Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

AimsIn this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril.Methods and resultsIn a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P < 0.001) to that observed in patients who had not experienced any dose reduction (HR 0.79, 95% CI 0.71-0.88, P < 0.001).ConclusionsIn PARADIGM-HF, study medication dose reduction identified patients at higher risk of a major cardiovascular event. The magnitude of benefit for patients on lower doses of sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs

Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin

BACKGROUND: Aging and sun exposure are the leading causes of skin cancer. It has been shown that epigenetic changes, such as DNA methylation, are well established mechanisms for cancer, and also have emerging roles in aging and common disease. Here, we directly ask whether DNA methylation is altered following skin aging and/or chronic sun exposure in humans. RESULTS: We compare epidermis and dermis of both sun-protected and sun-exposed skin derived from younger subjects (under 35 years old) and older subjects (over 60 years old), using the Infinium HumanMethylation450 array and whole genome bisulfite sequencing. We observe large blocks of the genome that are hypomethylated in older, sun-exposed epidermal samples, with the degree of hypomethylation associated with clinical measures of photo-aging. We replicate these findings using whole genome bisulfite sequencing, comparing epidermis from an additional set of younger and older subjects. These blocks largely overlap known hypomethylated blocks in colon cancer and we observe that these same regions are similarly hypomethylated in squamous cell carcinoma samples. CONCLUSIONS: These data implicate large scale epigenomic change in mediating the effects of environmental damage with photo-aging. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0644-y) contains supplementary material, which is available to authorized users

Forward ray tracing for image projection prediction and surface reconstruction in the evaluation of corneal topography systems

A forward ray tracing (FRT) model is presented to determine the exact image projection in a general corneal topography system. Consequently, the skew ray error in Placido-based topography is demonstrated. A quantitative analysis comparing FRT-based algorithms and Placido-based algorithms in reconstructing the front surface of the cornea shows that arc step algorithms are more sensitive to noise (imprecise). Furthermore, they are less accurate in determining corneal aberrations particularly the quadrafoil aberration. On the other hand, FRT-based algorithms are more accurate and more precise showing that point to point corneal topography is superior compared to its Placido-based counterpart

Status Kerentanan Aedes Aegypti Vektor Demam Berdarah Dengue di Kota Padang

Salah satu upaya untuk mengurangi kasus DBD adalah dengan pengendalian vektor DBD dengan larvisida. Temephos merupakan salah satu insektisida yang telah digunakan lebih dari 30 tahun dan berfungsi mengendalikan larva vektor. Penggunaan temephos yang tidak sesuai aturan dapat menyebabkan penurunan kerentanan pada vektor DBD.  Tujuan penelitian ini  adalah untuk  menilai  status  kerentanan larva Aedes aegypti di tiga kecamatan di Kota Padang. Penelitian ini menggunakan post  test  only  with  control  group design. Telur diambil dan dipelihara di laboratorium hingga mencapai larva instar III/IV. Uji kerentanan untuk temephos dilakukan berdasarkan standar WHO. Hasil penelitian menunjukkan pada Kecamatan Kuranji, kematian larva pada konsentrasi 0,005 mg/L sebesar 10%, 0,01 mg/L sebesar 45%, 0,02 mg/L sebesar 86%, dan pada konsentrasi 0,03 mg/L sebesar 100%. Pada Kecamatan Koto Tangah, kematian larva pada konsentrasi 0,005 mg/L sebesar 24%, 0,01 mg/L sebesar 48%, 0,02 mg/L sebesar 99%, dan pada konsentrasi 0,03 mg/L sebesar 100%. Pada Kecamatan Padang Timur pada konsentrasi 0,005 mg/L didapatkan kematian larva sebesar 12%, pada 0,01 mg/L sebesar 43%, pada 0,02 mg/L sebesar 99%, dan pada 0,03 mg/L sebesar 100%. Hasil uji One way-Anova adalah bermakna dengan nilai p<0,05 pada ketiga kecamatan dan LC99 sedikit diatas 0,02 mg/L. Simpulan penelitian ini adalah status kerentanan Aedes aegypti terhadap temephos di tiga kecamatan berkisar antara rentan dan toleran, belum mencapai resisten sehingga temephos masih dapat digunakan dalam pengendalian vektor DBD

Esophageal foreign body removal using endoscopy in cat

A 10-months-old cross long hair cat named Casper with clinical symptom of vomiting mixed with slimy cat feed was referred to Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Bogor Agricultural University to endoscopy examination and therapy. The owner believed that Casper ate a 5 cm long sewing needle a few days earlier. The history and physical examination were examined at DNA Clinic with symptoms of lack of appetite and becoming quieter and calmer. Radiogram showed the needle was in thorax area with a vertical needle penetrating the esophageal wall. Removal of the needle and observation of the esophagus area were done using endoscopy under general anesthesia. Using endoscopy, it was known that the needle was swallowed along with the sewing thread with position of all needles penetrating the esophagus wall and leaving a small amount of thread on the lumen. The needle was pulled back to the esophageal lumen by pulling the remaining thread and then both needle and the thread were pulled back out using an alligator grasping forceps that used through working channel. Therapy given after endoscopy was antibiotics and anti-emetics

Kasus swimmer syndrome pada seekor anak kucing

Swimmer syndrome merupakan kondisi gangguan muskuloskeletal kongenital yang dapat terjadi pada anak kucing yang menyebabkan kaki menjadi terbuka ke arah lateral dan menyebabkan postur seperti katak. Seekor anak kucing persia betina bernama NN berusia 2 minggu dibawa ke Klinik Hewan Pet Vet menunjukkan gejala klinis mengalami kesulitan berjalan dengan gerakan seperti berenang. Pemeriksaan fisik menunjukkan kucing memiliki flat chest sehingga pernafasan terlihat dangkal dan cepat. Anak kucing didiagnosa mengalami swimmer syndrome. Terapi yang dilakukan terhadap anak kucing yaitu dengan memakaikan alat penahan pada bagian dada yang berbentuk setengah lingkaran. Alat ini diikatkan melingkari bagian dada dan dikenakan setiap hari. Perkembangan yang cukup baik ditunjukkan setelah 7 hari, dimana NN mulai dapat mengangkat tubuh dan dapat berjalan secara normal. Penggunaan alat bantu sebagai terapi pada kasus ini tetap diteruskan karena pembentukan tulang bagian dada yang belum sempurna.Swimmer syndrome merupakan kondisi gangguan muskuloskeletal kongenital yang dapat terjadi pada anak kucing yang menyebabkan kaki menjadi terbuka ke arah lateral dan menyebabkan postur seperti katak. Seekor anak kucing persia betina bernama NN berusia 2 minggu dibawa ke Klinik Hewan Pet Vet menunjukkan gejala klinis mengalami kesulitan berjalan dengan gerakan seperti berenang. Pemeriksaan fisik menunjukkan kucing memiliki flat chest sehingga pernafasan terlihat dangkal dan cepat. Anak kucing didiagnosa mengalami swimmer syndrome. Terapi yang dilakukan terhadap anak kucing yaitu dengan memakaikan alat penahan pada bagian dada yang berbentuk setengah lingkaran. Alat ini diikatkan melingkari bagian dada dan dikenakan setiap hari. Perkembangan yang cukup baik ditunjukkan setelah 7 hari, dimana NN mulai dapat mengangkat tubuh dan dapat berjalan secara normal. Penggunaan alat bantu sebagai terapi pada kasus ini tetap diteruskan karena pembentukan tulang bagian dada yang belum sempurna

Measure-Based Inconsistency-Tolerant Maintenance of Database Integrity

[EN] To maintain integrity, constraint violations should be prevented or repaired. However, it may not be feasible to avoid inconsistency, or to repair all violations at once. Based on an abstract concept of violation measures, updates and repairs can be checked for keeping inconsistency bounded, such that integrity violations are guaranteed to never get out of control. This measure-based approach goes beyond conventional methods that are not meant to be applied in the presence of inconsistency. It also generalizes recently introduced concepts of inconsistency-tolerant integrity maintenance.Partially supported by FEDER and the Spanish grants TIN2009-14460-C03 and TIN2010-17139Decker, H. (2013). Measure-Based Inconsistency-Tolerant Maintenance of Database Integrity. Lecture Notes in Computer Science. 7693:149-173. https://doi.org/10.1007/978-3-642-36008-4_7S1491737693Abiteboul, S., Hull, R., Vianu, V.: Foundations of Databases. 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Springer, Heidelberg (2011)Decker, H.: Causes of the Violation of Integrity Constraints for Supporting the Quality of Databases. In: Murgante, B., Gervasi, O., Iglesias, A., Taniar, D., Apduhan, B.O. (eds.) ICCSA 2011, Part V. LNCS, vol. 6786, pp. 283–292. Springer, Heidelberg (2011)Decker, H.: Inconsistency-tolerant Integrity Checking based on Inconsistency Metrics. In: König, A., Dengel, A., Hinkelmann, K., Kise, K., Howlett, R.J., Jain, L.C. (eds.) KES 2011, Part II. LNCS, vol. 6882, pp. 548–558. Springer, Heidelberg (2011)Decker, H.: Partial Repairs that Tolerate Inconsistency. In: Eder, J., Bielikova, M., Tjoa, A.M. (eds.) ADBIS 2011. LNCS, vol. 6909, pp. 389–400. Springer, Heidelberg (2011)Decker, H.: Consistent Explanations of Answers to Queries in Inconsistent Knowledge Bases. In: Roth-Berghofer, T., Tintarev, N., Leake, D. (eds.) Explanation-aware Computing, Proc. IJCAI 2011 Workshop ExaCt 2011, pp. 71–80 (2011), http://exact2011.workshop.hm/index.phpDecker, H., Martinenghi, D.: Classifying integrity checking methods with regard to inconsistency tolerance. In: Proc. PPDP 2008, pp. 195–204. ACM Press (2008)Decker, H., Martinenghi, D.: Modeling, Measuring and Monitoring the Quality of Information. In: Heuser, C.A., Pernul, G. (eds.) ER 2009. LNCS, vol. 5833, pp. 212–221. Springer, Heidelberg (2009)Decker, H., Martinenghi, D.: Inconsistency-tolerant Integrity Checking. IEEE TKDE 23(2), 218–234 (2011)Decker, H., Muñoz-Escoí, F.D.: Revisiting and Improving a Result on Integrity Preservation by Concurrent Transactions. In: Meersman, R., Dillon, T., Herrero, P. (eds.) OTM 2010 Workshops. LNCS, vol. 6428, pp. 297–306. Springer, Heidelberg (2010)Dung, P., Kowalski, R., Toni, F.: Dialectic Proof Procedures for Assumption-based Admissible Argumentation. 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Reasoning 52(7), 978–999 (2011)Lloyd, J., Sonenberg, L., Topor, R.: Integrity constraint checking in stratified databases. J. Logic Programming 4(4), 331–343 (1987)Lozinskii, E.: Resolving contradictions: A plausible semantics for inconsistent systems. J. Automated Reasoning 12(1), 1–31 (1994)Ma, Y., Qi, G., Hitzler, P.: Computing inconsistency measure based on paraconsistent semantics. J. Logic Computation 21(6), 1257–1281 (2011)Martinenghi, D., Christiansen, H.: Transaction Management with Integrity Checking. In: Andersen, K.V., Debenham, J., Wagner, R. (eds.) DEXA 2005. LNCS, vol. 3588, pp. 606–615. Springer, Heidelberg (2005)Martinenghi, D., Christiansen, H., Decker, H.: Integrity Checking and Maintenance in Relational and Deductive Databases and Beyond. In: Ma, Z. (ed.) Intelligent Databases: Technologies and Applications, pp. 238–285. IGI Global (2006)Martinez, M.V., Pugliese, A., Simari, G.I., Subrahmanian, V.S., Prade, H.: How Dirty Is Your Relational Database? An Axiomatic Approach. In: Mellouli, K. (ed.) ECSQARU 2007. LNCS (LNAI), vol. 4724, pp. 103–114. Springer, Heidelberg (2007)Meyer, J., Wieringa, R. (eds.): Deontic Logic in Computer Science. Wiley (1994)Nicolas, J.M.: Logic for improving integrity checking in relational data bases. Acta Informatica 18, 227–253 (1982)Plexousakis, D., Mylopoulos, J.: Accommodating Integrity Constraints During Database Design. In: Apers, P.M.G., Bouzeghoub, M., Gardarin, G. (eds.) EDBT 1996. LNCS, vol. 1057, pp. 495–513. Springer, Heidelberg (1996)Rahm, E., Do, H.: Data Cleaning: Problems and Current Approaches. Data Engineering Bulletin 23(4), 3–13 (2000)Sadri, F., Kowalski, R.: A theorem-proving approach to database integrity. In: Minker, J. (ed.) Foundations of Deductive Databases and Logic Programming, pp. 313–362. Morgan Kaufmann (1988)Thimm, M.: Measuring Inconsistency in Probabilistic Knowledge Bases. In: Proc. 25th UAI, pp. 530–537. 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Refolding by High Pressure of a Toxin Containing Seven Disulfide Bonds: Bothropstoxin-1 from Bothrops jararacussu

Aggregation is a serious obstacle for recovery of biologically active heterologous proteins from inclusion bodies (IBs) produced by recombinant bacteria. E. coli transformed with a vector containing the cDNA for Bothropstoxin-1 (BthTx-1) expressed the recombinant product as IBs. In order to obtain the native toxin, insoluble and aggregated protein was refolded using high hydrostatic pressure (HHP). IBs were dissolved and refolded (2 kbar, 16 h), and the effects of protein concentration, as well as changes in ratio and concentration of oxido-shuffling reagents, guanidine hydrochloride (GdnHCl), and pH in the refolding buffer, were assayed. A 32% yield (7.6 mg per liter of bacterial culture) in refolding of the native BthTx-1 was obtained using optimal conditions of the refolding buffer (Tris–HCl buffer, pH 7.5, containing 3 mM of a 2:3 ratio of GSH/GSSG, and 1 M GdnHCl). Scanning electron microscopy (SEM) showed that that disaggregation of part of IBs particles occurred upon compression and that the morphology of the remaining IBs, spherical particles, was not substantially altered. Dose-dependent cytotoxic activity of high-pressure refolded BthTx-1 was shown in C2C12 muscle cells