group B using comprehensive treatment of Western medicine as control. The main drug was coated aldehyde oxystarch. After treatment, the symptoms didn't show marked improvement, symptom scores being 12.55 +/- 2.0 compared with 10.05 +/- 2.72 before treatment, P > 0.05. E2, T, P and CPK were of insignificant differences (P > 0.05); Hb remained almost unchanged, even though BUN and Cr lowered for 22% and 29% respectively. It is assumed that Baoyuan Dahuang decoction could improve CRF patients' quality of life, and the mechanism of which was not only to reduce the urea nitrogen, but also to adjust the anemia and regulate the membrane function.


Lipophilic statins suppress cytotoxicity by freshly isolated natural killer cells through modulation of granule exocytosis.
NK cells, a component of the innate immune system, provide a first line of defense against viral infections and malignancies, interact with the adaptive immune system and have a role in rejection of allogeneic bone marrow transplants and solid allo- and xenotransplants. Immunoregulatory activity by the anti-hypercholesterolemia agents, 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG-CoA) reductase inhibitors, known as statins, has recently been reported. We analyzed the effects of three statins on human NK cell cytotoxicity. Two lipophilic statins (simvastatin and fluvastatin) suppressed the cytotoxic activity of fresh and IL-2-stimulated NK cells, while pravastatin, a hydrophilic statin, did not. Suppression was not associated with changes in intracellular perforin, granzyme A or granzyme B levels, or with changes in expression of leukocyte function-associated antigen-1, an integrin known to regulate NK activity and reported to be altered by statin treatment. Decreased cytotoxicity was associated with decreased CD107a surface expression, indicating that the exocytosis pathway was compromised by simvastatin and fluvastatin but not by pravastatin. Mevalonate, the immediate downstream product of HMG-CoA reductase, partially reversed the effect of lipophilic statins on cytotoxicity and CD107a expression. Lipophilic statins also suppressed the release of the granule component, granzyme B, by IL-2-activated NK cells following stimulation with K562. That lipophilic statins suppress NK cell activity through inhibition of the exocytosis pathway suggest an additional potential role for statins in inhibition of transplantation responses.


Genetic influences on alcohol use behaviors have diverging developmental trajectories: a prospective study among male and female twins.
Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother-sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences. We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n = 1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders (AUD-GR) was indexed by his/her parents' and cotwin's DSM-IV Alcohol Dependence (AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders (EXT-GR) was indexed with a composite measure of parents' and cotwin's DSM-IV Conduct Disorder and Antisocial Personality Disorder criterion counts. EXT-GR was most strongly related to alcohol use behaviors during adolescence, while AUD-GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD-GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT-GR influenced age 22 AD more in males than in females. In addition, the associations of AUD-GR and EXT-GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers. We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD-GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT-GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins.


Differential responses of maize MIP genes to salt stress and ABA.
Salt stress is known to reduce root hydraulic conductivity and growth. To examine a concomitant regulation of aquaporins, the expression of the maize MIP gene family in response to NaCl was analysed by DNA array hybridization. Plants responded differentially to 100 versus 200 mM NaCl treatments. Leaf water content was reduced rapidly and persistently after the application of 200 mM NaCl in contrast to 100 mM NaCl. Endogenous ABA strongly accumulated in roots after 2 h; it remained at a highly elevated level for 48 h after the addition of 200 mM NaCl, but rapidly declined in plants treated with 100 mM NaCl, indicating an early recovery from water deficit. Interestingly, 2 h after the addition of 100 mM NaCl, when maize regained the osmotic potential allowing water uptake, three highly expressed, specific isoforms ZmPIP1;1, ZmPIP1;5, and ZmPIP2;4 were transiently induced. They were preferentially transcribed in the outer root tissue suggesting a role in cellular water transport. None of the ZmTIP genes was altered. By contrast, after the addition of 200 mM NaCl these responses were missing. Instead, multiple ZmPIP and ZmTIP genes were repressed by 200 mM NaCl after 24 h. After 48 h, deregulations were overridden in both cases indicating homeostasis. ABA (1 muM) exogenously applied to the roots transiently induced ZmPIP2;4 similar to 100 mM NaCl as well as ZmPIP1;2. Thus, the early induction of ZmPIP2;4 by NaCl may be mediated by ABA. Previously, an increase in root hydraulic conductivity had been observed upon ABA application. By contrast, 100 muM ABA led to a complete, possibly non-specific repression of all detected ZmPIP and ZmTIP genes after 24 h.


Successful Treatment of Synchronous Double Lung Primary Malignancies and Colon Cancer.
We report a rare case of multiple primary malignancies, double primary lung cancers, and synchronous colon cancer. Double primary lung cancers were synchronous with adenocarcinoma of the sigmoid (carcinoid tumor and adenocarcinoma). The patient subsequently underwent two surgeries, for lung and colon cancer, followed by four cycles of carboplatin and pemetrexed treatment for the lung adenocarcinoma, with an uneventful chemotherapy course. The patient has been followed up closely for the last 18 months via CT scans and tumor marker tests and has shown no evidence of recurrence or metastasis.


Motion-perception deficits and reading impairment: it's the noise, not the motion.
We tested the hypothesis that deficits on sensory-processing tasks frequently associated with poor reading and dyslexia are the result of impairments in external-noise exclusion, rather than motion perception or magnocellular processing. We compared the motion-direction discrimination thresholds of adults and children with good or poor reading performance, using coherent-motion displays embedded in external noise. Both adults and children who were poor readers had higher thresholds than their respective peers in the presence of high external noise, but not in the presence of low external noise or when the signal was clearly demarcated. Adults' performance in high external noise correlated with their general reading ability, whereas children's performance correlated with their language and verbal abilities. The results support the hypothesis that noise-exclusion deficits impair reading and language development and suggest that the impact of such deficits on the development of reading skills changes with age.


Glomerular microcapillary thrombosis demonstrated by the new technique of immunocathodoluminescence.
Fluorescein-labeled antigen-antibody complexes could be made visible by scanning electron microscopy using an intensifying device. This new method of immunocathodoluminescence was demonstrated on cryostat sections of rat kidneys containing glomerular fibrin as the result of endotoxin infusion. The resulting photographs correspond with those obtained by immunofluorescent microscopy. The advantage of this technique is, however, the larger depth of focus. By using thinner cyostat sections it is expected that the higher resolution of scanning microscopy will provide even better details in three dimensions.


Bilateral sex cord tumor with annular tubules of ovary without Peutz-Jeghers syndrome: a case report.
Ovarian sex cord tumor with annular tubules is a very rare tumor . Afourteen year old Nepali girl presented with abdominal distension and lower abdominal pain. On laparotomy bilateral ovarian masses were found. It was totally solid on the right side and was partially solid and partially cystic on the left side. The patient had no other symptoms and features of Peutz-Jeghers syndrome. Microscopic examination showed characteristic findings of sex cord tumor with annular tubules on both sides. The patient was doing well 2 months after surgery. The case is presented with review of literature because of the rare clinical presentation.