Alternative methods for the treatment of post-menopausal troubles

[english] Menopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only.The present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life).A systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated.In the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review.High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk’s pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases.No final statement can be drawn regarding the effectiveness of alter­ne treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.<br><br>[german] Als Wechseljahre wird der Übergang von der reproduktiven Phase der Frau zur nicht-reproduktiven beschrieben. Insbesondere in der Peri- und Postmenopause können Beschwerden aufgrund des sich veränderten Hormonspiegels auftreten. Aktuell wird die Hormontherapie wegen der mit dieser verbundenen Risiken nur noch zur kurzfristigen Behandlung akuter vasomotorischer Symptome empfohlen. Von den betroffenen Frauen werden alternative und komplementäre Heilmethoden eingesetzt.Im vorliegenden Health Technology Assessment (HTA) sollen die Effektivität und Kosteneffektivität alternativer Behandlungsmethoden von postmenopausalen Wechseljahresbeschwerden in Deutschland hinsichtlich der patientenrelevanten Endpunkte Verringerung der Symptomatik, Häufigkeit unerwünschter Ereignisse sowie Verbesserung der Lebensqualität bewertet werden. In 33 relevanten Datenbanken wird im September 2010 eine systematische Literatursuche durchgeführt. Gefundene und relevante Literaturstellen werden gemäß vorab definierter Kriterien selektiert. Die Daten der Literaturstellen werden gezielt herausgesucht, bewertet und zusammenfassend beurteilt.Aus der systematischen Recherche werden 22 Studien, davon 15 Primärstudien und ein Review zur Bewertung der Effektivität identifiziert.Hochdosiertes isoliertes Genistein reduziert die Anzahl/Schwere von Hitzewallungen, während niedrig dosiertes Genistein keinen signifikanten Effekt zeigt. Die Gabe von Isoflavonextrakten, die Genistein, Daidzein, Glycitein in unterschiedlicher Zusammensetzung enthalten, hat keinen signifikanten Einfluss auf die Verbesserung kognitiver Fähigkeiten oder vaginale Trockenheit. Traubensilberkerzen- und Hopfenextrakt führen zu unterschiedlichen Ergebnissen bezüglich der Wirksamkeit bei postmenopausalen Beschwerden, sodass keine abschließende Aussage zur Effektivität getroffen werden kann. Die Kombination von Isoflavonen, Traubensilberkerze, Mönchspfeffer, Baldrian und Vitamin E hat eine positive Wirkung auf postmenopausale Symptome. Ginkgo biloba zeigt keinen signifikanten Effekt auf postmenopausale Symptome und eine kognitive Verbesserung mit Ausnahme der mentalen Flexibilität. Akupunktur hat einen signifikanten Einfluss auf Hitzewallungen, insbesondere auf deren Schweregrad.Aufgrund der qualitativen Mängel (Concealment, Randomisierung, Fallzahlplanung) der eingeschlossenen Studien und der begrenzten Anzahl an Studien kann keine abschließende zusammenfassende Bewertung zur Wirksamkeit alternativer Heilmethoden gegeben werden. Die Verallgemeinerbarkeit des vorliegenden HTA wird durch die Beschränkung auf postmenopausale Frauen reduziert

The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock

RNA-binding proteins (RBPs) establish the cellular fate of a transcript, but an understanding of these processes has been limited by a lack of identified specific interactions between RNA and protein molecules. Using MS2 RNA tagging, we have purified proteins associated with individual mRNA species induced by osmotic stress, STL1 and GPD1. We found members of the Lsm1-7/Pat1 RBP complex to preferentially bind these mRNAs, relative to the non-stress induced mRNAs, HYP2 and ASH1. To assess the functional importance, we mutated components of the Lsm1-7/Pat1 RBP complex and analyzed the impact on expression of osmostress gene products. We observed a defect in global translation inhibition under osmotic stress in pat1 and lsm1 mutants, which correlated with an abnormally high association of both non-stress and stress-induced mRNAs to translationally active polysomes. Additionally, for stress-induced proteins normally triggered only by moderate or high osmostress, in the mutants the protein levels rose high already at weak hyperosmosis. Analysis of ribosome passage on mRNAs through co-translational decay from the 5' end (5P-Seq) showed increased ribosome accumulation in lsm1 and pat1 mutants upstream of the start codon. This effect was particularly strong for mRNAs induced under osmostress. Thus, our results indicate that, in addition to its role in degradation, the Lsm1-7/Pat1 complex acts as a selective translational repressor, having stronger effect over the translation initiation of heavily expressed mRNAs. Binding of the Lsm1-7/Pat1p complex to osmostress-induced mRNAs mitigates their translation, suppressing it in conditions of weak or no stress, and avoiding a hyperresponse when triggered

Biomechanics of a cemented short stem: a comparative in vitro study regarding primary stability and maximum fracture load

Purpose!#!In total hip arthroplasty, uncemented short stems have been used more and more frequently in recent years. Especially for short and curved femoral implants, bone-preserving and soft tissue-sparing properties are postulated. However, indication is limited to sufficient bone quality. At present, there are no curved short stems available which are based on cemented fixation.!##!Methods!#!In this in vitro study, primary stability and maximum fracture load of a newly developed cemented short-stem implant was evaluated in comparison to an already well-established cemented conventional straight stem using six pairs of human cadaver femurs with minor bone quality. Primary stability, including reversible micromotion and irreversible migration, was assessed in a dynamic material-testing machine. Furthermore, a subsequent load-to-failure test revealed the periprosthetic fracture characteristics.!##!Results!#!Reversible and irreversible micromotions showed no statistical difference between the two investigated stems. All short stems fractured under maximum load according to Vancouver type B3, whereas 4 out of 6 conventional stems suffered a periprosthetic fracture according to Vancouver type C. Mean fracture load of the short stems was 3062 N versus 3160 N for the conventional stems (p = 0.84).!##!Conclusion!#!Primary stability of the cemented short stem was not negatively influenced compared to the cemented conventional stem and no significant difference in fracture load was observed. However, a clear difference in the fracture pattern has been identified

Biomechanics of a calcar loading and a shortened tapered femoral stem: Comparative in-vitro testing of primary stability and strain distribution

Purpose!#!The most common femoral short stems available on the market can, in principle, be divided with regard to their anchoring concepts into a calcar loading and a shortened tapered design. The purpose of this study was to compare the primary stability and stress-shielding of two short stems, which correspond to these two different anchoring concepts.!##!Methods!#!Using seven paired fresh frozen human cadaver femurs, primary axial and rotational stabilities under dynamic load (100-1600 N) were evaluated by miniature displacement transducers after 100,000 load cycles. Changes in cortical strains were measured before and after implantation of both stem types to detect implant-specific load transmission and possible stress-shielding effects.!##!Results!#!Reversible and irreversible micromotions under dynamic load displayed no significant differences between the two implants. Implantation of either stem types resulted in a reduction of cortical strains in the proximal femur, which was less pronounced for the calcar loading implant.!##!Conclusions!#!Both short stems displayed comparable micromotions far below the critical threshold above which osseointegration may disturbed. Neither short stem could avoid proximal stress-shielding. This effect was less pronounced for the calcar loading short stem, which corresponds to a more physiological load transmission

Impact of five different medial patellofemoral ligament-reconstruction strategies and three different graft pre-tensioning states on the mean patellofemoral contact pressure: a biomechanical study on human cadaver knees

Abstract Background The medial patellofemoral ligament (MPFL) is the main stabiliser of the patella and thus mostly reconstructed in the surgical treatment of patellofemoral dislocation. The aims of this study were to gain a better understanding of the influence of altered MPFL graft-fixation locations and different graft pre-tensions on patellofemoral contact pressure. Methods Six human cadaveric knee joints were placed in a six-degree-of-freedom knee simulator. Mean PFCP (mPFCP) was evaluated in knee flexion of 0, 30 and 90° using a calibrated pressure-measurement system. After data assessment of the native knee joint, five MPFL reconstruction conditions were conducted: Anatomical double bundle; non-anatomical proximal patellar; non-anatomical distal patellar; non-anatomical proximal femoral; non-anatomical ventral femoral. The gracilis graft was fixed at a defined knee flexion of 30° and pre-tensioned to 2, 10 and 20 N. Results Kruskal-Wallis testing resulted in no mPFCP differences between the native and anatomical reconstruction states. Comparing the native and anatomical reconstruction states with the non-anatomical reconstruction states, no difference in the mPFCP both in knee extension (0°) (p>0.366) and in 30° knee flexion (p>0.349) was found. At 90° knee flexion, the following differences were identified: compared to the native knee state, the mPFCP increased after non-anatomical proximal femoral and non-anatomical ventral femoral reconstruction by 257% (p=0.04) and 292% (p=0.016), respectively. Compared to the anatomical reconstruction state, the mPFCP increased after non-anatomical proximal femoral reconstruction by 199% (p=0.042). Discussion and Conclusions With respect to all study findings and to restore a physiological PFCP, we recommend using the anatomical footprints for MPFL reconstruction and a moderate graft pretensioning of 2-10 N

Improved anchorage of Ti6Al4V orthopaedic bone implants through oligonucleotide mediated immobilization of BMP-2 in osteoporotic rats.

The aim of the present study was to test the biocompatibility and functionality of orthopaedic bone implants with immobilized oligonucleotides serving as anchor stands for rhBMP-2 and rhVEGF-A conjugated with complementary oligonucleotides in an osteoporotic rat model. Al2O3-blasted acid etched Ti6Al4V implants, carrying oligonucleotide anchor strands and hybridized with rhBMP-2 or rhVEGF-A through complementary 31-mer oligonucleotide stands were inserted into the proximal tibia of ovariectomized rats. At the time of surgery (15 weeks after ovariectomy) microCT analysis showed significantly lower bone mineral density compared to non-ovariectomized animals. Bone-implant contact (BIC) and pullout-force were not negatively affected by non-hybridized anchor strands. Twelve weeks after surgery, a significantly higher pullout force was found for BMP-2 hybridized to the anchor strands compared to non-hybridized anchor strands or native samples, and on histomorphometric analysis BIC was highest in the BMP group. Thus, we could show the biocompatibility and in vivo functionality of this modular, self-organizing system for immobilization and subsequent release of BMP-2 in vivo

Photograph of trichrome-stains of 100 µm sections of the orthopaedic implant and surrounding osseous tissue (bone tissue in green/blue).

<p>Four weeks after surgery no relevant difference of bone-to-implant contact rate or bone density around implant is seen between AAT (A), ODN (B), BMP-ODN (C), and VEGF-ODN group (D). Twelve weeks after surgery bone-to-implant contact rate was increased within the BMP-ODN group (G) when compared to AAT (E) whereas the other groups (AAT (E), ODN (F), VEGF-ODN group (H)) showed no relevant differences. AAT: Al₂O₃-blasted acid etched titanium; ODN: anchor strands of oligonucleotides bound to titanium; BMP-ODN: rhBMP modified with 31-mer Oligonucleotides; VEGF-ODN: rhVEGF modified with 31-mer Oligonucleotides.</p

Bone-to-implant contact rate of animals sacrificed four and twelve weeks after implant insertion according to the surface modification of the orthopaedic implant.

<p>Bone-to-implant contact rate was highest in the BMP group (median 60.7%) 12 weeks after surgery though no significant difference could be found. AAT: Al₂O₃-blasted acid etched titanium; ODN: anchor strands of oligonucleotides bound to titanium; BMP-ODN: rhBMP modified with 31-mer Oligonucleotides; VEGF-ODN: rhVEGF modified with 31-mer Oligonucleotides.</p

Boxplot of maximum pullout force according to surface modification four and 12 weeks after orthopaedic implant insertion.

<p>Asterisks represent significantly higher maximum pullout force in the BMP-ODN group 12 weeks after surgery (median 81.8 N) in comparison with both the AAT group (median 57.0 N) as well as the group (median 65.0 N) with p<0.05. AAT: Al₂O₃-blasted acid etched titanium; ODN: anchor strands of oligonucleotides bound to titanium; BMP-ODN: rhBMP modified with 31-mer Oligonucleotides; VEGF-ODN: rhVEGF modified with 31-mer Oligonucleotides.</p

Bone density – i.e. percentage of area of osseous tissue within a 1 mm strip of medullar cavity just distal to the orthopaedic implant – of animals sacrificed four weeks and twelve weeks after implant insertion according to the surface modification of the implant.

<p>AAT: Al₂O₃-blasted acid etched titanium; ODN: anchor strands of oligonucleotides bound to titanium; BMP-ODN: rhBMP modified with 31-mer Oligonucleotides; VEGF-ODN: rhVEGF modified with 31-mer Oligonucleotides.</p