Seasonal trends in depressive problems among United States children and adolescents: a representative population survey.
This study examined season-of-assessment differences in parent and child reports of depressive problems on well-validated instruments in 2009 U.S. children and adolescents, aged 6 to 18 years, from a nationally representative population survey. A parent completed the Child Behavior Checklist (CBCL) for each participant and 1226 of the 11-18-year-olds completed the Youth Self-Report (YSR). Outcome measures were CBCL and YSR withdrawn/depressed syndrome scale scores and rates of clinically elevated scores. Overall fall/winter versus spring/summer differences were not found on the CBCL or YSR for depressive problem severity or rates of depressive problems. Age, sex, and latitude were examined as potential moderators of the association between season-of-assessment and the outcomes. Of these, the effect of season-of-assessment on CBCL depressive problem severity depended upon age. Parents of 16-18-year-old adolescents rated depressive problems as significantly more severe in fall and winter than in spring and summer. Parents also rated depressive problems as significantly more severe in 16-18-year-olds than in 6-15-year-olds, but only when assessed in the fall and winter. There were no season-of-assessment differences among 6-15-year-old children and adolescents. The overall lack of season-of-assessment differences and the finding of age as a moderator on only one of four outcomes suggest minimal seasonality effects.


Pain Reduction After Laser Acupuncture Treatment in Geriatric Patients with Knee Osteoarthritis: a Randomized Controlled Trial.
to compare the effectiveness of active laser acupuncture with placebo on reducing pain intensity and improving functional outcome in geriatric patients with knee osteoarthritis (OA). a double-blind randomized controlled trial was conducted in geriatrics with knee OA at Medical Acupuncture Outpatient Clinic, Integrated Geriatric Outpatient Clinic, Rheumatology Outpatient Clinic of Cipto Mangunkusumo Hospital, Jakarta, during May to October 2015. Sixty two patients with knee OA were randomly assigned into two groups: active laser acupuncture group or placebo laser acupuncture group. Interventions were carried out using a gallium aluminum arsenide laser device at the ST35 Dubi, ST36 Zusanli, SP9 Yinlingquan, GB34 Yanglingquan and EX - LE - 4 Neixiyan acupuncture points on the affected knee for ten sessions of treatment, i.e. twice a week. Patients were assessed using a visual analogue scale (VAS) and Lequesne index at baseline, after four sessions, after nine sessions and at 2 weeks after the treatment had been stopped. the VAS scores were significantly improved in the active laser acupuncture group compared to the placebo group. The evaluation of VAS scores was carried out after four treatment sessions (mean difference: 0.39; p<0.001), after nine treatment sessions (mean difference: 37.48; p<0.001) and at 2 weeks post intervention (mean difference: 39.15; p<0.001). The evaluation also showed significant improvement of Lequesne index after four treatment sessions (mean difference: 4.68; p<0.001), after nine treatment sessions (mean difference: 5.90; p<0.001) and at 2 weeks post intervention (mean difference: 6.48; p<0.001). active laser acupuncture is effective in reducing pain.


[Total pancreatectomy for pancreatic malignancy - from history to the present day].
Currently, total pancreatectomy (TP) is indicated in approximately one in ten surgical patients with pancreatic cancer. Key role in the decision falls in the competence of the multidisciplinary team, alternatively of the surgeon in the intraoperative period in some cases. Exceptionally, TP is approached in the so-called salvage surgery. Perioperative mortality of TP as an elective procedure does not exceed that of partial resections; however, mortality of up to 50% is associated with salvage surgery in acute postoperative pancreatitis. Postoperatively, patients are afflicted with the so-called brittle diabetes comparable with type 1 diabetes. The aim of our overview is to inform about the current position of TP in the treatment of malignant pancreatic diseases.Key words: pancreatic cancer - total pancreatectomy - multidisciplinary team.


Breast cancer metastatic to uterine leiomyosarcoma. A case report and review of the literature.
An unusual case of breast cancer metastatic to leiomyosarcoma of the uterus is reported. The patient had multiple metastases from the breast carcinoma and presented a pelvic mass in its evolution. A laparotomy with total hysterectomy and bilateral oophorectomy was performed to give pain relief. A review of the world literature about these uncommon sites of breast metastases is presented.


The importance of employment status in determining exit rates from nursing.
To mitigate nurse shortages, health care decision makers tend to employ retention strategies that assume nurses employed in full-time, part-time, or casual positions and working in different sectors have similar preferences for work. However, this assumption has not been validated in the literature. The relationship between a nurse's propensity to exit the nurse profession in Ontario and employment status was explored by building an extended Cox Proportional Hazards Regression Model using a counting process technique. The differential exit patterns between part-time and casual nurses suggest that the common practice of treating part-time and casual nurses as equivalent is misleading. Health care decision makers should consider nurse retention strategies specifically targeting casual nurses because this segment of the profession is at the greatest risk of leaving. Nurse executives and nurse managers should investigate the different work preferences of part-time and casual nurses to devise tailored rather than "one-size fits all" nurse retention strategies to retain casual nurses.


Occurrence and fate of macrolide antibiotics in wastewater treatment plants and in the Glatt Valley watershed, Switzerland.
An analytical method was developed for determining macrolide antibiotics in treated wastewater effluents and in ambient water based on solid-phase extraction and LC/MS analysis as well as on LC/MS/MS for structural confirmation. In wastewater treatment plants (WWTPs) macrolides are only partly eliminated and can therefore reach the aquatic environment. In treated effluents from three WWTPs in Switzerland, clarithromycin, roxithromycin, and erythromycin-H2O, the main degradation product of erythromycin, were found. The most abundant, clarithromycin, reflects the consumption pattern of macrolide antibiotics. Summer concentrations of clarithromycin varied between 57 and 330 ng/L in treated WWTP effluents. In the WWTP Kloten-Opfikon seasonal differences revealed a load two times higher in winter than in summer. The higher abundance of erythromycin-H2O in the effluent of WWTP Kloten-Opfikon can be explained by distinct consumption patterns due to the main international airport of Switzerland in the catchment area. In the Glatt River clarithromycin reached concentrations of up to 75 ng/L. Mass flux determinations in treated effluents and in river water in the Glatt Valley watershed showed that elimination of clarithromycin along the river stretch of 36 km is insignificant (<20%). Investigations in the Glatt River before and after the diversion of the largest WWTP revealed an observable decrease in clarithromycin loads.


Lecithin:retinol acyltransferase and retinyl ester hydrolase activities are differentially regulated by retinoids and have distinct distributions between hepatocyte and nonparenchymal cell fractions of rat liver.
The cellular distribution of enzymes that esterify retinol and hydrolyze retinyl esters (RE) was studied in liver of vitamin A-sufficient, -deficient, and deficient rats treated with retinoic acid or N-(4-hydroxyphenyl)-retinamide. Livers were perfused and cell fractions enriched in hepatocytes, and nonparenchymal cells were obtained for assays of RE and enzyme activity. The specific activity of lecithin:retinol acyltransferase (LRAT) was approximately 10-fold greater in the nonparenchymal cell than the hepatocyte fraction from both vitamin A-sufficient and retinoid-treated rats. Total RE mass, newly synthesized [3H]RE and LRAT activity were positively correlated in liver and isolated cells of both normal (P < 0.0001) and retinoid-treated rats (P < 0.0002). In nonparenchymal cells, these three constituents were nearly equally enriched as evaluated by their relative specific activity values (RSA, defined as the percentage of recovered activity divided by the percentage of recovered protein), which were each significantly greater than 1.0, with values of 4.3 for total RE mass (P < 0.05), 3.6 for newly synthesized [3H]RE (P < 0.01) and 3.8 for LRAT activity (P < 0.01). In contrast, the specific activities of neutral and acid bile salt-independent retinyl ester hydrolases (REH) did not vary with vitamin A status, and their RSA values were close to 1.0 in both hepatocytes and nonparenchymal cells. These data show that LRAT and REH are differentially regulated by retinoids and that these enzymes also differ in their spacial distribution between liver parenchymal and nonparenchymal cells.


Consequences of oxidative damage and mitochondrial dysfunction on the fatty acid profile of muscle of Indian Major Carps considering metal toxicity.
Current study aims to find interrelation between mitochondrial enzyme function and fatty acid profile in fish muscle and role of antioxidant agents to maintain their balance in response to metal accumulation. Fishes (Labeo rohita, Catla catla, Cirrhinus cirrhosus) were collected from two sites (Nalban Bheri and Diamond Harbour, India). Concentrations of metals (lead, cadmium, copper, nickel, zinc), enzymatic and non-enzymatic antioxidant activity (malondialdehyde, superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione S-transferase), muscle enzyme activity (acetylcholinesterase, succinate dehydrogenase, lactate dehydrogenase, Ca2+ATPase, AMP-deaminase, lipoamide reductase, cytochrome C oxidase, aldolase) and fatty acid composition in muscle tissues were analyzed. Metal concentrations were significantly higher (P < 0.05) in fish muscles from Nalban compared to those in Diamond Harbour. Increased activity of antioxidant enzymes was noted with diminished mitochondrial enzymes activity and altered fatty acid composition in response to higher metal accumulation. Higher metal concentration in fish muscle of Nalban seems to significantly (P < 0.05) affect poly and monounsaturated fatty acid content, possibly due to oxidative damage and accumulation of hazardous reactive oxygen species (ROS) molecules. Changes in fatty acid contents following metal accumulation were observed to be species specific. Current study is the first correlative study to illuminate the level of oxidative damage and possible consequences on muscle cellular integrity, mitochondrial functionality and flesh quality against bioaccumulation of different metals in carps. Future studies are needed to quantify the relative contributions of enzymatic and low-molecular-mass antioxidants in protecting mitochondrial function and maintenance of proper fatty acid oxidation during acclimation to long term metal exposure.


Hydrogen breath test--diet and basal H2 excretion: a technical note.
Hydrogen breath tests are widely used in clinical practice. For a correct evaluation of data, low basal H2 excretion is required, thus, 12-hour fasting is usually prescribed. An additional reduction in the intake of complex carbohydrates in the preceding 24 h is suggested in some centers. The issue, however, has never been directly investigated. The aim of the present study was to analyze the effect of the pretest diet on the basal H2 excretion and the number of subjects excluded from the test due to high basal H2 excretion. Two cohorts of 500 consecutive patients undergoing a lactose tolerance test in the years 1997-1998 (when 12-hour fasting was required) and in 2007-2008 (when a low-carbohydrate diet in the preceding 24 h was also prescribed) were retrospectively reviewed. The mean basal H2 excretion was significantly lower (p < 0.0001) in the low-carbohydrate diet group (2.46 +/- 6.8 vs. 4.73 +/- 3.3 ppm). In 1997-1998, 46/500 patients (9.2%) were excluded from the test due to basal H2 values as compared to 7/500 (1.4%) in the period 2007-2008. To the best of our knowledge, ours is the first study to provide objective data on the advantage offered by reducing the intake of complex carbohydrates before H2 breath tests.


Hollow Au-Cu Nanocomposite for Real-Time Tracing Photothermal/Antiangiogenic Therapy.
High absorption in the near-infrared (NIR) region is essential for a photoabsorbing agents to realize efficient photothermal therapy (PTT) for cancer. Here, a novel hollow Au-Cu nanocomposite (HGCNs) is developed, which displays a significantly enhanced NIR surface plasmon resonance absorption and photothermal transduction efficiency. Besides, fluorescent polymer dots poly(9,9-dioctylfluorene-2,7-diyl-co-benzothiadiazole) (PFBT) and chemotherapeutic mammalian target of rapamycin (mTOR) inhibitor agent rapamycin (RAPA) are attached onto the HGCNs (RAPA/PFBT-HGCNs) for real-time NIR fluorescence tracing and combined PTT/antiangiogenesis therapy. In particular, due to the fluorescence resonance energy transfer effect, RAPA/PFBT-HGCNs can act as NIR-activatable on/off probe system for real-time tracing of tumor tissues. A standard in vitro cellular uptake study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dual-staining study, and flow cytometry assay reveal that the RAPA/PFBT-HGCNs combined with NIR laser exhibit higher drug accumulation and cytotoxicity in both tumor cells and epithelial cells. Moreover, the margins of tumor and normal tissue can be accurately indicated by NIR-stimulated dequenched PFBT after 24 h intravenous administration. Further, tumor growth can be considerably hampered by the optimal formulation plus laser treatment with relatively lower side effects. Consequently, the work highlights the real-time tracing and enhanced PTT/antiangiogenesis therapy prospects of the established HGCNs with tremendous potential for treatment of cancer.


Correlates of disablement in polyarticular juvenile chronic arthritis--a cross-sectional study.
To assess the impact of disease on the functional outcome of patients with polyarticular juvenile chronic arthritis (JCA), the relationship between impairments and functional limitations was studied. Therefore, variables from the impairment domain were correlated with variables of the functional limitation domain and outcome variables were analysed for differences as a result of inflammatory disease, rheumatoid factor (RF), disease duration and age at onset. Twenty-three patients with polyarticular JCA were subjected to auxologic evaluation, a laboratory check, radiographic evaluation, joint count on tenderness and swelling, joint mobility/deformity examination, functional assessment of skills, health assessment and psychosocial evaluation. Inflammatory disease parameters, like CRP, ESR, thrombocytosis and leucocytosis, were increased in 6/23 patients. The parameters of the impairment domain, like joint tenderness and swelling, showed mild outcome, while parameters of the functional limitation domain showed more severe outcome. Generally, perceived competence was found to be normal. A clinically relevant number of patients (10/13) showed low scores on the activity factor of the Child Behaviour Check List (CBCL). A significant relationship was found between inflammatory disease variables and functional limitation outcome. RF seropositivity was not a good outcome predictor. Disease duration and age of onset showed no significant difference in the outcome of the domains. Significant correlation was found between the parental report of the Childhood Health Assessment Questionnaire (CHAQ) and all impairment parameters. Joint swelling showed a significant relationship with CHAQ and Juvenile Arthritis Functional Assessment Report (JAFAR). Disability outcome did not correlate with functional limitation. In general, children with polyarticular JCA function rather well when using a multidomain evaluation approach. Compensatory and adaptational mechanisms might contribute to the poor correlation between impairment and functional limitation parameters. Laboratory evaluation of inflammatory disease, a joint count of swollen joints and parent's report of the child's health status related best in our study.


Orbital nematic order and interplay with magnetism in the two-orbital Hubbard model.
Motivated by the recent angle-resolved photoemission spectroscopy (ARPES) on FeSe and iron pnictide families of iron-based superconductors, we have studied the orbital nematic order and its interplay with antiferromagnetism within the two-orbital Hubbard model. We used random phase approximation (RPA) to calculate the dependence of the orbital and magnetic susceptibilities on the strength of interactions and electron density (doping). To account for strong electron correlations not captured by RPA, we further employed non-perturbative variational cluster approximation (VCA) capable of capturing symmetry broken magnetic and orbitally ordered phases. Both approaches show that the electron and hole doping affect the two orders differently. While hole doping tends to suppress both magnetism and orbital ordering, the electron doping suppresses magnetism faster. Crucially, we find a realistic parameter regime for moderate electron doping that stabilizes orbital nematicity in the absence of long-range antiferromagnetic order. This is reminiscent of the non-magnetic orbital nematic phase observed recently in FeSe and a number of iron pnictide materials and raises the possibility that at least in some cases, the observed electronic nematicity may be primarily due to orbital rather than magnetic fluctuations.


Time-varying predictors for clinical surveillance of small hepatocellular carcinoma.
Prognosis of small hepatocellular carcinoma depends on a constellation of time-varying predictors in association with liver function. We aimed to elucidate the impact of these time-dependent predictors on survival. A total of 108 patients with hepatocellular carcinoma smaller than 5 cm in diameter were recruited. Series of laboratory data and clinical assessments were retrieved from medical records. The time-dependent scoring system for the prediction of death was developed in accordance with a time-dependent Cox regression model. Time trends for biologic predictors parallel cumulative survival of small hepatocellular carcinoma cases. Higher serum alpha-fetoprotein level was identified as the most significant time-dependent predictor. Other significant predictors included aspartate transaminase, bilirubin, alkaline phosphatase, and albumin levels and prothrombin time. Time-dependent surveillance scoring system shows the cutoff points of scores at 6 months, 1 year, 2 years, and 3 years were 42, 21, 19, and 31, respectively; the estimates of sensitivity, 100%, 100%, 100%, and 87.5%, respectively; and the estimates of specificity, 91.26%, 67.02%, 60.27%, and 78.26%, respectively. Predictive validity for this time-dependent Cox regression model, particularly within 1-year of follow-up, is good. The dynamic relationships between time-dependent predictors and risk of death were illustrated. A time-dependent predictive scoring system using these dynamic relationships was developed for real-time surveillance.


Prediction of compensatory hyperhidrosis with botulinum toxin A and local anesthetic.
Compensatory hyperhidrosis (CH) is one of the most problematic complications of sympathectomy, which occurs often and is hard to treat. A predictive procedure (PP) for CH can help patients experience compensatory sweating before sympathectomy to determine whether or not to perform sympathectomy. Our study aimed to evaluate the CH after the PP and sympathectomy in patients with primary palmar hyperhidrosis using multiple drugs. We reviewed 83 patients who underwent a PP between July 2009 and August 2013 with primary palmar hyperhidrosis. In group A, we used levobupivacaine (n = 39). In group B, we used botulinum toxin A plus ropivacaine for the PP in group B (n = 44). The CH rate after the PP was 44 % (group A) and 25 % (group B), and after sympathectomy 80 % (group A) and 75 % (group B). The prediction value between the PP and the sympathectomy was statistically significant in group A (p < 0.05). The positive prediction rate was 73 % and the negative prediction rate was 27 % in group A. Local anesthetic alone has a better predictive value. From our finding, patients should be made aware that CH after sympathectomy is less severe in 73 % of cases than that experienced in the PP.


Interleukin-1-mediated PGE2 production and sphingomyelin metabolism. Evidence for the regulation of cyclooxygenase gene expression by sphingosine and ceramide.
We recently demonstrated that sphingosine enhances interleukin-1 beta (IL-1)-mediated prostaglandin E2 (PGE2) production in human dermal fibroblasts (Ballou, L. R., Barker, S. C., Postlethwaite, A. E., and Kang, A. H. (1990) J. Immunol. 145, 4245-4251). Because sphingosine and ceramide are interconvertable, we extended previous studies by treating cells with C2-ceramide (C2-cer), a membrane-soluble analogue of ceramide, and found that C2-cer stimulates IL-1-mediated PGE2 production to the same degree as sphingosine. In an effort to elucidate the mechanistic basis by which sphingosine and C2-cer affect PGE2 production, we examined the effect of these molecules on the expression of genes encoding cyclooxygenase (EC 1.14.99.1, Cox) and phospholipase A2 (EC 3.1.1.4, PLA2), the rate-limiting enzymes in PGE2 biosynthesis. We found that sphingosine and C2-cer treatment resulted in an 8-fold induction of Cox mRNA within 1-2 h which declined thereafter; concomitant changes in Cox protein were also observed. In contrast, expression of phospholipase A2 remained unaltered. We also found that IL-1-mediated PGE2 production was dramatically enhanced in cells treated simultaneously with sphingomyelinase which led us to directly test the effect of IL-1 on sphingomyelin turnover. IL-1 treatment induced the hydrolysis of a significant fraction of prelabeled sphingomyelin which was accompanied by increased levels of intracellular ceramide. Taken together, our results suggest that enhanced Cox expression may account for the observed enhancement of IL-1-mediated PGE2 production by sphingosine and C2-cer. These data also suggest that endogenous sphingomyelin metabolites, generated in response to IL-1, may play an important role in IL-1 signal transduction.


Incidence and type of meniscal injury and associated long-term clinical outcomes in dogs treated surgically for cranial cruciate ligament disease.
To evaluate factors related to meniscal pathology and their effect on clinical outcome in dogs treated for cranial cruciate ligament (CCL) disease. Prospective cross-sectional study. Dogs (n = 163) with CCL disease (n = 223 stifles). CCL disease was treated by (1) arthroscopy and TightRope (TR) stabilization; (2) arthroscopy and tibial plateau leveling osteotomy (TPLO); or (3) open arthrotomy and TPLO. Incidences of concurrent and subsequent meniscal tears, meniscal treatments, mid-(6 months) and long-(>1 year) term outcomes by owner assessment were compared among surgical treatment groups. Concurrent meniscal tears were diagnosed in 83% of stifles assessed by arthroscopy and 44% of stifles assessed by arthrotomy, with concurrent tear diagnosis being 1.9 times more likely by arthroscopy than arthrotomy (P < .001). Incidence of diagnosis of subsequent meniscal tears was 6.7% with median time to diagnosis of 5.8 months. Differences in proportion of subsequent meniscal tears among treatment groups were not significant (P = .69). Subsequent meniscal tears were diagnosed in 21% of cases without concurrent meniscal tears, but only 1.3% of cases with concurrent meniscal tears (P < .001). Cases treated with meniscal release did not have subsequent meniscal tears, whereas dogs not treated with meniscal release had a subsequent meniscal tear rate of 11% (P = .0013). Cases diagnosed and treated for concurrent meniscal tears were 1.3 times more likely to have a successful long-term outcome (P = .007). CCL surgical technique did not affect subsequent meniscal tear rate or mid-term or long-term functional outcomes, whereas diagnosis and treatment of concurrent meniscal tears did significantly affect both.


A novel glucanotransferase from a Bacillus circulans strain that produces a cyclomaltopentaose cyclized by an alpha-1,6-linkage.
A novel glucanotransferase, involved in the synthesis of a cyclomaltopentaose cyclized by an alpha-1,6-linkage [ICG5; cyclo-{-->6)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->}], from starch, was purified to homogeneity from the culture supernatant of Bacillus circulans AM7. The pI was estimated to be 7.5. The molecular mass of the enzyme was estimated to be 184 kDa by gel filtration and 106 kDa by SDS-PAGE. These results suggest that the enzyme forms a dimer structure. It was most active at pH 4.5 to 8.0 at 50 degrees C, and stable from pH 4.5 to 9.0 at up to 35 degrees C. The addition of 1 mM Ca(2+) enhanced the thermal stability of the enzyme up to 40 degrees C. It acted on maltooligosaccharides that have degrees of polymerization of 3 or more, amylose, and soluble starch, to produce ICG5 by an intramolecular alpha-1,6-glycosyl transfer reaction. It also catalyzed the transfer of part of a linear oligosaccharide to another oligosaccharide by an intermolecular alpha-1,4-glycosyl transfer reaction. Thus the ICG5-forming enzyme was found to be a novel glucanotransferase. We propose isocyclomaltooligosaccharide glucanotransferase (IGTase) as the trivial name of this enzyme.


[Gastroesophageal reflux update].
Authors describe importance of anatomical and functional factors in ethiopatogenesis of G.E.R., diagnostic iter and methods. Importance of 24-hour computerized pH-metry in pediatric age is particularly stressed out. Medical and surgical therapeutic procedures are emphasized.


Bone and cartilage repair by transplantation of induced pluripotent stem cells in murine joint defect model.
The establishment of cartilage regenerative medicine has been an important issue in the clinical field, because cartilage has the poor ability of self-repair. Currently, tissue engineering using autologous chondrocytes has risen, but we should investigate more appropriate cell sources that can be obtained without any quantitative limitation. In this study, we focused on induced pluripotent stem (iPS) cells, in which the ethical hurdle does not seem higher than that of embryonic stem cells. Mouse iPS cells were transplanted into the mouse joint defect model of the knee. Strains of the transplants and hosts were arranged to be either closest (homology 75% in genetic background) or identical (100%). For transplantation, we embedded the iPS cells within the collagen hydrogel in order to obtain the effective administration of the cells into defects, which induced the differentiation of the iPS cells. At 8 weeks of transplantation, although the iPS cells with a 75% homology to the host in the genetic background tended to form teratoma, those of 100% showed a joint regeneration. GFP immunohistochemistry proved that the transplanted iPS cells were responsible for the bone and cartilage repair. Taking these results together, the iPS cells are regarded as a promising cell source for the cartilage tissue engineering.


Naltrexone and disulfiram in patients with alcohol dependence and comorbid post-traumatic stress disorder.
Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, the effect of these medications on alcohol use outcomes and on psychiatric symptoms is still unknown in patients with co-occurring disorders post-traumatic stress disorder (PTSD). Patients (n = 254) with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in a medication study at three Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram; and (2) double-blind randomization to naltrexone or placebo. This resulted in four groups: (1) naltrexone alone; (2) placebo alone; (3) disulfiram and naltrexone; or (4) disulfiram and placebo. Outcomes were measures of alcohol use, PTSD symptoms, alcohol craving, GGT levels and adverse events. 93 individuals (36.6%) met DSM-IV criteria for PTSD. Subjects with PTSD had better alcohol outcomes with active medication (naltrexone, disulfiram or the combination) than they did on placebo; overall psychiatric symptoms of PTSD improved. Individuals with PTSD were more likely to report some side effects when treated with the combination. The results of this study suggest that disulfiram and naltrexone are effective and safe for individuals with PTSD and comorbid alcohol dependence.


Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials.
A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis.


Overview of surfactant replacement trials.
Clinical trials have evaluated the overall efficacy of surfactant therapy, as well as the relative efficacy of different surfactant preparations, the optimal timing of administration and the optimal dosage. Surfactant therapy leads to significant clinical improvement in infants at risk for, or having, respiratory distress syndrome (RDS). Clinical trials that compared the effects of synthetic or animal-derived surfactant preparations to placebo or no therapy demonstrate that surfactant therapy lead to rapid improvement in oxygenation, decreased ventilator support, decreased risk of pneumothorax, and mortality. Earlier treatment, prophylactic treatment of infants at high risk of developing RDS, and selective re-treatment leads to improved clinical outcome as well. Currently available animal-derived surfactants are superior to non-protein-containing synthetic surfactants. Ongoing evaluation will determine if important differences in animal-derived products are noted. Future trials will evaluate third-generation surfactant products and further refine what constitutes optimal use of surfactant.


Genome wide identification and characterization of microsatellite markers in black pepper (Piper nigrum): A valuable resource for boosting genomics applications.
Black pepper is one of the most valued and widely used spices in the world and dominates multi-billion dollar global spices trade. India is amongst the major producers, consumers and exporters of black pepper. In spite of its commercial and cultural importance, black pepper has received meagre attention in terms of generation of genomic resources. Availability of markers distributed throughout the genome would facilitate and accelerate genetic studies, QTL identification, genetic enhancement and crop improvement in black pepper. In this perspective, the sequence information from the recently sequenced black pepper (Piper nigrum) genome has been used for identification and characterisation of Simple Sequence Repeats (SSRs). Total 69,126 SSRs were identified from assembled genomic sequence of P. nigrum. The SSR frequency was 158 per MB making it, one SSR for every 6.3 kb in the assembled genome. Among the different types of microsatellite repeat motifs, dinucleotides were the most abundant (48.6%), followed by trinucleotide (23.7%) and compound repeats (20.62%). A set of 85 SSRs were used for validation, of which 74 produced amplification products of expected size. Genetic diversity of 30 black pepper accessions using 50 SSRs revealed four distinct clusters. Further, the cross species transferability of the SSRs was checked in nine other Piper species. Out of 50 SSRs used, 19 and 31 SSRs were amplified in nine and seven species, respectively. Thus the identified SSRs may have application in other species of the genus Piper where genome sequence is not available yet. Present study reports the first NGS based genomic SSRs in black pepper and thus constitute a valuable resource for a whole fleet of applications in genetics and plant breeding studies such as genetic map construction, QTL identification, map-based gene cloning, marker-assisted selection and evolutionary studies in Piper nigrum and related species.


Cardiovascular pharmacology of K2P17.1 (TASK-4, TALK-2) two-pore-domain K+ channels.
K2P17.1 (TASK-4, TALK-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. Reduced K2P17.1 expression was found in atria and ventricles of heart failure (HF) patients. Modulation of K2P17.1 currents by antiarrhythmic compounds has not been comprehensively studied to date. The objective of this study was to investigate acute effects of clinically relevant antiarrhythmic drugs on human K2P17.1 channels to provide a more complete picture of K2P17.1 electropharmacology. Whole-cell patch clamp and two-electrode voltage clamp electrophysiology was employed to study human K2P17.1 channel pharmacology. K2P17.1 channels expressed in Xenopus laevis oocytes were screened for sensitivity to antiarrhythmic drugs, revealing significant activation by propafenone (+ 296%; 100 μM), quinidine (+ 58%; 100 μM), mexiletine (+ 21%; 100 μM), propranolol (+ 139%; 100 μM), and metoprolol (+ 17%; 100 μM) within 60 min. In addition, the currents were inhibited by amiodarone (- 13%; 100 μM), sotalol (- 10%; 100 μM), verapamil (- 21%; 100 μM), and ranolazine (- 8%; 100 μM). K2P17.1 channels were not significantly affected by ajmaline and carvedilol. Concentration-dependent K2P17.1 activation by propafenone was characterized in more detail. The onset of activation was fast, and current-voltage relationships were not modulated by propafenone. K2P17.1 activation was confirmed in mammalian Chinese hamster ovary cells, revealing 7.8-fold current increase by 100 μM propafenone. Human K2P17.1 channels were sensitive to multiple antiarrhythmic drugs. Differential pharmacological regulation of repolarizing K2P17.1 background K+ channels may be employed for personalized antiarrhythmic therapy.


Do lunar phases influence menstruation? A year-long retrospective study.
We assessed with cross-approximate entropy menstruation onset versus moon phases in 74 women with 980 menstrual cycles over a calendar year. In defiance of traditional beliefs and contrary to what some researchers have argued with short-term research work, in this long-term study we did not find any synchrony of lunar phases with the menstrual cycle.


Structural model of the phospholamban ion channel complex in phospholipid membranes.
Phospholamban is a 52 amino acid residue membrane protein involved with the regulation of calcium levels across sarcoplasmic reticulum membranes in cardiac muscle cells. The N-terminal 30 amino acid residues of the protein are largely hydrophilic and include two sites whose phosphorylation is thought to dissociate an inhibitory complex between phospholamban and Ca2+ ATPase. The C-terminal 22 amino acid residues are largely hydrophobic, anchor the protein in the membrane and are responsible for Ca2+ selective ion conductance. Specific interactions between the transmembrane domains stabilize a pentameric protein complex. We have obtained circular dichroism (CD), transmission Fourier transform infrared (FTIR) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectra of the full-length protein and have compared these results to those from a 28 residue peptide that includes the transmembrane domain. Both proteins reconstituted into phospholipid membranes are largely alpha-helical by CD and FTIR. Polarized ATR-FTIR measurements show that both the cytosolic and transmembrane helices are oriented perpendicular to the membrane plane with a tilt of 28 (+/- 6) degrees with respect to the membrane normal. This tilt angle is in close agreement to that calculated from a model for the transmembrane domain of phospholamban suggested by mutagenesis and molecular modeling. Phosphorylation does not significantly change the secondary structure or orientation of the protein. The pentameric complex is modeled as a left-handed coiled-coil of five long helices (40 (+/- 3) residues) that extend across the membrane from the lumenal carboxy terminus to the phosphorylation site in the cytoplasm. The helix bundle forms a perpendicular ion pore that may begin at a distance (17 to 29 A) from the membrane surface. Based on the above, we propose a mechanism by which phospholamban regulates Ca2+ levels across membranes that takes into account both its selective ion conductance and inhibitory association with the Ca2+ pump.


[Total knee arthroplasty in hemophilic arthropathy].
The case of a bilateral total knee arthroplasty in a hemophiliac patient is presented below. Postoperative blood loss, required factor substitution, complications after surgery were observed. Functional results were evaluated using the Hospital for Special Surgery Score. The pathophysiology of hemophilic arthropathy is reviewed also. The arthroplasties were performed using factor substitution and a tourniquet, posterior stabilized prosthesis was implanted on both sides. The average postoperative blood-loss was 700 ml. After the first procedure hemarthrosis occurred, other complications were not observed. Follow-up time was 164 weeks in the first case and 112 in the second. The average improvement in Hospital for Special Surgery Score was 34 points reaching 97,5 points postoperatively. Range of movement was 0-120 degrees on the right and 0-135 degrees on the left side. The authors emphasize the importance of the adequate hematological and anaesthetical background when performing surgery in a hemophiliac patient.


Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.
In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.


Surgicopathological Quality Control and Protocol Adherence to Lymphadenectomy in the CRITICS Gastric Cancer Trial.
The purpose of this study was to evaluate surgicopathological quality and protocol adherence for lymphadenectomy in the CRITICS trial. Surgical quality assurance is a key element in multimodal studies for gastric cancer. In the multicenter CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients with resectable gastric cancer were randomized for preoperative chemotherapy, followed by gastrectomy with a D1+ lymphadenectomy (removal of stations 1 to 9 and 11), followed by either chemotherapy or chemoradiotherapy. Surgicopathological compliance was defined as removal of ≥15 lymph nodes. Surgical compliance was defined as removal of the indicated lymph node stations. Surgical contamination was defined as removal of lymph node stations that should be left in situ. The Maruyama Index (MI, lower is better), which has proven to be an indicator of surgical quality and is strongly associated with survival, was analyzed. Between 2007 and 2015, 788 patients were randomized, of whom 636 patients underwent a gastrectomy with curative intent. Surgicopathological compliance occurred in 72.8% (n = 460) of the patients and improved from 55.0% (2007) to 90.0% (2015). Surgical compliance occurred in 41.1% (n = 256). Surgical contamination occurred in 59.6% (n = 371). Median MI was 1 (range 0 to 136). Surgical quality in the CRITICS trial was excellent, with a MI of 1. Surgicopathological compliance improved over the years. This might be explained by the quality assurance program within the study and centralization of gastric cancer surgery in the Netherlands.


Radon emanation from low-grade uranium ore.
Estimation of radon emanation in uranium mines is given top priority to minimize the risk of inhalation exposure due to short-lived radon progeny. This paper describes the radon emanation studies conducted in the laboratory as well as inside an operating underground uranium mine at Jaduguda, India. Some of the important parameters, such as grade/(226)Ra activity, moisture content, bulk density, porosity and emanation fraction of ore, governing the migration of radon through the ore were determined. Emanation from the ore samples in terms of emanation rate and emanation fraction was measured in the laboratory under airtight condition in glass jar. The in situ radon emanation rate inside the mine was measured from drill holes made in the ore body. The in situ(222)Rn emanation rate from the mine walls varied in the range of 0.22-51.84 × 10(-3) Bq m(-2) s(-1) with the geometric mean of 8.68 × 10(-3) Bq m(-2) s(-1). A significant positive linear correlation (r = 0.99, p < 0.001) between in situ(222)Rn emanation rate and the ore grade was observed. The emanation fraction of the ore samples, which varied in the range of 0.004-0.089 with mean value of 0.025 ± 0.02, showed poor correlation with ore grade and porosity. Empirical relationships between radon emanation rate and the ore grade/(226)Ra were also established for quick prediction of radon emanation rate from the ore body.


Cardiomyopathy Caused by Antineoplastic Therapies.
The goals of care for patients at risk for cardiomyopathy induced by cancer treatment should include prevention, early diagnosis, treatment of subclinical cardiac dysfunction, prevention of disease progression, and prolongation of patient survival. Any strategy aimed to minimize the cardiotoxic effects of cancer treatment should maintain the treatment's antineoplastic efficacy. Successful therapy achieves the highest health-related quality of life that is defined by the balance between maximizing the efficacy of oncologic therapy and minimizing the toxicity of this therapy. Doxorubicin-induced cardiotoxicity can be reduced by limiting the overall cumulative dose. There is no specific treatment for cancer therapy-related cardiomyopathy, and symptomatic patients should receive standard treatments for congestive heart failure such as afterload reduction, beta-blockers, diuresis, and digoxin. Afterload reduction with angiotensin-converting enzyme inhibitors such as enalapril and captopril may be indicated in patients with elevated afterload and asymptomatic left ventricular dysfunction diagnosed by echocardiography. Beta-blockers may improve myocardial systolic dysfunction and may be useful in the treatment of cancer treatment-induced cardiomyopathy. Cardiac transplantation remains a viable option in patients with cancer treatment-induced end-stage heart disease.


[Eye tracking disorders in schizophrenic patients and their parents].
Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia. Ocular pursuit disorders, in particular, could be one of those vulnerability markers. Eye movements have been often tested in schizophrenia. Most of the schizophrenic patients have eye-tracking disorders and their biological relatives demonstrate an increased prevalence of eye-tracking impairments. The aim of the study was to research if smooth pursuit eye movements could be a vulnerability marker of schizophrenia. In order to have an indication about this hypothesis, impairments of smooth pursuit eye movements were researched in both schizophrenics and their parents. Fifteen DSM IV schizophrenic patients stabilized at the time of the inclusion and not treated with lithium, benzodiazepines, barbiturates, or chloral hydrate; 19 parents without history of schizophrenic spectrum disorders (SADSLA and IPDE), and 2 groups of healthy subjects matched in age and sex with probands and with the parents, were included in the study. Parents only were included (fathers or mothers) in order to have an homogeneous population for the genetic risk and age. The eye-tracking paradigm used was a smooth pursuit task. The stimulus was a sinusoidal wave form moving on a horizontal line, with a frequency of 0.4 Hz and an amplitude of 30 degrees. Different parameters were measured: gain (ratio between the eye velocity and the target velocity) and saccades frequencies (catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks). For each parameter, analysis of covariance (ANCOVA) with age as covariable was carried out. For the results reaching the significance of 0.05, the Bonferroni correction was applied (level of significance 0.016). The effect size of the parameter was calculated ((the mean of the subjects minus the mean of the matched controls) divided by standard deviation of the two groups). According to Cohen, 0.20 indicates a small effect size, 0.50 indicates a medium effect size and 0.80 indicates a large effect size. Comparison between patients and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between patients and their matched controls. The size effects are 0.31 for the global gain, 0.20 for the movements to the left and 0.41 for the movements to the right. The frequencies of total saccades, catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks did not differ significantly between patients and their controls. The size effects for those parameters were 0.09, 0.03, 0.00, 0.39 and 0.63 respectively. Comparison between parents and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between the two groups. The size effects for those parameters were 0.00, 0.05 and 0.17 respectively. The frequency of total saccades did not differ significantly between the groups whereas the size effect was 0.63. The frequency of catch-up saccades was significantly more important in parents than in controls (p = 0.006) and the size effect was 0.80. The other saccadic parameters did not differ significantly between groups, their size effects were 0.24 for the back-up saccades, 0.21 for the anticipatory saccades and 0.00 for the square-wave-jerks. Whereas the gain of the patients had a tendency to be lower than the gain of their controls, no significant difference was observed between patients and their controls. Only a size effect of 0.63 for the frequency of square-wave-jerks was obtained. This large effect size suggests that the difference between patients and controls might be significant in a larger sample. The catch-up saccades frequency between parents and controls was significant. The differences between our study and the previous studies could be due to several factors. The paradigms used were different between the studies and our sample was small (only 15 patients and 19 relatives). Moreover, some patients in the previous studies were treated by lithium, drug well known to modify ocular pursuit and, finally the relatives in the other studies were 10 years older than ours and age is known to alter ocular pursuit. Since an impairment of the smooth pursuit was observed in the relatives of schizophrenic patients but not in the probands, this study does not support the hypothesis that eye-tracking disorders could be considered as a marker of vulnerability of schizophrenia.


Cholecystokinin blocks some effects of kainic acid in CA3 region of hippocampal slices.
We investigated the relationship between the effects of cholecystokinin (CCK) and kainic acid (KA) in the CA3 region of hippocampal slices from rats. As has been reported previously, KA in nanomolar concentrations caused spontaneous epileptiform discharges (bursts) and an excitatory shift of the input/output (I/O) curve. CCK octapeptide (100-200 nM) applied alone had no effect on spontaneous activity or I/O curves. Pretreatment of slices with sulfated CCK blocked the effect of KA on synaptic transmission, but had no effect on KA-induced bursting. Pretreatment with nonsulfated CCK had no effect.


Computed tomography findings for a gastric lymphoepithelioma-like carcinoma: How often does it present as a submucosal mass?
To describe the anatomical location, size, tumour characteristics and morphology on CT of gastric lymphoepithelioma-like carcinoma (LELC) in order to determine the proportion of lesions that present as submucosal masses, and to review the clinicopathological findings. This retrospective study reviewed CT images of 186 lesions from 178 patients with LELC. CT morphologies and other findings were also analyzed. Pathology and medical records were reviewed. A pathology slide review of the lesions that presented with submucosal masses was performed. Gastric LELC presenting as a submucosal mass was found in 9.1 %. The most common CT morphology was eccentric wall thickening (67.7 %). On the pathology review, 14/17 submucosal mass lesions (82.4 %) had a central ulceration. 105 lesions were T1/T2 stage (94.1 %), and N0 stage was diagnosed in 66.1 %. Fifty-six of 63 metastatic lymph nodes (LNs) (88.9 %) demonstrated homogeneous enhancement, regardless of size. Male predominance (85.4 %), upper stomach location (45.7 %) and multiplicity (4.5 %) were found. Gastric LELC presenting as a submucosal mass is only detected in a small portion of all patients, and the most common finding is eccentric wall thickening. Central ulceration and enlarged LNs with homogeneous enhancement are occasionally other features on CT. • LELCs as submucosal masses on CT were detected in only 9.1 %. • The most common CT finding was eccentric wall thickening (67.7 %). • Central ulceration and enlarged LNs with homogeneous enhancement might be seen.


[Iatrogenic injury of the esophagus].
The author describes four patients treated in 1988 on account of iatrogenic oesophageal injury during diagnostic endoscopy. Twice the cervical portion of the oesophagus was perforated, once the lower thoracic portion and once subperitoneal perforation in hiatus hernia was involved. The latter was manifested only by a major pneumomediastinum and emphysema of the neck and face, while contrast examination of the oesophagus and stomach did not suggest perforation and recovery was achieved by conservative treatment. In the remaining three patients surgical revision and suture were performed and complete recovery was achieved, twice without complications after a hospitalization of 14 and 18 days and once the course was complicated by an abscess in the mediastinum. Its treatment called for repeated drainage and a total hospitalization period of 57 days. Finally the author emphasizes that early diagnosis of this serious complication and subsequent early treatment (with the exception of one female patient the others were treated within six hours after the injury) may get the patient over this complication without serious damage.


Risk of acquisition of genital herpes simplex virus type 2 in sex partners of persons with genital herpes: a prospective couple study.
In a prospective study of factors associated with genital herpes simplex virus (HSV) type 2 transmission in couples in whom 1 partner had clinical genital HSV and the other did not, 11 (19%) of the 57 history-negative partners had HSV-2 antibody by Western blot at entry. In follow-up (mean, 16 months) of 29 HSV-2-seronegative partners, overall 4 (14%) seroconverted compared with 3 (23%) of 13 HSV-1- and -2-seronegative partners and 1 (6%) of 16 HSV-1-seropositive partners. Since all seroconverters were women, the risk of transmission may be higher in HSV-seronegative women. No significant differences were found between HSV-2-seronegative partners and seroconverters regarding duration of relationships, number of partner recurrences, intercourse frequency, or contraceptive method. However, 2 seroconverters were exposed to lesions without barrier contraception. This study suggests that infection is commonly asymptomatic and that although the overall risk of genital HSV transmission in couples is low (10%/year), the risk may be significantly increased in women and in seronegative individuals.


Extraction and characterization of vascular bundle and fiber strand from date palm rachis as potential bio-reinforcement in composite.
Date palm rachis fibers are rich in cellulose, relatively inexpensive, and readily available in Algeria. The aim of this study is to investigate the morphology, structure, mechanical and physicochemical characteristics of both vascular bundles and fiber strands extracted from date palm rachis. The difficulties encountered are associated to the extraction of the fibers without damaging them. The study focuses on the morphological and surface roughness analysis using optical and scanning electron microscopies (SEM), and a non-contact 3D profiler. The chemical, physical and thermal properties have been studied using Fourier-transform infrared (FTIR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). The mechanical properties were accessed by tensile tests and they were analyzed using two-parameter Weibull distribution.


Apoptosis in chicken embryos induced by the infectious bursal disease virus.
Fifteen-day-old fertile eggs (specific pathogen-free) were inoculated with the infectious bursal disease virus (IBDV) by the allantoic route and were opened and examined 2, 4 or 6 days later. The bursas of Fabricius (BFs) were collected and processed for DNA extraction, flow cytometry, and light and electron microscopy. Cellular DNA was subjected to electrophoresis on 1.5% agarose gel and stained with ethidium bromide. Intense internucleosomal DNA fragmentation was detected in IBDV-infected bursas. Cytograms from cell suspensions derived from infected BFs displayed an increased population of cells with either high density and small size (apoptotic cells) or small size and high uptake of ethidium bromide (necrotic cells). Light and electron microscopical examination of the IBDV-infected BFs revealed death of lymphoid cells without surrounding inflammatory reaction, but with condensation of nuclear chromatin, crescent formation, and nuclear and cellular fragmentation. These data indicated that infection of chicken embryos with IBDV induced apoptosis in bursal lymphoid cells.


Increasing use of third-generation cephalosporins for pneumonia in the emergency department: may some prescriptions be avoided?
Third-generation cephalosporins are used to treat inpatients with community-acquired pneumonia. Some of these prescriptions may be avoided, i.e. replaced by agents less likely to promote ESBL-mediated resistance. Our objectives were to assess the recent trend of third-generation cephalosporins use for pneumonia in the emergency department, and the proportion of avoidable prescriptions. This was a retrospective study of patients treated for community-acquired pneumonia in an emergency department, and subsequently hospitalized in non ICU wards. Third-generation cephalosporin prescriptions were presumed unavoidable if they met both criteria: (i) age ≥ 65 yr or comorbid condition, and (ii) allergy or intolerance to penicillin, or failure of penicillin first-line therapy, or treatment with penicillin in three previous months. Prescriptions were otherwise deemed avoidable. The proportion of patients treated with a third generation cephalosporin increased significantly from 13.9 % (6.9-24.1 %) in 2002 to 29.5 % (18.5-42.6 %) in 2012 (OR = 1.07 [1.01-1.14] , P = 0.02). This increase was independent from other factors associated with the prescription of a third-generation cephalosporin (immunocompromising condition, antibacterial therapy in three previous months, fluid resuscitation and REA-ICU class). Treatment with third-generation cephalosporin was avoidable in 118 out of 147 patients (80.3 % [72.7-86.2 %]). On day 7 after admission in the ED, treatment with third-generation cephalosporins was stopped or de-escalated in, respectively, 17 % and 32 % of patients. Antibiotic stewardship programs should be implemented to restrict the third-generation cephalosporins use for pneumonia in the emergency department.


Fidelity of aminoacyl-tRNA selection on the ribosome: kinetic and structural mechanisms.
The ribosome discriminates between correct and incorrect aminoacyl-tRNAs (aa-tRNAs), or their complexes with elongation factor Tu (EF-Tu) and GTP, according to the match between anticodon and mRNA codon in the A site. Selection takes place at two stages, prior to GTP hydrolysis (initial selection) and after GTP hydrolysis but before peptide bond formation (proofreading). In part, discrimination results from different rejection rates that are due to different stabilities of the respective codon-anticodon complexes. An important additional contribution is provided by induced fit, in that only correct codon recognition leads to acceleration of rate-limiting rearrangements that precede chemical steps. Recent elucidation of ribosome structures and mutational analyses suggest which residues of the decoding center may be involved in signaling formation of the correct codon-anticodon duplex to the functional centers of the ribosome. In utilizing induced fit for substrate discrimination, the ribosome resembles other nucleic acid-programmed polymerases.


Epigenomics in hematopoietic transplantation: novel treatment strategies.
Allogeneic hematopoietic stem cell transplantation is a high risk but curative treatment option for leukemia, myelodysplasia and other hematological malignancies. After high dose radio- or chemo-therapy, recipient's hematopoiesis is replaced by a new immunosystem and residual malignant cells are eliminated by the graft-versus-leukemia reaction. The benefit of this immunological effect is limited by the most frequent complication of hematopoietic stem cell transplantation: graft-versus-host disease. In addition to their well-known anti-tumor activity, epigenetic drugs mediate immunotolerance without reducing alloreactivity or even enhance graft-versus-leukemia effect without inducing graft-versus-host disease by regulating cytokine release, increasing the circulating number of regulatory T cells and interacting with natural killer cells. We focus on the use of epigenetic drugs in the allogeneic transplantation setting in relation to their anti-tumor and immunomodulatory potential.


Gamma-Hydroxybutyrate content in dried bloodspots facilitates newborn detection of succinic semialdehyde dehydrogenase deficiency.
Increased gamma-hydroxybutyric acid in urine and blood are metabolic hallmarks of succinic semialdehyde dehydrogenase deficiency, a defect of 4-aminobutyric acid metabolism. Here, we examined the hypothesis that succinic semialdehyde dehydrogenase deficiency could be identified via measurement of gamma-hydroxybutyric acid in newborn and post-newborn dried bloodspots. Quantitation of gamma-hydroxybutyric acid using liquid chromatography-tandem mass spectrometry in twelve archival newborn patient dried bloodspots was 360 ± 57 μM (mean, standard error; range 111-767), all values exceeding the previously established cutoff for newborn detection of 78 μΜ established from 2831 dried bloodspots derived from newborns, neonates and children. Gamma-hydroxybutyric acid in post-newborn dried bloodspots (n = 19; ages 0.8-38 years) was 191 ± 65 μM (mean, standard error; range 20-1218), exceeding the aforementioned GHB cutoff for patients approximately 10 years of age or younger. Further, gamma-hydroxybutyric acid in post-newborn dried bloodspots displayed a significant (p < .0001) inverse correlation with age. This preliminary study suggests that succinic semialdehyde dehydrogenase deficiency may be identified in newborn and post-newborn dried bloodspots via quantitation of gamma-hydroxybutyric acid, while forming the platform for more extensive studies in affected and unaffected dried bloodspots.


Caveolin-1 scaffolding domain residue phenylalanine 92 modulates Akt signaling.
Caveolin-1 (Cav-1), the homo-oligomeric coat protein of cholesterol-rich caveolae signalosomes, regulates signaling proteins including endothelial nitric oxide synthase (eNOS). The Cav-1 scaffolding domain (a.a. 82-101) inhibits activated eNOS from producing vascular protective nitric oxide (NO), an enzymatic process involving trafficking and phosphorylation. However, we demonstrated that Cav-1 proteins and peptides bearing F92A substitution (CAV(F92A)) could promote cardioprotective NO, most likely by preventing inhibition of eNOS by Cav-1. Herein, we showed that wild-type CAV sequence could, similar to CAV(F92A), stimulate basal NO release, indicating a need to better characterize the importance of F92 in the regulation of eNOS by Cav-1/CAV. To reduce uptake sequence-associated effects, we conjugated a wild-type CAV derivative (CAV(WT)) or a F92A variant (CAV(F92A)) to antennapedia peptide (AP) or lipophilic myristic acid (Myr) and compared their effect on eNOS regulation in endothelial cells. We observed that both CAV(WT) and CAV(F92A) could increase basal NO release, although F92A substitution potentiates this response. We show that F92A substitution does not influence peptide uptake, endogenous Cav-1 oligomerization status and Cav-1 and eNOS distribution to cholesterol-enriched subcellular fractions. Instead, F92A substitution in CAV(WT) influences Akt activation and downstream eNOS phosphorylation status. Furthermore, we show that the cell permeabilization sequence could alter subcellular localization of endogenous proteins, an unexpected way to target different protein signaling cascades. Taken together, this suggests that we have identified the basis for two different pharmacophores to promote NO release; furthermore, there is a need to better characterize the effect of uptake sequences on the cellular trafficking of pharmacophores.


The cost-effectiveness of alternative strategies against HBV in Italy.
Nowadays, guidelines for the management of HBV infection in Italy, recommend using vaccines but the screening test among non-vaccinated people is useful to detect people that have a clear presence of the virus without symptoms of the disease. Thanks to the screening test, people infected with HBV are administered traditional therapy in order to stop the progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). These diseases cause the decrease of Qol and cause a high consumption of resources for the health system. The aim of this study is to evaluate the cost-effectiveness of a strategy (test strategy) involving the administration of the screening test to patients at risk and the treatment of the infected according to the protocol therapy. This programme is compared with a strategy (no test strategy) which does not include a screening and treats patients affected by cirrhosis or HCC. We created a Markov model following the natural history of the disease and considering the antigen HBeAg to evaluate the cost effectiveness of the test strategy. The analysis was carried out considering a third-party payer perspective. The time horizon considered was 40 cycles of one year. Patients who resulted positive to the test were administered either interferon treatment; or lamivudine or adefovir or entecavir or tenofovir, consistently with the Italian guidelines. Treatments were administered to patients included in the no-test arm after cirrhosis symptoms or HCC. The results of the base case analysis show that patients following the test strategy compared with patients of the no-test approach cost €17,179/QALY. The Monte Carlo simulation based on a probabilistic sensitivity analysis points out that in 95% of the scenarios assumed, the cost per QALY would be under a hypothetical threshold of €40,000 which is the amount that international guidelines for decision makers are likely to consider sustainable for a health system. In conclusion, anti-hbv test to all high-risk categories should be highly recommended.


[Clinical characteristics and gender identity among eating disordered patients subtypes].
Gender identity is a relevant issue in the approach to eating disorders. To compare psychological and behavioural characteristics and traits of gender identity among women with eating disorders and its subtypes and non eating disordered female subjects. An structured clinical interview based on the DSM-IV diagnostic criteria for eating disorders, the EAT-40 (Eating Attitudes Test), the Eating Disorders Inventory (EDI) and the Bem Sex Role Inventory (IBRS) were administered to 58 compulsive-purgative anorectics (AN/BN group), 15 restrictive anorectics (AN group), 33 patients suffering from eating disorder not otherwise identified, 33 purgative bulimics and to 82 female students without eating disorders. Patients with eating disorders ranked significantly higher on the EAT-40 and EDI and all its items (p < 0.001). The AN/BN group ranked significantly higher on the EDI (p < 0.001) and on Drive for thinness, Perfectionism and interpersonal distrust (p < 0.001). The AN group ranked higher on Maturity fears (p < 0.001). The BN group ranged higher on Body dissatisfaction, Ineffectiveness and Interoceptive awareness (p < 0.001). Patients with eating disorders were significantly identified with Feminine category and subjects without eating disorders with Androgynous and Undifferentiated categories on the IBRS (p = 0.002). The AN group showed the highest percentage on Feminine category and the lowest on Androgynous and Undifferentiated categories. All the groups rejected and approved feminine, masculine and neutral qualities. Femininity emerged as the main trait of gender identity in patients suffering from eating disorders, in contrast to androgyny, showed by healthy women.


Sorption of volatile flavor compounds by microcellular cereal starch.
Wheat starch based microcellular foam (MCF) forms of (dry) starch possess a significant percentage of micropores in the range of 5-14 A. The present study confirmed earlier preliminary studies that MCF starch (in a 0.25-1.0 mm diameter bead form) is effective in sorbing and lowering the headspace partial pressure of many volatile compounds in a manner similar (although less efficient) to that exhibited by other microcavity sorbants such as charcoal. It was found that the proportion of polar compounds sorbed was much greater than the proportion of nonpolar compounds. A major portion of the sorbed volatile compound was readily displaced from the MCF microcellular starch by the addition of water. These properties make this form of edible starch a potential useful carrier of flavor compounds for dried foods.


Early elevated neutrophil-to-lymphocyte ratio associated with remote diffusion-weighted imaging lesions in acute intracerebral hemorrhage.
To explore the relationship between the circulating neutrophil-to-lymphocyte ratio (NLR) and the remote diffusion-weighted imaging lesions (R-DWILs) after spontaneous intracerebral hemorrhage (ICH). Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24-48 hours after ICH ictus, while all complete MRI scans were performed at 5-8 days. R-DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri-hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R-DWILs. One hundred sixty-three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R-DWILs. Higher circulating NLR was documented in patients with R-DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R-DWILs (OR = 3.170, 95% CI 1.306-7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH. This study provides significant evidence of the association between circulating NLR and R-DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24-48 hours after ICH ictus should be paid more attention to when evaluating R-DWILs.


Degradation studies of hydrophilic, partially degradable and bioactive cements (HDBCs) incorporating chemically modified starch.
The degradation rate in Hydrophilic, Degradable and Bioactive Cements (HDBCs) containing starch/cellulose acetate blends (SCA) is still low. In order to increase degradation, higher amounts of starch are required to exceed the percolation threshold. In this work, gelatinization, acetylation and methacrylation of corn starch were performed and assessed as candidates to replace SCA in HDBCs. Formulations containing methacrylated starch were prepared with different molar ratios of 2-hydroxyethyl methacrylate and methyl methacrylate in the liquid component and the amount of residual monomer released into water was evaluated. The concentration of reducing sugars, percentage of weight loss and morphologic analyses after degradation all confirmed increased degradation of HDBC with α-amylase, with the appearance of pores and voids from enzymatic action. Methacrylated starch therefore is a better alternative to be used as the solid component of HDBC then SCA, since it leads to the formation of cements with a lower release of toxic monomers and more prone to hydrolytic degradation while keeping the other advantages of HDBCs.


Distribution of immunoreactive relaxin in the genital tract and in the mammary gland of non-pregnant women.
Relaxin was determined in healthy and pathological tissue samples from mammary gland, ovary, myometrium and cervix uteri of non-pregnant women. Relaxin could be detected in all groups of tissues examined. The highest values were found in healthy ovary, the lowest concentrations in the cervix, which is known as a target organ for relaxin activity during pregnancy. Mammary parenchyma showed the highest specific activity of all healthy tissues examined. The relaxin concentration in myoma tissue is significantly higher than in healthy myometrium.


An unusual high-Km hexokinase is expressed in the mhAT3F hepatoma cell line.
In most hepatoma cells, the high-Km GLUT2/glucokinase proteins are replaced by the ubiquitous low-Km GLUT1/hexokinase type I proteins. In the mhAT3F hepatoma cells, the stimulatory effect of glucose on gene expression and glycogen accumulation was not maximal at 5 mmol/liter glucose. This response to high glucose is observed in mhAT3F cells, where GLUT2 was expressed, but not glucokinase (assessed by Northern blotting and reverse transcription-polymerase chain reaction). A low-Km hexokinase activity (19.6 +/- 3.8 milliunits/mg of protein) was present, but a high-Km (40 mmol/liter) hexokinase activity (13.9 +/- 2.5 milliunits/mg) was also detected in mhAT3F cells. The high-Km hexokinase activity was dependent on both ATP (or PPi) and glucose in the assay and was recovered in a 10-50-kDa fraction after filtration. A 30-kDa protein was detected using an anti-glucokinase antibody and localized by confocal microscopy at the same sites as glucokinase in hepatocytes. In FAO cells, the high-Km hexokinase activity and 30-kDa protein were not found. We conclude that a high-Km hexokinase activity is present in mhAT3F cells. This might explain why the effects of glucose on gene expression were not maximal at a glucose concentration of 5 mmol/liter. A 30-kDa protein identified using an anti-glucokinase antibody may be responsible for this activity present in mhAT3F cells.


Interactive and individual effects of dietary non-digestible carbohydrates and oils on DNA damage, SCFA and bacteria in the large bowel of rats.
Dietary non-digestible carbohydrates (NDC) play an important role in large-bowel health and one form of NDC, resistant starch (RS), can promote low levels of DNA damage and other markers of colonic health. The objective of the present study was to determine whether the ability of dietary RS or other NDC to influence colonic health, particularly DNA damage, is dependent on the type of dietary oil. We compared the effects of diets containing 10 % of NDC from cellulose, wheat bran, high-amylose maize starch (HAS, a rich source of RS type 2) or a retrograded HAS (RHAS, a rich source of RS type 3) on DNA damage, SCFA production and bacterial changes in the large bowel of rats. Each carbohydrate source was combined with 10 % fish oil (FO) or Sunola oil (SO; rich in oleic acid). There was a significant interaction between NDC and oil treatments on single-strand DNA breaks in colonocytes isolated from the colon. The damage in rats consuming RHAS was greater for FO consumption than for SO consumption. There was a significant interaction between NDC and oils on caecum weights and treatment effects of NDC and oils were observed for the weights and lengths of other gut tissues. Significant differences were found in colonic SCFA pools and caecal numbers of lactobacilli, bifidobacteria, Escherichia coli and Bacteroides fragilis with the various NDC and oil treatments. The present results demonstrate that the effects of NDC and oils, particularly on colonic DNA damage, can depend on how they are combined within the diet.


Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin.
Patients with severe visual loss because of optic neuritis refractory to high dose corticosteroids have limited therapeutic options. The use of intravenous immunoglobulin (IVIG) has been advocated in the past, but data are scarce. In this study, we use a protocol different from those used in other studies, with different timing and dosage. Consecutive patients with corticosteroid-refractive optic neuropathy were treated with IVIG and compared with control patients who received only corticosteroids in an open-label, non-randomized, controlled prospective study. Twenty-three patients received treatment with IVIG and 24 matched patients who did not receive treatment with IVIG were followed as controls. All patients had visual acuity 20/400 or worse in the affected eye. There was significant improvement in the IVIG group with 18/23 (78%) subjects reaching near normal vision (20/30 or better), compared with the control group with only 3/24 (12.5%) responding similarly. The use of IVIG, following corticosteroids, may be useful using the protocol described herein, with sustained pulsed dosing. A larger controlled trial is indicated to confirm these results.


Control of Viral Latency by Episome Maintenance Proteins.
The human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) share the common property of persisting as multicopy episomes in the nuclei of rapidly dividing host cells. These episomes form the molecular basis for viral latency and are etiologically linked to virus-associated cancers. Episome maintenance requires epigenetic programming to ensure the proper control of viral gene expression, DNA replication, and genome copy number. For these viruses, episome maintenance requires a dedicated virus-encoded episome maintenance protein (EMP), namely LANA (KSHV), EBNA1 (EBV), and E2 (HPV). Here, we review common features of these viral EMPs and discuss recent advances in understanding how they contribute to the epigenetic control of viral episome maintenance during latency.


Risperidone, a risk factor for valproate-induced encephalopathy?
Valproate-induced encephalopathy (ViE) has been increasingly reported and several risk factors have been proposed. We report a case whereby a patient became encephalopathic while treated with valproate and upon initiation of risperidone. The underlying mechanism could be risperidone's interference with valproate's binding to albumin, raising free valproate levels, which would impair the urea cycle and reduce ammonia conversion, leading to a hyperammonemic encephalopathy. The present case suggests a causal link, although further studies will be necessary to establish this. Nevertheless, clinicians should be aware of this possible interaction and consider carefully before concomitant administration of valproate and risperidone, mainly in patients with other risk factors for ViE, so this complication can be avoid or promptly diagnosed and treated.


Epidemiology of Lung Cancer.
Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines.


The operative correction of symptomatic flat foot deformities in children: the relationship between static alignment and dynamic loading.
At our institution surgical correction of symptomatic flat foot deformities in children has been guided by a paradigm in which radiographs and pedobarography are used in the assessment of outcome following treatment. Retrospective review of children with symptomatic flat feet who had undergone surgical correction was performed to assess the outcome and establish the relationship between the static alignment and the dynamic loading of the foot. A total of 17 children (21 feet) were assessed before and after correction of soft-tissue contractures and lateral column lengthening, using standardised radiological and pedobarographic techniques for which normative data were available. We found significantly improved static segmental alignment of the foot, significantly improved mediolateral dimension foot loading, and worsened fore-aft foot loading, following surgical treatment. Only four significant associations were found between radiological measures of static segmental alignment and dynamic loading of the foot. Weakness of the plantar flexors of the ankle was a common post-operative finding. Surgeons should be judicious in the magnitude of lengthening of the plantar flexors that is undertaken and use techniques that minimise subsequent weakening of this muscle group.


Origins of the rabies viruses associated with an outbreak in Newfoundland during 2002-2003.
After being free of rabies of terrestrial mammals since 1988, an outbreak of rabies occurred on the Island of Newfoundland in December 2002 and continued into the middle of 2003. Twenty-one cases, all due to the arctic fox strain of rabies virus, were reported. To explore the immediate origins of this outbreak, viruses from the Newfoundland epizootic were genetically compared to two other rabies viruses recovered in mid-2002 from Cartwright, a mainland coastal community near the Island. While all Island isolates from the 2002-03 outbreak were genetically very similar, consistent with a single introduction from the mainland, they were phylogenetically quite distant from the two samples from Cartwright. A broader-based study examined the relationships between the Island viruses and arctic fox strain viruses originating from across Canada over a period of 14 yr. This analysis indicated that the Newfoundland outbreak viruses were most similar to a variant identified in Labrador in 2004 but also widely distributed in northern Quebec both before and after the Newfoundland incursion. The eastern coastline of mainland Labrador has harbored a particularly large number of variants during the study period, some of which have not been detected elsewhere. A small number of Greenland isolates included in this study were dispersed within the clades of the Canadian samples rather than forming a discrete cluster, an observation that may underline the relative ease of movement of the rabies arctic lineage between these two countries as a result of animal movements over pack ice.


Incidence and prevalence of hyperhidrosis.
Hyperhidrosis is a skin disorder characterized by excessive sweating that often causes significant impairment in social, occupational, and emotional wellbeing. Hyperhidrosis is thought to affect 2.8% of the US population and can be of primary or secondary origin. Primary hyperhidrosis is usually bilateral, symmetric, and focal. The most common focal sites include, but are not limited to, the palms, soles, and axillae. Secondary hyperhidrosis is usually caused by an underlying medical condition or medication. Secondary hyperhidrosis must be ruled out before a diagnosis of primary hyperhidrosis is made.


Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease.
Microelectrode recordings of single unit neuronal activity were used during stereotactic surgery to define the subthalamic nucleus for chronic deep brain stimulation in the treatment of Parkinson's disease. By using five parallel trajectories, often two to three microelectrodes allow us to recognize subthalamic nucleus (STN) neuronal activity. STN neurons were easily distinguished from cells of the overlying zona incerta and the underlying substantia nigra. During a typical exploratory track, we can observe a very low background noise in the zona incerta and almost complete absence of single cell recording. Penetration of the electrode tip into the STN is characterized by a sudden increase in background activity and single cell activity of spontaneously active neurons. The exit of electrode tip out of the STN corresponds to a decrease in background noise and a loss of single cell activity. Spontaneous neuronal activity increases again when the electrode tips enters the substantia nigra pars reticulata (SNr); however, the activity is less rich than in the STN, indicating a more cell-sparse nucleus. STN neurons are characterized by a mean firing rate of 42.30 +/- 22.00 spikes/sec (mean +/- SD). The STN cells exhibited irregular or bursty discharge pattern. The pattern of single cell activity in the SNr is a more regular tonic activity that can easily be distinguished from the bursting pattern in the STN. The most useful criteria to select a trajectory are (1) the length of an individual trajectory displaying typical STN activity, (2) the bursting pattern of activity, and (3) motor responses typical of the sensorimotor part of the nucleus. In conclusion, microelectrode recording of the subthalamic area improves the accuracy of targeting the STN.


Changes in the quality of life: a major goal of cardiac rehabilitation.
Quality of life (QOL) is a major goal in the context of preventive and therapeutic cardiology. In this article, quality of life concepts are reviewed, factors limiting QOL in cardiac disease are identified, methods of measurement are explored, and clinically significant changes are defined. The changes effected by cardiac rehabilitation are considered, together with their physiological and psychological correlates. A final section suggests avenues for future research. Relevant articles were identified by computer literature searches and review of extensive personal files. In the past, there has been an excessive focus on extending the length rather than the quality of the cardiac patient's life. The overall QOL is a broad concept, influenced by personal perceptions, coping mechanisms, and environmental constraints. The ideal test instrument would be reliable, valid, and responsive to clinical change. Potential options include a Gestalt-type instrument, a disease-specific instrument, a function-specific instrument, or a detailed generic questionnaire. There have been relatively few comparisons between these potential approaches. Currently, the Standard Gamble (Gestalt-type), and Living With Heart Failure Questionnaire (disease-specific type), and the Medical Outcomes Study Short-Form 36 (SF-36) Health Survey (generic-type) are among the most popular approaches. Problems arise in distinguishing a clinically important from a statistically significant change; commonly a score change of 1 standard error of the mean is regarded as clinically important. Correlations of scores with clinical, physiological, and psychological change are sometimes weak, in part because of floor and ceiling effects. Nevertheless, potential gains in QOL provide a stronger argument for preventive and therapeutic programs than do increases in longevity. The current literature supports the value of QOL measurements in the management of patients with cardiac disease. However, further research is needed to determine the optimum test instrument, and the best method of interpreting resultant scores.


[The concurrence of kidney and liver dysfunctions in decompensated heart failure].
To study the incidence, pattern, and predictive factors of concurrent kidney and liver dysfunctions in patients with decompensated heart failure (HF). The kidney and liver function indicators were estimated in 322 patients aged 69.5±10.6 years with decompensated HF (hypertension in 87%, myocardial infarction in 57%, atrial fibrillation in 65%, chronic kidney disease in 39%, type 2 diabetes in 42%, a left ventricular ejection fraction (EF) of 38±13%, EF <35% 39%, NYHA Functional Class IV in 56%). Cardiohepatic syndrome (CHS) was diagnosed if at least one indicator of liver function was increased; acute kidney injury (AKI) was diagnosed using the KDIGO criteria. AKI and CHS had been previously diagnosed in 60 (18.6%) and 274 (85.1%) patients, respectively. Among the patients with signs of kidney and/or liver dysfunction, the incidence of isolated CHS, concurrent AKI and CHS, and isolated AKI was 78.4, 20.1, and 1.5%, respectively. The patients with concurrent kidney and liver dysfunctions were observed to have more profound systemic hemodynamic changes (hypoperfusion and congestion). The risk of concurrent AKI and CHS increased glomerular filtration rate (GFR) <45 ml/min/1.73 m2, admission systolic blood pressure <110 mm Hg, needs for vasopressors, hydropericardium, and EF <35%. The concurrence of AKI and CHS was associated with longer hospital stay (15.7±6.5 and 13.5±4.8 days, respectively; p<0.05). The incidence of concurrent AKI and CHS in patients with decompensated HF is 20.1%. Concurrent kidney and liver dysfunctions is associated with more obvious signs of hypoperfusion and congestion and characterized by worse prognosis.


Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring.
Studies have shown that the risk of hypertension in adulthood can be affected by the in utero environment. It is established that hypertension is linked to compromised kidney function and that factors affecting organogenesis can increase the risk of later disease. Prostaglandins (PG) and growth factors are known to play an important role in regulating kidney function and renal organogenesis. The extent, however, to which global energy restriction (where all nutrients are reduced) of the mother can programme later blood pressure control or renal PG and growth factor status is unknown. A study is described that aimed to examine the long-term effects of maternal nutrient restriction (NR) and elucidate their relationship with compromised kidney development. First, it was necessary to establish animal models. A sheep model of 50% NR during specific stages of gestation was used to investigate fetal renal development, whilst a rat model of 50% NR throughout pregnancy was used to investigate postnatal kidney development and adult functioning. Molecular analysis has shown that expression of the growth hormone-insulin-like growth factor (GH-IGF) axis is affected by NR in the fetal sheep kidneys, and that changes are dependent on the timing of NR and whether the fetus is a singleton or a twin. Analysis of the kidneys from the rat model has shown nutritional differences in the expression of PG receptors and the enzymes responsible for PG synthesis and degradation that persist into adulthood. In conclusion, NR does affect the GH-IGF and PG axes, and these changes may be important in the nutritional programming of renal functioning and adult blood pressure control.


Evaluation of suspected osteoid osteoma.
A technique of computed tomography with intravenous contrast has proven useful in the differentiation between osteoid osteoma and other similar appearing lucent lesions of bone in 6 cases. The clinical evaluation of benign appearing radiolucent lesions of long bones has been greatly improved by the use of modern imaging techniques. The differential diagnosis often is narrowed to osteoid osteoma and osteomyelitis based on plain radiographs, computed tomography, or magnetic resonance imaging. The enhancement of the lucent center of the lesion was plotted against time. The rapid uptake of contrast medium by the osteoid osteoma was in sharp contrast to the much slower enhancement in osteomyelitis. The establishment of a preoperative diagnosis enabled the surgeon to excise the lesion without a biopsy. Histologic review verified the preoperative diagnosis in all cases.


Using music to stabilize NICU babies--as well as their parents.
Active, informed interventions, not passive background music, are the basis of music therapy. Use music and sound to calm not just infants but parents and the hospital environment, too. Include parents in music therapy, so they can continue interventions after babies are discharged.


Critical fluctuations in a mesoscopic superconducting ring.
The nonlocal magnetoconductivity fluctuations in a superconducting submicron ring, with radius comparable to the Ginzburg-Landau coherence length, are studied. The order parameter mode separation yields to the solution of the time-dependent Ginzburg-Landau equation and the paraconductivity Fourier components are calculated in the vicinity of the critical temperature, including the critical fluctuation region. The homogeneous component has a logarithmic singularity at T(c) while the other components are found to be not singular.


Right hemidiaphragmatic elevation with a right-to-left interatrial shunt through a patent foramen ovale: a case report and literature review.
A right-to-left shunt (RLS) is an uncommon complication of a patent foramen ovale (PFO) that may cause hypoxemia from venous admixture and ischemic complications from paradoxic embolization. This report presents the third described patient whose RLS through a PFO and profound hypoxemia developed in association with right hemidiaphragm dysfunction (but without a pressure gradient driving the right-to-left flow). In addition to extending the available experience with this unusual clinical event, we report on the successful closure of the PFO by a catheter-deployed double-umbrella device, after the positioning of which the patient's oxygenation normalized.


Eruption of permanent teeth in Brazilian Whites and Blacks.
A total of 302 White and 904 Black children six, nine and 12 years of age were studied for the eruption of their permanent teeth. Differences between the two ethnic groups were not large, but the Black subjects were generally more precocious at the beginning of the process (especially the girls, both in the upper and lower incisors). At nine and 12 years of age, however, these dissimilarities disappear. The latter do not seem to be related to distinct rates of extraction or agenesis of deciduous teeth. No significant differences were observed in the degree of asymmetry present in the permanent dentition of the White and Black individuals studied.


Natural history and morphology of secretagogue-induced duodenal ulcers in rats.
Morphologically typical ulcers were produced in the first part of the duodenum in 300 male Wistar rats by subcutaneous infusion for 24 hr of pentagastrin (4 mug per kg-min) and carbachol (0.8 mug per kg-min). Groups of animals were killed daily for 14 days, and their stomachs and duodenums were examined. Lesions were graded on a seven-point scale: 0, normal; 1, inflammation; 2, petechiae; 3, erosions; 4, definite ulcer crater; 5, penetrating ulcer; and 6, perforated ulcer. Every animal developed one or more definite ulcers (grades 4 to 6). Within the first 48 hr 34% of the animals died with grade 6 ulcers. Ulcer healing began on the 1st postinfusion day when 3 of 46 rats had erosions (grade 3) but no definite ulcer craters. By the following day some animals were found with normal mucosa. After the 5th postinfusion day the few remaining grade 5 or 6 ulcers were those which had perforated and sealed spontaneously. These long-standing ulcers had several features similar to human chronic duodenal ulcers. By the 12th postinfusion day definite ulcers were no longer seen. In this study duodenal ulcers have not only been produced in rats by secretagogues, but have also been observed to heal. This model can be used to compare the efficacy of various antiulcer regimens on ulcer healing.


Economic evaluation of citalopram use and expenditures among recipients in the Texas Medicaid program.
To describe the trends in the utilization and expenditures of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine within the Texas Medicaid program in 1999 and 2000; more specifically, to compare the use of citalopram with other SSRI agents and venlafaxine. A retrospective analysis of Texas Medicaid paid prescription claims data involving Texas Medicaid clients aged 18 to 64. The main outcome measures were allowed, discounted cost per day; dose per day; treatment days (persistence); adherence rates; and switching rates. Citalopram had a significantly lower calculated cost per day than all other comparator agents. There were no statistically significant differences between study agent groups when comparing treatment days and adherence days for newly started patients, except for lower rates with venlafaxine IR. Within the Texas Medicaid Program, citalopram had a positive economic impact on prescription drug costs compared to other comparator agents, while showing similar outcomes in utilization measures such as treatment days and adherence rates.


Stability of mitral reconstructive surgery at 10-12 years for predominantly rheumatic valvular disease.
All consecutive patients who underwent Duran flexible ring annuloplasty in 1975 and 1976 were reviewed until June 1987. Eighty-seven annuloplasties were performed in 85 patients. Aortic, tricuspid, or both surgeries were simultaneously performed in 44.8%. The hospital mortality was 2.3% (two of 85). Ten patients were lost to follow-up within 2 years after surgery, and there were three late deaths. Thromboembolic events were detected in 18 patients (seven peripheral and 11 central with one death); nine patients had partial recovery, and eight had full recovery. At the time of the thromboembolic event, eight patients were receiving anticoagulants; four, antiaggregants; one, both anticoagulants and antiaggregants; and five, none. Thirteen patients (13 of 73, 17.8%) required reoperation between 1 month and 11 years postoperatively. The valve was replaced in 11 patients, and two underwent a new flexible ring annuloplasty. The cause for reoperation was regurgitation in eight patients (10.9%), for whom the mean interval between operations was 20.6 months (range, 1 month-11 years). Stenosis was the cause for reoperation in five patients (6.8%), for whom the mean interval between operations was 87.8 months (range, 4-11 years). We conclude that reconstructive surgery after 10-12 years of follow-up for this group of predominantly rheumatic patients has an incidence of failure of approximately 18% attributable to incorrect surgery (11%) and restenosis (7%).