3-year prospective multicenter study on one-stage implant surgery and early loading in the edentulous mandible

Background: The long‐term success rates achieved in dental implantology suggest that flexibility might well exist within the various implant systems to a degree that an altered protocol (ie, one‐stage surgery and immediate or early loading) can be performed under controlled conditions. However, before variations of the protocol can be considered for general use, they must be subjected to critical analysis, particularly with respect to the predictability of osseointegration, alteration of soft tissue barrier, and relative change in bone height around the implants. Purpose: The aim of this prospective multicenter study was to evaluate implant survival and periimplant conditions around endosseous implants placed in a one‐stage surgical procedure and early loading. Materials and Methods: A total of 170 implants were placed in 40 patients with mandibular edentulism and were functionally loaded within 6 weeks with overdentures (n = 30) or fixed prostheses (n = 10). All patients and prosthetic constructions were evaluated according to a standardized protocol during 3 years of follow‐up. Cumulative implant survival rates were calculated, and implant loss in relation to implant size and bone quality and quantity were evaluated. Furthermore, the protocol included assessment of clinical (plaque and bleeding scores, prosthesis stability) and radiographic parameters. Results: Over a period of 3 years, the implant survival rate was 93% for both implants and prostheses (fixed or removable). No implants were lost after the first year of loading. The periimplant tissues were in a healthy condition. Mean marginal bone resorption from the time of loading to the 3‐year follow‐up was 0.41 mm (SD 0.52). Conclusions: From this study it may be concluded that early loading results in good implant survival and proper periimplant health in edentulous mandibles.     

Multiple quantitative trait loci for blood pressure interacting epistatically and additively on Dahl rat chromosome 2

Our previous work demonstrated 2 quantitative trait loci (QTLs), C2QTL1 and C2QTL2, for blood pressure (BP) located on chromosome (Chr) 2 of Dahl salt-sensitive (DSS) rats. However, for a lack of markers, the 2 congenic strains delineating C2QTL1 and C2QTL2 could not be separated. The position of the C2QTL1 was only inferred by comparing 2 congenic strains, one having and another lacking a BP effect. Furthermore, it was not known how adjacent QTLs would interact with one another on Chr 2. In the current investigation, first, a critical chromosome marker was developed to separate 2 C2QTLs. Second, a congenic substrain was created to cover a chromosome fragment thought to harbor C2QTL1. Finally, a series of congenic strains was produced to systematically and comprehensively cover the entire Chr 2 segment containing C2QTL2 and other regions previously untested. Consequently, a total of 3 QTLs were discovered, with C2QTL3 located between C2QTL1 and C2QTL2. C2QTL1, C2QTL2, and C2QTL3 reside in chromosome segments of 5.7 centiMorgan (cM), 3.5 cM, and 1.5 cM, respectively. C2QTL1 interacted epistatically with either C2QTL2 or C2QTL3, whereas C2QTL2 and C2QTL3 showed additive effects to each other. These results suggest that BP QTLs closely linked in a segment interact epistatically and additively to one another on Chr 2.     

Description of a method to support public health information management: organizational network analysis

In this case study, we describe a method that has potential to provide systematic support for public health information management. Public health agencies depend on specialized information that travels throughout an organization via communication networks among employees. Interactions that occur within these networks are poorly understood and are generally unmanaged. We applied organizational network analysis, a method for studying communication networks, to assess the method's utility to support decision making for public health managers, and to determine what links existed between information use and agency processes. Data on communication links among a health department's staff was obtained via survey with a 93% response rate, and analyzed using Organizational Risk Analyzer (ORA) software. The findings described the structure of information flow in the department's communication networks. The analysis succeeded in providing insights into organizational processes which informed public health managers' strategies to address problems and to take advantage of network strengths.     

Representing nursing assessments in clinical information systems using the logical observation identifiers, names, and codes database

In recent years, the Logical Observation Identifiers, Names, and Codes (LOINC) Database has been expanded to include assessment items of relevance to nursing and in 2002 met the criteria for "recognition" by the American Nurses Association. Assessment measures in LOINC include those related to vital signs, obstetric measurements, clinical assessment scales, assessments from standardized nursing terminologies, and research instruments. In order for LOINC to be of greater use in implementing information systems that support nursing practice, additional content is needed. Moreover, those implementing systems for nursing practice must be aware of the manner in which LOINC codes for assessments can be appropriately linked with other aspects of the nursing process such as diagnoses and interventions. Such linkages are necessary to document nursing contributions to healthcare outcomes within the context of a multidisciplinary care environment and to facilitate building of nursing knowledge from clinical practice. The purposes of this paper are to provide an overview of the LOINC database, to describe examples of assessments of relevance to nursing contained in LOINC, and to illustrate linkages of LOINC assessments with other nursing concepts.     

Physiology of meiosis-activating sterol: endogenous formation and mode of action

BACKGROUND: In the context of mammalian oocyte maturation, it has been suggested that intermediates of cholesterol biosynthesis may represent the physiological signal that instructs the oocyte to reinitiate meiosis. METHODS: Endogenous levels of follicular fluid meiosis-activating sterol (FF-MAS) were monitored in rabbit ovarian tissue, and the influence of exogenous gonadotrophins on sterol formation was assessed. The involvement of cAMP in FF-MAS-induced versus spontaneous oocyte maturation in vitro in mice was also investigated, as was the direct microinjection of FF-MAS into mouse oocytes. RESULTS: Levels of FF-MAS in rabbit ovaries were significantly elevated 1 h after hCG/LH induction and remained so for 4 and 12 h after induction. In naked oocytes undergoing spontaneous maturation, a significant decrease in cAMP was detected after 30 min of culture. However, FF-MAS-mediated induction of oocyte maturation in hypoxanthine-arrested naked oocytes was not associated with any detectable decrease in intracellular cAMP levels. Microinjected FF-MAS failed to induce any noticeable meiosis. CONCLUSIONS: A rapid increase in FF-MAS level occurred in vivo in the rabbit ovary in response to LH, and clear differences were seen in the cAMP pattern during spontaneous and induced oocyte maturation in mice.     

Interleukin-17A during Local and Systemic Staphylococcus aureus-Induced Arthritis in Mice

Staphylococcus aureus is one of the dominant pathogens that induce septic arthritis in immunocompromised hosts, e.g., patients suffering from rheumatoid arthritis treated with immunosuppressive drugs. S. aureus-induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Recently, interleukin-17A (IL-17A) has been discovered to be an important mediator of aseptic arthritis both in mice and humans, but its function in S. aureus-induced arthritis is largely unknown. Here, we investigated the role of IL-17A in host defense against arthritis following systemic and local S. aureus infection in vivo. IL-17A knockout mice and wild-type mice were inoculated systemically (intravenously) or locally (intra-articularly) with S. aureus. During systemic infection, IL-17A knockout mice lost significantly more weight than the wild-type mice did, but no differences were found in the mortality rate. The absence of IL-17A had no impact on clinical arthritis development but led to increased histopathological erosivity late during systemic S. aureus infection. Bacterial clearance in kidneys was increased in IL-17A knockout mice compared to the level in wild-type mice only 1 day after bacterial inoculation. During systemic S. aureus infection, serum IL-17F protein levels and mRNA levels in the lymph nodes were elevated in the IL-17A knockout mice compared to the level in wild-type mice. In contrast to systemic infection, the IL-17A knockout mice had increased synovitis and erosions and locally decreased clearance of bacteria 3 days after local bacterial inoculation. On the basis of these findings, we suggest that IL-17A is more important in local host defense than in systemic host defense against S. aureus-induced arthritis.Patients with rheumatoid arthritis (RA) are susceptible to bacterial joint infections as a result of immunosuppressive treatments and the disease per se (24). The most common agent causing joint infections is Staphylococcus aureus, a microbe that can also cause sepsis. S. aureus-induced arthritis is a severe problem with a mortality rate of 5 to 20%, and 25 to 70% of affected patients develop permanent joint damage despite treatment (24). Although substantial efforts have been made to understand the immunological mechanisms that lead to S. aureus-induced joint destruction, it remains difficult to treat the infection (by maintaining the host''s ability to clear bacteria) while simultaneously limiting the joint destruction (by suppressing the immunological response). Thus, there is a need to identify new ways to treat RA that do not increase the severity of S. aureus-induced arthritis following infection.Recent evidence from humans and mice suggesting that the proinflammatory cytokine interleukin-17A (IL-17A) is an important player in RA (3, 19, 21) prompted an ongoing clinical trial of IL-17A-blocking antibodies to treat RA (6). Interleukin-17A was first described in 1993, but it was not until 2005, when Harrington et al. (8) described the unique Th17 subset, that the relevance of this cytokine was widely recognized among immunologists (5, 13, 15). Interleukin-17A appears to play a key role in host defense against local Gram-negative extracellular bacterial infections (4, 7, 9, 10, 17, 22, 29, 30) and local S. aureus infections (18) by inducing the production of neutrophil-mobilizing chemokines and growth factors and the subsequent mobilization of neutrophils (5, 13, 15, 16). Importantly, Ishigame et al. have recently shown that genetical knockout of IL-17A plus IL-17F (double knockout) in mice has very little impact on the general outcome of systemic S. aureus infection, measured as mortality and bacterial clearance at a single time point after bacterial inoculation compared with wild-type mice (11). However, in that study, the respective roles of IL-17A and -17F in S. aureus-induced arthritis were not specifically addressed (11), and this aspect is the main focus of this study. S. aureus-induced arthritis is a great concern in RA (24), and the first phase I study using IL-17A-blocking antibodies as a treatment in RA has recently been published (6). Thus, it is clinically important to determine whether reduced IL-17A levels in RA patients would have a detrimental effect on S. aureus-induced arthritis.It is well-known that, within the IL-17 family, IL-17F is the cytokine that shares the greatest structural and functional homology with IL-17A (5, 15). Both IL-17A and IL-17F exist as homodimers or as IL-17A-IL-17F heterodimers and bind to the IL-17 receptor A (IL-17RA)-IL-17RC receptor complex (28). Furthermore, these three IL-17 cytokines may exert similar biological effects, in particular with reference to the local mobilization of neutrophils (23). Studies of healthy mice have also shown that IL-17A is capable of inhibiting the production of IL-17F under certain conditions, through a IL-17RA-dependent mechanism (27). Thus, IL-17A and IL-17F seem to be functionally linked.In the present study, we characterized the kinetics of systemic and local S. aureus infections in the presence and absence of IL-17A in mice. For this purpose, we used IL-17A knockout mice (21) and wild-type control mice in our well-established mouse models of systemic and local S. aureus-induced arthritis (1) and assessed specific aspects of arthritis and more-general clinical outcomes. Using this approach, we obtained evidence that bacterial clearance, cytokine pattern, and degree of arthritis vary over time during systemic S. aureus infection and that IL-17A plays a more important role in local host defense than in systemic host defense against S. aureus-induced arthritis.     

Neuroticism-related personality traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR

Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism.     

Resolving the composite trait of hypertension into its pharmacogenetic determinants by acute pharmacological modulation of blood pressure regulatory systems

Acute pharmacogenetic analysis was carried out in an intercross F2 population derived from Prague hypertensive-hypertriglyceridemic and Lewis rats. Quantitative trait loci (QTL) mapping was performed for baseline blood pressure (BP) and for BP after blockade of the renin-angiotensin system by losartan, of the sympathetic nervous system (SNS) by pentolinium, and of the nitric oxide system by N(G)-nitro- L-arginine methyl ester. Two significant loci for baseline BP were found on chromosome (Chr) 3 (logarithm of likelihood, LOD, 3.8) and Chr 5 (LOD 3.6), and one suggestive locus on Chr 1 (LOD 2.7). The QTL on Chr 3 persisted after treatment with the three agents while the QTL on Chr 5 and Chr 1 disappeared after pentolinium administration. This suggests independence of the locus on Chr 3 from each acute BP regulatory system examined, whereas the loci on Chr 5 and Chr 1 appeared to be controlled mainly by the SNS. Although not apparent at baseline, a significant locus appeared on Chr 8 (LOD 7.0) after blockade of the SNS, and NO system blockade led to the appearance of a new QTL on Chr 1 (LOD 3.6), indicating the contribution of the inhibited systems to these loci. Pharmacogenetic dissection of the BP trait is a powerful tool to unravel the underlying physiological mechanisms of QTL affecting baseline BP and to identify specific QTL for the response to drugs. This pharmocogenetic approach enabled us to determine the main causative acute BP regulatory systems and should lead to better selection of suitable antihypertensive drugs for individual patients.     

Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study

Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.