Elevated nitrate simplifies microbial community compositions and interactions in sulfide-rich river sediments.
Excessive nitrate in water systems is prevailing and a global risk of human health. Polluted river sediments are dominated by anaerobes and often the hotspot of denitrification. So far, little is known about the ecological effects of nitrate pollution on microbial dynamics, especially those in sulfide-rich sediments. Here we simulated a nitrate surge and monitored the microbial responses, as well as the changes of important environmental parameters in a sulfide-rich river sediment for a month. Our analysis of sediment microbial communities showed that elevated nitrate led to (i) a functional convergence at denitrification and sulfide oxidation, (ii) a taxonomic convergence at Proteobacteria, and (iii) a significant loss of biodiversity, community stability and other functions. Two chemolithotrophic denitrifiers Thiobacillus and Luteimonas were enriched after nitrate amendment, although the original communities were dominated by methanogens and syntrophic bacteria. Also, serial dilutions of sediment microbial communities found that Thiobacillus thiophilus dominated 18/30 communities because of its capability of simultaneous nitrate reduction and sulfide oxidation. Additionally, our network analysis indicated that keystone taxa seemed more likely to be native auxotrophs (e.g., syntrophic bacteria, methanogens) rather than dominant denitrifiers, possibly because of the extensive interspecific cross-feeding they estabilished, while environment perturbations probably disrupted that cross-feeding and simplified microbial interactions. This study advances our understanding of microbial community responses to nitrate pollution and possible mechanism in the sulfide-rich river sediment.


Marriage and fertility in China: 1950-1989.
"This article presents a graphical and a life table analysis that summarizes some 14,000 values of data by single year of age and time on marriage and fertility in China up to 1989. In the 1970s, age at first marriage shifted upward by about four years, and fertility dramatically declined. The age at marriage and childbearing decreased in [the] 1980s, which are associated with some socio-economic factors. Fertility rates slightly increased in the second half of the 1980s, from their low level in 1984. The analysis also reveals that Chinese marriage and childbearing remain virtually universal and occurred at rather young ages." Data are from the 1988 2-in-1,000 fertility and contraceptive survey. (SUMMARY IN FRE AND ITA)


Implementation of a national testing policy in Dutch nursing homes during SARS-CoV-2 outbreaks.
To evaluate how a national policy of testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms was implemented during outbreaks in Dutch nursing homes in the second wave of the pandemic and to explore barriers and facilitators to serial testing. We conducted a mixed-method study of nursing homes in the Netherlands with a SARS-CoV-2 outbreak after 15 September 2020. Direct care staff and management from 355 healthcare organizations were invited to participate in a digital survey. A total of 74 out of 355 (20.9%) healthcare organizations participated and provided information about 117 nursing homes. We conducted 26 in-depth interviews on the outbreak and the testing strategy used. We also conducted four focus group meetings involving managers, physicians, nurses, and certified health assistants. Recordings were transcribed and data were thematically analyzed. One hundred and four nursing homes (89%) tested residents regardless of their symptoms during the outbreak, and 85 nursing homes (73%) tested the staff regardless of their symptoms. However, interviews showed testing was sometimes implemented during later stages of the outbreak and was not always followed up with serial testing. Barriers to serial testing regardless of symptoms were lack of knowledge of local leaders with decisional making authority, lack of a cohort ward or skilled staff, and insufficient collaboration with laboratories or local public health services. Important facilitators to serial testing were staff willingness to undergo testing and the availability of polymerase chain reaction (PCR) tests. Serial testing regardless of symptoms was only partially implemented. The response rate of 21% of nursing home organizations gives a risk of selection bias. Barriers to testing need to be addressed. A national implementation policy that promotes collaboration between public health services and nursing homes and educates management and care staff is necessary.


Decompressive Hemicraniectomy Associated With Ultrasound-Guided Minimally Invasive Puncture and Drainage Has Better Feasibility Than the Traditional Hematoma Evacuation for Deteriorating Spontaneous Intracranial Hemorrhage in the Basal Ganglia Region: A Retrospective Observational Cohort Study.
Objectives: Spontaneous intracerebral hemorrhage (ICH) is a devastating disease with higher mortality and disability rates; however, ideal surgical management is still to be determined for critical ICH. The purpose of this study was to prove the feasibility and unique clinical value of a novel combination, decompressive hemicraniectomy associated with ultrasound-guided minimally invasive puncture and drainage (DH + MIPD), for deteriorating ICH in the basal ganglia region. Methods: According to the enrollment criteria, 168 ICH patients were analyzed retrospectively, of which 86 patients received DH + MIPD and 82 patients received DH associated with traditional hematoma evacuation as the control group. The change process of three parameters, including hematoma size, peri-hematoma edema, and intracranial pressure (ICP), in a period of time after operation, as well as the short- and long-term therapeutic effect, was compared. Results: The DH + MIPD method could effectively achieve the evacuation rate of hematoma up to 87% at 5 days post-operation and had the significant advantages of minimal injury to cerebral tissue, less degree of edema, better effect of decreasing ICP, shorter operation time, less blood loss, and lower mortality compared with the control method. The DH + MIPD group had a significantly higher survival rate within 1 year post-operation (P = 0.007) and better functional outcome at 90 and 180 days post-operation (P = 0.004). A subgroup analysis pointed out that the DH + MIPD method had a definite survival advantage for critical ICH patients older than 60 years old and with hematoma located in the left dominant hemisphere. Conclusions: Our results proved the better feasibility of DH + MIPD on hematoma evacuation and implicated its significant advantages of reducing mortality and improving functional recovery. This method provides one more choice for the individualized therapy of ICH in the basal ganglia region.


In vitro study on shRNA-mediated reduction of testis developmental related gene 1 expression and its effects on the proliferation, invasion and apoptosis of NTERA-2 cells.
Testis developmental related gene 1 (TDRG1) is a novel human testis-specific gene. TDRG1 is differentially expressed in cancerous tissue compared with normal testicular tissue and demonstrates a unique expression pattern in normal testes; therefore, this gene may be involved in the occurrence and development of testicular germ cell tumors (TGCT). In the present study, the expression level of TDRG1 was downregulated in human TGCT NTERA-2 cells by RNA interference (RNAi) in order to investigate the association between TDRG1 and TGCT. The TDRG1 mRNA and protein expression levels in NTERA-2 cells were significantly inhibited following transfection with specific RNAi plasmids. The ability to proliferate (inhibited by 15.4% at day 3 and 26.1% at day 5; P<0.001) and invade (reduced by 49.1%; P=0.01) in vitro was suppressed in cells in which the expression level of TDRG1 was reduced, and a corresponding increase in the apoptotic potential was observed (the early apoptotic potential and total apoptotic potential were increased by 75%; P=0.019 and 54.8%; P=0.009, respectively). The results of the present study indicated that the biological behavior of NTERA-2 cells is associated with TDRG1 expression levels, and that this gene may be a novel target candidate in the treatment of TGCT.


Experimental study on histological changes in the sinus membrane following sinus lift.
The aim of this study is to assess the histological changes in the sinus mucosa adjacent to the alloplastic material used for subantral augmentation. The study included ten sheep and a dog. The first group of five sheep underwent a sinus lift procedure, using PerioGlas as an augmentation material; the second similar group of sheep was the control group. The dog underwent a sinus lift procedure, with PerioGlas augmentation, after the sinus membrane was intentionally perforated and two implants were placed in the same operative step. Scanning electron microscopy (SEM) of the sinus mucosa in the control group revealed cells without cilia between goblet cells. The cilia were uniformly arranged in sections in the same direction. Changes occurred in the sinus mucosa after grafting, such as drastic reduction of ciliated cells, which seemed to be replaced by goblet cells. In all sheep undergoing grafting, generalized fibrosis was found in the mucosal area that came into contact with PerioGlas. In two of the sheep in which grafting was performed, mucoid cysts with pseudo stratified ciliated epithelium were present. Even when the sinus mucosa was perforated (in the dog), the inflammatory process developed in the mucosa did not prevent the integration of the graft and implants. In conclusion, following the sinus lift procedure, changes occur in the sinus membrane to adapt to the new situation, without the appearance of chronic or acute suppurative processes.


Mindfulness-Based Interventions for Undergraduate Nursing Students in a University Setting: A Narrative Review.
(1) Introduction: Undergraduate (UG) nursing students are vulnerable to stress throughout their education, known to result in burnout, with high attrition rates of up to 33%. There is a growing body of evidence to suggest that mindfulness-based interventions are effective for the management of anxiety, depression and wellbeing, thereby reducing stress in healthcare provider populations. The aim of this narrative review was to synthesize and provide a critical overview of the current evidence in relation to mindfulness-based interventions for UG nursing students in a university setting. (2) Methods: A review of the literature was conducted in March 2020 and updated in May 2021, utilising the databases CINAHL, Medline and PsycINFO. (3) Results: Fifteen studies were included in the review, with three common themes identified: (i) the positive impact of mindfulness on holistic wellbeing, (ii) mindfulness-based techniques as a positive coping mechanism within academic and clinical practice, and (iii) approaches to the delivery of mindfulness-based interventions. (4) Conclusions: Mindfulness-based interventions are effective strategies for the management of stress, development of self-awareness and enhanced academic and clinical performance in undergraduate nursing students. No ideal approach to delivery or duration of these interventions was evident from the literature. Best practice in relation to delivery of mindfulness-based interventions for nursing students is recommended for future studies.


Lipid peroxidation and irreversible cell damage: synergism between carbon tetrachloride and 1,2-dibromoethane in isolated rat hepatocytes.
The combination of 1,2-dibromoethane (DBE) with carbon tetrachloride (CCl4) in the isolated rat hepatocyte model produces a significant potentiation of both lipid peroxidation and plasma membrane damage induced by the latter compound. The increase in malondialdehyde production precedes the hepatocyte damage, evaluated in terms both of lactate dehydrogenase leakage and trypan blue exclusion. When hepatocytes are isolated from vitamin E pretreated rats, both the prooxidant and the cytotoxic effects of CCl4 are prevented. Also the synergism between CCl4 and DBE on lipid peroxidation disappears completely while that on cell damage is strongly reduced. The increased lipid peroxidation appears to be one of the mechanisms of the observed synergism between CCl4 and DBE on hepatocyte damage. Regarding the antioxidant status of the hepatocyte challenged with CCl4 and DBE, an early and significant consumption of vitamin E is observed only in the presence of the mixture of these xenobiotics. Total nonprotein thiol content is not significantly modified by CCl4 poisoning while DBE, alone and in association with CCl4, markedly decreases it. Vitamin E supplementation does not prevent but moderately delays total nonprotein thiol depletion due to DBE or to the mixture. Finally, glutathione transferase activity is significantly reduced by CCl4 treatment and not by DBE, and vitamin E supplementation totally prevents such inhibition. The increased prooxidant effect of CCl4 plus DBE compared to CCl4 alone seems related to the shift in DBE metabolism consequent to the CCl4-dependent inactivation of glutathione transferase.


Linking Quality and Quantity of Parental Linguistic Input to Child Language Skills: A Meta-Analysis.
This meta-analysis examined associations between the quantity and quality of parental linguistic input and children's language. Pooled effect size for quality (i.e., vocabulary diversity and syntactic complexity; k = 35; N = 1,958; r = .33) was more robust than for quantity (i.e., number of words/tokens/utterances; k = 33; N = 1,411; r = .20) of linguistic input. For quality and quantity of parental linguistic input, effect sizes were stronger when input was observed in naturalistic contexts compared to free play tasks. For quality of parental linguistic input, effect sizes also increased as child age and observation length increased. Effect sizes were not moderated by socioeconomic status or child gender. Findings highlight parental linguistic input as a key environmental factor in children's language skills.


Sleep apnoea and unscheduled re-admission in patients undergoing coronary artery bypass surgery.
Although it has been recognised as a cardiovascular risk factor, data on sleep apnoea screening before coronary artery bypass grafting (CABG) are scarce. This study sought to determine the prevalence, predictors and effects of sleep apnoea on re-admission in patients undergoing CABG. We prospectively recruited 152 patients to undergo an overnight sleep study before CABG. Sleep apnoea was defined as an apnoea-hypopnoea index of ≥15 events per hour. Data on unscheduled re-admission due to cardiovascular events were collected. Among the 138 patients who completed the sleep study, sleep apnoea was diagnosed in 69 (50%). The patients who had sleep apnoea had a lower left ventricular ejection fraction (p = 0.029), a larger left atrial diameter (p = 0.014) and a larger left ventricular end-systolic dimension (p = 0.019) than those who did not. Angiographic SYNTAX and Gensini scores were similar in patients with and without sleep apnoea. The generalised structural equation model revealed that hypertension, a high body mass index and chronic renal failure were independent predictors of sleep apnoea (p < 0.05). After an average follow-up of 6 ± 3 months, 12 patients with sleep apnoea (17.3%) and three patients without sleep apnoea (4.3%) were involved in unscheduled re-admission. Patients with sleep apnoea were almost five times more likely to have an unscheduled re-admission due to cardiovascular events (adjusted odds ratio: 4.63, 95% CI: 1.24-17.31, p = 0.023) than those without sleep apnoea. Sleep apnoea was prevalent and predictive of unscheduled re-admissions in patients scheduled for CABG.


Poland syndrome with intracranial germ cell tumor in a child.
Poland syndrome is an uncommon unilateral deformity of chest wall and upper extremity with variable manifestations. Although numerous case reports of Poland syndrome associated with malignancies have been published, intracranial germ cell tumor in Poland syndrome has not been previously reported. The authors describe a 15-year-old male patient with intracranial germ cell tumor and Poland syndrome.


Plasma markers of hypercoagulability in patients with serious infections and risk of septic shock.
Hyperthrombinogenesis due to bacterial septicemia may aggravate the risk of irreversible septic shock. In 22 patients with septicemia complicating urinary or alimentary infections, daily assessment of hemostasis was performed throughout 1 week. Standard screening of hemostasis revealed significantly increased mean values of prothrombin time, fibrinogen, and fibrinogen degradation product (FDP) concentration. However, platelet counts, activated partial thromboplastin times (APTT), thrombin times, ethanol gelation tests, and antithrombin activity remained within the normal range. By contrast, except for insignificant changes in protein C activity and activated factor VII content, specific markers of plasma hypercoagulability, that is, thrombin-antithrombin (TAT) complexes, prothrombin activating factor F 1+2, activated factor XII (XIIa), and dimer D were all markedly increased. Pathologic levels of TAT and Xlla were found in 82% and 73% of all plasma samples, respectively. The augmentation of TAT correlated with prolongation of thrombin time and increases in F 1+2 levels. The increase in XIIa correlated with thrombocytopenia, prolongation of APTT, exhaustion of antithrombin, and accumulation of F 1+2 and FDP in the plasma. Moreover, a significant increase in XIIa, stronger positivity of the ethanol gelation test, a greater increase in FDP, and a more pronounced decrease in protein C activity were observed in 8 patients with fatal septic shock. This study suggests the usefulness of TAT and XIIa measurements in the early recognition of plasma hypercoagulation in serious infections.


Secretin: a pleiotrophic hormone.
Secretin holds a unique place in the history of endocrinology and gastrointestinal physiology, as it is the first peptide designated as a hormone. During the last century since its first discovery, the hormonal effects of secretin in the gastrointestinal tract were extensively studied, and its principal role in the periphery was found to stimulate exocrine secretion from the pancreas. Recently, a functional role of secretin in the brain has also been substantiated, with evidence suggesting a possible role of secretin in embryonic brain development. Given that secretin and its receptors are widely expressed in multiple tissues, this peptide should therefore exhibit pleiotrophic functions throughout the body. The present article reviews the current knowledge on the central and peripheral effects of secretin as well as its therapeutic uses.


Detection of Defects in Reinforced Concrete Structures Using Ultrasonic Nondestructive Evaluation with Piezoceramic Transducers and the Time Reversal Method.
Reinforced concrete is of vital importance in many civil and industrial structural applications. The effective bonding between steel and concrete is the core guarantee of the safe operation of the structures. Corrosion or other interface debonding in steel-concrete is a typical failure mode during the long service period of the structures, which can severely reduce the load-bearing capacity. The Non-destructive Evaluation technique has been applied to civil engineering structures in recent years. This paper investigates the evaluation of reinforced concrete structures that have interface defects, including the cross-sectional loss and cracks, by using the piezoceramic induced ultrasonic wave and time reversal method. Ultrasonic wave is used as actuating wave to obtain the signals with defect information. Time reversal method is applied to localize and characterize defect along the interface of the steel-concrete and to image the defect through the cross-sectional scanning. Experiments were conducted to perform Nondestructive Evaluation by using six reinforced concrete components with different levels of defects. The invisible damages were made by the cutting part of the steel and embedding a table tennis ball inside concrete structures. The results show that the time reversed method can locate and evaluate the defects along the steel reinforced concrete, and the obtained defect images at the cross-section of the concrete structure are accurate.


[Factors in training and participation in childbirth care by non-physicians].
This study aimed to characterize midwives according to current concepts among health professionals and to identify the ideological premises underlying proposals for their training. Data from interviews with nine midwives, nurses, and physicians were interpreted using discourse analysis. The resulting empirical categories were "The Situation of Maternity Care in Brazil", "The Ideal (or Necessary) Midwife and the Possible Midwife". When these empirical categories were interpreted, it was possible to "construct" an "emerging midwife" by dialectically overcoming the concept of "the ideal midwife".


A niobaziridine hydride system for white phosphorus or dinitrogen activation and N- or P-atom transfer.
This short review describes a breakthrough embodied by the synthesis of a niobaziridine hydride complex. This reactive entity reacts directly with white phosphorus to provide a bridging diphosphorus diniobium complex that upon reduction splits to afford a terminal niobium phosphide anion, isolated as its sodium salt. Reactions of the latter with acid chlorides constitute a new synthesis of phosphaalkynes, while treatment with chlorodiorganophosphanes leads to complexed 1,1-diorganophosphanylphosphinidene systems. Additionally, reactions of the sodium salt of the niobium phosphide anion with divalent main group element salts (E = Ge, Sn, or Pb) provide complexed triatomic EP2 triangles. Dinitrogen cleavage was realized via reduction of a heterodinuclear niobium/molybdenum dinitrogen complex, and this provided an entry to a nitrogen-15 labeled terminal nitride anion of niobium as its sodium salt. In a fashion analogous to the aforementioned phosphaalkyne synthesis, acid chlorides are transformed upon reaction with the niobium nitride anion into corresponding nitrogen-15 labeled organic nitriles. Complete synthetic cycles are achieved in both the phosphaalkyne and the organic nitrile syntheses, as the oxoniobium(v) byproduct can be recycled in high yield to the title niobaziridine hydride complex.


Elongated telomeres in scid mice.
Severe combined immunodeficiency (scid) mice are deficient in the enzyme DNA-PK (DNA-dependent protein kinase) as a result of the mutation in the gene encoding the catalytic subunit (DNA-PKcs) of this enzyme. DNA-PKcs is a member of the phosphatidylinositol 3-kinase superfamily, which includes the human protein ATM (ataxia telangiectasia mutated) and the yeast protein Tel1. Using Q-FISH (quantitative fluorescence in situ hybridization), we show here that scid mice from four different genetic backgrounds have, on average, 1.5-2 times longer telomeres than those of corresponding wild-type mice. Our results point to the possibility that DNA-PKcs may, directly or indirectly, be involved in telomere length regulation in mammalian cells.


Insertion of depth electrodes with or without subdural grids using frameless stereotactic guidance systems--technique and outcome.
Over recent years frameless stereotactic systems have begun replacing framed systems for many neurosurgical procedures. However, little has been published regarding the use of these systems to guide intracranial electrode implantation for epilepsy surgery patients. Here we report our experience utilising such a system to insert depth electrodes and subdural grid electrodes. The SteathStation Image-Guided System (SSIGS) (Sofamor Danek, Memphis TN.) was used to insert bilateral depth electrodes in 13 patients, of whom 5 also underwent the insertion of subdural grids or strip electrodes. Initially, a surgical plan based on an entry and target point on axial and sagittal images was performed for the insertion of electrodes. Navigational views, using three-planar images, were then performed to determine which structures the electrodes would pass through to be correctly placed in the amygdala and hippocampus. The correct site of electrode implantation was confirmed post-operatively by spiral CT scans in 4 patients (which were then co-registered to the pre-implantation MRI using a surface matching technique) and the other 9 patients by post-implantation MRI. The SSIGS was found to have a mean registration error of 2.0 mm (range 1.8-2.5) in 10 cases; in the 3 cases where the error was greater than 2.5 mm a surfacemerge technique was used with a mean error 0.9 (0.8-1.00). The post-implantation MRI or CT-MRI co-registration confirmed an accurate electrode placement in the mesial temporal region in all cases. Seizure onset lateralisation was achieved in 11 patients, all of whom went onto formal resections based on these results. The only long-term complication was a case of osteomyelitis which required removal of the bone flap. 73% of patients had an excellent seizure outcome. Frameless stereotactic systems can be safely used to intracranial electrodes, avoid the disadvantages of the framed system and have the added advantage of the surgeon being able to visualise the trajectory and to adjust this to avoid vital structures. As well they eliminate surgical obstruction to the insertion of subdural grids at the same operation, which may be caused by a framed system.


Italian Guidelines.
Diverticular disease (DD) is a widespread condition, however limited evidences are available about its management and complications. In the last years, an Italian Consensus Conference promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) and a Guideline, by Italian Society of Colorectal Surgery (SICCR) were published. The aim of the Consensus was to provide clinical recommendation for appropriate definition, diagnosis, and management of DD, in particular 4 areas of interest were identified, namely: (i) definition and epidemiology, (ii) pathophysiology, (iii) diagnosis, and (iv) medical and surgical treatment. A total of 55 statements graded according to different level of evidence and strength of recommendation were approved. However, if we consider the grade of recommendation, their strength remains suboptimal, with only 3 statements with grade of evidence A in the area of diagnosis. The Clinical guidelines by SICCR focus mainly on acute diverticulitis, and surgical treatment of complicated DD. One of the main topic analyzed, is represented by the management of the acute uncomplicated diverticulitis, in particular about the use of antibiotics and need of hospitalization. Despite the presence of many recent European and western country guidelines, there is a lack of robust data on epidemiology, risk factors, and medical and surgical management of DD, calling the need of further studies aimed to obtain an evidence-based approach in this condition.


A role for extracellular copper in modulating prostaglandin E2 (PGE2) action: facilitation of PGE2 stimulation of the release of gonadotropin-releasing hormone (LHRH) from median eminence explants.
Copper is present in high concentrations in axonal terminals of hypothalamic neurons (1). We have previously postulated that copper is released from axonal terminals of hypothalamic neurons (2). In this study, we addressed the question: Does extracellular copper facilitate PGE2 action, specifically, the stimulation of LHRH release? The median eminence area (MEA) of male rats was incubated under in vitro conditions, and LHRH release into the medium was quantified by RIA. When MEA were incubated for 5 min with 100 microM copper and then for 15 min with 50 microM PGE2 (Cu/PGE2), Cu/PGE2-stimulated release of LHRH was significantly (P less than 0.001) greater (2 times) than the sum of copper- and PGE2-stimulated release. When MEA were first incubated for 15 min with PGE2 and then for 5 min with copper (PGE2/Cu), PGE2/Cu-stimulated release equalled the sum of PGE2- and copper-stimulated release of LHRH. Thus, copper facilitates PGE2 stimulation of LHRH release from the MEA, and the characteristics of this facilitation are consistent with an enhancement of PGE2 binding to its receptor. These results support the proposition that extracellular copper can serve as a modulator of PGE2 action.


Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials.
Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a dietary polyphenol derived from grapes, berries, peanuts, and other plant sources. During the last decade, resveratrol has been shown to possess a fascinating spectrum of pharmacologic properties. Multiple biochemical and molecular actions seem to contribute to resveratrol effects against precancerous or cancer cells. Resveratrol affects all three discrete stages of carcinogenesis (initiation, promotion, and progression) by modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis, and metastasis. The anticancer property of resveratrol has been supported by its ability to inhibit proliferation of a wide variety of human tumor cells in vitro. These in vitro data have led to numerous preclinical animal studies to evaluate the potential of this drug for cancer chemoprevention and chemotherapy. This review provides concise, comprehensive data from preclinical in vivo studies in various rodent models of human cancers, highlighting the related mechanisms of action. Bioavailability, pharmacokinetic, and potential toxicity studies of resveratrol in humans and ongoing interventional clinical trials are also presented. The conclusion describes directions for future resveratrol research to establish its activity and utility as a human cancer preventive and therapeutic drug.


[Outcomes of very severe aplastic anemia patients with different absolute neutrophil counts after frontline immnunosuppressive therapy].
To analyze early hematopoietic response and long-term survival of very severe aplastic anemia (VSAA) patients with different absolute neutrophil counts (ANC) after frontline immnunosuppressive therapy (IST). Clinical data and outcome of 145 VSAA patients treated with rabbit antithymocyte globulin combined with cyclosporine were retrospectively analyzed. Hematopoietic responses to IST and long-term survival were statistically analyzed for VSAA patients in different ANC subgroups. Pre-IST ANC=0.05×10(9)/L acted as the best cutoff level to predict IST response at 3, 6 months. For 145 VSAA patients, early death rate was 13.4% (11/82) vs 1.6% (1/63), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group (P<0.05). Hematopoietic response rates to IST was 22.0% vs 54.0% (P=0.000) at 3 months, 34.1% vs 63.5% (P=0.000) at 6 months; the overall five-year survival rate was only (62.5±5.4) % vs (91.4±3.7) % (P=0.000) and five-year event-free survival rate was (42.3±5.5) % vs (63.1±6.5) % (P=0.003), respectively, in the ANC≤0.05×10(9)/L group and ANC>0.05×10(9)/L group. VSAA patients with extremely low ANC (≤0.05×10(9)/L) had high early death rate and with very low response rate to frontline IST and poor survival, so it is urgent to seek for the alternative frontline therapy that will bring faster and better outcome for these patients.


Partial reversal of androgenetic alopecia with methotrexate therapy for psoriasis.
We report the case of a 64-year-old man with androgenetic alopecia who was started on methotrexate therapy for treatment of psoriasis after traditional modalities failed. Following treatment with methotrexate, he noted hair regrowth on the scalp. We propose that methotrexate may inhibit gonadal steroidogenesis, therefore leading to lower testosterone levels, or may increase testosterone aromatization at the hair follicles. These mechanisms may account for the hair growth observed in our patient, which indicates that partial reversal of androgenetic alopecia may be a side effect of methotrexate therapy.


Detection of Mycobacterium tuberculosis in respiratory specimens by strand displacement amplification of DNA.
A total of 294 clinical respiratory specimens, including 75 with culture-positive results, were tested for the presence of Mycobacterium tuberculosis by strand displacement amplification (SDA) of DNA. A region of the IS6110 insertion element and an internal control sequence were amplified and then detected by a chemiluminescence assay. Receiver operator-characteristic curves were used to evaluate three methods for declaring specimens positive for M. tuberculosis. By the preferred method, SDA chemiluminescence results were converted to theoretical numbers of M. tuberculosis organisms. A positive threshold (PT) value, above which 95% of the SDA results were judged to be M. tuberculosis positive (sensitivity = 95%), was found to be 2.4 M. tuberculosis organisms per SDA reaction. The analogous PT value for 95% sensitivity on smear-positive specimens was 3.6 M. tuberculosis organisms per reaction. The PT of 2.4 M. tuberculosis organisms per reaction detected 100% of culture-positive, smear-positive specimens (sensitivity = 100%), while 95% sensitivity was achieved with a PT of 15.5 M. tuberculosis organisms per reaction. Specificities, which were calculated with respect to culture- and smear-negative specimens, ranged from 96% at a PT of 15.5 M. tuberculosis organisms to 84% at a PT of 2.4 M. tuberculosis organisms per reaction. The M. tuberculosis-negative specimens were also segregated according to whether the patients received antituberculosis chemotherapy. SDA specificity ranged from 90% (PT = 2.4 M. tuberculosis organisms) to 98% (PT = 15.5 M. tuberculosis organisms) for the M. tuberculosis-negative specimens from patients who had not received chemotherapy. SDA specificity in the M. tuberculosis-negative specimens from patients who received chemotherapy was lower (85 to 94%). This study represents the first large-scale demonstration of M. tuberculosis detection in clinical sputum specimens by isothermal DNA amplification with SDA.


Anti-heart antibodies in postpericardiotomy syndrome: cause or epiphenomenon? A prospective, longitudinal pilot study.
To assess the role of anti-heart antibodies (AHA) in postpericardiotomy syndrome (PPS) and the timing of their appearance in relation to the initial manifestations of PPS. Twenty patients who were scheduled to undergo elective coronary artery bypass grafting (CABG) were enrolled in a prospective, longitudinal pilot study. Serum was sampled for AHA on the day prior to surgery and at regular intervalsfollowing surgery in all patients. In those who developed PPS, the serum AHA was determined on the day that typical clinical manifestations of PPS appeared and at regular intervals following the onset of PPS. All patients were negative for AHA on the day precedingsurgery. Three(15%) patients developed PPS. Their sera were negative for AHA on the day they were diagnosed as sufferingfrom PPS and the sera became positive for AHA within 14 days from the time of diagnosis. The intensity of immunofluorescence decreased markedly 30 days afterwards and AHA had disappeared within 90days after diagnosis of PPS. The other 17 (85%) patients were negative for AHA prior to surgery and remained so during the six-month postoperative follow-up period. The findings of this study suggest that serum AHA may not play a causal role inthe pathogenesis of PPS, but may rather be an epiphenomenon, reflecting an immune response to pericardial and/or myocardial injury.


Prevalence and Correlates of Elevated Blood Pressure in Chinese Children Aged 6-13 Years: a Nationwide School-Based Survey.
To estimate the prevalence of elevated blood pressure (EBP) in Chinese children and identify individual and family factors associated with EBP. A nationwide cross-sectional study was conducted in 2010 using stratified cluster sampling. Participants' blood pressure was measured, and their parents completed a questionnaire on personal and family characteristics. Prevalence and correlates of EBP were assessed. Among a total of 24,333 participants, 20.2% of boys and 16.3% of girls had EBP. The prevalence of EBP increased with the ascending trend of waist circumference, Waist-to-height ratio, and body mass index. The adjusted prevalence ratios (aPRs) for obese boys and girls were 2.50 and 2.97, respectively. Fewer urban boys (16.2%) had EBP than rural boys (21.7%). Boys with a family history of hypertension were 12% more likely to have EBP. Children whose mothers received a college education tended to have lower likelihood of EBP; with an aPR was 0.85 among boys and 0.78 among girls. EBP is common among obese students and those who have a family history of hypertension. A negative association between mothers' education levels and EBP risk in children was found.


Characterization and Research on Mechanical Properties of Bamboo Plastic Composites.
The focus of this study was to observe the mechanical properties of bamboo plastic composites (BPCs) with bamboo pulp fiber (BPF) or white mud (WM). The essential work of fracture (EWF) methodology was used to characterize the impact toughness of BPCs. The results revealed an increase in flexural, tensile and impact properties, when adding the BPF in the BPCs. While the flexural properties of WM-reinforced BPCs revealed increasing, there was a decrease in tensile and impact strength. In an impact strength analysis study, BPF-filled BPCs showed excellent impact property over WM-filled BPCs; scanning electron microscopy (SEM) helps to explain impact fracture behavior of BPCs. EWF analysis of impact results showed that the specific essential work of fracture (we) increased significantly with the amount of BPF used in BPCs but decreased with the increase of WM in the BPCs. There was similar variation for the non-essential plastic work (βwp) of BPCs. This result indicates that the fracture initiation and fracture propagation of BPCs are different.


Holmium laser enucleation of prostate: outcome and complications of self-taught learning curve.
To analyze the self-learning curve of a single surgeon with holmium laser enucleation of the prostate and to evaluate the safety, effectiveness, and outcome of the procedure after 2 years of experience. The data from the first 125 patients who underwent holmium laser enucleation of the prostate were retrospectively analyzed. The patients were assessed preoperatively and at 1, 3, 12, and 24 months postoperatively. The patient evaluations included serum prostate-specific antigen measurement, peak urinary flow rate determination, postvoid residual volume measurement, and symptom scores. To assess the effect of the learning curve on the perioperative data and complications, the patients were divided into subgroups of 25 consecutive patients. The mean patient age was 71.4 years. The average prostate volume was 75.8 mL, and the mean weight of the enucleated tissue was 46.7 g. The average operative time was 109.8 minutes. The operative times and enucleation and morcellation efficiency rates improved significantly during the learning process. The mean hemoglobin loss was 1.7 g/dL. The median catheter time and hospital stay was 44 and 30 hours, respectively. Compared with baseline, at 1 year postoperatively, the median postvoid residual urine volume had declined by 99 mL, the mean peak urinary flow rate had increased by 19 mL/s, and the mean American Urological Association symptom score had decreased by 16.5 points. All changes observed were significant and regardless of the prostate size. Persistent stress urinary incontinence (4.8%) occurred with the first enucleations of large-size prostates. Other complications included bladder neck contracture (4%) in small-size prostates and bulbar urethra stricture (1.6%). Holmium laser enucleation of the prostate is a safe, reproducible and effective surgical modality. Case selection is necessary to avoid the morbidity associated with the first stages of the self-taught learning curve, mainly urinary incontinence.


Competition among Eggs Shifts to Cooperation along a Sperm Supply Gradient in an External Fertilizer.
Competition among gametes for fertilization imposes strong selection. For external fertilizers, this selective pressure extends to eggs for which spawning conditions can range from sperm limitation (competition among eggs) to sexual conflict (overabundance of competing sperm toxic to eggs). Yet existing fertilization models ignore dynamics that can alter the functional nature of gamete interactions. These factors include attraction of sperm to eggs, egg crowding effects, or other nonlinearities in per capita rates of sperm-egg interaction. Such processes potentially allow egg concentrations to drastically affect viable fertilization probabilities. I experimentally tested whether such egg effects occur, using the urchin Strongylocentrotus purpuratus, and parameterized a newly derived model of fertilization dynamics and existing models modified to include such interactions. The experiments revealed that at low sperm concentrations, eggs compete for sperm, while at high sperm concentrations, eggs cooperatively reduce abnormal fertilization (a proxy for polyspermy). I show that these observations are consistent with declines in the per capita rate at which sperm and eggs interact as eggs increase in density. The results suggest a fitness trade-off of egg release during spawning: as sperm range from scarce to superabundant, interactions among eggs transition from highly competitive to cooperative in terms of viable fertilization probabilities.


A Korean family with Arg1448Cys mutation of SCN4A channel causing paramyotonia congenita: electrophysiologic, histopathologic, and molecular genetic studies.
A family with paramyotonia congenita (PC) is presented. At least 10 family members were affected in an autosomal dominant inheritance pattern. The proband had cold-sensitive muscle stiffness, paradoxical myotonia, and intermittent muscle weakness since childhood. The serum level of creatine kinase was mildly elevated and short exercise test with cooling revealed a drastic reduction of compound muscle action potentials with repetitive discharges. Muscle biopsy revealed marked variation in the fiber size and increased internal nuclei. The molecular biological study revealed a common missense mutation (Arg1448Cys) at the voltage-gated sodium channel gene (SCN4A). The repetitive CMAP discharges during short exercise test with cooling observed in the proband has not been reported previously. This observation needs to be confirmed among PC patients with different mutations. This is the first report on a PC family confirmed by the molecular biological technique in Korea.


Cluster A maladaptive personality patterns in a non-clinical adolescent population.
The prevalence and expression of Cluster A personality disorders in adolescence is poorly analyzed and understood. The main goal was to analyze the rate of Cluster A traits and maladaptive personality patterns in adolescents. In addition, the underlying dimensional structure and the possible influence of sex and age in its phenotypic expression were examined. The final sample was comprised of a total of 1,443 participants (M = 15.9 years, SD = 1.2). The instrument used was the Personality Diagnostic Questionnaire-4+ (PDQ-4+). Cluster A maladaptive personality traits are common among adolescents. According to the PDQ-4+, 13.1% (n = 189) of the sample reported a Cluster A maladaptive personality pattern. Analysis of the internal structure yielded two interrelated factors, namely Paranoid and Schizotypal-Schizoid. Males, compared with females, obtained higher scores on the schizotypal subscale when the score was dimensional and on the schizotypal and schizoid subscales when items were dichotomized. These data yield new clues that improve the understanding of Cluster A traits in this sector of the population, and advance in early detection of adolescents at risk of personality disorders.


Chromosome tips damaged in anaphase inhibit cytokinesis.
Genome maintenance is ensured by a variety of biochemical sensors and pathways that repair accumulated damage. During mitosis, the mechanisms that sense and resolve DNA damage remain elusive. Studies have demonstrated that damage accumulated on lagging chromosomes can activate the spindle assembly checkpoint. However, there is little known regarding damage to DNA after anaphase onset. In this study, we demonstrate that laser-induced damage to chromosome tips (presumptive telomeres) in anaphase of Potorous tridactylis cells (PtK2) inhibits cytokinesis. In contrast, equivalent irradiation of non-telomeric chromosome regions or control irradiations in either the adjacent cytoplasm or adjacent to chromosome tips near the spindle midzone during anaphase caused no change in the eventual completion of cytokinesis. Damage to only one chromosome tip caused either complete absence of furrow formation, a prolonged delay in furrow formation, or furrow regression. When multiple chromosome tips were irradiated in the same cell, the cytokinesis defects increased, suggesting a potential dose-dependent mechanism. These results suggest a mechanism in which dysfunctional telomeres inhibit mitotic exit.


Chemical composition and larvicidal activity of the essential oils from Eupatorium betonicaeforme (D.C.) Baker (Asteraceae).
The volatile composition of the essential oils from leaves and roots of Eupatorium betonicaeforme (D.C.) Baker was analyzed by GC-MS. A total of 12 compounds were identified. beta-Caryophyllene (12.4-41.7%), alpha-humulene (11.7-14.6%), gamma-muurolene (10.4-19.0%), bicyclogermacrene (15.0-17.5%), 2,2-dimethyl-6-vinylchroman-4-one (10.3-25.5%), and 2-senecioyl-4-vinylphenol (8.5-41.0%) were the most prominent constituents. The former two compounds were isolated and characterized by spectroscopic data. The essential oils and the isolated compounds were tested against Aedes aegypti larvae survival. The results obtained show that the essential oil from roots and 2,2-dimethyl-6-vinylchroman-4-one (10.3-25.5%) could be considered as natural larvicidal agents.


Reconstruction of complex maxillectomy defects with the scapular-free flap.
The defect resulting from partial or complete maxillectomy can often be reconstructed with a skin graft and a prosthesis. In situations where this simple maneuver is unsatisfactory, a more complex reconstructive modality, providing the restoration of composite tissue, is required. The scapular microvascular-free flap was used in this series of 11 patients, as a cutaneous flap in 3 and as an osteocutaneous flap in 8, to meet the specific reconstructive needs of each patient. Excellent to satisfactory restoration of facial contour and palatal function was achieved in 10 patients. There was 1 flap failure. There were no donor site complications. Selected case histories are presented to demonstrate a spectrum of reconstructive problems. There are clear limitations to its applicability, such as the odd scapular bone contour, the thickness of the cutaneous paddle, the position change required for flap harvesting, and the risk of flap failure. The scapular flap has proven to be useful in restoring bony and soft tissue contour of the face, rigid support for the velum, oronasal separation, support for the orbit, and obliteration of the maxillary sinus. We found the scapular-free flap to be a useful tool for reconstructing complex and variable maxillectomy defects.


Five-year clinical follow-up from the MISSION! Intervention Study: sirolimus-eluting stent versus bare metal stent implantation in patients with ST-segment elevation myocardial infarction, a randomised controlled trial.
To evaluate the clinical outcomes of sirolimus-eluting stent (SES) versus bare metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) at long-term follow-up. After five years, 310 STEMI patients randomly assigned to implantation of either SES or BMS, were compared. Survival rates were comparable between groups (SES 94.3% vs. BMS 92.8%, p=0.57), as were the rates of reinfarction (10.6% vs. 13.7%, p=0.40), freedom of death/re-MI (84.4% vs. 79.8%, p=0.29) and target vessel failure (14.9% vs. 21.7%, p=0.11). Likewise, rates of overall stent thrombosis (ST) (5.4% vs. 2.7%, p=0.28) and very late ST (4.1% vs. 0.7%, p=0.07) did not significantly differ between the SES- and BMS-group. In 184 patients with IVUS data, definite and definite/probable VLST was more common in those with late stent malapposition versus those without late stent malapposition (4.3% and 6.6% vs. no events [p=0.018 and p=0.004], respectively). The cumulative incidences of target vessel and target lesion revascularisation (TVR and TLR) were not significantly lower in the SES-group (11.2% vs. 17.9%, p=0.09 and 7.2% vs. 12.9%, p=0.08), as was the rate of clinically driven TLR (6.6% vs. 9.5%, p=0.30). SES implantation was neither associated with increased rates of major adverse cardiac events, nor with a reduction in re-intervention, compared to implantation of a BMS in patients with STEMI after five years. However, a trend of more very late stent thrombosis was observed after SES implantation (ISRCTN62825862).


[Characteristics of Plant Diversity and Heavy Metal Enrichment and Migration Under Different Ecological Restoration Modes in Abandoned Mining Areas].
In order to select plant materials suitable for the ecological restoration of abandoned mining land, ecological restoration experiments were set up in landfills. The effects of different ecological restoration measures on plant diversity and heavy metal enrichment and migration characteristics were studied. The results showed that under different ecological restoration measures, a total of eight families and 10 species of surviving plants appeared, most of which were herbs. The restoration effect of the arbor shrub and grass plots was the best; the plant coverage reached 100%, and the survival rate was over 69%. The diversity index of the plant community was as follows:arbor shrub grass > shrub grass > joe grass > grass. The dominant plants under different ecological restoration measures were Pinus elliottii, Ligustrum lucidum, Boehmeria nivea, Lagerstroemia indica, and Plantago asiatica. The contents of most heavy metals in plants were higher than the normal values. Among them, the enrichment and transfer coefficients of the leaf stems of P. elliottii and L. indica were close to or greater than 1, showing a strong ability of enrichment and transfer to Cd; these two plants belong to Cd-enrichment type plants. The roots of L. lucidum Ait and P. asiatica, which are root-hoarding plants, had a high retention rate of heavy metals. Boehmeria nivea was a heavy metal-avoidance plant with a low content of heavy metals in each part and had the ability to fix and repair potential soil heavy metal pollution. Considering the diversity of plants and the ability of plant enrichment and migration, the combination of trees, shrubs, and grasses was the best restoration mode. Pinus elliottii, L. indica, and P. asiatica can be the target plants for ecological restoration in the abandoned land of mining areas.


A regulated switch of chick neurofascin isoforms modulates ligand recognition and neurite extension.
Neural cell adhesion molecule neurofascin regulates the induction of neurite outgrowth, the establishment of synaptic connectivity and myelination. Neurofascin isoforms are generated by spatially and temporally controlled alternative splicing. Isoform NF166 is predominantly expressed in dorsal root ganglia from embryonal day 5 (E5) to E8, and a further neurofascin isoform NF185 appears at E9. Expression of neurofascin and its binding partner axonin-1 on sensory fibers implies functional interactions for neurite outgrowth. E7 sensory neurons require NF166-axonin-1 interactions for neurite extension, accordingly. The contribution of NF166-axonin-1 interaction for neurite outgrowth decreases in parallel with the appearance of NF185 on sensory neurons at E9. This finding may be explained by (1) alleviated intrinsic capability to use axonin-1 as a cellular receptor and (2) reduced binding of axonin-1 to NF185. Finally, NF166, but not NF185, serves as a cellular receptor for neurite induction via homophilic interactions with a neurofascin substrate.


[Isolated ventricular diverticulum in asymptomatic male].
Ventricular diverticulum are small outpouchings, in the cardiac wall, which are mostly described as a part of malformation syndromes. This finding is infrequent in asymptomatic patients with no pathology in the thoraco abdominal line. The case we present shows a diverticulum in the cardiac apex in a male patient with no cardiological clinic manifestations and with an abnormal electrocardiogram. At present, magnetic resonance is the best diagnostic test, for this kind of malformation, and is also the most reliable in the follow-up of these patients.


5-HT2A receptor-mediated Gαq/11 activation in psychiatric disorders: A postmortem study.
Serotonin-2A (5-HT2A) receptors play an important role in the regulation of many brain functions that are disturbed in patients with such psychiatric diseases as mood disorders and schizophrenia. The objective of this study was to evaluate 5-HT2A receptor-mediated signalling pathway through Gαq/11 activation in psychiatric patients by using post-mortem brain samples. Functional activation of Gαq/11 proteins coupled to 5-HT2A receptors was determined by means of [35S]GTPγS binding/immunoprecipitation assay in post-mortem prefrontal cortex of psychiatric patients diagnosed as bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia, and individually matched controls. The effects of antipsychotic treatment as well as suicide were also analysed. There was no significant difference in maximum percent increase (%Emax) or slope factor among the four groups. The negative logarithm of concentration eliciting the half-maximal effect (pEC50) was significantly reduced in BP and schizophrenia patients as compared to controls. These alterations were attributable to antipsychotic medication. The pEC50 values in 'non-suicide' group of schizophrenia, but not in 'suicide' group, were significantly reduced as compared with controls. Altered 5-HT2A receptor-mediated signalling pathway through Gαq/11 proteins in prefrontal cortex might be apparently involved in pathophysiology and pharmacotherapy of BP and schizophrenia. In schizophrenic patients, these alterations as a result of successful treatment with antipsychotic agents may help in prevention of suicidal behaviour.


Unexpected death due to infectious mononucleosis.
A 14-year-old boy with infectious mononucleosis died unexpectedly in hospital. The most significant finding at autopsy was the presence of marked bilateral tonsillar enlargement with considerable narrowing of the upper airway. There were no other underlying organic diseases that could have caused or contributed to death. Narcotic analgesia had been administered less than 2 h before death and may have contributed to respiratory compromise. The blood morphine level was 0.08 mg/L. Toxicological evaluation of individuals with obstructive lesions of the upper airway may, therefore, be a useful adjunct to the autopsy assessment of such cases as it may reveal factors exacerbating mechanical blockage.


Characterization and ion channel activities of novel antibacterial proteins from the skin mucosa of carp (Cyprinus carpio).
A detergent-solubilized fraction of skin mucus of carp (Cyprinus carpio) induced ion channels after reconstitution into planar lipid bilayers. A differential extraction using a non-ionic detergent followed by electrophoretic separation led to the isolation of two hydrophobic 31-kDa and 27-kDa proteins. In contrast to the 27-kDa protein, which was glycosylated, the 31-kDa did not bind to concanavalin A. The reconstitution of these proteins into a planar lipid bilayer restored the ionophore behavior already observed with the crude mucus. The main unit conductance levels were about 900 pS for the 27-kDa protein and 500 pS for the 31-kDa protein, and selectivity measurements gave Pcl/Pk ratios of 0.6 and 1.0, respectively. These proteins had large potent microbicidal activities (0.018-0.18 microM) against different strains of gram-negative and gram-positive bacteria. This behavior can be compared with insect defensins that are known to form large ion channels in the bacterial membrane. To exclude the eventuality of bacterial origin, the bacterial flora of the crude mucus were analysed and the following were identified: Pseudomonas cepacia; Micrococcus luteus; Micrococcus roseus; Flavobacterium sp.; Aeromonas hydrophila. Antibacterial assays with both proteins were performed against these specific strains and revealed good growth inhibition activities. Furthermore, microsequencing analysis showed that the 31-kDa protein was protected on its N-terminal extremity in contrast to the 27-kDa protein, which had a 19-amino-acid sequence. This last sequence, when compared with sequences in protein data banks, did not reveal any significant similarities to other proteins. These results suggest that these novel proteins could be involved in antibacterial defense processes in fish.


In vitro activity of climbazole, clotrimazole and silver-sulphadiazine against isolates of Malassezia pachydermatis.
Malassezia pachydermatis is a yeast-like, mainly zoophilic fungus, also known as Malassezia canis. It can be isolated in 20-50% from normal ear cerumen specimen from dogs or cats and has an even higher prevalence in non-suppurative otitis externa in animal species such as these. The genus Malassezia contains the two species M. furfur, a mainly anthropophilic fungus which physiologically occurs on human skin, and M. pachydermatis. We performed Minimal Inhibitory Concentration (MIC)-testings of 40 clinical isolates of M. pachydermatis against climbazole (CLIM), clotrimazole (CLOT) and silver-sulphadiazine (SILV). While CLOT and CLIM are broad-spectrum antimycotics of the azole-type, SILV is a sulphonamide compound with antibacterial and antimycotic properties used topically in veterinary medicine. For CLIM, the range of MICs was between < 0.06 and 1 micrograms/ml with an empirical median mean of 0.06 microgram/ml; for CLOT the range was between < 0.06 and 32 micrograms/ml (mean = 4 micrograms/ml), respectively. The MICs for SILV ranged between 0.25 and > 64 micrograms/ml (mean = 16 micrograms/ml) against all tested strains. In conclusion, the two azole-antimycotics CLIM and CLOT showed good in vitro activity against M. pachydermatis. The activity of CLIM was even higher than that of CLOT, which might be due to the better water solubility of CLIM. The activity of SILV was significantly lower.


Optical imaging of acute epileptic networks in mice.
The potential of intrinsic optical imaging and resting-state analysis under anesthetized conditions as a tool to study brain networks associated with epileptic seizures is investigated. Using an acute model of epileptiform activity, the 4-aminopyridine model in live mice, we observe the changes in resting-state networks with the onset of seizure activity and in conditions of spiking activity. Resting-state networks identified before and after the onset of epileptiform activity show both decreased and increased homologous correlations, with a small dependence on seizure intensity. The observed changes are not uniform across the different hemodynamic measures, suggesting a potential decoupling between blood flow and metabolism in the low-frequency networks. This study supports the need for a more extensive investigation of epileptic networks including more than one independent hemodynamic measurement.


Methylation status of epidermal growth factor receptor gene in lung carcinoma cells.
The methylation status of the epidermal growth factor receptor (EGFR) gene was compared in cell lines from four major types of lung carcinoma, small cell lung carcinoma (SCLC), large cell lung carcinoma, squamous cell carcinoma and adenocarcinoma, in order to examine whether DNA methylation is responsible for the suppression of EGFR gene in SCLC cells. Southern blot analysis revealed that the structural region of the EGFR gene is methylated to various degrees regardless of the expression of EGF receptor on the surface. An 8-kilobase EcoRI fragment which contains the EGFR gene promoter region is readily digested with various methylation-sensitive restriction enzymes in all types of cells, indicating that the EGFR gene 5' region is barely methylated. Thus, a mechanism other than DNA methylation appears to control EGFR gene expression and the lack of EGFR gene expression in SCLC cells may be caused by a paucity of some transcription regulatory factor(s).


Role of cyclinT/Cdk9 complex in basal and regulated transcription (review).
Cell division and proliferation of all eukaryotics must follow a genetic program, termed the cell cycle. To ensure proper progression through the cell cycle, proteins that are intimately involved in its regulation must be periodically expressed within an appropriate window of the cycle. Cyclin and cyclin-dependent kinases are the modular components of the core clock machinery of the cell cycle. Progression through the cell cycle requires the activation of Cdks. The activities of these classes of kinases are tightly regulated by both positive and negative factors, and most importantly perturbation of Cdk activities can result in tumorigenesis. Progress has been made recently in connecting specific cyclin-Cdk kinase complexes and transcription. It is still unclear how cyclin/Cdk complexes regulate transcription, and most importantly what their substrates are. The aim of this review is to discuss our current understanding of the molecular mechanisms underlying the transcription properties of defined cyclin-dependent kinases, with a particular emphasis on the cyclin T/Cdk9 (P-TEFb) complex, and its role in the regulation of cell cycle controlling genes.


Differences between breeds of sheep in their responses to Bacteroides nodosus vaccines.
In a field experiment on irrigated pasture, sheep of several breeds were vaccinated twice, subcutaneously, in the upper neck, with Bacteroides nodosus vaccine containing either depiliated cells (DC vaccine), or whole, piliated cells (WC vaccine) and the responses were measured over the following 14 weeks. DC vaccine was as effective as WC vaccine in protecting against the development of foot-rot under conditions of moderate challenge, although the WC vaccine induced significantly higher pilus agglutinating antibody titres. Foot-rot developed in significantly more vaccinated Merinos (Peppin and Saxon strains) than in Romney Marsh, Dorset Horn or Border Leicester breeds. Agglutinating antibody titres after WC vaccination were significantly lower in the Peppin Merino than in the other sheep for the first 6 weeks, while after DC vaccination the titres remained elevated longer in the Border Leicester and Saxon Merino and were significantly higher from 6 weeks onwards. Reactions at the inoculation sites were generally larger in the British breeds than in the Merinos and among the former the reactions were largest, most numerous and most frequently discharged their contents in the Dorset Horn. Bodyweight gains in all vaccinated sheep were initially reduced, compared with controls, but the differences were no longer significant after the eighth week.


Assessment of quality of life with the Nottingham Health Profile among patients with coronary heart disease.
The aim was to describe the quality of life of people suffering from coronary artery disease. The patients had been treated with medication (n = 80), percutaneous transluminal coronary angioplasty (n = 100) and coronary artery bypass surgery (n = 100). Of the 280 patients, 189 were men and 91 women. The patients who participated in this study were seriously ill, as nearly half of them had three or more stenosed coronary arteries. Male patients were most numerous in the bypass surgery group and female patients in the angioplasty group. The quality of life was evaluated using the Nottingham Health Profile (NHP) instrument relation to an age- and sex-matched general population, the background factors and the severity of the coronary disease. The NHP questionnaire consists of 38 statements on health problems, making up six dimensions of subjective health: physical mobility, pain, sleep, energy, emotional reactions and social isolation. The health-related quality of life of coronary patients before the invasive procedures was significantly poorer on all the six dimensions than the quality of life in an age- and sex-matched general population. The most obvious differences were seen on the following dimensions: energy, pain, emotional reactions, sleep and physical mobility. The smallest differences occurred in social isolation. Both males and females had the lowest value for energy and social isolation in the youngest age group (35-54 years). The index values of emotional reactions in the two youngest groups were significantly higher among females than males, which reflects poor quality of life. The women in the age group of 35-54 years found the manifestation of a serious disease extremely hard to face. Our findings clearly suggest that while choosing the mode of treatment, the patient's quality of life should be considered along with the clinical severity of the disease, especially in the case of young women. From the societal and social points of view, the patient's symptoms and quality of life are even more important than the objective medical outcome. In clinical decision-making, the goal is to integrate the results of health-related quality of life assessments with clinical decisions, and this underlines the need to evaluate whether the treatment given is congruent with the patient's quality of life. On the basis of the present findings, the NHP instrument seems to be applicable to quality of life measurements among coronary patients. It does not, however, necessarily give an accurate and profound view of an individual's overall quality of life.


Femtosecond spatial pulse shaping at the focal plane.
Spatial shaping of ultrashort laser beams at the focal plane is theoretically analyzed. The description of the pulse is performed by its expansion in terms of Laguerre-Gaussian orthonormal modes. This procedure gives both a comprehensive interpretation of the propagation dynamics and the required signal to encode onto a spatial light modulator for spatial shaping, without using iterative algorithms. As an example, pulses with top-hat and annular spatial profiles are designed and their dynamics analyzed. The interference of top-hat pulses is also investigated finding potential applications in high precision pump-probe experiments (without using delay lines) and for the creation of subwavelength ablation patterns. In addition, a novel class of ultrashort pulses possessing non-stationary orbital angular momentum is also proposed. These exotic pulses provide additional degrees of freedom that open up new perspectives in fields such as laser-matter interaction and micro-machining.


Alexithymia in severely obese patients seeking surgical treatment.
The purpose of the study was to examine the rate of alexithymia as measured by the Toronto Alexithymia Scale in a sample of severely obese subjects, as well as the relationships between this dimension and five other dimensions found in obesity: depression, anhedonia, external locus of control, impulsivity, and interpersonal dependency. A second purpose was to test the hypothesis that alexithymia could be a prognosis factor in severely obese subjects seeking bariatric surgery. 49 severely obese and 40 psychiatric patients presenting mood, neurotic, or personality disorders participated. Analyses showed a significantly lower rate of alexithymia in severely obese (42.9%) than in psychiatric patients (67.5%). Interpersonal dependency was the main predictor of alexithymia in the two samples and impulsivity as well as anhedonia were independent predictors of alexithymia only in the severely obese sample. Preoperative Body Mass Index was the sole predictor of 1-yr. postoperative Body Mass Index in severely obese subjects receiving surgical treatment.


Orbicularis oculi muscle stripping and tarsal fixation for recurrent entropion.
This prospective study highlights the result of a new technique for correction of recurrent lower lid entropion. The technique was designed to address the aetiological factors involved based on the pre- and per-operative findings. MATERIAL AND METHODS. 37 eyelids of 31 consecutive patients with recurrent entropion were enrolled. Under local anaesthesia, a horizontal incision was made at the lower border of the tarsus, involving the total width of the lower eyelid. Anterior lamellar (skin and orbicularis oculi muscle - OOM) inferior to the incision was dissected towards the orbital rim. An ellipse of the excess overriding OOM and overlying skin inferior to the incision was excised. The OOM was fixed to the lower border of the tarsus with three to four 6/0 Vicryl subcutaneous sutures. Skin was repaired with 6/0 silk sutures, which were removed five days post-operatively. Five cases underwent horizontal lid shortening and 15 had preaponeurosis fat sculpting in addition. RESULTS. 37 procedures were performed on 31 patients (23 M & 8 F). The mean age was 76.5 yrs. (range 63-90). The patients had had one to four (mean = 1.7) previous surgeries. All patients had OOM override. Fifteen had significant preaponeurosis fat prolapse. Lower lid laxity was not identified in all cases, in some due to previous lid surgery. There was no evidence of lower lid retractor laxity in the majority of cases. After a mean follow-up time of 18 months (5-36) there were three recurrences. One underwent further tarsal fixation and the other two had horizontal lid shortening with a favourable outcome. CONCLUSIONS. Excision of overriding OOM and tarsal fixation for recurrent entropion is simple and effective. Its success is due to direct tackling of the aetiological factors.


Prevalence of current smoking in Eastern province, Saudi Arabia.
All Saudi Arabian residents of the Eastern province of Saudi Arabia aged 30+ years completed a structured interview questionnaire about smoking. The prevalence of current smoking (smoked > 100 cigarettes or any tobacco products including waterpipe in lifetime and still smoking daily or occasionally for 1 month or more) among 196 268 respondents was 16.9% (28.7% among men and 4.5% among women). There was a significantly higher prevalence of smoking at younger ages in men and older ages in women. Multiple logistic regression analysis showed that factors independently associated with smoking were lower socioeconomic tatus, lower education, being divorced and occupations such as the military and self-employed.


Dialysis catheter-related bacteremia: treatment and prophylaxis.
Catheter-related bacteremia is a major cause of morbidity among hemodialysis patients. This article reviews the medical literature regarding the treatment and prophylaxis of catheter-related bacteremia. Bacterial biofilm that forms in the catheter lumen is the source of catheter-related bacteremia. Treatment with systemic antibiotics alone fails to definitively eradicate the infection in most patients. Catheter-related bacteremia can be managed by either catheter removal with delayed placement of a new catheter or exchange of the infected catheter with a new catheter over a guidewire. More recent studies suggested that instillation of an antibiotic-anticoagulant lock into the catheter lumen, as an adjunct to systemic antibiotic therapy, can cure approximately two thirds of catheter-related bacteremias without requiring catheter replacement. The frequency of catheter-related bacteremia may be reduced by using tunneled, rather than nontunneled, dialysis catheters and strict aseptic technique. In addition, several pharmacological measures may be useful for prophylaxis against catheter-related bacteremia. These include application of an antimicrobial ointment (mupirocin or polysporin [Pfizer, New York, NY]) to the catheter exit site or instillation of an antimicrobial solution (gentamicin or taurolidine) into the catheter lumen. Subcutaneous dialysis devices do not reduce the frequency of catheter-related bacteremia unless an antimicrobial solution is instilled into the device. The development and widespread adoption of effective approaches to the treatment and prophylaxis of catheter-related bacteremia will dramatically reduce the morbidity and economic burden associated with this complication.


ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).
Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients. SMC1 (structural maintenance of chromosomes 1) and KAP1 (KRAB-associated protein 1) were found to be unique substrates of ATM kinase by immunoblot detection following ionizing radiation. Using a pool of eight fluorescence in situ hybridization-negative CLL samples as a standard, the phosphorylation of SMC1 and KAP1 from 46 del (11q22-23) samples was analyzed using normal mixture model-based clustering. This identified 13 samples (28%) that were deficient in ATM function. Targeted sequencing of the ATM gene of these samples, with reference to genomic DNA, revealed 12 somatic mutations and 15 germline mutations in these samples. No strong correlation was observed between ATM mutation and function. Therefore, mutation status may not be taken as an indicator of ATM function. Rather, a direct assay of the kinase activity should be used in the development of therapies.


The pathocenosis moment: Mirko Grmek, the Annales and the vagaries of the longue durée.
Grmek's important article on pathocenosis, which appeared in 1969 in the Annales, did not achieve the fame and significance which it seemed to merit. This needs to be explained not only in terms of Grmek's own history, but also in changes in intellectual fashion, including in the Annales themselves. The work was also eclipsed by W.H. McNeill's best-selling Plagues and Peoples. History's 'cultural turn' since the 1980s has also limited the article's perceived utility. Nevertheless, the value of the concept is underlined by the articles in this collection.


Molecular architecture and assembly of the yeast kinetochore MIND complex.
The MIND multiprotein complex is a conserved, essential component of eukaryotic kinetochores and is a constituent of the tripartite KMN network that directly attaches the kinetochore to the mitotic spindle. The primary microtubule-binding complex in this network, NDC80, has been extensively characterized, but very little is known about the structure or function of the MIND complex. In this study, we present biochemical, hydrodynamic, electron microscopy, and small-angle x-ray scattering data that provide insight into the overall architecture and assembly of the MIND complex and the physical relationship of the complex with other components of the KMN network. We propose a model for the overall structure of the complex and provide data on the interactions with NDC80, Spc105p, and thus the mitotic spindle.


Theileria parva: sporozoite entry into bovine lymphocytes is not dependent on the parasite cytoskeleton.
The main conclusion from the present study is that T. parva sporozoite entry is dependent on a functional host cell actin cytoskeleton and is not driven by the parasite. Treating lymphocytes with cytochalasin D resulted in a dose-dependent reduction in the levels of host cell infection. However, the primary effect was to block sporozoite binding and only at the highest concentration (20 microM) was sporozoite internalization significantly reduced. In fact at lower concentrations (1-10 microM) cytochalasin treatment lead to a relative increase in sporozoite internalization. The results are consistent with sporozoite entry being primarily a passive process and with a functional host cell actin cytoskeleton that is required only to maintain the molecular integrity of the surface membrane. Thus T. parva sporozoite entry differs from the process in other apicomplexans, although the results are consistent with a number of features of sporozoite biology. Treatment of lymphocytes with either the microtubule-destabilizing agent, nocodazole, or taxol, which induces microtubule polymerization, had no significant effect on sporozoite binding or entry. As both reagents had the expected effects on the lymphocyte microtubule system, it is unlikely that host cell microtubules are essential for successful sporozoite invasion or establishment.


Characterization of Perina nuda nucleopolyhedrovirus (PenuNPV) polyhedrin gene.
The Perina nuda nucleopolyhedrovirus (PenuNPV) polyhedrin gene was located in EcoRI-G (6.3 kilobase pairs; kbp) and PstI-G (4.3 kbp) fragments of its genomic DNA. A portion of 1333 nucleotides (nt) containing this gene was sequenced. An open reading frame of 735 nt encoded a 245-amino-acid-long polyhedrin. A conserved TAAG motif which is associated with transcriptional start sites was identified 51 nt upstream of the translation initiation codon of PenuNPV polyhedrin gene. A putative polyadenylation signal, AATAAA, was found 116 nt downstream of the termination codon (TAA). Comparison of the amino acid sequences of PenuNPV polyhedrin with those of other NPVs showed that PenuNPV polyhedrin was most closely related to Orgyia pseudotsugata multiple NPV (OpMNPV) polyhedrin.


HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation.
High Mobility Group N (HMGN) proteins are a family of chromatin structural proteins that specifically bind to nucleosome core particles. HMGN5 is a novel and characteristic member of the HMGN protein family. We have previously found that HMGN5 is upregulated in prostate cancer and its downregulation had been demonstrated to induce apoptosis and G2-M cell cycle arrest. The radiosensitization effect of HMGN5 knockdown on PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. The DNA double-strand break (DSB) repair kinetics of HMGN5 knockdown and control cells after radiation exposure was evaluated using immunocytofluorescence. The mitochondrial reactive oxygen species (ROS) levels were estimated using Dihydrorhodamine 123 (DHR 123) probes. Expression of mitochondrial antioxidant MnSOD was measured by real-time PCR and Western blot. The expression of antiapoptotic proteins Bcl-2 and Bcl-xL as well as cleavage of caspase-3, caspase-9, and PARP were also measured using Western blot. HMGN5 knockdown cells exhibit decreased clonogenic survival and increased apoptosis rate in response to 2-8 Gy ionizing radiation (IR). Loss of HMGN5 does not affect the DSB repair kinetics after radiation exposure. HMGN5 knockdown cells demonstrated increased mitochondrial ROS level and suppressed induction of MnSOD upon radiation compared with control cells upon radiation. Further, MnSOD knockdown resulted in inhibited cell viability as well as increased mitochondrial ROS level and apoptosis upon radiation in PC3 and DU145 cells. Finally, HMGN5 knockdown cells showed significantly decreased levels of antiapoptotic proteins Bcl-2 and Bcl-xL as well as increased cleavage of caspase-3, caspase-9, and PARP compared with control cells after radiation. HMGN5 knockdown sensitizes prostate cancer cells to ionizing radiation, and the radiosensitization effect may be partially mediated through suppressed induction of MnSOD and enhanced activation of apoptosis pathway in response to IR.


Transmural Inflammation, Ileitis, and Granulomas at the Time of Proctocolectomy in Patients with Ulcerative Colitis Do Not Predict Future Development of Pouchitis.
The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA. We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis. Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08). Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC.


Change of collision efficiency with distance in bacterial transport experiments.
Understanding the mechanisms of bacterial transport in aquifers is important in developing bioremediation strategies. Collision efficiency (alpha) is one important parameter used in modeling bacterial transport. This study was undertaken to measure change in alpha with distance by performing a bacterial transport experiment in Oyster, Virginia. Following injection of a bacterium, Comamonas sp., into a well, water samples were collected at various distances along the flowpath and injected into columns packed with homogenized South Oyster focus area sediment. Zeta potentials of the bacteria in the samples were measured. Values of alpha were determined at various locations in the field in two ways: based on field breakthrough concentrations at the sampling points and based on column breakthrough concentrations. The alpha values estimated from field breakthrough decreased with distance, whereas those estimated from column breakthrough increased with distance. Bacterial cell surface charge became progressively more negative with distance in the field. We hypothesize that the apparent contradiction between field and column alpha values was caused by differences in the flow of the two systems. Flow in the columns was forced to occur through fine-grained zones of iron and aluminum hydroxide coatings that selectively removed the most negatively charged bacteria. In contrast, in the field, the injected cells did not come into contact with the positively charged coatings because the bulk solution bypassed them due to heterogeneous hydraulic properties. These results suggest that laboratory-based models may underestimate bacterial transport distance in the field. A more realistic approach may be necessary to capture the degree of heterogeneity.


Genetically engineered animals in drug discovery and development: a maturing resource for toxicologic research.
Genetically engineered mice that either over-express a foreign gene (transgenic) or in which the activity of a specific gene has been removed ("knock-out") or replaced ("knock-in") will be used increasingly to investigate molecular mechanisms of disease, to evaluate innovative therapeutic targets, and to screen novel agents for efficacy and/or toxicity. Recent innovations of relevance to toxicologic researchers include the construction of genetically engineered mice with (1) multiple engineered genes, (2) mutations that can be induced at specific sites and times throughout life, and (3) the substitution of human genes for their mouse counterparts ("humanized" mice) to allow in vivo investigation of xenobiotic toxicity. Contemporary applications of genetically engineered mice in toxicology include basic mechanistic research exploiting newly engineered mouse lines as well as applied screening for genotoxicity and carcinogenicity using commercially available animals. Many caveats must be considered when interpreting genetically engineered mice-derived toxicity data, the chief of which will be the extent to which the model's phenotype has been fully characterized, the type and incidence of background lesions for the given mouse strain and engineered gene, and the possibility of misinterpreting the presence or absence of a phenotype due to compensatory physiologic processes that mask the outcome produced by the engineering event. Toxicity data acquired using genetically engineered mice currently supplements and in time likely will supplant those gathered using the present "gold standard" bioassays, as genetically engineered mice typically develop more lesions after a shorter latency period than do age- and strain-matched, wild-type mice.


Effects of long-term moderate exercise on iron status in young women.
The impact of long-term (6-month) moderate exercise on the iron status of previously sedentary women was determined by randomly assigning 62 college-age women into one of the following four groups: 1) 50 mg.d-1 iron supplement, low iron diet (N = 16); 2) Placebo, free choice diet (N = 13); 3) Meat supplement to achieve 15 mg.d-1 iron intake (N = 13); and 4) Control, free choice diet (N = 20). All groups except the Control group exercised 3 d.wk-1 at 60%-75% of their heart rate reserve. VO2max was measured at baseline and week 24. Blood was sampled at baseline and every 4 wk thereafter for 24 wk to measure iron status and to elucidate the causes for alterations in iron status. Subjects had depleted iron stores throughout the study as indicated by their serum ferritin levels (< 15 ng.ml-1). Serum iron, total iron binding capacity and transferrin saturation were not compromised with exercise. Mean hemoglobin level in the Placebo/Ex group was significantly (P < 0.05) lower than the 50 Fe/Ex and the Meat/Ex groups by week 24. However, changes in serum albumin, haptoglobin, and erythropoietin data from the study cannot explain these changes.


Laxative misuse and behavioral disinhibition in bulimia nervosa.
Various reports suggest that purging with laxatives is associated with greater behavioral impulsivity in bulimia nervosa (BN) patients. We investigated the extent to which laxative misuse corresponds to specific impulse-control problems. Participants included bulimic women who misuse laxatives (BNL+; n = 12), bulimic women who do not misuse laxatives (BNL-; n = 33), and healthy normal eaters (NE; n = 26). Participants completed the Go/No-Go discrimination task (a well-validated computerized measure of response disinhibition), as well as self-report questionnaires of impulsivity, eating symptoms, and general psychopathology. Compared with the other groups, the BNL+ group made more commission errors on the Go/No-Go under cues for punishment, indicating they were more disinhibited when faced with possible negative outcomes. Compared with the BNL- group, the BNL+ group was also more likely to differ from the NE group on self-reported impulsivity. There were no differences between the two bulimic groups on eating symptoms and the three groups did not differ in terms of general psychopathology. Findings suggest that, controlling for eating symptoms and psychopathology, laxative misuse among BN patients is associated with difficulty inhibiting incorrect responses in the face of perceived threats.


Anionic Polymerization of Para-Diethynylbenzene: Synthesis of a Strictly Linear Polymer.
Anionic homo- and copolymerization of p-diethynylbenzene in the presence of n-BuLi in polar solvents was carried out. The use of hexamethylphosphortriamide (HMPA) makes it possible to synthesize a completely linear soluble polymer that does not have branching and phenylene fragments. A copolymer of p-diethynylbenzene with diphenyldiacetylene was synthesized. Homo- and copolymers of p-diethynylbenzene have high thermo- and thermo-oxidative stability. By the interaction of side reactive ethynylphenylene groups with various reagents, it is proposed to synthesize clusters along the conducting chain of poly-p-diethynylbenzene. Due to presenting C≡CH side groups, boron, copper, and cobalt derivatives were synthesized. It is shown that not all theoretically possible stereoisomers can be formed as a result of the polymerization. The application of p-diethynylbenzene polymers for the modification of industrial samples of epoxy novolac resin, oligoester acrylates, and carbon fibers has been demonstrated.


Development and validation of a couples measure of biased responding: the Marital Aggrandizement Scale.
More than 30 years ago, Edmonds (1967) recognized the need for a couples measure of biased responding. Like other categories of self-report instruments, marital measures are believed to be highly susceptible to distortion. In this study, we describe the development of the Marital Aggrandizement Scale (MAS). For this study, item analyses were performed on a subset of responses (n = 200). A priori inclusion criteria were applied from which a set of 18 items was selected. Three phases of validation research establish the reliability and validity of responses to the MAS among an international sample of older married adults (n = 410). The concurrent and discriminant validity of responses to this scale is demonstrated vis-à-vis separate measures of biased responding, marital satisfaction, and psychological well-being. Internal consistency was calculated as alpha = .84. Test-retest reliability was calculated as r(200) = .80 over an average interval of 15 months. The challenge remains to identify factors associated with the etiology and maintenance of this construct. Subsequent research is required to identify correlates and antecedents of marital aggrandizement across populations over time.


Association of polymorphic variants in IL1B gene with secretion of IL-1β protein and inflammatory markers in north Indian rheumatoid arthritis patients.
The proinflammatory cytokine interleukin-1beta (IL-1β) is a key mediator of inflammation which affects cell proliferation and differentiation. IL-1β is considered to contribute to the pathophysiology of rheumatoid arthritis (RA). Polymorphisms in cytokine genes are highly influenced by ethnicity. Hence, in this study polymorphism of the IL1B-511(C/T) within promoter region was analyzed by using polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP) in 187 RA patients and 214 controls. The prevalence of different genotypes and allelic frequency distribution was compared in RA patients and controls. Levels of inflammatory markers and serum levels of IL-1β were estimated by ELISA The serum inflammatory markers levels were significantly higher in RA patients as compared to controls (RF=127.3±21.3U/mL, Anti-CCP=17.8±8.3U/mL, CRP=17.86±7.1mg/L and IL-1β=21.25±4.19pg/mL in RA patients p<0.01). The frequency of heterozygous mutant (C/T) and homozygous mutant (T/T) variants were significantly higher in RA patients as compared to controls and the odds ratios by logistic regression were (OR=2.2, p<0.001) and (OR=3.21, p<0.01) respectively. The association persisted on combining the heterozygous mutant and homozygous mutant (CT+TT) together as compared to controls (OR=2.39; p<0.001). Positive and significant (p<0.05) correlation of circulating IL-1β levels with RF (r=0.232), anti-CCP (r=0.207) and CRP (r=0.166) among RA patients were found. The levels of anti-CCP were significantly higher in homozygous mutant variants (TT) as well as the heterozygous mutant variants (C/T) in comparison to the wild variants (CC) (p<0.01). The results of this study reveal that mutant allele (T) of IL1B-511 promoter SNP tends to be associated with elevated anti-CCP and IL-1β levels as observed in RA patients and hence disease susceptibility.


Postgraduate year-1 residency training in emergency psychiatry: an acute care psychiatric clinic at a community mental health center.
The purpose of this study was to determine resident satisfaction with an acute care psychiatric clinic designed in collaboration with a nearby community mental health center. We also sought to demonstrate that this rotation helps meet program requirements for emergency psychiatry training, provides direct assessments of resident interviewing skills and clinical knowledge in the postgraduate year-1, and provides exposure to public sector systems of care. We developed a resident satisfaction questionnaire and fielded it to each of the residents who participated in the clinic over the first 3 years. Data were collected, organized, and analyzed. Of the 15 residents in the acute care psychiatric clinic, 12 completed and returned the satisfaction questionnaires. Educational aspects of the clinic experience were rated favorably. This postgraduate year-1 acute care psychiatric clinic provides a mechanism for the fulfillment of emergency psychiatry training as well as direct supervision of clinical encounters, which is a satisfactory and useful educational experience for trainees.


N,N-Diethylamine appended binuclear Zn(ii) complexes: highly selective and sensitive fluorescent chemosensors for picric acid.
Novel binuclear Zn(ii) complexes (1-2) derived from bis-chelating salen type ligands (H2L(1) and H2L(2)) possessing N,N-diethylamine moieties on the periphery of the molecules have been synthesized and thoroughly characterized by satisfactory elemental analyses and spectral (FT-IR, (1)H, (13)C NMR, UV-vis, fluorescence and ESI-MS) studies. The structures of H2L(1) and 1 have been authenticated by single crystal X-ray diffraction analyses. Complexes 1 and 2 strongly fluoresce and act as highly selective and sensitive chemosensors for picric acid in different organic as well as aqueous media. Both 1 and 2 showed strong potential to detect traces of PA in vapour/solid phase through contact mode analysis. Spectral and theoretical (DFT) studies suggested that the observed fluorescence quenching may be associated with ground state (GS) charge transfer as well as electrostatic interactions between 1/2 and PA. The fluorescence lifetime for the representative complex 1 displayed a double exponential curve and unaltered lifetime (τav, 0.63 nm) in the absence and presence of PA and strongly suggested that quenching follows a static mechanism. Further, DFT calculations on 1 and 2 strongly supported the static mechanism through GS charge transfer between complexes and PA. In addition, (1)H NMR spectral studies on 1-2 in the presence of PA firmly advocated strong hydrogen bonding and π-π stacking between the phenolic rings of 1-2 and the aromatic ring of PA. These complexes are capable of detecting PA either individually or in a competitive environment of other nitro- explosives. Florescence spectral studies on the model complex M lacking N,N-diethylamine groups revealed moderate selectivity and sensitivity towards PA and supported the key role of N,N-diethylamine moieties in the selectivity and sensitivity of complexes.


Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses.
The complex retroviruses such as human immunodeficiency virus, type 1, employ a virally encoded protein, Rev, to mediate the nuclear export of unspliced and partially spliced mRNA. In contrast, the simian type D retroviruses act through a cis-acting constitutive transport element (CTE) that presumably interacts directly with cellular export proteins. We first reported that RNA helicase A (RHA) is a shuttle protein that binds to functional CTE in vitro and in vivo. Recently, we isolated a novel protein, HAP95, that specifically binds to the nuclear transport domain of RHA and up-regulates CTE-mediated gene expression. Here, using truncation and deletion mutations, we mapped the domains of HAP95 that are important for RHA binding, transactivation of CTE, and nuclear cytoplasmic shuttling. We report evidence for a novel nuclear export signal in HAP95 and showed that the domains involved in RHA binding and nuclear localization are required for CTE activation. Finally, we showed that HAP95 synergizes significantly with RHA on CTE-mediated reporter gene expression and promotes nuclear export of unspliced mRNA in transfected cells. Taken together, these data support the proposal that HAP95 specifically facilitates CTE-mediated gene expression by directly binding to RHA.


Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56lck.
With current anti-HIV treatments targeting only 4 of the 15 HIV proteins, many potential viral vulnerabilities remain unexploited. We report small-molecule inhibitors of the HIV-1 protein Nef. In addition to expanding the anti-HIV arsenal, small-molecule inhibitors against untargeted HIV proteins could be used to dissect key events in the HIV lifecycle. Numerous incompletely characterized interactions between Nef and cellular ligands, for example, present a challenge to understanding molecular events during HIV progression to AIDS. Assays with phage-displayed Nef from HIV(NL4-3) were used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck). The guanidines, synthetic analogs of batzellidine and crambescidin natural products, inhibit the Nef-ligand interactions with IC(50) values in the low micromolar range. In addition, sensitive in vivo assays for Nef inhibition are reported. Although compounds that are effective in vitro proved to be too cytotoxic for cellular assays, the reported Nef inhibitors provide proof-of-concept for disrupting a new HIV target and offer useful leads for drug development.