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        {
            "text": "\n181598\nAge progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.\n\nDahaba, AA\n\nXiao, Z\n\nZhu, X\n\nDong, H\n\nXiong, L\n\nRehak, P\n\nZelzer, S\n\nWang, K\n\nReibnegger, G\n\nBeiträge in Fachzeitschriften\nISI:000515900600001\n32100175.0\n10.1007/s10928-020-09678-0\nNone\nPharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task.\n                Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (Cp) to gradually reach 3.5 μg mL-1 over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis.\n                Age was significant covariate for baseline BIS effect (E0), inhibitory propofol concentration at 50% BIS decline (IC50) and maximum BIS decline (Emax). First-order rate constant Ke0 of 0.47 min-1 in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min-1 in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended Cp of 3.5 μg mL-1 for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year.\n                We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol Cp of 3.5 μg mL-1 might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of Cp 3.5 μg mL-1 for 20-29 year should be gradually decreased to 2.0 μg mL-1 for 80-89 year.\n                European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.\n\nReibnegger, Gilbert\n\nZelzer, Sieglinde\n\n\n"
        },
        {
            "text": "\n183695\nGrindr Users Take More Risks, but Are More Open to Human Immunodeficiency Virus (HIV) Pre-exposure Prophylaxis: Could This Dating App Provide a Platform for HIV Prevention Outreach?\n\nHoenigl, M\n\nLittle, SJ\n\nGrelotti, D\n\nSkaathun, B\n\nWagner, GA\n\nWeibel, N\n\nStockman, JK\n\nSmith, DM\n\nBeiträge in Fachzeitschriften\nISI:000593002000012\n31677383.0\n10.1093/cid/ciz1093\nPMC7583417\nTechnology has changed the way that men who have sex with men (MSM) seek sex. More than 60% of MSM in the United States use the internet and/or smartphone-based geospatial networking apps to find sex partners. We correlated use of the most popular app (Grindr) with sexual risk and prevention behavior among MSM.\n                A nested cohort study was conducted between September 2018 and June 2019 among MSM receiving community-based human immunodeficiency virus (HIV) and sexually transmitted infection (STI) screening in central San Diego. During the testing encounter, participants were surveyed for demographics, substance use, risk behavior (previous 3 months), HIV pre-exposure prophylaxis (PrEP) use, and Grindr usage. Participants who tested negative for HIV and who were not on PrEP were offered immediate PrEP.\n                The study included 1256 MSM, 1090 of whom (86.8%) were not taking PrEP. Overall, 580 of 1256 (46%) participants indicated that they used Grindr in the previous 7 days. Grindr users reported significantly higher risk behavior (greater number of male partners and condomless sex) and were more likely to test positive for chlamydia or gonorrhea (8.6% vs 4.7% of nonusers; P = .005). Grindr users were also more likely to be on PrEP (18.7% vs 8.7% of nonusers; P < .001) and had fewer newly diagnosed HIV infections (9 vs 26 among nonusers; P = .014). Grindr users were also nearly twice as likely as nonusers to initiate PrEP (24.6% vs 14%; P < .001).\n                Given the higher risk behavior and greater acceptance of PrEP among MSM who used Grindr, Grindr may provide a useful platform to promote HIV and STI testing and increase PrEP uptake.\n                © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.\n\nHönigl, Martin\n\n\n"
        },
        {
            "text": "\n1773\nNational rates and regional differences in sensitization to allergens of the standard series. Population-adjusted frequencies of sensitization (PAFS) in 40,000 patients from a multicenter study (IVDK).\n\nSchnuch, A\n\nGeier, J\n\nUter, W\n\nFrosch, PJ\n\nLehmacher, W\n\nAberer, W\n\nAgathos, M\n\nArnold, R\n\nFuchs, T\n\nLaubstein, B\n\nLischka, G\n\nPietrzyk, PM\n\nRakoski, J\n\nRichter, G\n\nRuëff, F\n\nBeiträge in Fachzeitschriften\nISI:A1997YG87100002\n9412746.0\n10.1111/j.1600-0536.1997.tb02435.x\nNone\nSensitization rates to contact allergens vary between centers and are influenced by sex and age. Eliminating the latter 2 factors by standardization of data by age and sex, the present analysis addresses possible differences between centers remaining after elimination of these confounders, and analyzes other factors which might influence rates, e.g., the MOAHL index. Overall standardized rates were well within the range reported in previous studies and may be regarded as representing the rates of the "patch test population" in Central Europe (e.g., nickel sulfate 12.9%, fragrance mix 10.5%, balsam of Peru 7.3%, thimerosal 5.6%). For this analysis, data of those departments which contributed more than 2000 patients, or of those with extreme proportions concerning sex, age and occupational cases were selected. Patients from these 10 departments differed considerably with regard to the items of the MOAHL index and with regard to standardized rates. The items of the MOAHL index proved to be suitable for describing different patch test populations and for explaining some differences between centers. Only 'atopic dermatitis' seems to have little influence on (standardized) rates. Face dermatitis is not yet represented in the MOAHL index, but should be included, together with age > 40 years, in an extended index (acronym: MOAHLFA). Regional allergen exposure (with striking differences between East Germany, West Germany and, to a lesser extent, Austria) seems to have a great influence on the sensitization pattern observed in a department. In addition, sociological factors may influence sensitization rates, which is exemplified by high rates of nickel allergy in a socially defined subgroup. Future studies should focus on these factors, as well as on factors concerning patch test practices and quality control.\n\nAberer, Werner\n\n\n"
        },
        {
            "text": "\n4054\nOxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT.\n\nBochkov, VN\n\nMechtcheriakova, D\n\nLucerna, M\n\nHuber, J\n\nMalli, R\n\nGraier, WF\n\nHofer, E\n\nBinder, BR\n\nLeitinger, N\n\nBeiträge in Fachzeitschriften\nISI:000172980800032\n11756172.0\n10.1182/blood.V99.1.199\nNone\nActivation of endothelial cells by lipid oxidation products is a key event in the initiation and progression of the atherosclerotic lesion. Minimally modified low-density lipoprotein (MM-LDL) induces the expression of certain inflammatory molecules such as tissue factor (TF) in endothelial cells. This study examined intracellular signaling pathways leading to TF up-regulation by oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a biologically active component of MM-LDL. OxPAPC induced TF activity and protein expression in human umbilical vein endothelial cells (HUVECs). However, OxPAPC neither induced phosphorylation or degradation of I kappa B alpha nor DNA binding of nuclear factor-kappa B (NF-kappa B). Furthermore, OxPAPC-induced TF expression was not inhibited by overexpression of I kappa B alpha. These results strongly indicate that OxPAPC-induced TF expression is independent of the classical NF-kappa B pathway. However, OxPAPC stimulated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and expression of early growth response factor 1 (EGR-1). Inhibitors of mitogen-activated kinase/ERK (MEK) or protein kinase C (PKC) blocked elevation of both EGR-1 and TF. Furthermore, overexpression of NAB2, a corepressor of EGR-1, inhibited effects of OxPAPC. In addition, OxPAPC induced rapid and reversible elevation of free cytosolic Ca(++) levels and nuclear factor of activated T cells (NFAT)/DNA binding. Induction of TF expression by OxPAPC was partially inhibited by cyclosporin A, known to block calcineurin, a Ca(++)-dependent phosphatase upstream of NFAT. Treatment of OxPAPC with phospholipase A(2) destroyed its biologic activity and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine was identified as one biologically active component of OxPAPC that induces TF expression. Together, the results demonstrate that OxPAPC induces TF expression in HUVECs through activation of PKC/ERK/EGR-1 and Ca(++)/calcineurin/NFAT pathways rather than by NF-kappa B-mediated transcription. Thus, oxidized phospholipids may contribute to inflammation by activating pathways alternative to the classical NF-kappa B pathway.\n\nGraier, Wolfgang\n\nMalli, Roland\n\n\n"
        },
        {
            "text": "\n5389\nThe lower trapezius musculocutaneous flap from pedicled to free flap: anatomical basis and clinical applications based on the dorsal scapular artery.\n\nHaas, F\n\nWeiglein, A\n\nSchwarzl, F\n\nScharnagl, E\n\nBeiträge in Fachzeitschriften\nISI:000221141000006\n15114117.0\n10.1097/01.PRS.0000117188.03152.10\nNone\nThe pedicled lower trapezius musculocutaneous flap is a standard flap in head and neck reconstruction. A review of the literature showed that there is no uniform nomenclature for the branches of the subclavian artery and the vessels supplying the trapezius muscle and that the different opinions on the vessels supplying this flap lead to confusion and technical problems when this flap is harvested. This article attempts to clarify the anatomical nomenclature, to describe exactly how the flap is planned and harvested, and to discuss the clinical relevance of this flap as an island or free flap. The authors dissected both sides of the neck in 124 cadavers to examine the variations of the subclavian artery and its branches, the vessel diameter at different levels, the course of the pedicle, the arc of rotation, and the variation of the segmental intercostal branches to the lower part of the trapezius muscle. Clinically, the flap was used in five cases as an island skin and island muscle flap and once as a free flap. The anatomical findings and clinical applications proved that there is a constant and dependable blood supply through the dorsal scapular artery (synonym for the deep branch of the transverse cervical artery in the case of a common trunk with the superficial cervical artery) as the main vessel. Harvesting an island flap or a free flap is technically demanding but possible. Planning the skin island far distally permitted a very long pedicle and wide arc of rotation. The lower part of the trapezius muscle alone could be classified as a type V muscle according to Mathes and Nahai because of its potential use as a turnover flap supplied by segmental intercostal perforators. The lower trapezius flap is a thin and pliable musculocutaneous flap with a very long constant pedicle and minor donor-site morbidity, permitting safe flap elevation and the possibility of free-tissue transfer.\n\n\n"
        },
        {
            "text": "\n8546\nAutonomic mechanisms underlying capsaicin induced oral sensations and salivation in man.\n\nDunér-Engström, M\n\nFredholm, BB\n\nLarsson, O\n\nLundberg, JM\n\nSaria, A\n\nBeiträge in Fachzeitschriften\nISI:A1986C043300005\n2427699.0\n10.1113/jphysiol.1986.sp016036\nPMC1182526\nThe effects of capsaicin, citric acid and nicotine applied to the apex or radix of the tongue on taste sensations and salivation were studied in relation to the presence of substance P immunoreactive neurones in man. Application of capsaicin (30 micron) to the apex of the tongue or to the palatinal mucosa, but not to the radix of the tongue, caused a reproducible burning sensation and salivation from the submandibular-sublingual and parotid glands. The salivation response to capsaicin was reduced by methylscopolamine pretreatment. Similar levels of substance P immunoreactivity were present in the lingual apex and radix area (including vallate papillae) of man, while in the cat about 4 times higher levels of substance P immunoreactivity were present in the vallate papillae than in the lingual apex. Immunohistochemistry showed that in the cat many substance P immunoreactive nerves were associated with the taste buds of the vallate papillae, while in man substance P immunoreactive fibres were only seen penetrating into the epithelium of the lingual apex. In addition some subepithelial blood vessels in all regions were surrounded by substance P immunoreactive nerves in both cat and man. Citric acid application to the tongue apex caused both submandibular-sublingual and parotid salivary secretion concomitant with a burning sensation. Salivary secretion was also seen after citric acid application to the radix of the tongue. This response was associated with a sour taste. The salivation response to citric acid was not significantly reduced by methylscopolamine pretreatment. Lingual apex application of nicotine was associated with a sweet taste and a small rise in salivary secretion rate. This response was not significantly reduced by methylscopolamine. In conclusion, the sensitivity to capsaicin of the human tongue is restricted to the apex portion. This is in parallel with the occurrence of intraepithelial substance P immunoreactive nerve fibres. Capsaicin induced salivary secretion seems mainly to be mediated via parasympathetic, cholinergic reflex mechanisms. Citric acid and nicotine induced salivation responses are comparatively more resistant to methylscopolamine pretreatment.\n\n\n"
        },
        {
            "text": "\n17529\nLong-term results of autologous stem cell transplantation for Hodgkin's disease (HD) and low-/intermediate-grade B non-Hodgkin's lymphoma (NHL): a report from the Austrian Stem Cell Transplantation Registry (ASCTR).\n\nNachbaur, D\n\nGreinix, HT\n\nKoller, E\n\nKrieger, O\n\nLinkesch, W\n\nKasparu, H\n\nPober, M\n\nHinterberger, W\n\nHausmaninger, H\n\nHeistinger, M\n\nUlsperger, E\n\nKarlhuber, S\n\nSchwinger, W\n\nLindner, B\n\nBeiträge in Fachzeitschriften\nISI:000229614500008\n15726362.0\n10.1007/s00277-004-1003-3\nNone\nBetween 1990 and 2001, 68 patients with advanced Hodgkin's disease (HD) and 86 patients classified as low-/intermediate-grade B non-Hodgkin's lymphoma (NHL) were reported to the Austrian Stem Cell Transplantation Registry (ASCTR). Following autologous stem cell transplantation (SCT) for HD, overall survival was 56% [95% confidence interval (CI): 40-72%] with a disease-/progression-free survival of 49%, reaching a plateau at 5 years. Using multivariate Cox regression analysis BEAM conditioning (carmustine, cytarabine, etoposide and melphalan) was predictive for favourable outcome, better disease-/progression-free survival and a significantly lower risk for relapse. The cumulative incidence of relapse was 30%, even for patients in complete remission at time of SCT. The cumulative risk for developing a secondary malignancy increased continuously over time, achieving 20% at 7 years and 46% at 10 years with previous radiotherapy as the only risk factor in the multivariate analysis. Overall survival for NHL patients was 45% (95% CI: 26-64%) with a disease-/progression-free survival of 26% at 7 years. In the multivariate Cox regression analysis stage of disease at time of SCT was the most powerful parameter for overall survival, disease-/progression-free survival and relapse. Mantle cell lymphoma, greater than or equal to three lines of previous therapy, and a conditioning regimen other than BEAM were also predictive for death. The main reason for treatment failure was relapse (cumulative incidence 54-75%). Because of the high risk of relapse/progression in both disease categories and the additional high rate of second malignancies in HD patients, allogeneic stem cells should be considered a valuable alternative for selected patients. The efficacy of allotransplantation following reduced-intensity conditioning should be tested in randomised trials.\n\nGreinix, Hildegard\n\nSchwinger, Wolfgang\n\n\n"
        },
        {
            "text": "\n17536\nEffect of ultrafiltration on thermal variables, skin temperature, skin blood flow, and energy expenditure during ultrapure hemodialysis.\n\nvan der Sande, FM\n\nRosales, LM\n\nBrener, Z\n\nKooman, JP\n\nKuhlmann, M\n\nHandelman, G\n\nGreenwood, RN\n\nCarter, M\n\nSchneditz, D\n\nLeunissen, KM\n\nLevin, NW\n\nBeiträge in Fachzeitschriften\nISI:000229393900035\n15857923.0\n10.1681/ASN.2004080655\nNone\nThe cause of the increase in core temperature (CT) during hemodialysis (HD) is still under debate. It has been suggested that peripheral vasoconstriction as a result of hypovolemia, leading to a reduced dissipation of heat from the skin, is the main cause of this increase in CT. If so, then it would be expected that extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T-control = 0, no change in CT) is largely different between body temperature control HD combined with ultrafiltration (UF) and body temperature control HD without UF (isovolemic). Consequently, significant differences in DeltaCT would be expected between isovolemic HD and HD combined with UF at zero Jex (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from the extracorporeal circulation). During the latter treatment, the CT is expected to increase. In this study, changes in thermal variables (CT and Jex), skin blood flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and IL-6) were compared in 13 patients, each undergoing body temperature control (T-control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/- 0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF. In body temperature control treatments, the relationship between Jex and UF tended to be significant (r = -0.51; P = 0.07); however, there was no significant difference in cooling requirements regardless of whether treatments were done without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy expenditure did not differ among the four treatment modes. There were no significant differences in pre- and postdialysis levels of cytokines within or between treatments. Although fluid removal has an effect on thermal variables, no single mechanism seems to be responsible for the increased heat accumulation during HD.\n\nSchneditz, Daniel\n\n\n"
        },
        {
            "text": "\n17965\nIntense cholesterol lowering therapy with a HMG-CoA reductase inhibitor does not improve nitric oxide dependent endothelial function in type-2-diabetes--a multicenter, randomised, double-blind, three-arm placebo-controlled clinical trial.\n\nBalletshofer, BM\n\nGoebbel, S\n\nRittig, K\n\nEnderle, M\n\nSchmölzer, I\n\nWascher, TC\n\nFerenc Pap, A\n\nWestermeier, T\n\nPetzinna, D\n\nMatthaei, S\n\nHäring, HU\n\nBeiträge in Fachzeitschriften\nISI:000230072700003\n15977099.0\n10.1055/s-2005-865642\nNone\nDisturbances in nitric oxide (NO) metabolism resulting in endothelial dysfunction play a central role in the pathogenesis of atherosclerosis in hypercholesterolemia and in individuals with type 2 diabetes. It is unclear whether lipid lowering therapy with HMG-CoA-reductase inhibitors might improve endothelial function in subjects with type 2 diabetes as it is demonstrated in non-diabetic subjects with hypercholesterolemia. We examined the influence of 0.2 mg and 0.8 mg cerivastatin on endothelial function in a multicenter, randomised, double-blind, and three-arm placebo-controlled clinical trial. Endothelial function was assessed by nitric oxide-dependent flow mediated vasodilatation (FMD) of the brachial artery. A total of 103 patients with type 2 diabetes were enrolled in the study. Bayer Company undertook a voluntary action to withdraw cerivastatin from market, therefore the study was terminated earlier. At this point 77 patients were randomised, of which 58 completed the study (mean age 60 +/- 8 years, HbA1c 7.4 +/- 0.9 %). At baseline mean FMD was disturbed in all three therapy arms (5.18 +/- 2.31 % in the placebo group, 3.88 +/- 1.68 in the 0.2-mg cerivastation group, and 4.86 +/- 2.25 in the 0.8-mg cerivastatin group). Despite a significant reduction in cholesterol and LDL-cholesterol-levels after 12 weeks of treatment (decrease in LDL-cholesterol - 26.8 +/- 13.9 % in the 0.2-mg group and - 40.3 +/- 16.0 % in the 0.8-mg group, p = 0.0001, ANCOVA) there was no difference in flow mediated vasodilatation (p = 0.52 and p = 0.56 vs. placebo, respectively, ANCOVA). HbA1c, CRP, and HDL-cholesterol did not change during the study. Furthermore no difference in safety profile between cerivastatin and placebo was found. Despite a significant improvement in lipid profile under statin therapy, no improvement of endothelial dysfunction in terms of nitric oxide bioavailability could be detected.\n\n\n"
        },
        {
            "text": "\n22699\nIn vitro formation and activity-dependent plasticity of synapses between Helix neurons involved in the neural control of feeding and withdrawal behaviors.\n\nFiumara, F\n\nLeitinger, G\n\nMilanese, C\n\nMontarolo, PG\n\nGhirardi, M\n\nBeiträge in Fachzeitschriften\nISI:000231894500005\n16054762.0\n10.1016/j.neuroscience.2005.05.021\nNone\nShort-term activity-dependent synaptic plasticity has a fundamental role in short-term memory and information processing in the nervous system. Although the neuronal circuitry controlling different behaviors of land snails of the genus Helix has been characterized in some detail, little is known about the activity-dependent plasticity of synapses between identified neurons regulating specific behavioral acts. In order to study homosynaptic activity-dependent plasticity of behaviorally relevant Helix synapses independently of heterosynaptic influences, we sought to reconstruct them in cell culture. To this aim, we first investigated in culture the factors regulating synapse formation between Helix neurons, and then we studied the short-term plasticity of in vitro-reconstructed monosynaptic connections involved in the neural control of salivary secretion and whole-body withdrawal. We found that independently of extrinsic factors, cell-cell interactions are seemingly sufficient to trigger the formation of electrical and chemical synapses, although mostly inappropriate--in their type or association--with respect to the in vivo synaptic connectivity. The presence of ganglia-derived factors in the culture medium was required for the in vitro reestablishment of the appropriate in vivo-like connectivity, by reducing the occurrence of electrical connections and promoting the formation of chemical excitatory synapses, while apparently not influencing the formation of inhibitory connections. These heat-labile factors modulated electrical and chemical synaptogenesis through distinct protein tyrosine kinase signal transduction pathways. Taking advantage of in vitro-reconstructed synapses, we have found that feeding interneuron-efferent neuron synapses and mechanosensory neuron-withdrawal interneuron synapses display multiple forms of short-term enhancement-like facilitation, augmentation and posttetanic potentiation as well as homosynaptic depression. These forms of plasticity are thought to be relevant in the regulation of Helix feeding and withdrawal behaviors by inducing dramatic activity-dependent changes in the strength of input and output synapses of high-order interneurons with a crucial role in the control of Helix behavioral hierarchy.\n\nLeitinger, Gerd\n\n\n"
        },
        {
            "text": "\n77666\nVariation in pudendal nerve terminal motor latency according to disease.\n\nPfeifer, J\n\nSalanga, VD\n\nAgachan, F\n\nWeiss, EG\n\nWexner, SD\n\nBeiträge in Fachzeitschriften\nISI:A1997WB90000017\n9102266.0\n10.1007/BF02055686\nNone\nPURPOSE: The aims of this study were first to establish whether any difference among pudendal nerve terminal motor latency (PNTML) values exists relative to diagnosis, second to determine whether left and right latencies are similar, and third to assess any correlation between age and neuropathy. Latency was elicited three times on each side, and an average latency was recorded as a result. MATERIALS AND METHODS: Between June 1989 and April 1995, 1, 26 patients (775 females and 251 males) underwent PNTML study. These patients were divided into four groups according to diagnosis: Group I, fecal incontinence; Group II, chronic constipation; Group III, idiopathic rectal pain; Group IV, rectal prolapse. Overall mean age was 61.5 (range, 6-95) years. Student's t-test was used to calculate statistical differences. Patients were then analyzed according to age and gender. Correlation was calculated with the nonparametric Mann-Whitney U test. RESULTS: Unilateral or bilateral prolongation of PNTML was noted in 90 patients (21.2 percent) in Group I, 80 (20.4 percent) in Group II, 22 (18.1 percent) in Group III, and 38 (42.6 percent) in Group IV. Average PNTML on the left side was 1.88 ms in Group I, 1.94 ms in Group II, 1.98 ms in Group III, and 2.12 ms in Group IV. Average PNTML on the right side was 1.85 ms in Group I, 1.94 ms in Group II, 1.99 ms in Group III, and 2.07 ms in Group IV. The only statistically significant differences in PNTML were between Groups I and IV (left, P < 0.005; right, < 0.05) and between females and males (P < 0.0001). CONCLUSION: There is no statistically significant difference between latencies of left and right pudendal nerves. Similarly, there are no statistically significant differences among patients with fecal incontinence, chronic constipation, or chronic idiopathic rectal pain. Normal latency can be expected in patients with constipation or fecal incontinence. However, patients with rectal prolapse have a more prolonged PNTML. Age is correlated with a higher incidence of pudendal neuropathy. This study reveals significant overlap among PNTML values and diagnosis.\n\nPfeifer, Johann\n\n\n"
        },
        {
            "text": "\n82626\nThe registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement.\n\nHunzelmann, N\n\nGenth, E\n\nKrieg, T\n\nLehmacher, W\n\nMelchers, I\n\nMeurer, M\n\nMoinzadeh, P\n\nMuller-Ladner, U\n\nPfeiffer, C\n\nRiemekasten, G\n\nSchulze-Lohoff, E\n\nSunderkoetter, C\n\nWeber, M\n\nWorm, M\n\nKlaus, P\n\nRubbert, A\n\nSteinbrink, K\n\nGrundt, B\n\nHein, R\n\nScharffetter-Kochanek, K\n\nHinrichs, R\n\nWalker, K\n\nSzeimies, RM\n\nKarrer, S\n\nMuller, A\n\nSeitz, C\n\nSchmidt, E\n\nLehmann, P\n\nFoeldvari, I\n\nReichenberger, F\n\nGross, WL\n\nKuhn, A\n\nHaust, M\n\nReich, K\n\nBohm, M\n\nSaar, P\n\nFierlbeck, G\n\nKotter, I\n\nLorenz, HM\n\nBlank, N\n\nGrafenstein, K\n\nJuche, A\n\nAberer, E\n\nBali, G\n\nFiehn, C\n\nStadler, R\n\nBartels, V\n\nBeiträge in Fachzeitschriften\nISI:000257787200014\n18515867.0\n10.1093/rheumatology/ken179\nPMC2468885\nOBJECTIVE: Systemic sclerosis (SSc) is a rare, heterogeneous disease, which affects different organs and therefore requires interdisciplinary diagnostic and therapeutic management. To improve the detection and follow-up of patients presenting with different disease manifestations, an interdisciplinary registry was founded with contributions from different subspecialties involved in the care of patients with SSc. METHODS: A questionnaire was developed to collect a core set of clinical data to determine the current disease status. Patients were grouped into five descriptive disease subsets, i.e. lcSSc, dcSSc, SSc sine scleroderma, overlap-syndrome and UCTD with scleroderma features. RESULTS: Of the 1483 patients, 45.5% of patients had lcSSc and 32.7% dcSSc. Overlap syndrome was diagnosed in 10.9% of patients, while 8.8% had an undifferentiated form. SSc sine scleroderma was present in 1.5% of patients. Organ involvement was markedly different between subsets; pulmonary fibrosis for instance was significantly more frequent in dcSSc (56.1%) than in overlap syndrome (30.6%) or lcSSc (20.8%). Pulmonary hypertension was more common in dcSSc (18.5%) compared with lcSSc (14.9%), overlap syndrome (8.2%) and undifferentiated disease (4.1%). Musculoskeletal involvement was typical for overlap syndromes (67.6%). A family history of rheumatic disease was reported in 17.2% of patients and was associated with early disease onset (P < 0.005). CONCLUSION: In this nationwide register, a descriptive classification of patients with disease manifestations characteristic of SSc in five groups allows to include a broader spectrum of patients with features of SSc.\n\n\n"
        },
        {
            "text": "\n120280\nThe Influence of verbalization on the pattern of cortical activation during mental arithmetic.\n\nZarnhofer, S\n\nBraunstein, V\n\nEbner, F\n\nKoschutnig, K\n\nNeuper, C\n\nReishofer, G\n\nIschebeck, A\n\n\n\nBeiträge in Fachzeitschriften\nISI:000304346100001\n22404872.0\n10.1186/1744-9081-8-13\nPMC3359281\nThe aim of the present functional magnetic resonance imaging (fMRI) study at 3 T was to investigate the influence of the verbal-visual cognitive style on cerebral activation patterns during mental arithmetic. In the domain of arithmetic, a visual style might for example mean to visualize numbers and (intermediate) results, and a verbal style might mean, that numbers and (intermediate) results are verbally repeated. In this study, we investigated, first, whether verbalizers show activations in areas for language processing, and whether visualizers show activations in areas for visual processing during mental arithmetic. Some researchers have proposed that the left and right intraparietal sulcus (IPS), and the left angular gyrus (AG), two areas involved in number processing, show some domain or modality specificity. That is, verbal for the left AG, and visual for the left and right IPS. We investigated, second, whether the activation in these areas implied in number processing depended on an individual's cognitive style.\n                42 young healthy adults participated in the fMRI study. The study comprised two functional sessions. In the first session, subtraction and multiplication problems were presented in an event-related design, and in the second functional session, multiplications were presented in two formats, as Arabic numerals and as written number words, in an event-related design. The individual's habitual use of visualization and verbalization during mental arithmetic was assessed by a short self-report assessment.\n                We observed in both functional sessions that the use of verbalization predicts activation in brain areas associated with language (supramarginal gyrus) and auditory processing (Heschl's gyrus, Rolandic operculum). However, we found no modulation of activation in the left AG as a function of verbalization.\n                Our results confirm that strong verbalizers use mental speech as a form of mental imagination more strongly than weak verbalizers. Moreover, our results suggest that the left AG has no specific affinity to the verbal domain and subserves number processing in a modality-general way.\n\nReishofer, Gernot\n\n\n"
        },
        {
            "text": "\n131435\nDo patients in Dutch nursing homes have more pressure ulcers than patients in German nursing homes? A prospective multicenter cohort study.\n\nMeesterberends, E\n\nHalfens, RJ\n\nSpreeuwenberg, MD\n\nAmbergen, TA\n\nLohrmann, C\n\nNeyens, JC\n\nSchols, JM\n\nBeiträge in Fachzeitschriften\nISI:000324328200013\n23628407.0\n10.1016/j.jamda.2013.03.005\nNone\nTo investigate whether the incidence of pressure ulcers in nursing homes in the Netherlands and Germany differs and, if so, to identify resident-related risk factors, nursing-related interventions, and structural factors associated with pressure ulcer development in nursing home residents.\n                A prospective multicenter cohort study.\n                Ten nursing homes in the Netherlands and 11 nursing homes in Germany (around Berlin and Brandenburg).\n                A total of 547 newly admitted nursing home residents, of which 240 were Dutch and 307 were German. Residents had an expected length of stay of 12 weeks or longer.\n                Data were collected for each resident over a 12-week period and included resident characteristics (eg, demographics, medical history, Braden scale scores, nutritional factors), pressure ulcer prevention and treatment characteristics, staffing ratios and other structural nursing home characteristics, and outcome (pressure ulcer development during the study). Data were obtained by trained research assistants.\n                A significantly higher pressure ulcer incidence rate was found for the Dutch nursing homes (33.3%) compared with the German nursing homes (14.3%). Six factors that explain the difference in pressure ulcer incidence rates were identified: dementia, analgesics use, the use of transfer aids, repositioning the residents, the availability of a tissue viability nurse on the ward, and regular internal quality controls in the nursing home.\n                The pressure ulcer incidence was significantly higher in Dutch nursing homes than in German nursing homes. Factors related to residents, nursing care and structure explain this difference in incidence rates. Continuous attention to pressure ulcer care is important for all health care settings and countries, but Dutch nursing homes especially should pay more attention to repositioning residents, the necessity and correct use of transfer aids, the necessity of analgesics use, the tasks of the tissue viability nurse, and the performance of regular internal quality controls.\n                Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.\n\nLohrmann, Christa\n\n\n"
        },
        {
            "text": "\n148381\nResults From a European Multicenter Randomized Trial of Physical Activity and/or Healthy Eating to Reduce the Risk of Gestational Diabetes Mellitus: The DALI Lifestyle Pilot.\n\nSimmons, D\n\nJelsma, JG\n\nGaljaard, S\n\nDevlieger, R\n\nvan Assche, A\n\nJans, G\n\nCorcoy, R\n\nAdelantado, JM\n\nDunne, F\n\nDesoye, G\n\nHarreiter, J\n\nKautzky-Willer, A\n\nDamm, P\n\nMathiesen, ER\n\nJensen, DM\n\nAndersen, LL\n\nLapolla, A\n\nDalfra, M\n\nBertolotto, A\n\nWender-Ozegowska, E\n\nZawiejska, A\n\nHill, D\n\nRebollo, P\n\nSnoek, FJ\n\nvan Poppel, MN\n\nBeiträge in Fachzeitschriften\nISI:000363416500018\n26112044.0\n10.2337/dc15-0360\nNone\nWays to prevent gestational diabetes mellitus (GDM) remain unproven. We compared the impact of three lifestyle interventions (healthy eating [HE], physical activity [PA], and both HE and PA [HE+PA]) on GDM risk in a pilot multicenter randomized trial.\n                Pregnant women at risk for GDM (BMI ≥29 kg/m2) from nine European countries were invited to undertake a 75-g oral glucose tolerance test before 20 weeks' gestation. Those without GDM were randomized to HE, PA, or HE+PA. Women received five face-to-face and four optional telephone coaching sessions, based on the principles of motivational interviewing. A gestational weight gain (GWG) <5 kg was targeted. Coaches received standardized training and an intervention toolkit. Primary outcome measures were GWG, fasting glucose, and insulin sensitivity (HOMA) at 35-37 weeks.\n                Among the 150 trial participants, 32% developed GDM by 35-37 weeks and 20% achieved GWG <5 kg. HE women had less GWG (-2.6 kg [95% CI -4.9, -0.2]; P = 0.03) and lower fasting glucose (-0.3 mmol/L [-0.4, -0.1]; P = 0.01) than those in the PA group at 24-28 weeks. HOMA was comparable. No significant differences between HE+PA and the other groups were observed.\n                An antenatal HE intervention is associated with less GWG and lower fasting glucose compared with PA alone. These findings require a larger trial for confirmation but support the use of early HE interventions in obese pregnant women.\n                © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.\n\nDesoye, Gernot\n\n\n"
        },
        {
            "text": "\n155851\nAnalysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B.\n\nEsser-Nobis, K\n\nRomero-Brey, I\n\nGanten, TM\n\nGouttenoire, J\n\nHarak, C\n\nKlein, R\n\nSchemmer, P\n\nBinder, M\n\nSchnitzler, P\n\nMoradpour, D\n\nBartenschlager, R\n\nPolyak, SJ\n\nStremmel, W\n\nPenin, F\n\nEisenbach, C\n\nLohmann, V\n\nBeiträge in Fachzeitschriften\nISI:000315644200016\n23322644.0\n10.1002/hep.26260\nPMC3593759\nIntravenous silibinin (SIL) is an approved therapeutic that has recently been applied to patients with chronic hepatitis C, successfully clearing hepatitis C virus (HCV) infection in some patients even in monotherapy. Previous studies suggested multiple antiviral mechanisms of SIL; however, the dominant mode of action has not been determined. We first analyzed the impact of SIL on replication of subgenomic replicons from different HCV genotypes in vitro and found a strong inhibition of RNA replication for genotype 1a and genotype 1b. In contrast, RNA replication and infection of genotype 2a were minimally affected by SIL. To identify the viral target of SIL we analyzed resistance to SIL in vitro and in vivo. Selection for drug resistance in cell culture identified a mutation in HCV nonstructural protein (NS) 4B conferring partial resistance to SIL. This was corroborated by sequence analyses of HCV from a liver transplant recipient experiencing viral breakthrough under SIL monotherapy. Again, we identified distinct mutations affecting highly conserved amino acid residues within NS4B, which mediated phenotypic SIL resistance also in vitro. Analyses of chimeric viral genomes suggest that SIL might target an interaction between NS4B and NS3/4A. Ultrastructural studies revealed changes in the morphology of viral membrane alterations upon SIL treatment of a susceptible genotype 1b isolate, but not of a resistant NS4B mutant or genotype 2a, indicating that SIL might interfere with the formation of HCV replication sites.\n                Mutations conferring partial resistance to SIL treatment in vivo and in cell culture argue for a mechanism involving NS4B. This novel mode of action renders SIL an attractive candidate for combination therapies with other directly acting antiviral drugs, particularly in difficult-to-treat patient cohorts.\n                Copyright © 2013 American Association for the Study of Liver Diseases.\n\nSchemmer, Peter\n\n\n"
        },
        {
            "text": "\n156690\nLipoprotein(a) concentrations, apolipoprotein(a) isoforms and clinical endpoints in haemodialysis patients with type 2 diabetes mellitus: results from the 4D Study.\n\nKollerits, B\n\nDrechsler, C\n\nKrane, V\n\nLamina, C\n\nMärz, W\n\nDieplinger, H\n\nRitz, E\n\nWanner, C\n\nKronenberg, F\n\nGerman Diabetes and Dialysis Study Investigators\n\nBeiträge in Fachzeitschriften\nISI:000388595700025\n26754832.0\n10.1093/ndt/gfv428\nNone\nHigh lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apolipoprotein(a) [apo(a)] isoforms are associated with cardiovascular disease and mortality in the general population. We examined the association of both with all-cause mortality and cardiovascular endpoints in haemodialysis patients with diabetes mellitus.\n                This is a post hoc analysis of the prospective 4D Study (German Diabetes Dialysis Study) that evaluated atorvastatin compared with placebo in 1255 haemodialysis patients with type 2 diabetes mellitus (median follow-up 4 years). The association of natural logarithm-transformed Lp(a) concentrations (increment one unit) and apo(a) isoforms with outcomes was analysed by Cox proportional hazards regression. The influence of age (median 66 years) was evaluated by stratified survival analyses.\n                The median baseline Lp(a) concentration was 11.5 mg/dL (IQR 5.0-41.8). A quarter of patients had at least one LMW apo(a) isoform. Increased Lp(a) concentrations were associated with all-cause mortality in the total group [hazard ratio (HR) 1.09 (95% CI 1.03-1.16), P = 0.004]. LMW apo(a) isoforms were only associated with all-cause mortality in patients ≤ 66 years [HR 1.38 (95% CI 1.05-1.80), P = 0.02]. The strongest association for Lp(a) concentrations and LMW apo(a) isoforms was found for death due to infection in patients ≤ 66 years [HR 1.39 (95% CI 1.14-1.71), P = 0.001; HR 2.17 (95% CI 1.26-3.75), P = 0.005]. Lp(a) concentrations were also associated with fatal stroke in patients ≤66 years of age [HR 1.54 (95% CI 1.05-2.24), P = 0.03]. Neither Lp(a) nor LMW apo(a) isoforms were associated with other atherosclerosis-related events.\n                High Lp(a) concentrations and LMW apo(a) isoforms are risk predictors for all-cause mortality and death due to infection in haemodialysis patients with diabetes mellitus. These associations are modified by age.\n                © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.\n\nMärz, Winfried\n\n\n"
        },
        {
            "text": "\n168848\nInduction of sustained remission in early inflammatory arthritis with the combination of infliximab plus methotrexate: the DINORA trial.\n\nStamm, TA\n\nMachold, KP\n\nAletaha, D\n\nAlasti, F\n\nLipsky, P\n\nPisetsky, D\n\nLandewe, R\n\nvan der Heijde, D\n\nSepriano, A\n\nAringer, M\n\nBoumpas, D\n\nBurmester, G\n\nCutolo, M\n\nEbner, W\n\nGraninger, W\n\nHuizinga, T\n\nSchett, G\n\nSchulze-Koops, H\n\nTak, PP\n\nMartin-Mola, E\n\nBreedveld, F\n\nSmolen, J\n\nBeiträge in Fachzeitschriften\nISI:000441210000002\n30092827.0\n10.1186/s13075-018-1667-z\nPMC6085639\nIn the present study, we explored the effects of immediate induction therapy with the anti-tumour necrosis factor (TNF)α antibody infliximab (IFX) plus methotrexate (MTX) compared with MTX alone and with placebo (PL) in patients with very early inflammatory arthritis.\n                In an investigator-initiated, double-blind, randomised, placebo-controlled, multi-centre trial (ISRCTN21272423, http://www.isrctn.com/ISRCTN21272423 ), patients with synovitis of 12 weeks duration in at least two joints underwent 1 year of treatment with IFX in combination with MTX, MTX monotherapy, or PL randomised in a 2:2:1 ratio. The primary endpoint was clinical remission after 1 year (sustained for at least two consecutive visits 8 weeks apart) with remission defined as no swollen joints, 0-2 tender joints, and an acute-phase reactant within the normal range.\n                Ninety patients participated in the present study. At week 54 (primary endpoint), 32% of the patients in the IFX + MTX group achieved sustained remission compared with 14% on MTX alone and 0% on PL. This difference (p < 0.05 over all three groups) was statistically significant for IFX + MTX vs PL (p < 0.05), but not for IFX + MTX vs MTX (p = 0.10), nor for MTX vs PL (p = 0.31). Remission was maintained during the second year on no therapy in 75% of the IFX + MTX patients compared with 20% of the MTX-only patients.\n                These results indicate that patients with early arthritis can benefit from induction therapy with anti-TNF plus MTX compared with MTX alone, suggesting that intensive treatment can alter the disease evolution.\n                The trial was registered at http://www.isrctn.com/ISRCTN21272423 on 4 October 2007 (date applied)/12 December 2007 (date assigned). The first patient was included on 24 October 2007.\n\nGraninger, Winfried\n\n\n"
        },
        {
            "text": "\n173055\nStructural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA.\n\nRedrejo-Rodríguez, M\n\nVigouroux, A\n\nMursalimov, A\n\nGrin, I\n\nAlili, D\n\nKoshenov, Z\n\nAkishev, Z\n\nMaksimenko, A\n\nBissenbaev, AK\n\nMatkarimov, BT\n\nSaparbaev, M\n\nIshchenko, AA\n\nMoréra, S\n\nBeiträge in Fachzeitschriften\nISI:000385327700003\n27343627.0\n10.1016/j.biochi.2016.06.011\nNone\nOxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, an AP endonuclease cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in the NIR pathway, the same AP endonuclease incises DNA 5' to an oxidized base. The majority of characterized AP endonucleases possess classic BER activities, and approximately a half of them can also have a NIR activity. At present, the molecular mechanism underlying DNA substrate specificity of AP endonucleases remains unclear mainly due to the absence of a published structure of the enzyme in complex with a damaged base. To identify critical residues involved in the NIR function, we performed biochemical and structural characterization of Bacillus subtilis AP endonuclease ExoA and compared its crystal structure with the structures of other AP endonucleases: Escherichia coli exonuclease III (Xth), human APE1, and archaeal Mth212. We found conserved amino acid residues in the NIR-specific enzymes APE1, Mth212, and ExoA. Four of these positions were studied by means of point mutations in APE1: we applied substitution with the corresponding residue found in NIR-deficient E. coli Xth (Y128H, N174Q, G231S, and T268D). The APE1-T268D mutant showed a drastically decreased NIR activity and an inverted Mg(2+) dependence of the AP site cleavage activity, which is in line with the presence of an aspartic residue at the equivalent position among other known NIR-deficient AP endonucleases. Taken together, these data show that NIR is an evolutionarily conserved function in the Xth family of AP endonucleases. \n                Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.\n\nKoshenov, Zhanat\n\n\n"
        },
        {
            "text": "\n175368\nEstimating the additional costs per life saved due to transcatheter aortic valve replacement: a secondary data analysis of electronic health records in Germany.\n\nKaier, K\n\nvon Zur Mühlen, C\n\nZirlik, A\n\nBothe, W\n\nHehn, P\n\nZehender, M\n\nBode, C\n\nStachon, P\n\nBeiträge in Fachzeitschriften\nISI:000467943600012\n30600467.0\n10.1007/s10198-018-1023-x\nNone\nAortic stenosis (AS) is the most common valvular heart disease, with a dismal prognosis when untreated. Recommended therapy is surgical (SAVR) or transcatheter (TAVR) aortic valve replacement. Based on a retrospective cohort of isolated SAVR and TAVR procedures performed in Germany in 2015 (N = 17, 26), we examine the impact of treatment selection on in-hospital mortality and total in-hospital costs for a variety of at-risk populations. Since patients were not randomized to the two treatment options, the two endpoints in-hospital mortality and reimbursement are analyzed using logistic and linear regression models with 20 predefined patient characteristics as potential confounders. Incremental cost-effectiveness ratios were calculated as a ratio of the risk-adjusted reimbursement and mortality differences with 95% confidence intervals obtained by Fieller's theorem. Our study shows that TF-TAVR is more costly that SAVR and that cost differences between the procedures vary little between patient groups. Results regarding in-hospital mortality are mixed. SAVR is the predominant procedure among younger patients. For patients older than 85 years or at intermediate and higher pre-operative risk TF-TAVR seems to be the treatment of choice. Incremental cost-effectiveness ratios (ICER) are most favorable for patients older than 85 years (ICER €154, 39, 95% CI €89, 63-€302, 62), followed by patients at higher pre-operative risk (ICER €413, 45, 95% CI €258, 27-€952, 73). A hypothetical shift from SAVR towards TF-TAVR among patients at intermediate pre-operative risk is associated with a less favorable ICER (€1, 86, 18, 95% CI €764, 32-€23, 92, 23), as the risk-adjusted mortality benefit is relatively small (- 0.97% point), while the additional reimbursement is still eminent (+€14, 64). From a German healthcare system payer's perspective, the additional costs per life saved due to TAVR are most favorable for patients older than 85 and/or at higher pre-operative risk.\n\nZirlik, Andreas\n\n\n"
        }
    ]
}