The efficacy of pharmacotherapy in postmenopausal osteoporosis: a longitudinal observational study

Introduction: The aim of the study was an assessment of longitudinal changes in fracture probability in postmenopausal women. Material and methods: A group of 226 postmenopausal women at baseline mean age 66.46 ± 7.96 years were studied. There were 21 women without therapy, 102 taking calcium + vitamin D, and 103 women on antiresorptive therapy, in the study group. Data concerning clinical risk factors for osteoporosis and hip BMD were gathered. Fracture probability for major and hip fractures was established using FRAXTM. Results: Mean follow-up time was 2.43 ± 0.59 years. Baseline FRAX value in the whole group for major fracture was 7.1 ± 4.18, and at follow-up it was 7.44 ± 4.04. Respective results for FRAX for hip fracture were 3.17 ± 2.69 and 3.02 ± 2.35. In the whole group the probability for major fractures significantly increased during follow-up (p < 0.05) and for hip fracture did not change. In non-treated patients and patients taking calcium + vitamin D the fracture probability increased significantly. In patients on antiresorptive therapy the fracture probability did not change, which was connected with an improvement in bone status assessed by DXA. Femoral neck T-score in the whole group did not change, in those not treated and taking calcium + vitamin D it decreased significantly (p < 0.05), while in treated women it increased significantly (p < 0.05). In patients with improved bone status the FRAX values for major and hip fractures decreased by 0.44 ± 1.62 and 0.36 ± 1.19, respectively. Conversely, in patients with worsening T-score value the FRAX values increased by 1.33 ± 1.42 and 0.66 ± 1.25, respectively. Conclusion: Antiresorptive therapy stabilises fracture probability in postmenopausal women due to improvement in bone status

Careers in Training—For Female Scholars?

Der immer noch geringe Anteil von Frauen in den oberen Positionen von Hochschulen und Forschungseinrichtungen ist der Hintergrund für die in dem vorliegenden Band dokumentierten Programme zur Frauenförderung. Eine männlich geprägte Wissenschaftskultur und geschlechtsspezifische Leistungserwartungen werden als wirkmächtige Barrieren für Frauen auf dem Weg zur Professur ausgemacht. Die verbreitete Ansicht, dass die akademische Elite sich allein aufgrund ihrer Exzellenz in die oberen Hierarchieebenen vorarbeitet, wird in den Bereich der Mythenbildung verwiesen. Die Autorinnen des Bandes setzen dagegen auf persönliche Trainings und Coachings, um den Frauenanteil in den oberen wissenschaftlichen Ebenen zu erhöhen. Denn besonders für Frauen sei eine frühzeitige Karriereplanung, die Bildung von Netzwerken, die Aneignung sozialer Kompetenz, gutes Zeitmanagement sowie eine besondere Vorbereitung auf Berufungsverfahren wichtig. Als gleichstellungspolitisches Instrument sollen diese Programme langfristig institutionalisiert und etabliert werden. Eine Reflexion der Prämissen und Implikationen dieser Instrumente ist in dem Sammelband allerdings nicht zu finden.The still relatively small number of women in leadership positions at institutes of higher education and research centers provides the basis for the programs for the promotion of women documented in the volume at hand. The study identifies the male-oriented culture of science and the gender-specific expectations placed on performance as the most influential barriers standing in the way of women’s path to professorship. The authors in this volume banish the wide-spread belief that the academic elite work their way up the ladder of hierarchy merely due to their own excellence is placed to the realm of myth. Instead they suggest that personal training and coaching will raise the quotient of women in the upper levels of the academy. Early career planning, networking, development of social competence, good time management, and special preparation for tenure procedures are all of particular import to women. The proposed programs should be utilized as a political instrument for equality and should be institutionalized and established for the long term. However, the collected volume does not reflect on the premises or implications of such an instrument

I-complex plasmids – a story about incompatibility and host adaptation.

Antimicrobial resistance (AMR) is a growing problem worldwide. This is mainly the result of the presence of resistance genes in bacteria. When these genes are located in small pieces of DNA, so called plasmids, they can easily spread between bacteria. This thesis gives an overview the different types of plasmids, all with their different resistance genes, and their presence around the globe. Bacteria may contain a number of different plasmids in a single cell. whether any of these plasmids can be stably maintained depends on several factors. One of these factors is called incompatibility, which is the inability of plasmids to be maintained in one cell. Based on this incompatibility plasmids can be categorized in 40 different “Inc” groups, a biological phenomenon that was long used as a typing system to study epidemiology. This thesis focusses on the members of the “I-complex” incompatibility group, found in Enterobacteriaceae and frequently associated with important resistance gene classes such as the so-called Extended Spectrum Beta-lactamases (ESBLs). The I-complex includes IncI1α, IncI1γ, IncI2, IncK, IncB/O and IncZ plasmids. In this thesis the basis of their incompatibility is analysed and the results show that a single mutation (change in DNA) can determine if two plasmids are compatible or not. It concludes that IncB/O and IncZ plasmids, which were previously considered compatible and thus different plasmids, were actually incompatible and should be considered as highly similar. It also shows that the IncK plasmid group, which is an important carrier of resistance genes in human and poultry bacteria, consists of two compatible plasmid lineages, designated IncK1 and IncK2. Studies into the molecular effects of these plasmid types on the physiology of their host cell showed that IncK2 plasmids provide a fitness advantage at a higher environmental temperature which may have resulted in their predominance in poultry over IncK1, which is mostly found in mammals. Overall, the results presented in this thesis highlight the importance of plasmids in the spread of AMR, and it underlines the importance of understanding the plasmid compatibility and its adaptation to the bacterial or animal host

I-complex plasmids – a story about incompatibility and host adaptation.

Antimicrobial resistance (AMR) is a growing problem worldwide. This is mainly the result of the presence of resistance genes in bacteria. When these genes are located in small pieces of DNA, so called plasmids, they can easily spread between bacteria. This thesis gives an overview the different types of plasmids, all with their different resistance genes, and their presence around the globe. Bacteria may contain a number of different plasmids in a single cell. whether any of these plasmids can be stably maintained depends on several factors. One of these factors is called incompatibility, which is the inability of plasmids to be maintained in one cell. Based on this incompatibility plasmids can be categorized in 40 different “Inc” groups, a biological phenomenon that was long used as a typing system to study epidemiology. This thesis focusses on the members of the “I-complex” incompatibility group, found in Enterobacteriaceae and frequently associated with important resistance gene classes such as the so-called Extended Spectrum Beta-lactamases (ESBLs). The I-complex includes IncI1α, IncI1γ, IncI2, IncK, IncB/O and IncZ plasmids. In this thesis the basis of their incompatibility is analysed and the results show that a single mutation (change in DNA) can determine if two plasmids are compatible or not. It concludes that IncB/O and IncZ plasmids, which were previously considered compatible and thus different plasmids, were actually incompatible and should be considered as highly similar. It also shows that the IncK plasmid group, which is an important carrier of resistance genes in human and poultry bacteria, consists of two compatible plasmid lineages, designated IncK1 and IncK2. Studies into the molecular effects of these plasmid types on the physiology of their host cell showed that IncK2 plasmids provide a fitness advantage at a higher environmental temperature which may have resulted in their predominance in poultry over IncK1, which is mostly found in mammals. Overall, the results presented in this thesis highlight the importance of plasmids in the spread of AMR, and it underlines the importance of understanding the plasmid compatibility and its adaptation to the bacterial or animal host

Understanding the genetic basis of the incompatibility of IncK1 and IncK2 plasmids.

Antimicrobial resistance is a persistent challenge in human and veterinary medicine, which is often encoded on plasmids which are transmissible between bacterial cells. Incompatibility is the inability of two plasmids to be stably maintained in one cell which is caused by the presence of identical or closely related shared determinants between two plasmids originating from partition or replication mechanisms. For I-complex plasmids in Enterobacteriacae, replication- based incompatibility is caused by the small antisense RNA stem-loop structure called RNAI. The I-complex plasmid group IncK consists of two compatible subgroups, IncK1 and IncK2, for which the RNAI differs only by five nucleotides. In this study we focussed on the interaction of the IncK1 and IncK2 RNAI structures by constructing minireplicons containing the replication region of IncK1 or IncK2 plasmids coupled with a kanamycin resistance marker. Using minireplicons excludes involvement of incompatibility mechanisms other than RNAI. Additionally, we performed single nucleotide mutagenesis targeting the five nucleotides that differ between the IncK1 and IncK2 RNAI sequences of these minireplicons. The obtained results show that a single nucleotide change in the RNAI structure is responsible for the compatible phenotype of IncK1 with IncK2 plasmids. Only nucleotides in the RNAI top loop and interior loop have an effect on minireplicon incompatibility with wild type plasmids, while mutations in the stem of the RNAI structure had no significant effect on incompatibility. Understanding the molecular basis of incompatibility is relevant for future in silico predictions of plasmid incompatibility

Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae

Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal gene transfer through plasmids plays a major role. The identification of plasmid characteristics and their association with different bacterial hosts provides crucial knowledge that is essential to understand the contribution of plasmids to the transmission of AMR determinants. Molecular identification of plasmid and strain genotypes elicits a distinction between spread of AMR genes by plasmids and dissemination of these genes by spread of bacterial clones. For this reason several methods are used to type the plasmids, e.g. PCR-based replicon typing (PBRT) or relaxase typing. Currently, there are 28 known plasmid types in Enterobacteriaceae distinguished by PBRT. Frequently reported plasmids [IncF, IncI, IncA/C, IncL (previously designated IncL/M), IncN and IncH] are the ones that bear the greatest variety of resistance genes. The purpose of this review is to provide an overview of all known AMR-related plasmid families in Enterobacteriaceae, the resistance genes they carry and their geographical distribution

Incompatibility and phylogenetic relationship of I-complex plasmids

Plasmid incompatibility is the inability of two plasmids to be stably maintained in one cell, resulting in loss of one of the plasmids in daughter cells. Dislodgement is a phenotypically distinct form of incompatibility, described as an imperfect reproduction, manifesting in rapid exclusion of a resident plasmid after superinfection. The relationship between plasmids of the phenotypic incompatibility groups IncB/O and IncZ is unclear. Their inability to co-exist was initially referred to as dislodgement while other research reached the conclusion that IncB/O and IncZ plasmids are incompatible. In this manuscript we re-evaluated the relationship between IncB/O and IncZ plasmids to settle these conflicting conclusions. We performed dislodgement testing of R16Δ (IncB/O) and pSFE-059 (IncZ) plasmids by electroporation in a bacterial cell and checked their stability. Stability tests of the obtained plasmid pair showed that the IncB/O plasmid was exclusively and almost completely lost from the heteroplasmid Escherichia coli population. Other IncB/O - IncZ pairs could not form a heteroplasmid population, using conjugation or electroporation. Our data supports the previous suggestion that IncB/O and IncZ plasmids may be considered phenotypically incompatible