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The development of health indicators to measure healthy life expectancy (HLE) is an active field of research aimed at summarizing the health of a population. Although many health indicators have emerged in the literature as critical metrics in public health assessments, the methods and data to conduct this evaluation vary considerably in nature and quality. Traditionally, health data collection relies on population surveys. However, these studies, typically of limited size, encompass only a small yet representative segment of the population. This limitation can necessitate the separate estimation of incidence and mortality rates, significantly restricting the available analysis methods. In this article, we leverage an extract from the French National Hospital Discharge database to define health indicators. Our analysis focuses on the resulting Disease-Free Life Expectancy (Dis-FLE) indicator, which provides insights based on the hospital trajectory of each patient admitted to hospital in France during 2008–2013. Through this research, we illustrate the advantages and disadvantages of employing large clinical datasets as the foundation for more robust health indicators. We shed light on the opportunities that such data offer for a more comprehensive understanding of the health status of a population. In particular, we estimate age-dependent hazard rates associated with sex, alcohol abuse, tobacco consumption, and obesity, as well as geographic location. Simultaneously, we delve into the challenges and limitations that arise when adopting such a data-driven approach. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most prevalent cancers in Japan with hepatocellular carcinoma (HCC) as the major histological subtype. Successful novel treatments for HCC have been reported; however, recurrences or metastasis may occur, which results in poor prognoses and high mortality of HCC patients. Fascin, an actin-bundling protein, regulates cell adhesion, migration, and invasion. Its overexpression positively correlates with poor prognosis of malignant tumors, and Fascin is considered as one of the tumor biomarkers and therapeutic target proteins. In this study, we attempted to reveal the relationship between Fascin and HCC using HLE, one of the human HCC cell lines. We performed the study with classical immunocytochemistry and recently developed techniques, such as wound-healing assay, spheroid cultivation, and low-vacuum scanning electron microscopy (LV-SEM). Non-Fascin-knockdown (FKD) cell spheroid had a regular spherical appearance with tight cell–cell connections, while FKD cell spheroid had an irregular shape with loose cell–cell connections. Cells of non-FKD spheroid presented fibrous protrusions on the cell surface, contrarily, cells of FKD spheroids showed bulbous-shaped protrusions. Morphological observation of FKD and non-FKD HLE spheroids were performed using LV-SEM. Our study may help to reveal the roles of Fascin in the process of HCC formation and its malignancy. [ABSTRACT FROM AUTHOR]

The development of health indicators to measure healthy life expectancy (HLE) is an active field of research aimed at summarizing the health of a population. Although many health indicators have emerged in the literature as critical metrics in public health assessments, the methods and data to conduct this evaluation vary considerably in nature and quality. Traditionally, health data collection relies on population surveys. However, these studies, typically of limited size, encompass only a small yet representative segment of the population. This limitation can necessitate the separate estimation of incidence and mortality rates, significantly restricting the available analysis methods. In this article, we leverage an extract from the French National Hospital Discharge database to define health indicators. Our analysis focuses on the resulting Disease-Free Life Expectancy (Dis-FLE) indicator, which provides insights based on the hospital trajectory of each patient admitted to hospital in France during 2008–2013. Through this research, we illustrate the advantages and disadvantages of employing large clinical datasets as the foundation for more robust health indicators. We shed light on the opportunities that such data offer for a more comprehensive understanding of the health status of a population. In particular, we estimate age-dependent hazard rates associated with sex, alcohol abuse, tobacco consumption, and obesity, as well as geographic location. Simultaneously, we delve into the challenges and limitations that arise when adopting such a data-driven approach.

Female hybrids of the cross Chironomus t. thummi female × Ch. t. piger male which are largely affected by the sterility inducing Rud syndrome were backcrossed with males of both parental strains. The aim of the study was to provide information about those egg volumes that are insufficient for a normal embryogenesis and to ascertain whether in the hybrids the lethally small egg size represents a new abnormal trait of the Rud syndrome. The egg masses obtained contain eggs of very different sizes with volumes ranging from 0.5 nl to 3.49 nl. Embryo mortality is unusually frequent in those eggs of the backcrosses and of the parental strains that have volumes smaller than 1.5 nl. An egg volume of 1.5 nl represents in Ch. thummi the lower limit for those volumes that are sufficient for a normal embryogenesis. Mortality increases with decreasing egg size, reaching 100% in backcross eggs with volumes of 0.99 nl and smaller. Small egg size is a new trait of the Rud syndrome affected thummi female × piger male hybrids. This trait is part of a postzygotic reproductive isolation barrier between thummi and piger and manifests first in the backcrosses. Most backcross eggs show volumes between 1.5 nl and 2.99 nl. Within this volume range the amount of mortality does not depend upon egg volume. Here, embryo death is great in the backcrosses but normal in the parental strains. The high frequency of embryo death in the backcrosses must be predominantly due to the action of the Rud syndrome and a second hybrid syndrome, called HLE syndrome. Since further characteristic traits of these syndromes could be detected in surviving backcross individuals, the study demonstrates the occurrence of the syndromes in this generation also. Therefore, the postzygotic reproductive isolation mechanism of both hybrid syndromes is effective in the hybrids and in their progeny as well.

Background: Little empirical research examines the process in which home literacy environment (HLE) in toddlerhood is associated with preschoolers' vocabulary and decoding skills using a large-scale dataset. Objective: The purposes of the current study were to (a) examine the differential effect of HLE in toddlerhood on preschoolers' vocabulary versus decoding skills, and (b) test a mediational role of children's vocabulary in the association between HLE and decoding skills based on a phonological approach (i.e. examining the contribution of vocabulary to the acquisition of decoding skills). Method: Using the ECLS-B dataset, the study investigated HLE in toddlerhood and vocabulary and decoding skills at preschool age among nearly 6050 monolingual English-speaking, typically developing children and their parents of diverse ethnic and socioeconomic backgrounds. Results: HLE measured in toddlerhood predicted both vocabulary and decoding skills measured at preschool age. Vocabulary at preschool age partially accounted for the effect of HLE at age two on decoding skills at preschool age. In other words, HLE at age two indirectly influenced children's decoding skills at preschool age through vocabulary at preschool age. Conclusion: Enriched HLE during the toddlerhood leads to preschoolers' increased vocabulary, which consequently results in preschoolers' proficiency of decoding skills. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA) are produced against lysozomal constituents and primary granules of myeloid cells (Neutrophiles & monocytes) in some rheumatic diseases and wegner’s granulomtosis (WG). This antibodies not only may related to onset of vasculitis lesions, but also have a valuable diagnostic tool, thus, first we tired to evaluated the prevalence of this antibodies in 65 serum of patients with RA and 42 serum of patients with SLE. By using of indirect immunoflourescence assay (IFA), two staining patterns are recognized: Cytoplasmic (C-ANCA) pattern which in 80% of results from anti-PR3, and prenuclear (P-ANCA) pattern, which can result from any antibody directed to myeloperoxidase (MPO), cathepsin G (CG) lactoferrin (LF), elastsae (HLE) and lysozyme (LZ). The sensitivity and specificity for SLE from 1:128 serum dilution was 8% and 85.1% respectively, and for RA from 1:16 dilution was 32.2% and 87.5% respectively. Of the 19 SLE, ANCA positive patients 18 (94.7%) had P-ANCA and 1 patient (5.3%) had C-ANCA and of the 23 RA, ANCA positive patients, 17 (73.9%) had P-ANCA and 6 patients (26.1%) had C-ANCA.

Not all young children benefit from book exposure in preschool age. It is claimed that the ability to hold information in mind ( short- term memory), to ignore distraction ( inhibition), and to focus attention and stay focused ( sustained attention) may have a moderating effect on children's reactions to the home literacy environment. In a group of 228 junior kindergarten children with a native Dutch background, with a mean age of 54.29 months (SD = 2.12 months), we explored therefore the relationship between book exposure, cognitive control and early literacy skills. Parents filled in a HLE questionnaire (book sharing frequency and an author recognition checklist as indicator of parental leisure reading habits), and children completed several tests in individual sessions with the researcher (a book-cover recognition test, PPVT, letter knowledge test, the subtests categories and patterns of the SON, and cognitive control measures namely digit span of the KABC, a peg tapping task and sustained attention of the ANT). Main findings were: (1) Children's storybook knowledge mediated the relationship between home literacy environment and literacy skills. (2) Both vocabulary and letter knowledge were predicted by book exposure. (3) Short-term memory predicted vocabulary over and above book exposure. (4) None of the cognitive control mechanisms moderated the beneficial effects of book exposure. [ABSTRACT FROM AUTHOR]

The synthesis of novel monocyclic di- and triphenyl-substituted hydroperoxysultims rac-cis 7 and 8 and sultams 11 and 12, as well as the 3-oxosultams 15 and 16, by oxidation of corresponding salts 1 and 2 with H 2 O 2 in acetic acid is described. For the first time, it was possible to isolate a 3-hydroperoxide (3a) and also to determine the position of the primary oxidizing attack on the C-3 atom of isothiazolium salts 1, which have generally a much lower oxidation reactivity. Novel 3-hydroxysultams 13 and 14 were obtained by oxidation reaction of salts 1 and 2 with magnesium monoperoxyphthalate (MMPP) in acetonitrile in the ultrasound bath. [ABSTRACT FROM AUTHOR]

Epidermal hyperproliferation and neutrophil infiltration are major histopathological changes observed in psoriasis. Neutrophils contain human leukocyte elastase (HLE), which is released at sites of inflammation. HLE is present in psoriatic lesions and induces keratinocyte hyperproliferation in vitro and in vivo. To determine the molecular mechanisms linking a proteolytic effect of HLE and epidermal hyperproliferation, we examined the effects of HLE-induced signaling in human keratinocytes. Application of 100 nM HLE resulted in a transient calcium influx in FURA2-loaded human HaCaT keratinocytes observed by single-cell fluorescence imaging. The calcium signal was concentration dependent and was inhibited by addition of the HLE inhibitors elafin and secretory leukocyte protease inhibitor. The calcium signal was neither inhibited by pertussis toxin, cholera, or by pre-stimulation with trypsin. Incubation with the tyrosine kinase inhibitor genistein, a protein kinase C inhibitor, as well as incubation with neutralizing EGFR antibodies abolished the HLE-induced calcium influx. The supernatants of HLE-treated keratinocytes induced a calcium signal in separately cultured keratinocytes. This could be inhibited by the addition of anti-TGF-α antibodies. Application of HLE-induced keratinocyte proliferation, which could be inhibited by neutralizing of anti-EGFR and anti-TGF-α antibodies. Herein we demonstrate that HLE induces keratinocyte proliferation by proteolytic activation of an EGFR signaling cascade involving TGF-α. [ABSTRACT FROM AUTHOR]

(1) Background: the objective of this study was to improve certain psycholinguistic and cognitive skills that are fundamental to the development of the reading process, such as phonological awareness, reading decoding, vocabulary and oral narrative comprehension, through the introduction of an Home Literacy Environment Active (HLE(A)) program that involved 54 participants enrolled in the first and second grades of elementary school (from 6 to 8 years old) in the city of Malaga area. (2) Methods: The central task of the intervention program was for the child to read aloud to an adult in the family for between 10 and 15 min, four days per week. In addition, the school students were evaluated on four occasions, at the beginning and end of each academic year, using the Batería de Evaluación de los Procesos Lectores Revisada, Test para la Detección de la Dislexia en niños and Escala Weschsler de Inteligencia instruments. (3) Results: the results demonstrated the efficacy of the HLE(A) program in the improvement of psycholinguistic and cognitive variables measured and, consequently, to an improvement in reading learning and cognitive development. Ultimately, the scientific literature on the subject and the data from the study led us to suggest that it would not only be beneficial for HLE(A) programs to be instituted in early childhood education stage (up to 6 years of age), but that they should be continued after age 6, in elementary education.

Purpose: It is well established now that protein sumoylation acts as an important regulatory mechanism mediating control of ocular development through regulation of multiple transcription factors. Yet the functional mechanisms of each factor modulated remain to be further explored using the available in vitro systems. In this regard, various ocular cell lines including HLE, FHL124, αTN4-1, N/N1003A and ARPE-19 have been demonstrated to be useful for biochemical and molecular analyses of normal physiology and pathogenesis. We have recently examined that these cell lines express a full set of sumoylation enzymes E1, E2 and E3. Following this study, here we have examined the localization of these enzymes and determined their differential localization patterns in these major ocular cell lines., Methods: The 5 major ocular cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) containing fetal bovine serum (FBS) or rabbit serum (RBS) and 1% Penicillin- Streptomycin. The localization of the 3 major sumoylation enzymes in the 5 major ocular cell lines were determined with immunohistochemistry. The images were captured with a Zeiss LSM 880 confocal microscope., Results: we have obtained the following results: 1) The sumoylation enzymes SAE1, UBC9 and PIAS1 are distributed in both nucleus and cytoplasm, with a much higher level concentrated in the nucleus and the neighboring cellular organelle zone in all cell lines; 2) The sumoylation enzyme UBA2 was highly concentrated in both cytoplasm membrane, cytoskeleton and nucleus of all cell lines; 3) The ligase E3, RanBP2 was exclusively localized in the nucleus with homogeneous distribution., Conclusions: Our results for the first time established the differential localization patterns of the three types of sumoylation enzymes in 5 major ocular cell lines. Our establishment of the differential localization patterns of the three types of sumoylation enzymes in these cell lines help to predict their functional importance of sumoylation in the vision system. Together, our results demonstrate that these cell lines can be used for assay systems to explore the functional mechanisms of sumoylation mediating ocular development and pathogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Accumulated evidence have well established that protein sumoylation plays multiple roles in various cellular processes. In the vertebrate eye, we and others have demonstrated that sumoylation displays indispensable roles in regulating eye development. Various ocular cell lines including human embryonic cell line (FHL124), the SV40-large T-transformed human lens epithelial cell line (HLE), the SV40-large T-transformed mouse lens epithelial cell line (αTN4-1), the rabbit lens epithelial cell line (N/N1003A) and the human retina pigment epithelial cell line (ARPE-19) have been extensively used for studying various cellular functions and disease processes including sumoylation functions, and mechanisms for cataract and age-related macular degeneration (AMD). However, the sumoylation enzyme systems have not been well established., Methods: FHL124, HLE, αTN4-1, N/N1003A and ARPE-19 were cultured in Dulbecco's modified eagle medium (DMEM) containing 10% FBS and 1% penicillin & streptomycin. The expression levels of seven SENP mRNAs were analyzed with qRT-PCR, and the expression levels of seven SENP proteins were detected with Western blot analysis., Results: Using both qRT-PCR and Western blot analysis, we have obtained the followings: 1). The 3 human ocular cell lines, FHL124, HLE and ARPE-19 express all types of SENP mRNA and proteins. 2). In mouse lens epithelial cell line αTN4-1, and rabbit lens epithelial cells line N/N1003A, however, only the mRNAs for SENP1, 2, 3, 6 and 7 are expressed. At the protein level, SENP8 was absent in both αTN4-1 and N/N1003A cells; 3). Each cell line has different dominant SENP enzymes. For FHL124, SENP3, 5, 7 and 8 proteins are relatively dominant. SENP3, 5 and 6 are the major de-sumoylation enzymes in HLE cells. Different from human lens epithelial cells, FHL124 and HLE, human retina pigment epithelial cells (ARPE-19) have SENP3, 7, and 8 as the dominant forms of de-sumoylation enzymes. For mouse lens epithelial cells, SENP1, 3 and 7 are the major de-sumoylation enzymes. On the other hand, the rabbit lens epithelial cells have SENP1, 2 and 7 as the major isoforms., Conclusion: Our results for the first time defined the differential expression patterns of the seven types of de-sumoylation enzymes (SENPs) in 5 major ocular cell lines. These results help to establish the basis for the future study of sumoylation functions and the related mechanisms in vertebrate eye., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: It is now well established that protein sumoylation acts as an important regulatory mechanism modulating functions over three thousand proteins. In the vision system, protein conjugation with SUMO peptides can regulate differentiation of multiple ocular tissues. Such regulation is often explored through analysis of biochemical and physiological changes with various cell lines in vitro. We have recently analyzed the expression levels of both mRNAs and proteins for seven de-sumoylation enzymes (SENPs) in five major ocular cell lines. In continuing the previous study, here we have determined their cellular localization of the seven de-sumoylation enzymes (SENP1, 2, 3, 5, 6, 7 and 8) in the above 5 major ocular cell lines using immunocytochemistry., Methods: The 5 major ocular cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) containing fetal bovine serum (FBS) or rabbit serum (RBS) and 1% Penicillin- Streptomycin. The localization of the 7 major de-sumoylation enzymes (SENPs) in the 5 major ocular cell lines were determined with immunohistochemistry. The images were captured with a Zeiss LSM 880 confocal microscope., Results: 1) The SENP1 was localized in both cytoplasm and nucleus of 3 human ocular cell lines, FHL124, HLE and ARPE-19; In N/N1003A and αTN4-1, SENP 1 was more concentrated in the cytoplasm. SENP1 appears in patches; 2) SENP2 was distributed in both cytoplasm and nucleus of all ocular cell lines in patches. In HLE and ARPE-19 cells, SENP2 level was higher in nucleus than in cytoplasm; 3) SENP3 was almost exclusively concentrated in the nuclei in all ocular cells except for N/N1003A cells. In the later cells, a substantial amount of SENP3 was also detected in the cytoplasm although nuclear SENP3 level was higher than the cytoplasmic SENP3 level. SENP3 appeared in obvious patches in the nuclei; 4) SENP5 was dominantly localized in the cytoplasm (cellular organelles) near nuclear membrane or cytoplasmic membrane ; 5) SENP6 was largely concentrated in the nuclei of all cell lines except for αTN4-1 cells. In the later cells, a substantial amount of SENP6 was also detected in the cytoplasm although nuclear SENP6 level was higher than the cytoplasmic SENP6 level. 6) SENP7 has an opposite localization pattern between human and animal cell lines. In human cell lines, a majority of SENP7 was localized in nuclei whereas in mouse and rabbit lens epithelial cells, most SENP7 was distributed in the cytoplasm. SENP8 was found present in human cell lines. The 3 human ocular cell lines had relatively similar distribution pattern. In FHL124 and ARPE-19 cells, SENP8 was detected only in the cytoplasm, but in HLE cells, patches of SENP8 in small amount was also detected in the nuclei., Conclusions: Our results for the first time defined the differential distribution patterns of seven desumoylation enzymes (SENPs) in 5 major ocular cell lines. These results help to understand the different functions of various SENPs in maintaining the homeostasis of protein sumoylation patterns during their functioning processes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Protein sumoylation is a well established regulatory mechanism to control many cellular processes such as chromatin structure dynamics, transcriptional regulation of gene expression, cell proliferation and differentiation, cell transformation and carcinogenesis, autophagy and senescence. In the vertebrate vision system, we and others have revealed that sumoylation plays important roles in regulating differentiation of several ocular tissues during eye development. To further elucidate the functional mechanisms of sumoylation, in vitro assay systems are needed. Currently, the five major cell lines including αTN4-1, FHL124, HLE, N/N1003A and ARPE-19 have been extensively used to test the biochemical and molecular aspects of normal vision physiology and various disease processes. Thus, we conducted the study on the expression patterns of the three types of sumoylation enzymes, the activating enzymes SAE1 and UBA2, the conjugating enzyme UBC9, and the ligating enzymes such as RanBP2 and PIAS1 in these ocular cell lines., Methods: The 5 major ocular cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) containing fetal bovine serum (FBS) or rabbit serum (RBS) and 1% Penicillin- Streptomycin. The mRNA levels were analysed with qRT-PCR. The protein levels were determined with western blot analysis and quantitated with Image J., Results: we have obtained the following results: 1) For the mRNAs encoding E1 SAE1 and UBA2, E2 UBC9 and E3 PIAS1, the highest level of expression was observed in αTN4-1 cells; For the mRNA encoding RanBP2, the highest level of expression was detected in N/N1003A cells; 2) In contrast to the mRNA expression patterns, a similar level of the SAE1 protein was observed in the all five cell lines, and so is true with UBA2 protein in all cells except for N/N1003A where over fourfold of enrichment in UBA2 protein was observed compared with other cell lines; 3) A similar level of UBC9 protein was also detected in all cells except for N/N1003A where more than one-fold of decrease in UBC9 level was found compared with other cell lines; 4) For E3 ligases, we did not identify the regular PIAS1 band in N/N1003A cells, the remaining cells have a level of PIAS1 with difference of less than 0.6-fold; all cells except for FHL124 cells have a similar level of RanBP2, and a 70% drop in RanBP2 was observed in FHL124 cell., Conclusions: Our determination of the differential expression patterns of the three types of sumoylation enzymes in the 5 ocular cell lines help to understand sumoylation functions in vertebrate eye., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

F-actin plays a crucial role in fundamental cellular processes, and is extremely susceptible to peroxynitrite attack due to the high abundance of tyrosine in the peptide. Methionine sulfoxide reductase (Msr) B1 is a selenium-dependent enzyme (selenoprotein R) that may act as a reactive oxygen species (ROS) scavenger. However, its function in coping with reactive nitrogen species (RNS)-mediated stress and the physiological significance remain unclear. Thus, the present study was conducted to elucidate the role and mechanism of MsrB1 in protecting human lens epithelial (hLE) cells against peroxynitrite-induced F-actin disruption. While exposure to high concentrations of peroxynitrite and gene silencing of MsrB1 by siRNA alone caused disassembly of F-actin via inactivation of extracellular signal-regulated kinase (ERK) in hLE cells, the latter substantially aggravated the disassembly of F-actin triggered by the former. This aggravation concurred with elevated nitration of F-actin and inactivation of ERK compared with that induced by the peroxynitrite treatment alone. In conclusion, MsrB1 protected hLE cells against the peroxynitrite-induced F-actin disruption, and the protection was mediated by inhibiting the resultant nitration of F-actin and inactivation of ERKs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We describe here successful designs of strong inhibitors for porcine pancreatic elastase (PPE) and Streptomyces griseus protease B (SGPB). For each enzyme two inhibitor variants were designed. In one, the reactive site residue (position 18) was retained and the best residues were substituted at contact positions 13, 14, and 15. In the other variant the best residues were substituted at all contact positions except the reactive site where a Gly was substituted. The four designed variants were: for PPE, T(13)E(14)Y(15)-OMTKY3 and T(13)E(14)Y(15)G(18)M(21)P(32)V(36)-OMTKY3, and for SGPB, S(13)D(14)Y(15)-OMTKY3 and S(13)D(14)Y(15)G(18)I(19)K(21)-OMTKY3. The free energies of association (ΔG(0)) of expressed variants have been measured with the proteases for which they were designed as well as with five other serine proteases and the results are discussed., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Swiss chard (Beta vulgaris cicla, BVc) and beetroot (Beta vulgaris rubra, BVr) are vegetables of the Chenopodiaceae family, widely consumed in traditional western cooking. These vegetables represent a highly renewable and cheap source of nutrients. They can be cultivated in soils with scarce organic material and little light and water. BVc and BVr have a long history of use in folk medicine. Modern pharmacology shows that BVc extracts possess antihypertensive and hypoglycaemic activity as well as excellent antioxidant activity. BVc contains apigenin flavonoids, namely vitexin, vitexin-2-O-rhamnoside and vitexin-2-O-xyloside, which show antiproliferative activity on cancer cell lines. BVr contains secondary metabolites, called betalains, which are used as natural dyes in food industry and show anticancer activity. In this light, BVc and BVr can be considered functional foods. Moreover, the promising results of their phytochemicals in health protection suggest the opportunity to take advantage of the large availability of this crop for purification of chemopreventive molecules to be used in functional foods and nutraceutical products., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The ideal proof-of-principle study design provides a strong efficacy signal over the shortest duration, while exposing the fewest patients possible. Data from a large database (Pfizer Inc) which studied add-on pregabalin for the treatment of partial seizures was used to model how duration of baseline, post-randomization treatment period, and number of subjects impact the likelihood of an interpretable efficacy signal. Data from four double-blind, randomized, placebo-controlled, phase III studies that had at least one 600 mg/day treatment arm were combined. The common 6-week baseline period was divided into weekly intervals, as was the 12-week post-randomization period. Two methods of analysis were used: logistic regression performed on 50% responder rate and the Hodges-Lehmann estimate on percentage reduction from baseline seizure rate. A simulation-based re-sampling approach was used to determine sufficient sample size. Four weeks of baseline with 3 weeks of treatment were determined to be clinically and statistically sufficient. A reasonable sample size was estimated to be 40-50 patients per group, if a highly efficacious drug was used. These modeling results indicate that the efficacy of an antiepileptic drug can be demonstrated in a relatively short period of time with a reasonable sample size., (Copyright © 2013 Elsevier B.V. All rights reserved.)