Switching from originator recombinant growth hormone (Genotropin™) to biosimilar (CRISCY™): Results from a 6-month, multicentric, non-inferiority, extension trial.

OBJECTIVE: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm. DESIGN: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). RESULTS: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group. CONCLUSIONS: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch.

Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial.

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

The trans-10,cis-12 conjugated linoleic acid increases triacylglycerol hydrolysis in yeast Saccharomyces cerevisiae.

AIMS: The trans-10,cis-12 conjugated linoleic acid (CLA) is known for its antilipogenic effect but the mechanism is not fully clear. In this study, the potential of yeast (Saccharomyces cerevisiae) metabolism to offer evidence for the mechanism was investigated. METHODS AND RESULTS: The inhibitory effect of CLA on lipid accumulation was studied by analysing the transcript abundance of selected genes involved in triacylglycerol synthesis (LRO1, DGA1, ARE1 and ARE2) in the presence of the two bioactive CLA isomers: trans-10,cis-12 and the cis-9,trans-11 CLA. None of the enzymes was reduced in transcription but the expression of ARE2 was induced by trans-10,cis-12 CLA. However, the ARE2 overexpression did not contribute to lipid accumulation. The expression of the Δ9 desaturase gene, OLE1, was reduced by the cis-9,trans-11 but not by the trans-10,cis-12 isomer. In the TGL3/TGL4-knockout strain the triacylglycerol content also remained high in the CLA fed cells. CONCLUSIONS: Triacylglycerol hydrolysis rather than synthesis was the most probable reason for the reduced lipid content in yeast induced by CLA. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed new aspects of the functionality of CLA in eukaryotic lipid metabolism. Yeast was proven to be an applicable model to study further the mechanism of trans-10,cis-12 CLA functionality on lipid metabolism.

Factors associated with acute-phase response of bisphosphonate-naïve or pretreated women with osteoporosis receiving an intravenous first dose of zoledronate or ibandronate.

A first intravenous dose of bisphosphonates may be associated with an acute-phase response (APR). In bisphosphonate-naïve women with postmenopausal osteoporosis, the characteristics and frequency of APR may differ by compound. Prior bisphosphonate exposure was predictive of APR risk and severity. INTRODUCTION: Intravenous (IV) administration of bisphosphonates (BP), such as zoledronate (ZOL) and ibandronate (IBN), may be associated with an APR. The characteristics of APR may differ by compound. The aim of the present study was to evaluate the characteristics of APR (rates, signs and symptoms, severity), in the absence of any preventive measure, after a first IV application of ZOL or IBN in patients naïve or previously exposed to BP in a real-world clinical setting. METHODS: This is an open-label prospective exploratory study with two cohorts of consecutive postmenopausal women with osteoporosis treated with either IV ZOL or IBN at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. RESULTS: Intravenous BP was administered to 725 women (411 ZOL and 314 IBN). Prior oral or IV BP use was less frequent in the ZOL group (61.8 vs. 71.7%, p = 0.005). In total, 301 women (41.5%) reported the presence of one or more signs or symptoms of APR with rates for ZOL and IBN of 47.7 and 33.4%, respectively (p < 0.001). Corresponding APR rates in the subgroup of BP-naïve patients were 55.6 and 32.4%, respectively (p < 0.001). The leading APR clinical sign was the presence of post-dose myalgia or arthralgia (68.1%). Prior BP exposure was predictive of both APR risk and severity, and lower serum 25-hydroxy vitamin D (25(OH)D) levels were possibly predictive of severity. CONCLUSIONS: In a real-world setting, APR rates with ZOL and IBN may be higher than reported in randomised controlled trials and may differ by compound, prior BP exposure, and serum 25(OH)D levels.

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study.

UNLABELLED: Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION: The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS: Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS: Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS: In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

Cortical bone loss at the tibia in postmenopausal women with osteoporosis is associated with incident non-vertebral fractures: results of a randomized controlled ancillary study of HORIZON.

BACKGROUND: In postmenopausal women, yearly intravenous zoledronate (ZOL) compared to placebo (PLB) significantly increased bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN), and total hip (TH) and decreased fracture risk. The effects of ZOL on BMD at the tibial epiphysis (T-EPI) and diaphysis (T-DIA) are unknown. METHODS: A randomized controlled ancillary study of the HORIZON trial was conducted at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. Women with ≥1 follow-up DXA measurement who had received ≥1 dose of either ZOL (n=55) or PLB (n=55) were included. BMD was measured at LS, FN, TH, T-EPI, and T-DIA at baseline, 6, 12, 24, and 36 months. Morphometric vertebral fractures were assessed. Incident clinical fractures were recorded as adverse events. RESULTS: Baseline characteristics were comparable with those in HORIZON and between groups. After 36 months, BMD was significantly higher in women treated with ZOL vs. PLB at LS, FN, TH, and T-EPI (+7.6%, +3.7%, +5.6%, and +5.5%, respectively, p<0.01 for all) but not T-DIA (+1.1%). The number of patients with ≥1 incident non-vertebral or morphometric fracture did not differ between groups (9 ZOL/11 PLB). Mean changes in BMD did not differ between groups with and without incident fracture, except that women with an incident non-vertebral fracture had significantly higher bone loss at predominantly cortical T-DIA (p=0.005). CONCLUSION: ZOL was significantly superior to PLB at T-EPI but not at T-DIA. Women with an incident non-vertebral fracture experienced bone loss at T-DIA.

Comparative trends in hospitalizations for osteoporotic fractures and other frequent diseases between 2000 and 2008.

UNLABELLED: In Switzerland, the number, incidence, and cost of acute hospitalizations for major osteoporotic fractures (MOF) and major cardiovascular events (MCE) increased in both women and men between 2000 and 2008, although the mean length of stay (LOS) was significantly reduced. Similar trend patterns were observed for hip fractures and strokes (decrease) and nonhip fractures and acute myocardial infarctions (increase). INTRODUCTION: The purpose of this study was to compare the trends and epidemiological characteristics of hospitalizations for MOF and other frequent diseases between years 2000 and 2008 in Switzerland. METHODS: Trends in the number, age-standardized incidence, mean LOS, and cost of hospitalized MOF and MCE (acute myocardial infarction, stroke, and heart failure) were compared in women and men aged ≥ 45 years, based on data from the Swiss Federal Statistical Office. RESULTS: Between 2000 and 2008, the incidence of acute hospitalizations for MOF increased by 3.4% in women and 0.3% in men. In both sexes, a significant decrease in hip fractures (-15.0% and -11.0%) was compensated by a concomitant, significant increase in nonhip fractures (+24.8% and +13.8%). Similarly, the incidence of acute hospitalizations for MCE increased by 4.4% in women and 8.2% in men, as an aggregated result from significantly increasing acute myocardial infarctions and significantly decreasing strokes. While the mean LOS in the acute inpatient setting decreased almost linearly between years 2000 and 2008 in all indications, the inpatient costs increased significantly (p < 0.001) for MOF (+30.1% and +42.7%) and MCE (+22.6% and +47.1%) in women and men, respectively. CONCLUSIONS: Between years 2000 and 2008, the burden of hospitalized osteoporotic fractures to the Swiss healthcare system has continued to increase in both sexes. In women, this burden was significantly higher than that of MCE and the gap widened over time.

Fracture hospitalizations between years 2000 and 2007 in Switzerland: a trend analysis.

UNLABELLED: In Switzerland, the total number and incidence of hospitalizations for major osteoporotic fractures increased between years 2000 and 2007, while hospitalizations due to hip fracture decreased. The cost impact of shorter hospital stays was offset by the increasing cost per day of hospitalization. INTRODUCTION: The aim of the study was to establish the trends and epidemiological characteristics of hospitalizations for major osteoporotic fractures (MOF) between years 2000 and 2007 in Switzerland. METHODS: Sex- and age-specific trends in the number and crude and age-standardized incidences of hospitalized MOF (hip, clinical spine, distal radius, and proximal humerus) in women and men aged ≥45 years were analyzed, together with the number of hospital days and cost of hospitalization, based on data from the Swiss Federal Statistical Office hospital database and population statistics. RESULTS: Between 2000 and 2007, the absolute number of hospitalizations for MOF increased by 15.9% in women and 20.0% in men, mainly due to an increased number of non-hip fractures (+37.7% in women and +39.7% in men). Hospitalizations for hip fractures were comparatively stable (-1.8% in women and +3.3% in men). In a rapidly aging population, in which the number of individuals aged ≥45 years grew by 11.1% (women) and 14.6% (men) over the study period, the crude and age-standardized incidences of hospitalizations decreased for hip fractures and increased for non-hip MOF, both in women and men. The length of hospital stay decreased for all MOF in women and men, the cost impact of which was offset by an increase in the daily costs of hospitalization. CONCLUSIONS: Between years 2000 and 2007, hospitalizations for MOF continued to increase in Switzerland, driven by an increasing number and incidence of hospitalizations for non-hip fractures, although the incidence of hip fractures has declined.

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women.

SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

Concordance of phenotypic expression and gender identity in a large kindred with a mutation in the androgen receptor.

A 14-year-old female presented to the Pediatric Endocrine Clinic, Universidade Federal o Parana Curitiba, Brazil, for obesity. A few years later, despite normal breast development, the patient had failed to menstruate and lacked pubic and axillary hair. Laboratory analyses revealed high levels of testosterone. Karyotype analysis was XY. Direct sequencing of her genomic DNA showed a G to T transition at nucleotide 2089 at exon 2 in the androgen receptor gene, resulting in a substitution of Phe for Cys at position 576. This mutation disrupts the first Zn finger critical to DNA binding and transcriptional activity and results in complete androgen-insensitivity syndrome (CAIS). This individual was part of 700-member multigenerational kindred of German origin living in small villages in Southern Brazil. Family members who gave informed consent were screened using a polymerase chain reaction-based method. Nineteen CAIS-affected individuals and carriers were identified. All presented with infertility and lack of or sparse pubic hair. The prevalence of common AIS within the kindred greatly exceeds that of the general population and is due in part to their isolated familial and community structures. All individuals are genuinely feminine in their appearance, sex behavior, gender identity, and integration within their communities. We conclude that CAIS leads to complete feminization of XY individuals and results in individuals who are psychologically and socially established and integrated as women within the familial and cultural contexts of their communities.

Methodologic concerns regarding estimates of physical violence in sexual coercion: overstatement or understatement?

Self-report measures of sexual violence that ask women whether they have experienced threats of physical violence have attracted criticism in recent years; detractors claim that these measures lead researchers to overestimate the prevalence of sexual violence. Our study explored this issue by collecting data on the prevalence of threats versus force in the context of sexual aggression. Female undergraduates at two universities (n1 = 69; n2 = 111) were asked about their experiences with sexual coercion using a revised version of the Sexual Experiences Scale (Koss and Gidycz, 1985). Four of the original items were modified to distinguish between sexual contact that occurred as a result of a perpetrator using physical force and sexual contact that occurred because a perpetrator threatened physical violence. Analyses of the revised items revealed that the use of physical force was at least as likely as threats and that for some types of sexual acts, physical force was actually more likely than verbal threats. Furthermore, prevalence figures for three of the four types of sexual acts considered were not significantly altered by collapsing threat of force with use of force. Implications for future research on women's experiences of sexual coercion are discussed.

Exploring negative dating experiences and beliefs about rape among younger and older women.

Although there is extensive research describing negative dating experiences and rape myth beliefs among university- and college-age women, there is little exploration of these issues among older dating women. An exploratory study that extends existing research by investigating rape myth beliefs and negative dating experiences of women ranging in age from 18 to 85 years is described. Participants (N = 115) completed a questionnaire which included a standardized measure of rape myth adherence (R-Scale; Costin, 1985), and a series of questions that assessed concerns about the potential for negative experiences while dating and actual negative dating experiences (ranging from unwanted affection to rape). There were remarkable similarities among younger and older women with respect to their dating behaviors and experiences. Women from both age groups reported being the target of negative dating experiences and being concerned about these experiences--with older women expressing slightly more concern. Older women, however, endorsed rape myths to a greater extent. This suggests that older women may be at greater risk for self-deprecation because they may be more likely to attribute the negative experiences they encounter to personal faults. Findings highlight the need for more life-span research of dating experiences and attitudes towards dating violence.

Evidence for involvement of the carboxy terminus of helix 1 of growth hormone in receptor binding: use of charge reversal mutagenesis to account for calcium dependence of binding and for design of higher affinity analogues.

In this study we have demonstrated that the C-terminus of helix 1 of porcine GH (pGH) is a receptor-interactive region, thus extending the current binding site model of GH. This was achieved by introducing charge reversal mutations into this region of pGH, which influenced receptor affinity and Ca2+ dependence of binding. The first mutant (R34E pGH, conversion of Arg 34 to Glu) introduced a putative Ca2+ binding site which is present in human GH (hGH) [Barnard et al. (1989) J. Theor. Biol. 140, 355-367] and sits opposite E220 of receptor subunit 1. This mutant exhibited increased Ca2+ dependence of receptor binding but even at optimal Ca2+ did not display higher than wild-type affinity. Introduction of a second Ca2+ binding site adjacent to the first by a second charge reversal (K30E R34E pGH) further increased Ca2+ dependence of binding and also increased affinity for the rabbit GH receptor (2.4 +/- 0.4)-fold relative to wild-type pGH at optimal Ca2+. Equilibrium dialysis and Scatchard analysis of binding of 45Ca2+ to pGH and K30E R34E pGH revealed two Ca2+ binding sites on wild-type pGH and an additional two Ca2+ binding sites on the K30E R34E pGH mutant (Kd 0.5-0.8 mM), as predicted. A third partial charge reversal mutant in the fourth helix (H170D) also led to enhanced Ca2+ dependence of binding, supporting our proposal that E34 and D170 are responsible for the Ca2+ dependence of hGH binding to the rabbit GH receptor. Examination of the crystal structure shows that E34 and D170 are in close proximity and would interact repulsively with a cluster of acidic residues on the receptor consisting of E126, E127, and E220 unless neutralized by Ca2+ or an introduced basic residue. Accordingly, charge reversal at the adjacent pGH residue E33 (E33K pGH) led to a Ca2+ independent (3.0 +/- 0.4)-fold increase in affinity of binding. As well as extending the binding site model of GH, these studies provide a mechanistic explanation for the unique Ca2+ dependence of hGH binding to the rabbit GH receptor. They also indicate that charge reversal can be used to design higher affinity GH analogues and could assist in the mapping of interactive regions in ligand-receptor complexes generally.

Anterior aesthetic considerations for the placement and restoration of nonsubmerged endosseous implants.

Nonsubmerged endosseous dental implants should be considered when planning optimal anterior implant rehabilitation. Detailed diagnostic records are a necessity, along with preoperative and preprosthetic treatment plans that are designed to address the unique challenges of anterior restorations. This paper discusses these concerns and presents two case reports which utilize some of the techniques that can be incorporated into achieving predictable anterior aesthetic rehabilitation using a single-stage implant. The learning objective of this article is to familiarize the reader with those challenges and techniques.

Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency.

An efficient expression system in Escherichia coli for several biologically active insulin-like growth factor-I (IGF-I) fusion peptide analogues is described. These novel IGF-I fusion protein analogues have properties that make them very useful reagents in the investigation of IGF-I action. The analogues comprise an IGF-I sequence and the first 11 amino acids of methionyl porcine growth hormone (pGH) and include [Met1]-pGH(1-11)-Val-Asn-IGF-I, which contains the authentic IGF-I sequence, and two analogues, [Met1]-pGH(1-11)-Val-Asn-[Gly3]-IGF-I and [Met1]-pGH(1-11)-Val-Asn-[Arg3]-IGF-I, where Glu-3 in the human IGF-I sequence has been replaced by Gly or Arg respectively. The three peptides are referred to as Long IGF-I, Long [Gly3]-IGF-I or Long [Arg3]-IGF-I depending on the IGF-I sequence present. Production of the purified fusion peptides was aided by folding the reduced and denatured fusion peptide sequence under conditions that gave very high yields of biologically active product. Introduction of a hydrophobic N-terminal extension peptide appears to facilitate the correct folding of the IGF-I analogues compared with that obtained previously when folding normal-length IGFs. The biological activities of the IGF-I fusion peptides were compared with authentic IGF-I and the truncated analogue, des(1-3)IGF-I. In L6 rat myoblasts, all the analogues were more potent than authentic IGF-I in their abilities to stimulate protein and DNA synthesis and inhibit protein breakdown. In H35 hepatoma cells, where the IGFs act through the insulin receptor, the Long IGF-I analogues maintained a similar potency relative to IGF-I as was observed in the L6 myoblasts. The order of biological potency in cell lines secreting IGF-binding proteins (IGFBPs) into the medium was Long [Arg3]-IGF-I-des(1-3)IGF-I greater than Long [Gly3]-IGF-I greater than Long IGF-I greater than IGF-I. In chicken embryo fibroblasts, a cell line that does not secrete detectable IGFBPs into the medium, Long [Arg3]-IGF-I, was less potent than IGF-I. Investigation of receptor and IGFBP association by these analogues reinforced our previous findings that N-terminal analogues of IGF-I show increased biological potency due to changes in the degree of their IGFBP interactions.

Bleeding on probing as it relates to probing pressure and gingival health.

The present study was designed to determine the threshold pressure value to be applied in provoking bleeding on probing (BOP) in clinically healthy gingival units. 12 female dental hygiene students volunteered for the study. They were selected on the basis of excellent oral hygiene standards, absence of probing depths greater than 3 mm and absence of caries or dental restorations on smooth and proximal tooth surfaces. Applying a probing force of 0.25, 0.5, 0.75 and 1.0 N in one of the 4 jaw quadrants, respectively, on 2 different occasions with an interval of 10 days, bleeding on probing was assessed. Oral hygiene and gingival conditions were determined using the criteria of the plaque control record and the gingival index. On the basis of the BOP values, obtained using the lowest probing force (0.25 N), the subjects were divided into 2 groups: group 1 ("minimal BOP" value) consisted of 6 subjects yielding practically no bleeding (mean BOP = 0.9%) at both examinations, while the subjects of group 2 ("low BOP" value) had slightly higher BOP% (mean BOP = 13.4%). Both groups showed significant increase in mean BOP% with increasing probing force (0.9%-36.1% in group 1 and 13.4%-47.0% in group 2). Regression analysis revealed an almost linear correlation and a high correlation coefficient between BOP% and probing force. The comparison of the regression lines of the 2 groups showed almost identical slope inclination. However, slight differences in slope inclination were found for different sites: approximal sites clearly yielded steeper regression lines than buccal/oral sites.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sebastian Fey, Zuben and Erlen (Thurgau), 1791-1825]. / Sebastian FEY, Zuben and Erlen (TG), 1791-1825.

Sebastian Fey (1791-1825) was a young veterinarian of the Swiss canton of Thurgau (founded 1803). He had first made an apprenticeship as a country veterinarian, and his educational background was very modest. But his zealousness to come out of the darknesses of empirical veterinary medicine was very strong. With a cantonal scholarship, he managed to spend a year (1813/14) at the Vienna Veterinary School. He was one of the first members of the Swiss Veterinary Association founded 1813, and published a series of papers in the early volumes of its Schweizer Archiv für Tierheilkunde, on from 1816. He also had two monographs printed in Constance publishing houses. In the second of them, he confirmed and defended the statements of Skellett, a British pioneer of foetotomy in cattle.

Wearable digital speech processor for cochlear implants using a TMS320C25.

Based on a single-chip DSP (TMS320C25, Texas Instruments) a programmable battery-operated sound processor with a digital encoder interface for the Nucleus-22 cochlear implant (CI) was built. The number of quasi-simultaneously addressed electrodes is only limited by the selected pulse width and the maximum rate of stimulation and can be as high as 10 electrodes at 300 Hz repetition rate. Implementation of various processing strategies (formant or channel vocoder, filterbank, zero crossings, etc.) is possible as well as sophisticated adaptive noise reduction. Programs and stimulation parameters are stored in electrically erasable memory and may be updated via a host computer. The built-in analog output may be used for single-channel stimulation or acoustic verifications of the sound processing algorithms. The power consumption with current 16K word data memory and at maximum stimulation rate is about 1 Watt, which necessitates recharging of batteries after 11 h.

Women's evaluations of and affective reactions to mainstream violent pornography, nonviolent pornography, and erotica.

Women's reactions to three types of sexually explicit materials were examined. Ninety-six female undergraduates completed questionnaires measuring previous exposure to pornography, past history of coercive sexual experiences, attitudes toward feminism, hostility toward men, adversarial sexual beliefs, and rape myth acceptance. They were then randomly assigned to one of four conditions: (a) erotica, (b) nonviolent pornography, (c) violent pornography, and (d) control. They viewed 50 slides during each of two 30-minute sessions, completed a measure of mood disturbance, and evaluated each slide. The erotica was evaluated positively, while the pornography was evaluated negatively, and the violent pornography was evaluated more negatively than the other three conditions. Mood disturbance increased significantly from pre- to postexposure in the violent and nonviolent pornography conditions only. In addition, women with past coercive sexual experiences evaluated pornography more negatively and erotica more positively than women who had no such experience.