[The Diagnostic Test: Goodness, Characteristics, and Interpretation: Under the Impact of the Corona Pandemic and Different SARS-CoV-2 Tests]. / Der diagnostische Test: Güte, Kennwerte und Interpretation Unter dem Eindruck der Corona-Pandemie und unterschiedlicher SARS-CoV-2-Tests.

INTRODUCTION: Many diagnostic tests are currently being performed around the world to detect SARS-CoV-2 infection. Positive and negative test results are not one hundred percent accurate, but have far-reaching consequences. There are false positives (test positive, uninfected) and false negatives (test negative, infected). A positive/negative result does not necessarily mean that the test subject is actually infected/non-infected. This article has two objectives: 1. to explain the most important characteristics of diagnostic tests with binary outcome 2. to point out problems and phenomena of interpretation of diagnostic tests, on the basis of different scenarios. METHOD: Presentation of the basic concepts of the quality of a diagnostic test (sensitivity, specificity) and pre-test probability (prevalence of test group). Calculation (including formulas) of further important quantities. RESULTS: In the basic scenario, sensitivity is 100%, specificity 98.8%, and pre-test probability of 1.0% (10 infected persons per 1,000 tested). For 1,000 diagnostic tests, the statistical mean is 22 positive cases, 10 of which are true-positive. The positive predictive probability is 45.7%. The prevalence calculated from this (22/1,000 tests) overestimates the actual prevalence (10/1,000 tests) by a factor of 2.2. All cases with a negative test outcome are true negative. The prevalence has a strong influence on the positive and negative predictive value. This phenomenon occurs even with otherwise very good test values of sensitivity and specificity. At a prevalence of only 5 infected persons per 10,000 (0.05%), the positive predictive probability drops to 4.0%. Lower specificity amplifies this effect, especially with small numbers of infected persons. CONCLUSION: If the sensitivity or specificity is below 100%, diagnostic tests are always error-prone. If the prevalence of infected persons is low, a large number of false positive results are to be expected - even if the test is of good quality with a high sensitivity and especially a high specificity. This is accompanied by low positive predictive values, i. e. positive tested persons are not infected. A false positive test result in the first test can be clarified by carrying out a second test.

[The Importance of High Quality Discharge Letters: An Empirical Investigation]. / Die Bedeutung qualitativ hochwertiger Entlassbriefe: Eine empirische Untersuchung.

INTRODUCTION: The discharge letter is part of the discharge management. This study empirically examines the quality of discharge letters after a stay in a psychiatric/psychosomatic clinic using a self-developed code list. Suggestions are made for the creation and structuring of high-quality discharge letters that provide information to practitioners and institutions that should help in the seamless further treatment of patients. METHOD: Different aspects of the social-psychiatric and social-medical assessments in 50 discharge letters were evaluated by 2 raters each; in case of disagreements in evaluation, a consensus was reached. RESULTS: The average time between discharge from hospital and completion of the discharge letter was 22.4 days (median: 15.0 days). In 18% of cases, the letter of discharge was available at the time of discharge and in 14% within one week. In 24% of cases, the letter of discharge was only available after 27 days or longer. In 97.5% of the cases, the medication was completely listed, but in 52% of the cases, there was no information on further medical treatment by the specialist. When further treatment was recommended (n=10, e. g. day clinic or PIA), it was initiated in only three cases. At the time of admission, 28 patients had a job. Information on the employment status of 11 patients was missing. Information on the ability to work at the time of admission was complete in 44% and incomplete in 20%. At the time of discharge, seven patients were able to work, 19 were incapacitated and information on work ability was missing in the discharge report of 24 patients. CONCLUSION: A high quality discharge letter contains clear formulations, is structured, contains only relevant information and a separate chapter "Therapy recommendations/recommendations for further action". Electronic discharge letters with automated inclusion of examination findings/assessments save time and money during preparation and reading.

Outcome quality of in-patient cardiac rehabilitation in elderly patients--identification of relevant parameters.

BACKGROUND: Outcome quality management requires the consecutive registration of defined variables. The aim was to identify relevant parameters in order to objectively assess the in-patient rehabilitation outcome. METHODS: From February 2009 to June 2010 1253 patients (70.9 ± 7.0 years, 78.1% men) at 12 rehabilitation clinics were enrolled. Items concerning sociodemographic data, the impairment group (surgery, conservative/interventional treatment), cardiovascular risk factors, structural and functional parameters and subjective health were tested in respect of their measurability, sensitivity to change and their propensity to be influenced by rehabilitation. RESULTS: The majority of patients (61.1%) were referred for rehabilitation after cardiac surgery, 38.9% after conservative or interventional treatment for an acute coronary syndrome. Functionally relevant comorbidities were seen in 49.2% (diabetes mellitus, stroke, peripheral artery disease, chronic obstructive lung disease). In three key areas 13 parameters were identified as being sensitive to change and subject to modification by rehabilitation: cardiovascular risk factors (blood pressure, low-density lipoprotein cholesterol, triglycerides), exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure, angina pectoris) and subjective health (IRES-24 (indicators of rehabilitation status): pain, somatic health, psychological well-being and depression as well as anxiety on the Hospital Anxiety and Depression Scale). CONCLUSION: The outcome of in-patient rehabilitation in elderly patients can be comprehensively assessed by the identification of appropriate key areas, that is, cardiovascular risk factors, exercise capacity and subjective health. This may well serve as a benchmark for internal and external quality management.

Induction of tolerogenic lung CD4+ T cells by local treatment with a pSTAT-3 and pSTAT-5 inhibitor ameliorated experimental allergic asthma.

Signal transducer and activator of transcription (STAT)-3 inhibitors play an important role in regulating immune responses. Galiellalactone (GL) is a fungal secondary metabolite known to interfere with the binding of phosphorylated signal transducer and activator of transcription (pSTAT)-3 as well of pSTAT-6 dimers to their target DNA in vitro. Intra nasal delivery of 50 µg GL into the lung of naive Balb/c mice induced FoxP3 expression locally and IL-10 production and IL-12p40 in RNA expression in the airways in vivo. In a murine model of allergic asthma, GL significantly suppressed the cardinal features of asthma, such as airway hyperresponsiveness, eosinophilia and mucus production, after sensitization and subsequent challenge with ovalbumin (OVA). These changes resulted in induction of IL-12p70 and IL-10 production by lung CD11c(+) dendritic cells (DCs) accompanied by an increase of IL-3 receptor α chain and indoleamine-2,3-dioxygenase expression in these cells. Furthermore, GL inhibited IL-4 production in T-bet-deficient CD4(+) T cells and down-regulated the suppressor of cytokine signaling-3 (SOCS-3), also in the absence of STAT-3 in T cells, in the lung in a murine model of asthma. In addition, we found reduced amounts of pSTAT-5 in the lung of GL-treated mice that correlated with decreased release of IL-2 by lung OVA-specific CD4(+) T cells after treatment with GL in vitro also in the absence of T-bet. Thus, GL treatment in vivo and in vitro emerges as a novel therapeutic approach for allergic asthma by modulating lung DC phenotype and function resulting in a protective response via CD4(+)FoxP3(+) regulatory T cells locally.

Sample size calculation in clinical trials: part 13 of a series on evaluation of scientific publications.

BACKGROUND: In this article, we discuss the purpose of sample size calculation in clinical trials, the need for it, and the methods by which it is accomplished. Study samples that are either too small or too large are unacceptable, for clinical, methodological, and ethical reasons. The physicians participating in clinical trials should be directly involved in sample size planning, because their expertise and knowledge of the literature are indispensable. METHODS: We explain the process of sample size calculation on the basis of articles retrieved by a selective search of the international literature, as well as our own experience. RESULTS: We present a fictitious clinical trial in which two antihypertensive agents are to be compared to each other with a t-test and then show how the appropriate size of the study sample should be calculated. Next, we describe the general principles of sample size calculation that apply when any kind of statistical test is to be used. We give further illustrative examples and explain what types of expert medical knowledge and assumptions are needed to calculate the appropriate sample size for each. These generally depend on the particular statistical test that is to be performed. CONCLUSION: In any clinical trial, the sample size has to be planned on a justifiable, rational basis. The purpose of sample size calculation is to determine the optimal number of participants (patients) to be included in the trial. Sample size calculation requires the collaboration of experienced biostatisticians and physician-researchers: expert medical knowledge is an essential part of it.

Choosing statistical tests: part 12 of a series on evaluation of scientific publications.

BACKGROUND: The interpretation of scientific articles often requires an understanding of the methods of inferential statistics. This article informs the reader about frequently used statistical tests and their correct application. METHODS: The most commonly used statistical tests were identified through a selective literature search on the methodology of medical research publications. These tests are discussed in this article, along with a selection of other standard methods of inferential statistics. RESULTS AND CONCLUSIONS: Readers who are acquainted not just with descriptive methods, but also with Pearson's chi-square test, Fisher's exact test, and Student's t test will be able to interpret a large proportion of medical research articles. Criteria are presented for choosing the proper statistical test to be used out of the most frequently applied tests. An algorithm and a table are provided to facilitate the selection of the appropriate test.

The combination of diffractive and refractive multifocal intraocular lenses to provide full visual function after cataract surgery.

PURPOSE: To investigate if implantation of a far dominant refractive multifocal intraocular lens (IOL) in one eye and a near dominant diffractive multifocal IOL in the fellow eye improves range of vision following cataract surgery. METHODS: This was a prospective, nonrandomized, case-control study involving 20 patients (40 eyes) scheduled for cataract surgery. Inclusion criteria were bilateral cataracts, minimum age 50 years, availability for follow-up visits, and informed consent. All patients received a far dominant refractive multifocal IOL (ReZoom, Abbott Medical Optics) in their dominant eye and a near dominant diffractive multifocal IOL (Tecnis ZM900, AMO) in their nondominant eye. Preoperative and postoperative measurements (3 months) included refraction, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), reading acuity, and reading speed. RESULTS: All patients completed the study. We present results of the 3-month postoperative visit. The patient group comprised 14 females and 6 males, with mean age 72 years (SD 6.1 years). Postoperatively, the mean sphere was 0.05 +/- 0.31 D and the cylinder -0.31 +/- 0.37 D. At the 3-month visit, mean binocular distance UCVA was 0.080 logMAR (SD 0.070) and BCVA was 0.030 logMAR (SD 0.066). The mean binocular near visual acuity was 0.140 logMAR (SD 0.068), mean binocular best-corrected, near visual acuity 0.060 logMAR (SD 0.060). CONCLUSIONS: The combination of a far dominant refractive multifocal IOL (with better distance performance) with a near dominant diffractive multifocal IOL (with better near vision) proved to be very suitable to help meet cataract patients' visual needs.

A comparison of micropore membrane inlet mass spectrometry-derived pulmonary shunt measurement with Riley shunt in a porcine model.

BACKGROUND: The multiple inert gas elimination technique was developed to measure shunt and the ratio of alveolar ventilation to simultaneous alveolar capillary blood flow in any part of the lung (V(A)'/Q') distributions. Micropore membrane inlet mass spectrometry (MMIMS), instead of gas chromatography, has been introduced for inert gas measurement and shunt determination in a rabbit lung model. However, agreement with a frequently used and accepted method for quantifying deficits in arterial oxygenation has not been established. We compared MMIMS-derived shunt (M-S) as a fraction of total cardiac output (CO) with Riley shunt (R-S) derived from the R-S formula in a porcine lung injury model. METHODS: To allow a broad variance of atelectasis and therefore shunt fraction, 8 sham animals did not receive lavage, and 8 animals were treated by lung lavages with 30 mL/kg warmed lactated Ringer's solution as follows: 2 animals were lavaged once, 5 animals twice, and 1 animal 3 times. Variables were recorded at baseline and twice after induction of lung injury (T1 and T2). Retention data of sulfur hexafluoride, krypton, desflurane, enflurane, diethyl ether, and acetone were analyzed by MMIMS, and M-S was derived using a known algorithm for the multiple inert gas elimination technique. Standard formulas were used for the calculation of R-S. RESULTS: Forty-four pairs of M-S and R-S were recorded. M-S ranged from 0.1% to 35.4% and R-S from 3.7% to 62.1%. M-S showed a correlation with R-S described by linear regression: M-S = -4.26 + 0.59 x R-S (r(2) = 0.83). M-S was on average lower than R-S (mean = -15.0% CO, sd = 6.5% CO, and median = -15.1), with lower and upper limits of agreement of -28.0% and -2.0%, respectively. The lower and upper limits of the 95% confidence intervals were -17.0 and -13.1 (P < 0.001, Student's t-test). CONCLUSIONS: Shunt derived from MMIMS inert gas retention data correlated well with R-S during breathing of oxygen. Shunt as derived by MMIMS was generally less than R-S.

Descriptive statistics: the specification of statistical measures and their presentation in tables and graphs. Part 7 of a series on evaluation of scientific publications.

BACKGROUND: Descriptive statistics are an essential part of biometric analysis and a prerequisite for the understanding of further statistical evaluations, including the drawing of inferences. When data are well presented, it is usually obvious whether the author has collected and evaluated them correctly and in keeping with accepted practice in the field. METHODS: Statistical variables in medicine may be of either the metric (continuous, quantitative) or categorical (nominal, ordinal) type. Easily understandable examples are given. Basic techniques for the statistical description of collected data are presented and illustrated with examples. RESULTS: The goal of a scientific study must always be clearly defined. The definition of the target value or clinical endpoint determines the level of measurement of the variables in question. Nearly all variables, whatever their level of measurement, can be usefully presented graphically and numerically. The level of measurement determines what types of diagrams and statistical values are appropriate. There are also different ways of presenting combinations of two independent variables graphically and numerically. CONCLUSIONS: The description of collected data is indispensable. If the data are of good quality, valid and important conclusions can already be drawn when they are properly described. Furthermore, data description provides a basis for inferential statistics.

Study design in medical research: part 2 of a series on the evaluation of scientific publications.

BACKGROUND: The scientific value and informativeness of a medical study are determined to a major extent by the study design. Errors in study design cannot be corrected afterwards. Various aspects of study design are discussed in this article. METHODS: Six essential considerations in the planning and evaluation of medical research studies are presented and discussed in the light of selected scientific articles from the international literature as well as the authors' own scientific expertise with regard to study design. RESULTS: The six main considerations for study design are the question to be answered, the study population, the unit of analysis, the type of study, the measuring technique, and the calculation of sample size. CONCLUSIONS: This article is intended to give the reader guidance in evaluating the design of studies in medical research. This should enable the reader to categorize medical studies better and to assess their scientific quality more accurately.

Evaluation of physical and mental recovery status after elective liver resection.

BACKGROUND AND OBJECTIVE: This prospective, clinical pilot trial compared the Short Form 36 Health Survey (SF-36) and a nine-item quality of recovery [Quality of Recovery 9 (QoR-9)] survey to assess the 1-week outcome after liver resection and prediction of postoperative complications from baseline values before liver resection. METHODS: In 19 patients, the SF-36 was recorded preoperatively (baseline) and on postoperative day (POD) 7. SF-36 z-values (means +/- SD) for the physical component summary (PCS) and mental component summary (MCS) were calculated. QoR-9 (score 0-18) was performed at baseline, POD1, POD3, POD5 and POD7. Descriptive analysis and effect sizes (d) were calculated. RESULTS: From baseline to POD7, PCS decreased from -0.38 +/- 1.30 to -2.10 +/- 0.76 (P = 0.002, d = -1.57) and MCS from -0.71 +/- 1.50 to -1.33 +/- 1.11 (P = 0.061, d = -0.46). QoR-9 was significantly lower at POD1, POD3 and POD5 compared with baseline (P < 0.050, d < -2.0), but not at POD7 (P = 0.060, d = -1.08). Baseline PCS was significantly lower with a high effect size in patients with complications (n = 12) compared with patients without complications (n = 7) (-0.76 +/- 1.46 vs. 0.27 +/- 0.56; P = 0.044, d = -0.84) but not baseline MCS (P = 0.831, d = -0.10) or baseline QoR-9 (P = 0.384, d = -0.44). CONCLUSIONS: The SF-36 indicates that liver resection surgery has a higher impact on physical health than on mental health. QoR-9 determines the feasible time course of recovery with a 1-week return to baseline. Preoperative impaired physical health might predict postoperative complications.

Types of study in medical research: part 3 of a series on evaluation of scientific publications.

BACKGROUND: The choice of study type is an important aspect of the design of medical studies. The study design and consequent study type are major determinants of a study's scientific quality and clinical value. METHODS: This article describes the structured classification of studies into two types, primary and secondary, as well as a further subclassification of studies of primary type. This is done on the basis of a selective literature search concerning study types in medical research, in addition to the authors' own experience. RESULTS: Three main areas of medical research can be distinguished by study type: basic (experimental), clinical, and epidemiological research. Furthermore, clinical and epidemiological studies can be further subclassified as either interventional or noninterventional. CONCLUSIONS: The study type that can best answer the particular research question at hand must be determined not only on a purely scientific basis, but also in view of the available financial resources, staffing, and practical feasibility (organization, medical prerequisites, number of patients, etc.).

Confidence interval or p-value?: part 4 of a series on evaluation of scientific publications.

BACKGROUND: An understanding of p-values and confidence intervals is necessary for the evaluation of scientific articles. This article will inform the reader of the meaning and interpretation of these two statistical concepts. METHODS: The uses of these two statistical concepts and the differences between them are discussed on the basis of a selective literature search concerning the methods employed in scientific articles. RESULTS/CONCLUSIONS: P-values in scientific studies are used to determine whether a null hypothesis formulated before the performance of the study is to be accepted or rejected. In exploratory studies, p-values enable the recognition of any statistically noteworthy findings. Confidence intervals provide information about a range in which the true value lies with a certain degree of probability, as well as about the direction and strength of the demonstrated effect. This enables conclusions to be drawn about the statistical plausibility and clinical relevance of the study findings. It is often useful for both statistical measures to be reported in scientific articles, because they provide complementary types of information.

Critical appraisal of scientific articles: part 1 of a series on evaluation of scientific publications.

INTRODUCTION: In the era of evidence-based medicine, one of the most important skills a physician needs is the ability to analyze scientific literature critically. This is necessary to keep medical knowledge up to date and to ensure optimal patient care. The aim of this paper is to present an accessible introduction into critical appraisal of scientific articles. METHODS: Using a selection of international literature, the reader is introduced to the principles of critical reading of scientific articles in medicine. For the sake of conciseness, detailed description of statistical methods is omitted. RESULTS: Widely accepted principles for critically appraising scientific articles are outlined. Basic knowledge of study design, structuring of an article, the role of different sections, of statistical presentations as well as sources of error and limitation are presented. The reader does not require extensive methodological knowledge. As far as necessary for critical appraisal of scientific articles, differences in research areas like epidemiology, clinical, and basic research are outlined. Further useful references are presented. CONCLUSION: Basic methodological knowledge is required to select and interpret scientific articles correctly.

The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes.

BACKGROUND: The lymphoid tyrosine phosphatase (LYP) encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene is a strong inhibitor of T cells. The single nucleotide polymorphism (SNP) C1858T within the PTPN22 gene was recently associated with autoimmune thyroid disease (AITD) and type I diabetes (T1D). The purpose of this study was to examine the joint association of this polymorphism with the co-occurrence of AITD and T1D. METHODS: In this association study, 310 white subjects were genotyped for the C1858T polymorphism. The study population included 70 patients with both AITD and T1D (AITD+T1D), 70 patients with AITD only, 70 patients with T1D only, and 100 healthy controls. Patients with both AITD and T1D, and controls were also typed for HLA-DRB1. PTPN22 C1858T genotyping was performed by minisequencing. For HLA-DRB1 typing, polymerase chain reaction (PCR) sequence-specific oligonucleotide probes were used. RESULTS: The PTPN22 1858 minor T-allele frequency was strongly increased in patients with AITD+T1D (23.6%) compared with controls (8.0%, pc<0.001), with patients with AITD only (8.6%, pc=0.006), or with T1D only (10.7%, pc=0.028). T-allele carriers were also more frequently present in the group with AITD+T1D versus controls (41.4% vs. 14.0%, OR=4.35, 95% CI=2.08-9.09), AITD (17.1%, OR=3.42, 95% CI=1.56-7.48), and T1D (21.4%, OR=2.59, 95% CI=1.23-5.45). Especially in subjects with Hashimoto's thyroiditis (HT)+T1D, T-allele carriers were mostly frequent (50% vs. 14%, OR=6.14, 95% CI=2.62-14.38, pc<0.001). Considering all included patients with AITD, T-allele carriers were 29.3% vs. 14.0% in controls (p=0.008, OR=2.54, 95% CI=1.30-4.98). Patients carrying the PTPN22 1858 T allele had a twofold increased frequency of the HLA-DRB1*03 allele (64.7% vs. 37.3%, pc=0.034). CONCLUSION: The PTPN22 gene is a joint susceptibility locus for AITD (especially HT) and T1D.

[Fatigue and its determinants in radio-oncology]. / Fatigue und deren Determinanten in der Radioonkologie.

BACKGROUND: Fatigue is a common symptom among cancer patients, influencing their quality of life. The primary goal of his study was to identify parameters influencing fatigue, both prior to radiotherapy (RT) and changes in fatigue during RT. METHODS: 239 patients could be assessed prior to RT, 208 patients were reassessed at the end of RT. Measures comprised the Multidimensional Fatigue Inventory (MFI-20), the Resilience Scale (RS) and the SF-12 as a measure of health related Quality of Life (QoL). RESULTS: The sample revealed higher scores in the MFI and in the RS as well as lower scores in the SF-12 than normative samples. Fatigue increased significantly during RT. Fatigue at the beginning of RT was best predicted by the patients' resilience scores, changes of fatigue scores during RT depended on the patients' initial fatigue scores, the decrease in haemoglobin and the patients' experience with RT. CONCLUSIONS: Fatigue appears to be an important problem among cancer patients receiving RT. Resilience proved to powerfully predict the patients' fatigue at the beginning of RT. This result confirms other studies showing resilience to be an important psychological predictor of QoL and coping in cancer patients. The change of fatigue during RT is mainly related to disease- and treatment-related factors.

In vitro evaluation of various bioabsorbable and nonresorbable barrier membranes for guided tissue regeneration.

BACKGROUND: Different types of bioabsorbable and nonresorbable membranes have been widely used for guided tissue regeneration (GTR) with its ultimate goal of regenerating lost periodontal structures. The purpose of the present study was to evaluate the biological effects of various bioabsorbable and nonresorbable membranes in cultures of primary human gingival fibroblasts (HGF), periodontal ligament fibroblasts (PDLF) and human osteoblast-like (HOB) cells in vitro. METHODS: Three commercially available collagen membranes [TutoDent (TD), Resodont (RD) and BioGide (BG)] as well as three nonresorbable polytetrafluoroethylene (PTFE) membranes [ACE (AC), Cytoplast (CT) and TefGen-FD (TG)] were tested. Cells plated on culture dishes (CD) served as positive controls. The effect of the barrier membranes on HGF, PDLF as well as HOB cells was assessed by the Alamar Blue fluorometric proliferation assay after 1, 2.5, 4, 24 and 48 h time periods. The structural and morphological properties of the membranes were evaluated by scanning electron microscopy (SEM). RESULTS: The results showed that of the six barriers tested, TD and RD demonstrated the highest rate of HGF proliferation at both earlier (1 h) and later (48 h) time periods (P < 0.001) compared to all other tested barriers and CD. Similarly, TD, RD and BG had significantly higher numbers of cells at all time periods when compared with the positive control in PDLF culture (P < or = 0.001). In HOB cell culture, the highest rate of cell proliferation was also calculated for TD at all time periods (P < 0.001). SEM observations demonstrated a microporous structure of all collagen membranes, with a compact top surface and a porous bottom surface, whereas the nonresorbable PTFE membranes demonstrated a homogenous structure with a symmetric dense skin layer. CONCLUSION: Results from the present study suggested that GTR membrane materials, per se, may influence cell proliferation in the process of periodontal tissue/bone regeneration. Among the six membranes examined, the bioabsorbable membranes demonstrated to be more suitable to stimulate cellular proliferation compared to nonresorbable PTFE membranes.

Ability of nanocrystalline hydroxyapatite paste to promote human periodontal ligament cell proliferation.

Recent studies indicate that nanocrystalline hydroxyapatite (nano-HA) paste represents a promising class of bone graft substitute. However, the underlying molecular mechanisms of nano-HA function have not yet been determined. This study was conducted to investigate the proliferation of human periodontal ligament (PDL) cells cultured in the presence of nano-HA paste and to characterize associated changes in intracellular signaling pathways. Cultured PDL cells were stimulated with nano-HA paste and enamel matrix derivative (EMD) in a soluble form. Proliferation of PDL cells was determined by incorporation of bromodeoxyuridine (BrdU) in the DNA of proliferating cells. In order to understand the signaling mechanisms underlying the increased cell proliferation of PDL cells exposed to nano-HA, the phosphorylation status of the serine/threonine protein kinase Akt, of the signal regulated kinases ERK 1/2 and of the epidermal growth factor receptor (EGFR) was analyzed by Western blotting using phospho-specific antibodies. Nano-HA paste showed two-fold less proliferation potential than EMD, but both substrates increased the proliferation rate significantly (P < 0.05) as compared with the negative control. The increased proliferation rate of PDL cells in the presence of nano-HA paste was mechanistically linked to activation of the epidermal growth factor receptor (EGFR) and its downstream targets ERK1/2 and Akt. In conclusion, our findings suggest that nano-HA paste is a stimulator of cell proliferation, possibly contributing to the main processes of periodontal tissue regeneration.

Intermediate vision and reading speed with array, Tecnis, and ReSTOR intraocular lenses.

PURPOSE: To retrospectively evaluate reading performance at intermediate distances of three types of multifocal intraocular lenses (IOLs) under different light conditions based on reading acuity and reading speed tests. METHODS: Thirty cataract patients (60 eyes) randomly assigned to receive the Array SA40N lens (n = 20 eyes), the Tecnis ZM001 lens (n = 20 eyes), and the ReSTOR lens (n = 20 eyes) were retrospectively tested for their reading abilities at distances of 40 cm, 60 cm, and 80 cm under low light conditions (6 cd/m2) and bright light conditions (100 cd/m2). RESULTS: LogMAR distance-corrected acuity in dim (bright) light at 40 cm was 0.456 (0.363) (Array), 0.446 (0.293) (ReSTOR), and 0.299 (0.140) (Tecnis); at 60 cm, it was 0.417 (0.259) (Array), 0.448 (0.318) (ReSTOR), and 0.381 (0.121) (Tecnis); at 80 cm, it was 0.359 (0.195) (Array), 0.395 (0.245) (ReSTOR), and 0.373 (0.124) (Tecnis). Uncorrected reading speed (words/min) in dim (bright) light at 40 cm was 25 (69) (Array), 58 (138) (ReSTOR), and 110 (166) (Tecnis); at 60 cm, it was 65 (129) (Array), 58 (129) (ReSTOR), and 135 (173) (Tecnis); and at 80 cm, it was 59 (153) (Array), 79 (164) (ReSTOR), and 121 (176 (Tecnis). CONCLUSIONS: Our study indicates that Array, ReSTOR, and Tecnis IOLs provide functional intermediate vision in bright light. In dim light, however, the Tecnis IOL provides better uncorrected reading speed at intermediate distances than Array and ReSTOR IOLs.