An efficient algorithm to perform local concerted movements of a chain molecule

The devising of efficient concerted rotation moves that modify only selected local portions of chain molecules is a long studied problem. Possible applications range from speeding the uncorrelated sampling of polymeric dense systems to loop reconstruction and structure refinement in protein modeling. Here, we propose and validate, on a few pedagogical examples, a novel numerical strategy that generalizes the notion of concerted rotation. The usage of the Denavit-Hartenberg parameters for chain description allows all possible choices for the subset of degrees of freedom to be modified in the move. They can be arbitrarily distributed along the chain and can be distanced between consecutive monomers as well. The efficiency of the methodology capitalizes on the inherent geometrical structure of the manifold defined by all chain configurations compatible with the fixed degrees of freedom. The chain portion to be moved is first opened along a direction chosen in the tangent space to the manifold, and then closed in the orthogonal space. As a consequence, in Monte Carlo simulations detailed balance is easily enforced without the need of using Jacobian reweighting. Moreover, the relative fluctuations of the degrees of freedom involved in the move can be easily tuned. We show different applications: the manifold of possible configurations is explored in a very efficient way for a protein fragment and for a cyclic molecule; the "local backbone volume", related to the volume spanned by the manifold, reproduces the mobility profile of all-α helical proteins; the refinement of small protein fragments with different secondary structures is addressed. The presented results suggest our methodology as a valuable exploration and sampling tool in the context of bio-molecular simulations

Impact of benign prostatic hyperplasia pharmacological treatment on transrectal prostate biopsy adverse effects

Background. Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Among 242 consecutive unselected patients who underwent prostate biopsy, after excluding those with history of prostate biopsy/surgery or using medications not for BPH, we studied 190 patients. On the 15th day after procedure patients were questioned about symptoms lasting over a week and classified according to pharmacological BPH treatment. Results. Thirty-three patients (17%) were using alpha-blocker exclusively, five (3%) 5-alpha-reductase inhibitor exclusively, twelve (6%) patients used both medications, and 140 (74%) patients used none. There was no difference in regard to age among groups (P = 0.5). Postbiopsy adverse effects occurred as follows: hematuria 96 (50%), hematospermia 53 (28%), hematochezia 22 (12%), urethrorrhagia 19 (10%), fever 5 (3%), and pain 20 (10%). There was a significant negative correlation between postbiopsy hematuria and BPH pharmacological treatment with stronger correlation for combined use of 5-alpha-reductase inhibitor and alpha-blocker over 6 months (P = 0.0027). Conclusion. BPH pharmacological treatment, mainly combined for at least 6 months seems to protect against prostate biopsy adverse effects. Future studies are necessary to confirm our novel results. © 2014 Marina Zamuner et al.Benign prostatic hyperplasia (BPH) pharmacological treatment may promote a decrease in prostate vascularization and bladder neck relaxation with theoretical improvement in prostate biopsy morbidity, though never explored in the literature. Methods. Amongsem informaçãosem informação(2013) Overview: Prostate Cancer. How Many Men Get Prostate Cancer?, , http://www.cancer.org/acs/groups/cid/documents/webcontent/003072-pdf.pdfRabbani, F., Stroumbakis, N., Kava, B.R., Cookson, M.S., Fair, W.R., Incidence and clinical significance of false-negative sextant prostate biopsies (1998) Urologe - Ausgabe A, 37 (6), p. 660Thompson, I.M., Pauler, D.K., Goodman, P.J., Tangen, C.M., Lucia, M.S., Parnes, H.L., Minasian, L.M., Coltman Jr., C.A., Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter (2004) New England Journal of Medicine, 350 (22), pp. 2239-2246+2321. , DOI 10.1056/NEJMoa031918Ahrens, M.J., Bertin, P.A., Vonesh, E.F., Meade, T.J., Catalona, W.J., Georganopoulou, D., PSA enzymatic activity: A new biomarker for assessing prostate cancer aggressiveness (2013) Prostate, 73 (16), pp. 1731-1737. , 10.1002/pros.22714Rifkin, M.D., Alexander, A.A., Pisarchick, J., Matteucci, T., Palpable masses in the prostate: Superior accuracy of US-guided biopsy compared with accuracy of digitally guided biopsy (1991) Radiology, 179 (1), pp. 41-42. , 2-s2.0-0025969342Loeb, S., Vellekoop, A., Ahmed, H.U., Catto, J., Emberton, M., Nam, R., Rosario, D.J., Lotan, Y., Systematic review of complications of prostate biopsy (2013) European Urology, 64 (6), pp. 876-892. , 10.1016/j.eururo.2013.05.049Shen, P.-F., Zhu, Y.-C., Wei, W.-R., Li, Y.-Z., Yang, J., Li, Y.-T., Li, D.-M., Zeng, H., The results of transperineal versus transrectal prostate biopsy: A systematic review and meta-analysis (2012) Asian Journal of Andrology, 14 (2), pp. 310-315. , 2-s2.0-84858059084 10.1038/aja.2011.130Kravchick, S., Cytron, S., Mamonov, A., Peled, R., Linov, L., Effect of short-term dutasteride therapy on prostate vascularity in patients with benign prostatic hyperplasia: A pilot study (2009) Urology, 73 (6), pp. 1274-1278. , 2-s2.0-67349198057 10.1016/j.urology.2008.08.461Liao, C.-H., Guh, J.-H., Chueh, S.-C., Yu, H.-J., Anti-angiogenic effects and mechanism of prazosin (2011) Prostate, 71 (9), pp. 976-984. , 2-s2.0-79955575350 10.1002/pros.21313Keledjian, K., Borkowski, A., Kim, G., Isaacs, J.T., Jacobs, S.C., Kyprianou, N., Reduction of human prostate tumor vascularity by the α1- adrenoceptor antagonist terazosin (2001) Prostate, 48 (2), pp. 71-78. , DOI 10.1002/pros.1083Angulo, J., Cuevas, P., Fernández, A., La Fuente, J.M., Allona, A., Moncada, I., De Tejada, I.S., Tadalafil enhances the inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck (2012) The Journal of Sexual Medicine, 9 (9), pp. 2293-2306. , 10.1111/j.1743-6109.2012.02821.xReis, L.O., Zani, E.L., Alonso, J.C., Simões, F.A., Rejowski, R.F., Ferreira, U., Does the criterion for prostate biopsy indication impact its accuracy? A prospective population-based outpatient clinical setting study (2011) Actas Urologicas Espanolas, 35 (1), pp. 10-14. , 2-s2.0-79151485525 10.1016/j.acuro.2010.06.011Junqueira, V.C.N., Zogbi, O., Cologna, A., Dos Reis, R.B., Tucci, Jr.S., Reis, L.O., Westphalen, A.C., Muglia, V.F., Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? (2012) Ultrasound in Medicine and Biology, 38 (10), pp. 1689-1694. , 10.1016/j.ultrasmedbio.2012.06.006Reis, L.O., Reinato, J.A.S., Silva, D.C., Matheus, W.E., Denardi, F., Ferreira, U., The impact of core biopsy fragmentation in prostate cancer (2010) International Urology and Nephrology, 42 (4), pp. 965-969. , 2-s2.0-78751646334 10.1007/s11255-010-9720-0Anastasiadis, A., Zapała, L., Cordeiro, E., Antoniewicz, A., Dimitriadis, G., De Reijke, T., Complications of prostate biopsy (2013) Expert Review of Anticancer Therapy, 13 (7), pp. 829-837. , 10.1586/14737140.2013.811056Campeggi, A., Ouzaid, I., Xylinas, E., Lesprit, P., Hoznek, A., Vordos, D., Abbou, C.C., De La Taille, A., Acute bacterial prostatitis after transrectal ultrasound-guided prostate biopsy: Epidemiological, bacteria and treatment patterns from a 4-year prospective study (2013) International Journal of Urology, 21 (2), pp. 152-155. , 10.1111/iju.12207Pinkhasov, G.I., Lin, Y.-K., Palmerola, R., Smith, P., Mahon, F., Kaag, M.G., Dagen, J.E., Raman, J.D., Complications following prostate needle biopsy requiring hospital admission or emergency department visits - Experience from 1000 consecutive cases (2012) BJU International, 110, pp. 369-374. , 2-s2.0-84856569661 10.1111/j.1464-410X.2011.10926.xPeyromaure, M., Ravery, V., Messas, A., Toublanc, M., Boccon-Gibod, L., Boccon-Gibod, L., Pain and morbidity of an extensive prostate 10-biopsy protocol: A prospective study in 289 patients (2002) Journal of Urology, 167 (1), pp. 218-221Ozdal, O.L., Ozden, C., Benli, K., Gokkaya, S., Bulut, S., Memis, A., Effect of short-term finasteride therapy on peroperative bleeding in patients who were candidates for transurethral resection of the prostate (TUR-P): A randomized controlled study (2005) Prostate Cancer and Prostatic Diseases, 8 (3), pp. 215-218. , DOI 10.1038/sj.pcan.4500818, PII 4500818Pastore, A.L., Mariani, S., Barrese, F., Palleschi, G., Valentini, A.M., Pacini, L., Petrozza, V., Cappa, M., Transurethral resection of prostate and the role of pharmacological treatment with dutasteride in decreasing surgical blood loss (2013) Journal of Endourology, 27 (1), pp. 68-70. , 10.1089/end.2012.0231Hahn, R.G., Fagerström, T., Tammela, T.L.J., Van Vierssen Trip, O., Beisland, H.O., Duggan, A., Morrill, B., Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride (2007) BJU International, 99 (3), pp. 587-594. , 2-s2.0-33846934500 10.1111/j.1464-410X.2006.06619.xArratia-Maqueo, J.A., Garza-Cortés, R., Gómez-Guerra, L.S., Cortés-Gonzlez, J.R., Effect of one month treatment with dutasteride on transurethral resection of the prostate (2010) Actas Urologicas Espanolas, 34 (10), pp. 866-869. , 2-s2.0-78049478337 10.1016/j.acuro.2010.06.00

Is Metabolic syndrome truly a risk factor for male lower urinary tract symptoms or just an epiphenomenon?

To define whether the association of male lower urinary tract symptoms (LUTS) and metabolic syndrome (MS) is real or simply an epiphenomenon, 490 male adults (mean age 58 ± 9 years) underwent International Prostate Symptom Score (IPSS), physical and prostate digital examinations, blood analysis, and urinary tract transabdominal ultrasound with prostate volume measurement. Mild, moderate, and severe LUTS were found in 350 (71.4%), 116 (23.7%), and 24 (4.9%) patients, respectively. MS was present in 198 (40.4%) patients, representing 37.4% (131 of 350) of those with mild LUTS, 46.5% (54 of 116) of those with moderate, and 54.1% (13 of 24) of those with severe. The odds ratio of MS having moderate or severe LUTS was 2.1. MS was more common in older age, higher body mass index, and larger prostate size. Moderate and severe LUTS were more frequent in older age, lower levels of high density cholesterol, and higher blood pressure. Older age and body mass index had significant relative risk for lower urinary tract symptoms and only age remained independent factor for LUTS on multivariate analysis. Our results suggest that the association of male LUTS, prostate volume, and MS might be coincidental and related to older age2014sem informaçã

Mn-Containing Bioactive Glass-Ceramics: BMP-2-Mimetic Peptide Covalent Grafting Boosts Human-Osteoblast Proliferation and Mineral Deposition

The addition of Mn in bioceramic formulation is gaining interest in the field of bone implants. Mn activates human osteoblast (h-osteoblast) integrins, enhancing cell proliferation with a dose-dependent effect, whereas Mn-enriched glasses induce inhibition of Gram-negative or Gram-positive bacteria and fungi. In an effort to further optimize Mn-containing scaffolds' beneficial interaction with h-osteoblasts, a selective and specific covalent functionalization with a bioactive peptide was carried out. The anchoring of a peptide, mapped on the BMP-2 wrist epitope, to the scaffold was performed by a reaction between an aldehyde group of the peptide and the aminic groups of silanized Mn-containing bioceramic. SEM-EDX, FT-IR, and Raman studies confirmed the presence of the peptide grafted onto the scaffold. In in vitro assays, a significant improvement in h-osteoblast proliferation, gene expression, and calcium salt deposition after 7 days was detected in the functionalized Mn-containing bioceramic compared to the controls

Integration of ground remote sensing surveys and archaeological excavation to characterize the medieval mound (Scarlino, Tuscany-Italy)

The landscape of Scarlino (Grosseto, Italy) has been studied by the Department of Archaeology (University of Siena) since 1979. The archaeological site was identified in vertical air photos, but the unavailability of GPS devices at the time made location in the field difficult. Aerial photo analysis allowed us to interpret the evidence as a triple enclosure. This paper presents the data collected with magnetic, GPR and Automatic Resistivity Profiler (ARP) surveys with the purpose of opening a..

Integrating demand uncertainty in inventory routing for recyclable waste collection

Osteoblast cell adhesion to the extracellular matrix is established through two main pathways: one is mediated by the binding between integrin and a minimal adhesion sequence (RGD) on the extracellular protein, the other is based on the interactions between transmembrane proteoglycans and heparin-binding sequences found in many matrix proteins. The aim of this study is the evaluation in an in vivo endosseous implant model of the early osteogenic response of the peri-implant bone to a biomimetic titanium surface functionalized with the retro-inverso 2DHVP peptide, an analogue of Vitronectin heparin binding site. The experimental plan is based on a bilateral study design of Control and 2DHVP implants inserted respectively in the right and left femur distal metaphysis of adult male Wistar rats (n=16) weighing about 300 gr and evaluated after 15 days. Fluorochromic bone vital markers, were given at specific time frame, in order to monitor the dynamic of new bone deposition. The effect inducted by the peptidomimetic coating on the surrounding bone were qualitatively and quantitatively evaluated by means of static and dynamic histomorphometric analyses performed within three concentric and subsequent circular Regions of Interest (ROI) of equivalent thickness (220 μm), ROI1 adjacent to the interface, ROI2, the middle, and ROI3 the farthest. The data indicated that these functionalized implants stimulated a higher bone apposition rate (p<0,01) and larger and rapid osteoblast activation in terms of mineralising surface within ROI1 compared to the Control (p<0,01). These higher osteoblast recruitment and activation leads to a greater bone to implant contact reached for DHVP samples (p<0,5). This represents an initial stimulus of the osteogenic activity that might results in a faster and better osteointegration process

Can strenuous exercise harm the heart? Insights from a study of cardiovascular neural regulation in amateur triathletes

Regular exercise is recommended to improve the cardiovascular risk profile. However, there is growing evidence that extreme volumes and intensity of long-term exertion may increase the risk of acute cardiac events. The aim of this study is to investigate the aftereffects of regular, strenuous physical training on the cardiovascular neural regulation in a group of amateur triathletes compared to age-matched sedentary controls. We enrolled 11 non-elite triathletes (4 women, age 24 +/- 4 years), who had refrained from exercise for 72 hours, and 11 age-matched healthy non-athletes (3 women, age 25 +/- 2 years). Comprehensive echocardiographic and cardiopulmonary exercise tests were performed at baseline. Electrocardiogram, non-invasive blood pressure, respiratory activity, and muscle sympathetic nerve activity (MSNA) were continuously recorded in a supine position (REST) and during an incremental 15 degrees step-wise head-up tilt test up to 75 degrees (TILT). Blood samples were collected for determination of stress mediators. Autoregressive spectral analysis provided the indices of the cardiac sympathetic (LFRR) and vagal (HFRR) activity, the vascular sympathetic control (LFSAP), and the cardiac sympatho-vagal modulation (LF/HF). Compared to controls, triathletes were characterized by greater LFRR, LF/HF ratio, LFSAP, MSNA, and lower HFRR at REST and during TILT, i.e. greater overall cardiovascular sympathetic modulation together with lower cardiac vagal activity. Cortisol and adrenocorticotropic hormone concentrations were also higher in triathletes. In conclusion, triathletes were characterized by signs of sustained cardiovascular sympathetic overactivity. This might represent a risk factor for future cardiovascular events, given the known association between chronic excessive sympathetic activity and increased cardiovascular risk

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome