Lumbopelvic neuromuscular training and injury rehabilitation: a systematic review.
The aim of this systematic review was to assess the evidence for lumbopelvic neuromuscular training (LNMT) in individuals after musculoskeletal (MSK) injury. A literature search of PubMed and EMBASE databases was performed for English studies from January 1990 to March 2012. Search terms including and related to trunk, core, stability, injury, and LNMT were used. All studies directly involving LNMT for MSK injuries were reviewed by 2 authors. These articles were assessed based on the inclusion criteria and if appropriate selected for further analysis. Expert opinion, review articles, and articles involving non-MSK injuries were excluded. Four authors then scored the selected articles for methodological quality. A total of 2312 articles were initially identified. Twenty-nine articles met the inclusion criteria for review and were divided into categories of lower extremity (LE), lumbar, and upper extremity (UE). No trials involving the UE met the inclusion criteria. Data including subject demographics (age, height, weight, gender, etc), injury type, intervention type, and outcome measurements were extracted from the relevant articles. A variety of baseline and follow-up scores were extracted including pain levels, patient satisfaction, disability questionnaires, and other functional outcomes. Two out of 3 LE randomized controlled trials (RCTs) and 9/26 lumbar RCTs were rated with high methodological quality based on the scoring system described by van Tulder et al. The average quality score for the LE RCTs was 6.3 (range = 4-9) and for the lumbar RCTs was 5.1 (range = 2-9). The evidence for the effectiveness of the 3 LE studies was rated as conflicting, whereas 24 lumbar studies demonstrated moderate-to-strong evidence. Unfortunately, heterogeneity of populations, interventions, and outcomes precluded a quantitative meta-analysis and specific clinical recommendations. High-quality evidence is lacking to make specific clinical recommendations for or against the use of LNMT in the rehabilitation of individuals after MSK injury. Based on this review, future research should focus on well-defined, homogeneous populations, interventions specifically addressing neuromuscular activation of the lumbopelvic musculature, patient-specific clinical outcomes, measures of motor control, biomechanics, and return to specific activities.


Psychometric validation of a German version of the compulsive Internet use scale.
Excessive Internet use and Internet addiction are currently increasing in many industrial nations. Verified and validated measuring instruments could contribute to a better understanding of this still quite recent development. The aim of this survey was to investigate the psychometric properties of a German version of the Compulsive Internet Use Scale (CIUS). We surveyed a representative German quota sample of 1,723 adolescents aged between 14 and 17 years, as well as one parent each, with standardized questionnaires. In addition, adolescents and parents were asked whether the media use by the youth was considered problematic or excessive, and whether it led to arguments at home. We conducted confirmatory factor analyses (CFA) with maximum likelihood estimation to examine the factorial validity of the German CIUS, as well as reliability and correlation analyses. The results of the CFA indicate good psychometric properties for the German version of the CIUS. They appear in line with the findings for the original version of the questionnaire. Furthermore, the CIUS showed high internal consistency, and we found significant correlations between the "CIUS-summary score" and different ratings of problems with the media usage by the youth and the parents. The German version of the CIUS seems to be a valid and suitable diagnostic tool for measuring problematic to pathological Internet use.


Community-based parenteral anti-infective therapy (CoPAT). Pharmacokinetic and monitoring issues.
Community-based parenteral anti-infective therapy (CoPAT) has, over the past 20 years, increased rapidly in many parts of the world including North America, Europe, South America and Australia. CoPAT is a multidisciplinary activity demanding close cooperation between nurses, pharmacists and physicians, as well as with the patient. The selection of an anti-infective drug for use outside the hospital setting must take into account not only the therapeutic effectiveness, cost effectiveness and safety of the drug, but also pharmacological factors such as the dosage schedule and the stability of the drug. Dosage schedules vary with pharmacokinetic factors (e.g. the use of drugs with long half-lives are favoured by CoPAT programmes) and pharmacodynamic features (e.g. once daily gentamicin therapy is attractive and practical because of concentration-dependent bactericidal killing and prolonged post-antibiotic effect). With selected drugs, the renal and, to a lesser degree, liver function of the patient will influence the dosage schedule. The mode of intravenous (i.v.) drugs administration will vary with volume considerations (limiting the use of syringe-infusion therapy for some drugs), stability issues (prevents drugs that are stable at room temperature for less than 24 hours from being used in multidose computerised delivery systems), as well as patient factors (ability to self administer an i.v. drug). Monitoring serum anti-microbial concentrations is undertaken to assure effectiveness and avoid toxicity, and is indicated for drugs with a narrow therapeutic window, such as the aminoglycosides. With the advent of the single daily dose administration of aminoglycosides, checking serum concentrations at the mid-point, i.e. 6 to 14 hours following administration of the first dose, is one approach. Because the toxic effects of vancomycin have been overstated, serum concentrations should only be obtained for defined indications primarily to assure therapeutic effectiveness.


MCPIP1 is a positive regulator of type I interferons antiviral activity.
Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity. We found that MCPIP1 can promote innate antiviral immunity independently of both its RNase and deubiquitinase activity. Furthermore, we reveal that MCPIP1 is an IFN-induced positive feedback signal molecule which promotes IFN-I-mediated antiviral efficacy. Mechanistically, MCPIP1 does not affect the activation of JAK/STAT upstream of IFN-I signaling, but significantly promotes IFN-I signaling by enhancing ISRE promoter activity and expression of interferon-stimulated genes (ISGs). And MCPIP1-mediated activation of IFN-I signaling is independently of its RNase and deubiquitinase activity. These findings uncover a novel innate antiviral mechanism mediated by the IFN-MCPIP1 axis, and may provide potential targets for enhancing IFNs antiviral therapy.


Impaired subcortical and cortical sensory evoked potential pathways in septic patients.
Sensory evoked potential (SEP) peak latencies were recorded in order to evaluate the incidence and severity of septic encephalopathy, testing the hypothesis that the occurrence of septic encephalopathy is more frequent than generally assumed. Prospective cohort study. Medical intensive care unit of a university hospital. Sixty-eight critically ill patients were studied within 48 hrs after the development of severe sepsis (n = 41) or septic shock (n = 27). None. Septic encephalopathy was defined as prolongation of SEP peak latencies beyond the upper limit of the reference range of subcortical (N13-N20 interpeak latency) and cortical SEP pathways (N20-N70 interpeak latency), as well as asymmetry of peak latencies marked by the presence of subclinical cerebral focal signs. Subcortical SEP pathways were impaired in 34% and cortical SEP pathways in 84% of all patients. The prolongation of the cortical SEP pathway correlated with the Acute Physiology and Chronic Health Evaluation III score (r = 0.23; p <.0001). SEP peak latencies did not differ in patients with severe sepsis compared with those with septic shock. Subclinical cerebral focal signs were present in 24% of the subcortical SEP pathways and in 6% of the cortical SEP pathways. Septic encephalopathy occurs more frequently than generally assumed, and its severity is associated with the severity of illness. The impairment of subcortical and cortical SEP pathways was not different between patients with severe sepsis and those with septic shock.


[Patient flow in a social psychiatric treatment model].
The Department of Social Psychiatry at the Free University of Berlin offers a mode of treatment that comprises semi-inpatient, complementary and outpatient treatment in close cooperation with facilities for full inpatient treatment. This relatively comprehensive system is examined for its patient flow. The authors observed over a period of three years to what extent patient flow followed lines as recommended in literature for step-by-step rehabilitation and flexible retransfer. Furthermore the differences in utilising the system by first admissions and readmissions to the Department are described.


Changes in glutathione, glutathione reductase and glutathione-S-transferase as a function of cell concentration and age.
The activities of glutathione-S-transferase (GST) and glutathione reductase (GSR) in mouse lymphocytes as a function of cell concentration and age were determined. Lymphocytes from 2-, 9- and 24-month-old mice were isolated and the activity of GST was determined spectrophotometrically using 1-chloro-2,4-dinitrobenzene as the substrate. Lymphocyte concentrations of 0.44, 0.75 and 0.55 X 10(6) cells/ml were found to be optimal for assaying GST in 2-, 9- and 24-month-old mice, respectively. Determination of GSR activity was based on NADPH reduction of oxidized glutathione and cell concentrations of 0.29, 0.30 and 0.22 X 10(6) cells/ml were chosen for assaying the enzyme activity for the three age groups, respectively. Glutathione levels and GSR activity of mice lymphocytes were higher in 2- and 24-month-old mice as compared to 9-month-old animals. However, GST activity of mouse lymphocytes was low in 2- and 9-month-old mice and increased significantly in 24-month-old animals.


Mizoribine reduces renal injury and macrophage infiltration in non-insulin-dependent diabetic rats.
Macrophage infiltration in kidney is one of the most important events for the progression of diabetic nephropathy. Mycophenolate mofetil (MMF), an anti-inflammatory agent, has been shown to suppress macrophage infiltration and to improve renal injury in streptozotocin-induced diabetic kidneys. We examined whether mizoribine, which acts through immunosuppressive mechanisms similar to MMF, inhibits progression of diabetic nephropathy in non-insulin-dependent diabetic rats. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a non-insulin-dependent diabetic model, and Long-Evans Tokushima Otsuka (LETO) rats, a non-diabetic control, were studied at 35 weeks of age. OLETF rats were randomized to receive mizoribine (5 or 10 mg/kg) or normal saline for 8 weeks. Histological changes such as glomerulosclerosis and interstitial fibrosis and the number of ED1- and CD5-positive cells in the kidney were assessed. By using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, monocyte chemoattractant protein-1 (MCP-1), osteopontin (OPN) and transforming growth factor (TGF)-beta1 expression in the kidney was also analysed. Urinary albumin excretion in OLETF rats increased compared with that in LETO rats. Administration of mizoribine suppressed urinary albumin excretion. Development of glomerulosclerosis, interstitial fibrosis and macrophage infiltration in the kidney was also inhibited by treatment with mizoribine. The expression of MCP-1, OPN and TGF-beta1 mRNA in untreated OLETF rats was significantly increased compared with that in LETO rats. By immunohistochemistry, increased expression of MCP-1, OPN and TGF-beta1 was found in the tubules and glomeruli of untreated OLETF rats. This expression was significantly suppressed by treatment with mizoribine. Mizoribine inhibited renal macrophage accumulation and prevented the progression of glomerulosclerosis and interstitial fibrosis in non-insulin-dependent diabetic kidneys. In addition to standard treatments, anti-inflammatory agents may be useful for management of non-insulin-dependent diabetic nephropathy.


Syndecans, signaling, and cell adhesion.
Syndecans are transmembrane proteoglycans which can participate in diverse cell surface interactions, involving extracellular matrix macromolecules, growth factors, protease inhibitors, and even viral entry. Currently, all extracellular interactions are believed to be mediated by distinct structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link with the microfilament cytoskeleton, thereby mediating signaling events. The molecular details are unknown, but the conservation of regions of syndecan cytoplasmic domains, and a strong tendency for homotypic association, support the idea that the ligand-induced clustering may be a discrete source of specific transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors.


[Systemic lupus erythematosus presenting as Stevens-Johnson syndrome].
Stevens-Johnson syndrome and toxic epidermal necrolysis are life-threatening dermatological conditions. Their most common cause is medication. However, in a small proportion of patients these dermatological conditions could be the first presentation of systemic lupus erythematosus. We now describe a 34-year-old patient who presented with manifestations of Stevens-Johnson as a first feature of systemic lupus erythematosus. Systemic lupus erythematosus reveled by Stevens-Johnson syndrome has been infrequently reviewed in the previous literature. This diagnosis should be considered when cutaneous adverse drug reactions occur without clear drug causality.


Quantum dynamics in the highly discrete, commensurate Frenkel Kontorova model: a path-integral molecular dynamics study.
The commensurate Frenkel Kontorova (FK) model is studied using path-integral molecular dynamics (PIMD). We focus on the highly discrete case, in which the embedding potential has a much greater maximum curvature than the harmonic potential connecting two particles in the FK chain. When efficient sampling methods are used, the dynamical interpretation of adiabatic PIMD appears to represent quite accurately the true time correlation functions of this highly correlated many-body system. We have found that the discrete, quantum FK model shows different behavior than its continuum version. The spectral density does not show the characteristic omega-2Theta(omega-omegac) cusp of the continuum solution in the pinned phase (m>m(c)). We also identify a dynamical quantum hysteresis in addition to the regular classical hysteresis when an external force is applied to the FK chain. In the unpinned phase (m<or=m(c)), we find a linear response damping coefficient which is finite and only weakly dependent on temperature T at small values of T.


[Size and type of frequent use of ambulatory medical care among the elderly population in Germany: a study based on statutory health insurance data].
The authors report the results of a study on frequent attenders in ambulatory medical care among elderly people in Germany and on the factors related to frequent attendance such as age, sex, multi-morbidity and long-term care dependency. The study was based on claims data of all policy holders aged 65 and over of a statutory health insurance company operating nationwide in Germany in 2004 (n=123,224). Utilisation was analysed by the number of contacts with practices of physicians working in the ambulatory medical care sector and by the number of different practices contacted. The criteria for frequent attendance included greater than or equal to 50 contacts and/or greater than or equal to 10 different practices contacted and/or greater than or equal to 3 practices of the same discipline contacted within one year. Descriptive statistical analysis and logistic regression were used. 19% of the elderly were identified as frequent attenders, which corresponds to some 3.5 million people in Germany. Two main types of frequent attendance were identified: one is characterised by very many contacts, old age, frequent presence of multi-morbidity, and/or long-term care dependency. The other type is the younger, less frequently multi-morbid attender who is considerably less often dependent on long-term care, and characterised by large numbers of contacted practices and/or practices of the same discipline. Frequent attendance is due to several factors. The problem of frequent attendance needs further research that is not exclusively based on claims data. We found a high rate of frequent attendance. Further research should clarify if this is to the benefit of elderly people.


Manufacture of multimicrotubule chitosan nerve conduits with novel molds and characterization in vitro.
Multimicrotubule chitosan conduits (M-conduits) were fabricated using novel molds and a thermal-induced phase-separation technique. Hollow chitosan conduits (H-conduits) with an inner diameter of 1-5 mm and a wall thickness of 0.2-1.0 mm were made, and then a novel mold composed of a styrofoam insulating pedestal with several holes and a stainless steel cover plate was used to make M-conduits. In brief, corresponding H-conduits were inserted upright into the holes of the styrofoam pedestal, and filled with chitosan solution, then rapidly covered with the precooled stainless steel cover plate, and then placed in a freezer. The styrofoam insulating pedestal enclosing the conduits could reduce the heat transfer through the side wall of the conduits. Gradual phase separation then occurred uniaxially in the presence of a unidirectional temperature gradient from the top end to the bottom end of the chitosan conduits. The phase-separated polymer/solvent systems were then dried in a freeze-dryer. The microtubule diameters were controlled by adjusting the polymer concentration and cooling temperature. In vitro characterization demonstrated that the mold-based multimicrotubule chitosan conduits possessed suitable mechanical strength, microtubule diameter distribution, porosity, swelling, biodegradability, and nerve cell affinity, and so they showed potential for application as nerve tissue engineering scaffolds.


Natural radionuclides in waste water discharged from coal-fired power plants in Serbia.
Investigation of the natural radioactivity levels in water around power plants, as well as in plants, coal, ash, slag and soil, and to assess the associated radiation hazard is becoming an emerging and interesting topic. This paper is focused on the results of the radioactivity analysis in waste water samples from five coal-fired power plants in Serbia (Nikola Tesla A, Nikola Tesla B, Kolubara, Morava and Kostolac), which were analyzed in the period 2003-2015. River water samples taken upstream and downstream from the power plants, drain water and overflow water were analyzed. In the water samples gamma spectrometry analysis was performed as well as determination of gross alpha and beta activity. Natural radionuclide 40K was detected by gamma spectrometry, while the concentrations of other radionuclides, 226Ra, 235U and 238U, usually were below the minimum detection activity (MDA). 232Th and artificial radionuclide 137Cs were not detected in these samples. Gross alpha and beta activities were determined by the α/β low level proportional counter Thermo Eberline FHT 770 T. In the analyzed samples, gross alpha activity ranged from MDA to 0.47 Bq L-1, while the gross beta activity ranged from MDA to 1.55 Bq L-1.


[Anatomical and functional results after macular hole surgery].
In a retrospective study we examined the anatomical and functional effects of a combined macular hole surgery with and without the application of indocyanin green (ICG) as well as phacoemulsification. Out of 91 patients (91 eyes) with idiopatic macular holes 82 eyes were phacic. 25 cases received during the first surgery a combined pars plana vitrectomy with phacoemulsification. In 46 eyes the vitrectomy and consecutive peeling of the inner limiting membrane (ILM) was performed without ICG (Group A), in 45 eyes with ICG-assisted staining of the ILM (Group B). The average follow-up time was 19 months (12 - 24 months). The primary closure rate was 82.4 % and 94.5 % after reoperation. In Group A there were primarily 76 % and at the end 89.1 % closed results compared with 88.9 % and 100 % in group 2 (p = 0.172). Five persisting holes had a preoperative diameter above 600 microm (p = 0.014). Visual acuity improved in Group A preoperatively from 0.17 to postoperatively 0.33 and in Group B from 0.22 to postoperatively 0.38. The difference between both groups was not significant (p = 0.106). From 82 phacic eyes 25 were treated by a combined vitrectomy with phacoemulsification, 23 eyes received later a phacoemulsification while 34 remained phacic. Peeling of the ILM was complete after staining with ICG resulting in an increased closure rate. The functional results between both groups did not differ significantly. Phacic eyes may keep their clear lens even after multiple surgeries.


Bone mineralization enhancing activity of a methoxyellagic acid glucoside from a Feijoa sellowiana leaf extract.
The capability of an aqueous methanol extract obtained from the leaves of Feijoa sellowiana Berg. on possible prevention and treatment of osteoporosis has been examined by evaluating its stimulating effect on the two human osteoblastic cell lines HOS58 and SaOS-2. The extract was found to increase significantly the mineralization of cultivated human bone cell, whereby a clear increment (15.3 +/- 2.7%) in von Kossa positive area was determined when administering 25 microg/ml leaf extract. A phytochemical investigation of the extract has demonstrated the high phenolic content and led to the isolation and identification of twenty three of them, among which the new 3-methoxyellagic acid 4-O-beta-glucopyranoside was fully identified. All structures were elucidated on the basis of conventional analytical methods and confirmed by FTMS, 1D- and 2D-NMR data. The new compound was found to cause a significant increase of mineralized area at 20 microg/mL, while at lower concentrations the effect was not significant. However, an increase of the number of mineralized spots (nodules) at all tested concentrations of the compound was observed.


Ene reactions between two alkynes? Doors open to thermally induced cycloisomerization of macrocyclic triynes and enediynes.
A domino process is described combining an ene reaction between two alkynes and a Diels-Alder cycloaddition of the vinylallene formed. The process accounts for the thermally induced cycloisomerization of macrocyclic triynes and enediynes to give fused tetracycles in a stereoselective manner.


[Possible ways of regulating detoxifying processes in the alcohol dehydrogenase reaction with pantothenic acid derivatives].
Oxidation of derivatives and precursors of pantothenic acid was studied in alcohol dehydrogenase reactions. Despite the presence of free hydroxymethyl groups in a number of pantothenic acid derivatives only panthenol with Km = 8 x 10(-3) M was shown to serve as a substrate for alcohol dehydrogenase from horse liver tissue (EC 1.1.1.1) Pantethine, sodium phosphopantothenate, CoA and acetyl-CoA decreased the rate of ethanol oxidation, where pantethine and sodium phosphopantothenate were competitive inhibitors, while CoA and acetyl-CoA inhibited the enzyme noncompetitively Ki = 1.2 x 10(-2) M, 2.1 x 10(-2) M, 4.4 x 10(-4) M and 5.1 x 10(-4) M, respectively. Metabolic precursors, which were different from pantothenic acid in their structure, were not involved in the alcohol dehydrogenase reaction. Possible regulation of alcohol intoxication using derivatives and precursors of vitamin B3 is discussed.


Transient global amnesia--a review.
Transient global amnesia (TGA) is an isolated amnesic syndrome with normal neurological examination where patients remain alert and communicative with no loss of personal identity; however, they experience striking loss of memory for recent events and an impaired ability to retain new information. TGA could be triggered by venous congestion and there is evidence of association between younger patients and history of migraine. Most episodes last 2-12 h and the recurrence rate of future amnesic events is very low.


Antibodies to Plasmodium falciparum sporozoites following a malarial outbreak in a non-endemic area of Sri Lanka.
An enzyme-linked immunosorbent assay (ELISA) based on the synthetic peptide (NANP)40 was used to characterize the sporozoite antibodies in an unusual Plasmodium falciparum outbreak in a non-malarious area in Sri Lanka. A positive antibody response was seen in 62% of patients with their first P. falciparum illness. There was no correlation between sporozoite antibodies and the antibody against blood stages, determined by immunofluorescence assay. The majority (91%) of the patients lost the antibodies to circumsporozoite (CS) protein within one year (in the absence of re-exposure). Three patients had high levels of CS antibodies even after one year, and this persistence was related to the level of the initial antibody response. In the area of the outbreak 10% of schoolchildren had antibodies to the (NANP)40 peptide. 21% of the 42 children with present or past overt malaria were antibody positive. Of the children with no such background, 8% were antibody positive. The corresponding seropositivity rates for asexual blood stages were 31% and 1% for the 2 groups respectively. It is concluded that (NANP)40 ELISA is potentially a valuable tool in sero-epidemiology, particularly in situations of seasonal transmission and recurrences due to drug resistance.


Resin restorations for anterior teeth--1995.
Resin restorations for anterior teeth, properly planned and well placed, should be expected to serve many years. Small resin restorations in anterior teeth may even be lifetime restorations. Class III, IV and V resin restorations with large facial display are best when hybrid resin is placed internally and microfill resin is placed facially. Restorations without significant facial display are best treated with hybrid resin alone. Although new, more refined resin systems will come, the current state of the art for anterior resin restorations is excellent and certainly the best it has ever been.


Effect of short-time aerobic digestion on bioflocculation of extracellular polymeric substances from waste activated sludge.
The effect of short-time aerobic digestion on bioflocculation of extracellular polymeric substances (EPSs) from waste activated sludge (WAS) was investigated. Bioflocculation of the EPS was found to be enhanced by 2∼6 h of WAS aerobic digestion under the conditions of natural sludge pH (about 7), high sludge concentration by gravity thickening, and dissolved oxygen of about 2 mg/L. With the same EPS extraction method, the total suspended solid content reduction of 0.20 and 0.36 g/L and the volatile suspended solid content reduction of 0.19 and 0.26 g/L were found for the WAS samples before and after aerobic digestion of 4 h. It indicates that more EPS is produced by short-time aerobic digestion of WAS. The scanning electron microscopy images of the WAS samples before and after aerobic digestion of 4 h showed that more EPS appeared on the surface of zoogloea by aerobic digestion, which reconfirmed that WAS aerobic digestion induced abundant formation of EPS. By WAS aerobic digestion, the flocculating rate of the EPS showed about 31 % growth, almost consistent with the growth of its yield (about 34 %). The EPSs obtained before and after the aerobic digestion presented nearly the same components, structures, and Fourier transform infrared spectra. These results revealed that short-time aerobic digestion of WAS enhanced the flocculation of the EPS by promoting its production.


Sexual and reproductive health and rights: integration as a holistic and rights-based response to HIV/AIDS.
For decades, donors, governments, and civil society have recognized the importance of sexual and reproductive health and rights (SRHR) in efforts to alleviate poverty and advance gender equality and women's rights. More recently, in the battle against HIV/AIDS--and given the unique challenges the pandemic presents for health and development--the global community has acknowledged the benefits of synergizing sexual and reproductive health and HIV/AIDS interventions. However, the United States has been slow to incorporate lessons learned from the international experience when it comes to integrating HIV/AIDS, SRHR, and gender equality in the fight against HIV/AIDS. This article highlights the importance of SRHR and lessons learned from SRHR-HIV integration to inform U.S. domestic and global AIDS strategies and interventions.


Quantification of cellulase activity using cellulose-azure.
Despite wide application of cellulose-azure as a substrate for measuring cellulase activity, there is no quantification of hydrolysis rate or enzymatic activities using this substrate. The aim of this study was to quantify the hydrolysis rate in terms of product formation and dye released using cellulose-azure. The amount of dye released was correlated with the production of glucose and the enzyme concentrations. It is shown that the lack of correlation can be due to (1) repression of the release of the azure-dye when azure-dye accumulates, (2) presence of degradable substrates in the cellulase powder which inflate the glucose measurements and (3) the degradation of cellulose which is not linked to the dye in the cellulose-azure. Based on the lack of correlation, it is recommended that cellulose-azure should only be applied in assays when the aim is to compare relative activities of different enzymatic systems.


MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats.
The systemic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) , has previously been found to reverse the motor response alterations that develop during long-term levodopa treatment of parkinsonian rats. To determine whether co-administration of MK801 with levodopa might prevent the initial appearance of these response changes, rats, rendered parkinsonian by a 6-hydroxydopamine lesion of the medial forebrain bundle, received either levodopa alone or levodopa with the NMDA receptor antagonist. After four weeks of treatment with levodopa alone, the duration of the turning response declined by 37% (P < 0.05) and the number of ineffectual levodopa injections had more than doubled (P < 0.05). MK801 co-treatment completely blocked the shortening in response duration and prevented the frequency of ineffectual levodopa injection from exceeding baseline levels in animals receiving levodopa alone. The total magnitude of the turning response to levodopa was not affected. These results suggest that NMDA receptor blockade may act prophylactically to prevent the appearance of motor response alterations in levodopa-treated parkinsonian rodents that resemble those occurring in levodopa-treated patients with Parkinson's disease.


Approaches to environmental restoration of a polluted harbour with submerged archaeology: the Alexandria case study.
Many invaluable underwater buildings of archaeological interest in Alexandria were discovered in 1996 at different sites in the Eastern Harbour of Alexandria. There is a belief that the best way to protect these invaluable heritages is to transfer them to an underwater park or museum. Obviously, the execution of such a project depends essentially upon the water quality (including water transparency) improving in the future. The harbour is presently polluted by discharge of wastewater effluents from different sources. It has recently been decided to restore this important coastal area through: (1) stopping the direct discharge of wastewater effluents into this semi-enclosed harbour in 1993 and (2) gradually reducing the discharge of the municipal wastewater through marine outfalls at two sites lying at the outer sides of the harbour. Zero discharge is expected to be effective by the end of the year 2001. The present work, therefore, is a follow up of the study of water quality in the harbour after 1993: in 1996 and 1999-2000. The water quality of an open sea reference station was also studied for comparison. The results reveal occurrence of an improvement of the environmental conditions in the harbour. The water has turned from being eutrophic to mesotrophic. The harbour is expected to become meso/oligotrophic as soon as the complete cessation of the discharge from the two outside sources is attained.


Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography.
Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross-sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function. Eighty-three men with COPD had completed five annual assessments of CT scans and pulmonary function tests over 4 years. Airway dimensions of the basal segment bronchi and lung attenuation on CT images were analysed in 38 subjects in whom the same airway could be measured at least three times, including at entry and at the end of the study. Mean annual decline in FEV(1) was 21 mL/year. Annual changes in the percentage of low attenuation areas were not significantly correlated with decline in FEV(1). On the other hand, annual changes in the percentage of wall area (WA%/year) were significantly inversely correlated with annual changes in FEV(1) (r = -0.363, P = 0.025), whereas WA%/year did not differ among severity stages at entry and did not correlate with baseline FEV(1). The results showing that annual changes in airway thickening correlated with annual decline in air flow limitation suggests the importance of treatment of airway inflammation in COPD. CT is a useful tool for quantitative estimation not only of emphysema but also of airway lesions in longitudinal studies.


Introduction to pharmacokinetics in clinical toxicology.
In clinical toxicology, a better understanding of the pharmacokinetics of the drugs may be useful in both risk assessment and formulating treatment guidelines for patients. Pharmacokinetics describes the time course of drug concentrations and is a driver for the time course of drug effects. In this chapter pharmacokinetics is described from a mathematical modeling perspective as applied to clinical toxicology. The pharmacokinetics of drugs are described using a combination of input and disposition (distribution and elimination) phases. A description of the time course of the input and disposition of drugs in overdose provides a basis for understanding the time course of effects of drugs in overdose. Relevant clinical toxicology examples are provided to explain various pharmacokinetic principles. Throughout this chapter we have taken a pragmatic approach to understanding and interpreting the time course of drug effects.


Subchronic treatment with prazosin improves passive avoidance learning in aged mice: possible relationships to alpha1-receptor up-regulation.
While many evidences indicate that deficits of central noradrenergic neurotransmission are involved in the age-related decline of cognitive functions in animals and man, very little is known about the specific role of central alpha1-adrenergic receptors. Therefore, this problem was specifically addressed in the present communication using the alpha1-adrenoceptor antagonist prazosin as pharmacological tool. While the acute administration of prazosin did not affect passive avoidance learning of young or aged mice, an improvement of learning capabilities was seen after subchronic treatment, but for the aged animals only. An U-shaped dose response curve was seen. 0.3 mg/kg prazosin was most effective. Very interestingly, only for this dose a significant up-regulation of the density of alpha1-adrenoceptors in the mouse brain was found in the aged animals only. The data suggest a possible causal relationship between effects of prazosin on passive avoidance learning and central alpha1-receptor density.


Plantar fasciitis.
Thirty patients presenting with the heel pain syndrome, commonly referred to as "plantar fasciitis", were studied prospectively over a two year period. The pain was associated with a calcaneal spur in 21 patients (70%). In a control series of 25 patients without heel symptoms, calcaneal spurs were present in only 4 out of 50 heels (8%). This difference is highly significant (p 0.001). Seven patients (22%) in the plantar fasciitis group complained of ipsilateral sciatica.


You bet-cha: a novel family of transcriptional regulators.
The BET proteins are a novel class of transcriptional regulators whose members can be found in animals, plants and fungi. Founding members are Human RING3, Drosophila Fsh and yeast Bdf1p. BET proteins are distinguished by an N-terminal bromodomain or bromodomains and an ET domain. As predicted by the presence of the bromodomain(s), these proteins have been found to be associated with chromatin. The poorly characterized ET domain functions as a protein-protein interaction motif and may be part of a serine-kinase activity. Other regions ("modular domains"), which are conserved only in certain BET proteins, are likely to provide sub-family specific functions. Genetic, biochemical and molecular techniques have implicated BET proteins in functions as diverse as meiosis, cell cycle control and homeosis. The data suggest that BET proteins may modulate chromatin structure and affect transcription via a sequence-independent mechanism. This review will attempt to summarize current research on BET proteins and envision where future research is likely to lead.


An empiric integrative approach to the management of cough: ACCP evidence-based clinical practice guidelines.
Review the literature to provide a comprehensive approach, including algorithms for the clinician to follow in evaluating and treating the patient with acute, subacute, and chronic cough. We searched MEDLINE (through May 2004) for studies published in the English language since 1980 on human subjects using the medical subject heading terms "cough," "treatment of cough," and "empiric treatment of cough." We selected case series and prospective descriptive clinical trials. We also obtained any references from these studies that were pertinent to the topic. The relative frequency of the disorders (alone and in combination) that can cause cough as well as the sensitivity and specificity of many but not all diagnostic tests in predicting the cause of cough are known. An effective approach to successfully manage chronic cough is to sequentially evaluate and treat for the common causes of cough using a combination of selected diagnostic tests and empiric therapy. Sequential and additive therapy is often crucial because more than one cause of cough is frequently present. Algorithms that provide a "road map" that the clinician can follow are useful and are presented for acute, subacute, and chronic cough.


Growth, carcass characteristics, and profitability of organic versus conventional dairy beef steers.
Bull calves (n=49), born at the University of Minnesota West Central Research and Outreach Center (Morris) between March and May 2011, were used to compare growth measurements and profitability of conventional and organic dairy steers. Calves were assigned to 1 of 3 replicated groups at birth: conventional (CONV; n=16), organic (pasture and concentrate; ORG; n=16), or organic grass only (GRS; n=17), and analysis of variables was on a pen basis. Breed groups of calves were Holstein (HO; n=9); Holsteins (n=11) maintained at 1964 breed average level; crossbreds (n=19) including combinations of HO, Montbéliarde, and Swedish Red; and crossbreds (n=10) including combinations of HO, Jersey, Swedish Red, and Normande. The CONV steers were fed a diet of 80% concentrate and 20% forage. The ORG steers were fed a diet of organic corn, organic corn silage, and at least 30% of their diet consisted of organic pasture during the grazing season. The GRS steers grazed pasture during the grazing season and were fed high-quality hay or hay silage during the nongrazing season. Intakes of a total mixed ration were recorded daily with herd management software. A profit function was defined to include revenues and expenses for beef value, feed intake, pasture intake, health cost, and yardage. The GRS (358.6 kg) steers had lesser total gains from birth to slaughter than ORG (429.6 kg) and CONV (534.5 kg) steers. Furthermore, the GRS (0.61 kg/d) steers had lesser average daily gain from birth compared with ORG (0.81 kg/d) and CONV (1.1 kg/d) steers. The GRS and ORG steers had smaller rib eye area (49.5 and 65.8 cm(2), respectively) compared with CONV (75.4 cm(2)) steers. For profitability, GRS steers had 43% greater profit than CONV steers due to organic beef price premiums and lower feed costs. On the other hand, ORG steers had substantially less profit than CONV steers. The higher cost of production for the ORG steers is due to the extreme high value of organic corn. The results of the current study illustrate the economic potential of alternative strategies for growing and marketing male offspring of organic dairy cattle in the Midwest.


Beta-ketothiolase genes in Azotobacter vinelandii.
Azotobacter vinelandii is proposed to contain a single beta-ketothiolase activity participating in the formation of acetoacetyl-CoA, a precursor for poly-beta-hydroxybutyrate (PHB) synthesis, and in beta-oxidation (Manchak, J., Page, W.J., 1994. Control of polyhydroxyalkanoate synthesis in Azotobacter vinelandii strain UWD. Microbiology 140, 953-963). We designed a degenerate oligonucleotide from a highly conserved region among bacterial beta-ketothiolases and used it to identify bktA, a gene with a deduced protein product with a high similarity to beta-ketothiolases. Immediately downstream of bktA, we identified a gene called hbdH, which encodes a protein exhibiting similarity to beta-hydroxyacyl-CoA and beta-hydroxybutyryl-CoA dehydrogenases. Two regions with homology to bktA were also observed. One of these was cloned and allowed the identification of the phbA gene, encoding a second beta-ketothiolase. Strains EV132, EV133, and GM1 carrying bktA, hbdH and phbA mutations, respectively, as well as strain EG1 carrying both bktA and phbA mutations, were constructed. The hbdH mutation had no effect on beta-hydroxybutyryl-CoA dehydrogenase activity or on fatty acid assimilation. The bktA mutation had no effect on beta-ketothiolase activity, PHB synthesis or fatty acid assimilation, whereas the phbA mutation significantly reduced beta-ketothiolase activity and PHB accumulation, showing that this is the beta-ketothiolase involved in PHB biosynthesis. Strain EG1 was found to grow under beta-oxidation conditions and to possess beta-ketothiolase activity. Taken together, these results demonstrate the presence of three genes coding for beta-ketothiolases in A. vinelandii.


Treatable factors associated with severe anaemia in adults admitted to medical wards in Blantyre, Malawi, an area of high HIV seroprevalence.
Severe anaemia is a common presentation in non-pregnant adults admitted to hospital in southern Africa. Standard syndromic treatment based on data from the pre-HIV era is for iron deficiency, worms and malaria. We prospectively investigated 105 adults admitted consecutively to medical wards with haemoglobin < 7 g/dl. Those with acute blood loss were excluded. Patients were investigated for possible parasitic, bacterial, mycobacterial and nutritional causes of anaemia, including bone marrow aspiration, to identify potentially treatable causes. Seventy-nine per cent of patients were HIV-positive. One-third of patients had tuberculosis, which was diagnosed only by bone marrow culture in 8% of HIV-positive patients. In 21% of individuals bacteria were cultured, with non-typhi salmonella predominating and Streptococcus pneumoniae rare. Iron deficiency, hookworm infection and malaria were not common in HIV-positive anaemic adults, although heavy hookworm infections were found in 6 (27%) of the 22 HIV-negative anaemic adults. In conclusion, conventional treatment for severe anaemia in adults is not appropriate in an area of high HIV prevalence. Occult mycobacterial disease and bacteraemia are common, but iron deficiency is not common in HIV-positive patients. In addition to iron supplements, management of severe anaemia should include investigation for tuberculosis, and consideration of antibiotics active against enterobacteria.


Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells.
A proportion of patients with Hodgkin lymphoma carry Epstein-Barr virus (EBV), an oncogenic herpesvirus, in their tumor cells. Although it is generally assumed that EBV contributes to the malignant phenotype of Hodgkin lymphoma cells, direct evidence in support of this is lacking. Here we show that EBV infection of Hodgkin lymphoma cells results in the induction of autotaxin, a secreted tumor-associated factor with lysophospholipase-D activity. Up-regulation of autotaxin increased the generation of lysophosphatidic acid (LPA) and led to the enhanced growth and survival of Hodgkin lymphoma cells, whereas specific down-regulation of autotaxin decreased LPA levels and reduced cell growth and viability. In lymphoma tissues, autotaxin expression was mainly restricted to CD30+ anaplastic large-cell lymphomas and Hodgkin lymphoma; in the latter, high levels of autotaxin were strongly associated with EBV positivity (P = .006). Our results identify the induction of autotaxin and the subsequent generation of LPA as key molecular events that mediate the EBV-induced growth and survival of Hodgkin lymphoma cells and suggest that this pathway may provide opportunities for novel therapeutic intervention.


Toward the development of chemoprevention agents. Part II: Chemo-enzymatic synthesis and anti-inflammatory activities of a new class of 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes.
A new series of optically pure 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes were designed and synthesized via a chemo-enzymatic combined method to develop new chemoprevention agents. Twenty-four of newly synthesized compounds significantly inhibited xylene-induced rat ear edema and exhibited comparable or better anti-inflammatory activities than the reference drug aspirin. Treatment of these anti-inflammatory agents did not prolong the tail bleeding time in rat. In addition, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes exhibited good membrane permeability based on in vitro Caco-2 cell monolayer permeability assay. Furthermore, some preliminary structure-activity relationships were further analyzed among these compounds. Taken together, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes may represent a new class of anti-inflammatory drugs with safer pharmacological profile.


Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression.
To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. Adult obese patients (N = 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH + F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.


A general framework for the fusion of anatomical and functional medical images.
The collection of various data coming from anatomical and functional imagery is becoming very common for the study of a given pathology, and their aggregation generally allows for a better medical decision in clinical studies. A fusion process is described in this article for the modeling of this aggregation. The process is illustrated in the case of anatomical and functional images of the brain, but the general principle may be extended to other organs. The whole three-step fusion process based on possibilistic logic is detailed and a new class of fusion operator is introduced. The use of fuzziness in the process in general and in the operator in particular allows for the management of uncertainty and imprecision inherent to the images. The fusion process is illustrated in two clinical cases: the study of Alzheimer's disease by MR/SPECT fusion and the study of epilepsy by MR/SPECT/PET fusion. Results are presented and evaluated, and a preliminary clinical validation is achieved. The assessment of the method is encouraging, allowing its application on several clinical problems.


Efficacy of methoprene pellets against Coquillettidia perturbans larvae.
Of 21 wetlands in the Minneapolis-St. Paul area that supported similar densities of Coquillettidia perturbans larvae, 7 wetlands were treated with Altosid methoprene pellets at 5.6 kg/ha on May 28, 1992, 7 were treated with Altosid XR extended residual methoprene briquets at 1 briquet/9.3 m2 in March 1992, and the final 7 remained untreated. Emergence data collected from May 28 through late August in all sites indicated pellet and briquet treatments achieved greater than 90% control.


Prostate-specific antigen response to withdrawal of megestrol acetate in a patient with hormone-refractory prostate cancer.
Clinically significant responses after withdrawal of flutamide in patients with hormone-refractory prostate cancer (HRPC) are well documented. Failure to recognize this syndrome of response results in potential morbidity due to salvage therapy, confusion in interpretation of disease state, and introduction of a possible source of error in clinical trials. In this case report, we describe a patient with HRPC whose prostate-specific antigen levels decreased substantially in response to withdrawal of megestrol acetate. Such a response should be considered when megestrol acetate is used in the treatment of HRPC.


beta-adrenergic receptor regulation and left ventricular function in idiopathic dilated cardiomyopathy.
Alterations in the myocardial receptor-G protein-adenylate cyclase (RGC) complex and cardiac adrenergic neurons in the failing human heart result in subsensitivity to beta-adrenergic stimulation. Pharmacologic interventions such as beta blockade may modify critical components of the RGC complex and partially restore the sensitivity of the beta-adrenergic pathway. Among the receptors coupled to the stimulatory (Gs) protein are the beta 1 and beta 2 receptors. Because of differences in receptor population and agonist (i.e., norepinephrine) affinity, the beta 1-receptor is the predominate adrenergic subtype regulating contractility in the nonfailing myocardium. Down-regulation occurs in the myocardial beta-receptor component of the RGC complex with mild-to-moderate and severe left ventricular dysfunction. However, abnormalities of the RGC complex vary with the etiology of heart failure; beta 1-receptor down-regulation is greater in idiopathic dilated cardiomyopathy than in post-infarction cardiomyopathy, while beta-receptor uncoupling is greater in post-infarction disease. In chronic heart failure, the adrenergic nervous system is activated in the heart and kidney. There is evidence that an increased cardiac norepinephrine concentration contributes to the decrease in beta 1-receptor density in heart failure. However, norepinephrine exposure is not the only factor responsible for regulating beta-adrenergic receptors in heart failure. Chronic beta blockade may improve hemodynamic and clinical response in patients with idiopathic dilated cardiomyopathy by protecting the myocardium from the cardiotoxic effects of increased catecholamines and by up-regulating the beta 1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of nicotinic agonists on the NMDA receptor.
The cholinergic nicotinic agonists (-)nicotine and lobeline were observed to partially inhibit whole-cell N-methyl-D-aspartate (NMDA)-induced responses in rat cortical neurons in culture. In addition we found that (-)nicotine, (+)nicotine, and lobeline, but not the nicotine metabolite (-)cotinine nor acetylcholine, were able to displace [3H]dizocilpine ([3H]MK 801) binding in well-washed membranes obtained from rat brain. These results show that certain nicotinic agonists can interact with the NMDA receptor and block its function.


Structures of Fe(II) spin-crossover complexes from synchrotron powder-diffraction data.
Crystal structure determination and analysis have been carried out for the two spin-crossover compounds [Fe(teeX)(6)](BF(4))(2) (teeX is haloethyltetrazole; X = I: teei; X = Br: teeb), in both their high-spin (near 300 K) and their low-spin states (T = 90 K), using high-resolution powder-diffraction data collected at the ESRF (Grenoble, France) and SPring8 (Japan) synchrotron radiation facilities. The structures of teei have been solved using various direct-space structure determination techniques (grid search, genetic algorithm and parallel tempering) and refined with the Rietveld method using geometrical restraints. In the case of teeb, a structural model was found but a full refinement was not successful because of the presence of a significant amount of an amorphous component. Analysis of the structures (space group P2(1)/c, Z = 2) and diffraction data, and the absence of phase transitions, show the overall structural similarity of these compounds and lead to the conclusion that the gradual spin-crossovers are likely to be accompanied by small structural changes only.


National outcomes and uptake of laparoscopic gastrectomy for cancer in England.
Gastrectomy remains the mainstay of curative treatment for gastric cancer, yet it is associated with significant postoperative mortality. The laparoscopic approach has been introduced in an attempt to improve surgical outcomes. This study examines the uptake of laparoscopic gastrectomy in England and quantifies postoperative mortality and morbidity following gastrectomy for cancer. A population-based study of a national administrative database was undertaken. Patients undergoing gastrectomy for cancer in any National Health Services hospital in England between April 2000 and March 2010 were included. The main outcome measures were mortality, morbidity and length of stay. A total of 10,713 patients underwent gastrectomy, of which 10,233 (95.5%) underwent open gastrectomy (OG), and 480 (4.5%) underwent laparoscopic gastrectomy (LG). There was no significant difference in 30-day in-hospital mortality between OG and LG (5.6% vs. 4.8%; p = 0.461). Medical complications occurred in 2,311 (22.6%) and 120 (25%) patients from OG and LG groups respectively (p = 0.217). Patients in the LG groups had a shorter hospital stay than OG with median (interquartile range) of 11 (8-17) versus 14 (11-19) days respectively (p < 0.001). Readmission and reoperation rates were 10.2 versus 12.1% (p = 0.175) and 4 versus 4.6% (p = 0.523) for OG and LG respectively. LG is increasingly being performed in England. Postoperative morbidity and mortality of LG is similar to that of OG, but it is associated with a shorter hospital stay. Data from randomised controlled trials evaluating long term survival and patients' reported outcomes are essential before the final judgement on the value of LG in the management of gastric cancer.


Impact of obesity on perioperative outcomes and survival following pancreaticoduodenectomy for pancreatic cancer: a large single-institution study.
To examine the effect of body mass index (BMI) on clinicopathologic factors and long-term survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. Data on BMI, weight loss, operative details, surgical pathology, and long-term survival were collected on 795 patients who underwent pancreaticoduodenectomy. Patients were categorized as obese (BMI > 30 kg/m(2)), overweight (BMI 25 to <30 kg/m(2)), or normal weight (BMI < 25 kg/m(2)) and compared using univariate and multivariate analyses. At the time of surgery, 14% of patients were obese, 33% overweight, and 53% normal weight. Overall, 32% of patients had preoperative weight loss of >10%. There were no differences in operative times among the groups; however, higher BMI was associated with increased risk of blood loss (P < 0.001) and pancreatic fistula (P = 0.01). On pathologic analysis, BMI was not associated with tumor stage or number of lymph nodes harvested (both P > 0.05). Higher BMI patients had a lower incidence of a positive retroperitoneal/uncinate margin versus normal weight patients (P = 0.03). Perioperative morbidity and mortality were similar among the groups. Obese and overweight patients had better 5-year survival (22% and 22%, respectively) versus normal weight patients (15%; P = 0.02). After adjusting for other prognostic factors, as well as preoperative weight loss, higher BMI remained independently associated with improved cancer-specific survival (overweight: hazard ratio, 0.68; obese: hazard ratio, 0.72; both P < 0.05). Obese patients had similar tumor-specific characteristics, as well as perioperative outcomes, compared with normal weight patients. However, obese patients undergoing pancreaticoduodenectomy for pancreatic cancer had an improved long-term survival independent of known clinicopathologic factors.


Uncemented surface replacement of the knee joint.
A method of surface replacement of the knee joint using an uncemented titanium-on-high-density-polyethylene prosthesis has been investigated in 61 patients. The results show that pain is relieved in the vast majority of cases. Overall, the joint range is marginally improved. Preoperative deformities can be considerably correced. The procedure appears to give a functional result that is comparable with other types of replacement arthroplasty and leaves complete freedom for revisional surgery at a later date should it become necessary.


Use of SSR markers to determine the anther-derived homozygous lines in coconut.
Anther culture was used to obtain dihaploid (DH) coconut plants and their ploidy level was determined by flow cytometric analysis. Simple sequence repeat (SSR) marker analysis was conducted to identify the homozygous diploid individuals. Ploidy analysis showed that 50% of the tested plantlets were haploid and 50% were diploid. Polymorphic fragments of the mother palm and their segregation patterns in anther-derived plantlets were used to determine the origin of the diploid plantlets. Using a diagnostic SSR marker (CNZ43), all the diploid plantlets tested were identified as being derived from microspores (i.e. were homozygous) and were thus candidates for use in coconut breeding programs.


Characterization of 14 microsatellite loci in a tropical palm, Attalea phalerata (Arecaceae).
We developed microsatellite primers for the widely distributed tropical palm Attalea phalerata for studies on the dispersal and spatial genetic structure of palm populations. • Fourteen di-, tri-, and tetra-nucleotide microsatellite primer pairs were identified. The number of alleles in the population tested ranged between 3 and 25, with a mean of 12.1. Ten microsatellite loci exhibited no significant deviations from Hardy-Weinberg Equilibrium or presence of null alleles, and their combined probability of exclusion was 0.998. • These microsatellite loci will be useful in parentage analysis and population genetics studies of Attalea phalerata.


Surface features and ultrastructure of isolated Kupffer cells as seen by scanning and transmission electron microscopy.
The present report describes ultrastructural and surface features of hepatic Kupffer cells, with particular emphasis on the characteristics of these cells in suspension, as seen under the scanning electron microscopy (SEM), after their successful isolation by pronase digestion of liver tissue. Kupffer cells were readily recognized in sections of the liver examined by transmission electron microscopy, particularly after tagging by carbon, heat-damaged erythrocytes, and latex spheres. Their ultrastructural features in suspension and in liver sections were similar to those described for peritoneal macrophages. In the present study, a high yield of well-preserved Kupffer cells was obtained after selective enzymatic digestion of intact rat liver. Kupffer cells were readily distinguished from lymphocytes and hepatocytes on the basis of their surface architecture, and showed transverse ridge-like profiles and ruffled folds which became more prominent during phagocytosis. The sequence of events during the various stages of latex bead phagocytosis was well visualized with the SEM. Kupffer cells in suspension, during spreading and attachment to glass and during phagocytosis, resembled peritoneal macrophages isolated from rats, providing further evidence that these cell types are closely related.


Crohn's Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production.
Crohn's disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. Eligible CD patients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn's disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, -interleukin 6 [IL-6], IL-1β) and M2 cytokines (transforming growth factor [TGF]-β1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. Depressed CD patients (n = 91) presented higher HBI, -SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1β were increased while -classical monocyte (CD14++CD16-) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1β correlated with HADS-D scores. Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CD patients with depressive symptoms.


[Drugs epidemiology].
Any drug can be construed as a universal marker of physicians' tasks and knowledge (or ignorance thereof). Presently, pre-marketing studies and trials imply that, after a thorough, basic and/or preclinical research has been conducted, a clinical research stage is in a position to be carried on over a 4- to 6-year lapse of time so that all necessary data are collected thus paving the way for the marketing of the drug involved to be eventually authorized. In most countries, an adequate regulation framework is required in order to eliminate unnecessary drugs, besides setting up efficiency, innocuousness, and purpose criteria for new drugs to be approved.


The significance of interleukin-6 and lactate in the synovial fluid for diagnosing native septic arthritis.
Aim of this study was to evaluate the role of synovial interleukin-6 and synovial lactate for predicting native septic arthritis. We analyzed retrospectively synovial fluid parameters (interleukin-6, total-protein, glucose, lactate, synovial-fluid-white-blood-cell-count) of 62 patients with culture-verified native septic arthritis and compared them to 57 patients with acute aseptic arthritis. Receiver-Operating-Characteristic-curves were calculated to determine the 'Area-under-the-curves' (AUC), the best thresholds and the corresponding likelihood-ratios. The best parameter for diagnosing septic arthritis was synovial lactate (AUC = 0.864, sensitivity = 74.5%, specificity = 87.2%), followed by synovial interleukin-6 (AUC = 0.803, sensitivity = 92.5%, specificity = 64.1%) and the synovial-fluid-white-blood-cell-count (AUC = 0.782, sensitivity = 71.2%, specificity = 84.9%). Synovial lactate levels above 10 mmol/l almost proofed septic arthritis (interval-Likelihood-Ratio = 20.4), synovial interleukin-6 levels lower than 7000 pg/ml almost ruled out infection (interval-Likelihood-Ratio = 0.12). If none of these thresholds are met, physicians should estimate disease probability by the simultaneous use of the interval-Likelihood-Ratios of synovial lactate, synovial interleukin-6 and synovial-fluid-white-blood-cell-count.


Simultaneous visualization and electrophysiology of corneal A-delta and C fiber afferents.
Fluorescent staining of neuronal elements has become an important tool in neuroscience research; however, investigations have been limited by the toxic effects produced by most dyes, especially following excitation by strong epifluorescent illumination. The present study investigated effects produced by the methylpyridinium fluorescent dyes, 4-di-1-ASP and 4-di-2-ASP, on electrophysiologic responses from corneal A-delta and C fiber afferents. Rabbit corneal tissue was isolated and maintained in vitro to facilitate staining, visualization, and electrophysiologic recording of corneal nerves. Nerve fibers were selectively stained by the dyes and could be followed from their point of entry in small nerve bundles at the cornea-sclera border to individual free nerve ending terminals in the corneal epithelium. Neither the dyes nor epifluorescence, alone or in combination, produced any statistically significant changes (P greater than 0.1; t test) in spontaneous discharge activity, spike amplitude, spike dV/dt or stimulus evoked activity in A-delta and C fibers. Epifluorescent visualization of corneal afferents and simultaneous electrophysiologic recording will permit detailed investigations of sensory transduction processes and structure-function relationships in mammalian sensory nerves.


Barefoot running: does it prevent injuries?
Endurance running has evolved over the course of millions of years and it is now one of the most popular sports today. However, the risk of stress injury in distance runners is high because of the repetitive ground impact forces exerted. These injuries are not only detrimental to the runner, but also place a burden on the medical community. Preventative measures are essential to decrease the risk of injury within the sport. Common running injuries include patellofemoral pain syndrome, tibial stress fractures, plantar fasciitis, and Achilles tendonitis. Barefoot running, as opposed to shod running (with shoes), has recently received significant attention in both the media and the market place for the potential to promote the healing process, increase performance, and decrease injury rates. However, there is controversy over the use of barefoot running to decrease the overall risk of injury secondary to individual differences in lower extremity alignment, gait patterns, and running biomechanics. While barefoot running may benefit certain types of individuals, differences in running stance and individual biomechanics may actually increase injury risk when transitioning to barefoot running. The purpose of this article is to review the currently available clinical evidence on barefoot running and its effectiveness for preventing injury in the runner. Based on a review of current literature, barefoot running is not a substantiated preventative running measure to reduce injury rates in runners. However, barefoot running utility should be assessed on an athlete-specific basis to determine whether barefoot running will be beneficial.


Correlation between echocardiographically demonstrated segmental dyskinesis and regional myocardial perfusion.
In order to evaluate the relationship between regional myocardial perfusion and segmental dyskinesis, 22 open chest dogs were studied using ultrasound to register cardiac wall motion and radioactive labeled microspheres to determine myocardial perfusion. In six dogs, motion and perfusion were correlated at two levels of partial circumflex coronary artery occlusion followed by complete occlusion. A good correlation between declining myocardial perfusion of all the ischemic segments and development of aneurysmal bulging (during isometric contraction) was seen: r = minus 0.80. A similar correlation between myocardial perfusion and endocardial wall velocity (during systolic ejection) was observed: r = 0.92. In nine dogs, the effect of 45 minutes of complete coronary occlusion followed by 30 minutes of reperfusion was evaluated with respect to perfusion and motion. After coronary reperfusion myocardial perfusion of the ischemic area returned to control levels (from 32.6 +/- 3.5 to 130.3 +/- 13.3 ml/100 g/min), but aneurysmal bulging during isometric contraction persisted. Endocardial wall velocity during systolic ejection showed a variable response to reperfusion, achieving values ranging from 32% to 162% of the preocclusion levels. In seven dogs the ultrasound beam was reflected off nonischemic myocardium adjacent to areas of ischemia resulting from coronary occlusion. Despite preservation of normal myocardial perfusion in these nonischemic areas wall motion abnormalities were evident: endocardial wall velocity declined from 25.8 +/- 5.8 to 14.0 +/- 4.9 mm/sec (P less than 0.01), and aneurysmal bulging in three animals. These changes may be due to transient undetected ischemia in the segments struck by the ultrasound beam, or to passive alteration of the motion of the normally perfused areas by the severe dyskinesis of the adjacent ischemic myocardium.


Sandwich mesh abdominal closure.
The open abdomen carries a high mortality rate and represents a big surgical challenge. The recent introduction of vacuum assisted closure (VAC) introduced new techniques of its management, including STAR--Staged Abdominal Repair, Fabian Protocol, VAC supported with PDS, support with polyglactin mesh and the use of tissue expanders in the staged closure of the open abdomen. One of the methods, SMAC--sandwich mesh abdominal closure, emerged in April 2008 by the clinical group from Germany. The authors present their own modification of SMAC and a case report, where it was used. By current literary research it was the first patient in the Central European hospital managed by SMAC VAC. The authors of the article conclude that SMAC VAC and its modification is highly effective in the management of the open abdomen (Fig. 5, Ref. 4).


Delayed implantation. A case report.
In cycles in which conception takes place, serum human chorionic gonadotropin (hCG) becomes detectable between 8 and 12 days after ovulation. A delayed appearance of hCG has been reported in a limited number of cases, most of them ending in spontaneous abortion. We encountered a case of ectopic pregnancy characterized by a delayed appearance of hCG and accompanied by a complete, albeit temporary, halt in the steroidogenic activity of the corpus luteum. Although the patient was at risk of developing an ectopic pregnancy, the findings made an early diagnosis extremely difficult.


Reactions upstream of glycerate-1,3-bisphosphate drive Corynebacterium glutamicum (D)-lactate productivity under oxygen deprivation.
We previously demonstrated the simplicity of oxygen-deprived Corynebacterium glutamicum to produce D-lactate, a primary building block of next-generation biodegradable plastics, at very high optical purity by introducing heterologous D-ldhA gene from Lactobacillus delbrueckii. Here, we independently evaluated the effects of overexpressing each of genes encoding the ten glycolytic enzymes on D-lactate production in C. glutamicum. We consequently show that while the reactions catalyzed by glucokinase (GLK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), phosphofructokinase (PFK), triosephosphate isomerase (TPI), and bisphosphate aldolase had positive effects on D-lactate productivity by increasing 98, 39, 15, 13, and 10 %, respectively, in 10 h reactions in minimal salts medium, the reaction catalyzed by pyruvate kinase had large negative effect by decreasing 70 %. The other glycolytic enzymes did not affect D-lactate productivity when each of encoding genes was overexpressed. It is noteworthy that all reactions associated with positive effects are located upstream of glycerate-1,3-bisphosphate in the glycolytic pathway. The D-lactate yield also increased by especially overexpressing TPI encoding gene up to 94.5 %. Interestingly, overexpression of PFK encoding gene reduced the yield of succinate, one of the main by-products of D-lactate production, by 52 %, whereas overexpression of GAPDH encoding gene increased succinate yield by 26 %. Overexpression of GLK encoding gene markedly increased the yield of dihydroxyacetone and glycerol by 10- and 5.8-fold in exchange with decreasing the D-lactate yield. The effect of overexpressing glycolytic genes was also evaluated in 80 h long-term reactions. The variety of effects of overexpressing each of genes encoding the ten glycolytic enzymes on D-lactate production is discussed.


A 26-week repeated dose toxicity study of Xian-ling-gu-bao in Sprague-Dawley rats.
Xian-ling-gu-bao (XLGB) is a traditional Chinese prescription commonly used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, climacteric syndrome, and bone fracture. However, there is limited toxicological information available on XLGB in preclinical animal model studies. It has also been recently reported that XLGB may be related to liver injury in humans. This study was designed to determine the potential toxic effects of XLGB, particularly hepatotoxicity, in Sprague-Dawley rats following oral administration for up to 26 weeks. Male and female rats were administered XLGB by oral gavage at doses of 0, 100, 300, and 1000 mg/kg for 26 weeks followed by a recovery period of 4 weeks. Clinical signs, body weight, food consumption, ophthalmology, hematology, coagulation, serum chemistry, urinalysis, bone mineral density, hormone concentration, organ weights and histopathology were examined at the end of 13- and 26-week dosing period as well as after the recovery period. Neither hepatotoxicity nor any other toxic effects were observed in the XLGB treated rats at doses up to 1000 mg/kg for 26 weeks except for a slight increase in the organ weight of the uterus in female rats at doses higher than 300 mg/kg on week 26. In this study, we found the no-observed-adverse-effect level (NOAEL) for XLGB in Sprague-Dawley rats was 1000 mg/kg, a dose that was equivalent to 3.3 times human dose based on body surface area.


Platelet-rich fibrin in the treatment of localized gingival recessions: a split-mouth randomized clinical trial.
The aim of this study is to evaluate the clinical efficacy of platelet-rich fibrin (PRF) in combination with coronally advanced flap (CAF) in the treatment of localized gingival recessions. Twenty-two patients with localized gingival recession defects (Miller I, II) participated in this split-mouth trial. Forty-four defects received either CAF + PRF (test) or CAF with subepithelial connective tissue graft (SCTG) (control). Gingival recession depth (RD), gingival recession width (RW), keratinized tissue width (KTW), recession area (RA), probing depth (PD), clinical attachment level (CAL) and gingival thickness (GT) were evaluated at baseline and 6 months. RD, RW, RA and KTW were calculated on standardized photographs with a computer image analysis program. Percentage of root coverage in test group was 92.7 % and in control group was 94.2 % (p > 0.05). Percentage of complete root coverage of the test and control groups was 72.7 and 77.3 %, respectively (p > 0.05). KTW and GT were increased in both groups from baseline to 6 months (p < 0.001), but there was no statistically significant difference between treatment groups (p > 0.05). Within the limits of the present study, it can be concluded that localized gingival recessions could be successfully treated with CAF + PRF as well as CAF + SCTG. The digital measuring method provided high accuracy and precision in the evaluation of treatment outcomes after both surgical procedures. PRF might be suggested as an alternative to SCTG for the treatment of localized gingival recessions.


Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment.
Intracranial germ cell tumors (GCTs) originating in the basal ganglia are rare. The authors investigated factors related to the diagnosis of these lesions as well as outcome in order to help decrease the time to diagnosis and improve treatment efficacy. The authors reviewed the clinical features of 142 cases of intracranial GCT in their institute. Fourteen cases of basal ganglia GCT were identified. The symptoms, neuroimaging findings, delay between symptom onset and diagnosis or treatment, initial and further treatment, and outcome were investigated. Major symptoms were motor weakness and precocious puberty. Gadolinium-enhanced T1-weighted MR images showed enhancement in 8 of 11 patients examined, but only slight hyperintensity without enhancement in 2 patients. Ipsilateral peduncle and hemispheric atrophy were found in 3 and 4 patients, respectively. Cases of basal ganglia GCT were characterized by a longer delay from the initial neuroimaging examination to diagnosis compared with GCT in other regions. Five patients had aggravated hemiparesis in the extremities due to the delay in diagnosis. Despite good response to the initial therapy, 5 patients experienced recurrence; 2 of these 5 had malignant GCTs, and 3 had been treated only with chemotherapy or radiochemotherapy with insufficient radiation dose and field. Finally, the 2 patients with malignant GCTs died of the disease, and 1 died of aspiration pneumonia due to dissemination around the brainstem. Early diagnosis requires MR imaging with administration of contrast medium in young patients presenting with motor weakness and/or precocious puberty. Serial neuroimaging studies should be performed if any tiny lesion is detected in the basal ganglia. Since insufficient treatment resulted in early recurrence, radiation therapy with adequate dose and field is essential.


Grouping of coefficients for the calculation of inter-molecular similarity and dissimilarity using 2D fragment bit-strings.
This paper compares 22 different similarity coefficients when they are used for searching databases of 2D fragment bit-strings. Experiments with the National Cancer Institute s AIDS and IDAlert databases show that the coefficients fall into several well-marked clusters, in which the members of a cluster will produce comparable rankings of a set of molecules. These clusters provide a basis for selecting combinations of coefficients for use in data fusion experiments. The results of these experiments provide a simple way of increasing the effectiveness of fragment-based similarity searching systems.


Risks for bacteremia and urinary tract infections in young febrile children with bronchiolitis.
To compare the risks for bacteremia and urinary tract injections (UTI) in young febrile children with and without bronchiolitis. A prospective cohort study. The emergency departments of 3 pediatric referral hospitals. A convenience sample of 432 previously healthy febrile patients aged 24 months or younger. Patients were divided into groups, based on the presence (n = 163, bronchiolitis group) or absence (n = 269, control group) of wheezing and/or retractions on examination. Blood cultures were obtained from all patients, and urine cultures were obtained from female patients, and male patients aged 6 months or younger. Chest radiographs were obtained on patients with lower respiratory tract signs, and those with lobar pneumonias were excluded (7 wheezing and 8 nonwheezing patients), leaving 156 patients with bronchiolitis and 261 control patients. Growth of any bacterial pathogens from the blood or 10(4) colony-forming units per milliliter or more from the urine. None of the 156 patients with bronchiolitis had bacteremia (95% confidence interval, 0%-1.9%) vs 2.7% of the 261 controls (95% confidence interval, 1.1%-5.4%; P = .049); 1.9% of the patients with bronchiolitis had UTI vs 13.6% of the controls (odds ratio, 0.12; 95% confidence interval, 0.02-0.55; P = .001). None of the subset of patients with bronchiolitis aged 2 months or younger (n = 36) had bacteremia or UTI; however, there were not enough of these younger patients to make statistically conclusive comparisons. Previously healthy febrile children aged 24 months or younger with bronchiolitis are unlikely to have bacteremia or UTI. Therefore, routine cultures of the blood and urine in these patients are unnecessary. More data are needed regarding the subset of febrile infants aged 2 months or younger with bronchiolitis.


Application of specific red blood cell adherence test to the human cornea and conjunctiva.
We modified the specific red blood cell adherence test used in the study of blood group antigens to apply to the human cornea and conjuctiva. For the first time this test was applied to these ocular tissues with considerably specificity and sensitivity. The test revealed a concentration of blood group antigens in the epithelium of cornea and conjunctiva and along the corneal endothelium, whereas it was absent in the stroma. The test is useful in studying ABO compatibility in corneal transplants.


Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation.
The study of the human pathogen papillomaviruses (HPVs) has been hampered by the inability to propagate the virus in tissue culture. The addition of 12-O-tetradecanoyl phorbol-13-acetate to the media of organotypic (raft) cultures increased expression of physiological markers of keratinocyte differentiation and concomitantly induced production of virions. Capsid production was detected in differentiated suprabasal cells. Virions approximately 54 nanometers in size were observed by electron microscopy in raft tissue cross sections in the suprabasal layers. Virions purified through isopycnic gradients were found to contain type 31b DNA and exhibited an icosahedral shape similar to that of papillomaviruses found in clinical samples.


An evaluation of roflumilast and PDE4 inhibitors with a focus on the treatment of asthma.
Asthma is a common chronic airway inflammatory disease characterized by diverse inflammatory events leading to airway hyperresponsiveness and reversible airflow obstruction. Corticosteroids have been the mainstay for asthma treatment due to their broad anti-inflammatory actions; however, other medications such as phosphodiesterase 4 inhibitors also demonstrate anti-inflammatory activity in the airways. This review describes tissue expression of phosphodiesterase 4 in the airways, the different phosphodiesterase 4 isoenzymes identified, and the anti-inflammatory activities of phosphodiesterase 4 inhibition in asthma and related findings in chronic obstructive pulmonary disease (COPD). The authors further review clinical trials demonstrating that drugs such as roflumilast have an excellent safety profile and efficacy in patients with asthma and COPD. Phosphodiesterase 4 inhibitors suppress the activity of immune cells, an effect similar to corticosteroids although by acting through different anti-inflammatory pathways and uniquely blocking neutrophilic inflammation. Roflumilast and other phosphodiesterase 4 inhibitors have been shown to provide additive protection in asthma when added to corticosteroid and anti-leukotriene treatment. Developmental drugs with dual phosphodiesterase 3 and 4 inhibition are thought to be able to provide bronchodilation and anti-inflammatory activities and will consequently be pushed forward in their clinical development for the treatment of asthma and COPD.


Non-hexagonal Large-Pitch Fibers for enhanced mode discrimination.
Photonic-Crystal Fibers (PCF) are among the most promising concepts to achieve large mode field areas suitable for the reduction of nonlinearities in fibers. Differential mode propagation loss is the cornerstone of effective single-mode behavior in passive and core-pumped active PCFs. In this work, we explore non-hexagonal PCF designs with increased mode discrimination in comparison to the classical hexagonal PCF designs. It is shown that a pentagonal design can increase the mode discrimination and, simultaneously, also improve the beam quality of Large-Pitch Fibers with mode field diameters well beyond 100 µm.


Gross and histological variations along the length of the rat vas deferens.
The gross morphology of the vas deferens of the rat and the changes that occur along its length are reported. It is shown that the organ can be divided into proximal, distal and terminal portions. Each portion is histologically unique and is situated in a different part of the body. The differences are discussed in relation to the function of the organ and their possible role in the consequences of vasectomy.


Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: a pilot study.
The present study aims to conduct a pilot study examining the effectiveness of intranasal (IN) ketamine as an analgesic for children in the ED. The present study used an observational study on a convenience sample of paediatric ED patients aged 3-13 years, with moderate to severe (≥6/10) pain from isolated limb injury. IN ketamine was administered at enrolment, with a supplementary dose after 15 min, if required. Primary outcome was change in median pain rating at 30 min. Secondary outcomes included change in median pain rating at 60 min, patient/parent satisfaction, need for additional analgesia and adverse events being reported. For the 28 children included in the primary analysis, median age was 9 years (interquartile range [IQR] 6-10). Twenty-three (82.1%) were male. Eighteen (64%) received only one dose of IN ketamine (mean dose 0.84 mg/kg), whereas 10 (36%) required a second dose at 15 min (mean for second dose 0.54 mg/kg). The total mean dose for all patients was 1.0 mg/kg (95% CI: 0.92-1.14). The median pain rating decreased from 74.5 mm (IQR 60-85) to 30 mm (IQR 12-51.5) at 30 min (P < 0.001, Mann-Whitney). For the 24 children who contributed data at 60 min, the median pain rating was 25 mm (IQR 4-44). Twenty (83%) subjects were satisfied with their analgesia. Eight (33%) were given additional opioid analgesia and the 28 reported adverse events were all transient and mild. In this population, an average dose of 1.0 mg/kg IN ketamine provided adequate analgesia by 30 min for most patients.


Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions.
Background and aim The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.


Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins.
Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then ∼5μM (IC50) were further analyzed and showed to induce apoptotic cell death and SubG1 cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggered oxidative stress induced apoptosis through ASK-1 protein activation and Akt protein inhibition as demonstrated by downstream targets such as GSK3β, β-catenin and cyclin D1. QSAR and molecular docking models provide insight into the mechanism of inhibition and indicate the optimal direction of future synthetic efforts. Furthermore, molecular docking results were confirmed with in vitro COX bioactivity studies. This study demonstrates that the novel triazolothiadiazine derivatives are promising drug candidates for epithelial cancers, especially liver cancer.


Cholesterol-lowering with statins: are they all the same? Summary of the expert symposium at the 53rd Annual Scientific Sessions of the American College of Cardiology.
Since they share a common mode of action and certain structural features, all statins exhibit the same broad pharmacological effects. Nevertheless, important differences exist between the statins in terms of LDL cholesterol-lowering, endpoint reduction, pleiotropic effects and toxicity. For this reason, it is incorrect to view all statins as being interchangeable as lipid-lowering therapy. In addition, it should be remembered that perhaps the main difficulty in clinical practice today does not concern details of the differences between statins but rather the fact that in many studies long-term compliance has been shown to be only around 30%.


[Possibilities of prophylaxis of the induced "suture" astigmatism in cataract extraction].
Due to a number of reasons, the traditional methods of cataract extraction, i.e. through 8-12 mm limbic incisions, are still widely used in the clinical practice. A frequent occurrence of a high postoperative astigmatism, even if the operation is successful, is the main shortcoming of different variations of the traditional method of cataract extraction. Possibilities of how to neutralize the induced "suture-like" corneal astigmatism were investigated in this study by using two methods: A. a modified technique of applying a continuous corneal Pirs' suture with elements of an accentuated impact in the projection of the horizontal meridian. B. Meridian keratorraphia--application, in the cornea, of an additional compensatory suture in the projection of the horizontal meridian. Studies were made in two groups of patients after extracapsular cataract extraction (ECE) with intraocular lens (IOL) implantation--a total of 30 patients, 30 eyes. The main group was divided into two subgroups--A and B--(10 patients and 10 eye in each) in accordance with a used method of compensating the induced astigmatism. 10 patients were in the control group. A comparative evaluation of changes of a degree of the original astigmatism, which occurred under the influence of the sealing suture, showed that the parameters of induced astigmatism in the control group essentially and reliably (p < 0.001) exceeded the similar parameters registered in both subgroups of the main group; finally, the efficiency of method B in respect to neutralizing the "suture" astigmatism out did the possibilities of method A (p < 0.01).


Fabrication of zero contact angle ultra-super hydrophilic surfaces.
Zero contact angle surfaces have been created with the combined effect of nanostructure and UV illumination. The contact angle of titanium surface has been optimized to 3.25°±1°. with nanotubular structures through electrochemical surface modification. The porosity and surface energy of tubular TiO2 layer play critical role over the surface wettability and the hydrophilicity of the surface. The surface free energy has been enhanced from 23.72mJ/m2 (bare titanium surface) to 87.11mJ/m2 (nanotubular surface). Similar surface with TiO2 nanoparticles coating shows superhydrophilicity with contact angle up to 5.63°±0.95°. This implies liquid imbibition and surface curvature play a crucial role in surface hydrophilicity. The contact angle has been further reduced to 0°±0.86° by illuminating the surface with UV radiation. Results shows that by tuning the nanotube morphology, highly porous surfaces can be fabricated to reduce contact angle and enhance wettability. This study provides an insight into the inter-relationship between surface structural factors and ultra-superhydrophilic surfaces which can help to optimize thermal hydraulic and self cleaning surfaces.


Investigation of space flight effects on Escherichia coli and a proposed model of underlying physical mechanisms.
Previous investigations have reported that space flight may produce a stimulating effect on microbial metabolism; however, the specific underlying mechanisms associated with the observed changes have not yet been identified. In an effort to systematically evaluate the effect of space flight on each phase of microbial growth (lag, exponential and stationary), a series of experiments was carried out using in vitro suspension cultures of Escherichia coli aboard seven US Space Shuttle missions. The results indicated that, as a result of space flight, the lag phase was shortened, the duration of exponential growth was increased, and the final cell population density was approximately doubled. A model was derived from these cumulative data in an attempt t associate gravity-dependent, extracellular transport phenomena with unique changes observed in each specific phase of growth. It is suggested that a cumulative effect of gravity may have a significant impact on suspended cells via their fluid environment, where an immediate, direct influence of gravity might otherwise be deemed negligible.


Characterization of the protein binding of chiral drugs by high-performance affinity chromatography. Interactions of R- and S-ibuprofen with human serum albumin.
Zonal elution and high-performance affinity chromatography were used to study the different binding characteristics of R- and S-ibuprofen with the protein human serum albumin (HSA). This was done by injecting small amounts of R- and S-ibuprofen onto an immobilized HSA column in the presence of a mobile phase that contained a known concentration of R- or S-ibuprofen as a competing agent. These studies indicated that R- and S-ibuprofen had one common binding site on the immobilized HSA column. In addition, S-ibuprofen had at least one other major binding region. The association equilibrium constant for R-ibuprofen with HSA was found to be 5.3 x 10(5) M-1 at pH 6.9 and 25 degrees C. Under the same conditions, the association constants for S-ibuprofen at its two sites were 1.1 x 10(5) M-1 and 1.2 x 10(5) M-1. The S-ibuprofen sites were present in about a 1:1 ratio and appeared to exhibit some allosteric interactions at high S-ibuprofen concentrations. The chromatographic technique used in this work is a general one which can be adapted for use in studying the interactions of other chiral compounds with either HSA or additional proteins.