Stress Urinary Incontinence: An Unsolved Clinical Challenge

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective

Role of laparoscopy in ureteropelvic junction obstruction with concomitant pathology: a case series study

INTRODUCTION: Laparoscopic pyeloplasty is considered a standard treatment for ureteropelvic junction obstruction (UPJO). However, the presence of another pathology makes it a more challenging operation and guides the surgeon towards open conversion. In this study, we present our experience in difficult pyeloplasty cases managed by laparoscopy. MATERIAL AND METHODS: Six patients (4 females and 2 males) with an average age of 44 and a range of 27 to 60 years old, were diagnosed for UPJO. Three were on the left side and 3 on the right side. In addition to UPJO, 2 patients had renal stones, one patient had both renal ptosis and an umbilical hernia, 3 patients had a para-pelvic cyst, hepatomegaly and malrotated kidney, respectively. All patients had a preoperative ultrasound, CT or IVU, and a renal isotope scan. Laparoscopic pyeloplasty was performed according to the dismembered Anderson-Hynes technique with auxiliary maneuver, according to the pathology. RESULTS: All patients were treated successfully for UPJO and the concomitant pathologies, except hepatomegaly and malrotation. Mean operative time was 125 minutes and estimated blood loss was <50 ml. CONCLUSIONS: Laparoscopic pyeloplasty can be performed in difficult situations provided that the surgeon has enough experience with laparoscopy

Phylogenetic organization of bacterial activity.

Phylogeny is an ecologically meaningful way to classify plants and animals, as closely related taxa frequently have similar ecological characteristics, functional traits and effects on ecosystem processes. For bacteria, however, phylogeny has been argued to be an unreliable indicator of an organism\u27s ecology owing to evolutionary processes more common to microbes such as gene loss and lateral gene transfer, as well as convergent evolution. Here we use advanced stable isotope probing with (13)C and (18)O to show that evolutionary history has ecological significance for in situ bacterial activity. Phylogenetic organization in the activity of bacteria sets the stage for characterizing the functional attributes of bacterial taxonomic groups. Connecting identity with function in this way will allow scientists to begin building a mechanistic understanding of how bacterial community composition regulates critical ecosystem functions.The ISME Journal advance online publication, 4 March 2016; doi:10.1038/ismej.2016.28

Microbiomes of ant castes implicate new microbial roles in the fungus-growing ant Trachymyrmex septentrionalis

Fungus-growing ants employ several defenses against diseases, including disease-suppressing microbial biofilms on their integument and in fungal gardens. Here, we compare the phenology of microbiomes in natural nests of the temperate fungus-growing ant Trachymyrmex septentrionalis using culture-dependent isolations and culture-independent 16S-amplicon 454-sequencing. 454-sequencing revealed diverse actinobacteria associated with ants, including most prominently Solirubrobacter (12.2–30.9% of sequence reads), Pseudonocardia (3.5–42.0%), and Microlunatus (0.4–10.8%). Bacterial abundances remained relatively constant in monthly surveys throughout the annual active period (late winter to late summer), except Pseudonocardia abundance declined in females during the reproductive phase. Pseudonocardia species found on ants are phylogenetically different from those in gardens and soil, indicating ecological separation of these Pseudonocardia types. Because the pathogen Escovopsis is not known to infect gardens of T. septentrionalis, the ant-associated microbes do not seem to function in Escovopsis suppression, but could protect against ant diseases, help in nest sanitation, or serve unknown functions

Mechanisms for the development of autoimmunity in the central nervous system

Die experimentelle autoimmune Enzephalomyelitis (EAE) gilt als Modellerkrankung der Multiplen Sklerose und stellt eine Forschungsgrundlage zur Aufklärung von Me-chanismen organspezifischer Autoimmunerkrankungen dar. SJL-Mäuse entwickeln nach Immunisierung mit einem Peptid des Proteolipid Protein (PLP139-151), einem Bestandteil des Myelins im zentralen Nervensystem (ZNS), eine chronische EAE, die dem Verlauf einer schubförmig-remittierenden Multiplen Sklerose nahe kommt. Dies beruht auf der Aktivierung und Expansion präexistenter, im Immunrepertoire natürli-cherweise vorhandener PLP139-151-spezifischer T-Zellen. Unter Verwendung von re-kombinanten, oligomerisierten MHC-Klasse II Molekülen, die mit PLP139-151 beladen sind (sog. MHC-Klasse II-Tetramere) lassen sich CD4+ Antigen-spezifische T-Zellen ohne vorherige Manipulation ex vivo im Gewebe und im zirkulierenden Blut detektie-ren. Mit dieser neuartigen und hochspezifischen Methode wurden im Verlauf der EAE detaillierte Untersuchungen zur Populationsdynamik Antigen-spezifischer CD4+ T-Helfer-Zellen in Lymphknoten, Milz und ZNS durchgeführt und Veränderungen ihres Phänotyps nach Durchwanderung der Blut-Hirnschranke im ZNS quantitativ erfasst. Abschließend wurde die Frage verfolgt, auf welchem Weg diese T-Helfer-Zellen nach Erfüllung ihrer Effektorfunktion wieder eliminiert werden. Nach der Immunisierung mit PLP139-151 entwickelten nur die Tiere Krankheitssym-ptome einer EAE, die zusätzlich Pertussistoxin (PTX) erhalten hatten. Ohne PTX waren nur vereinzelt CD4+ T-Zellen im ZNS nachweisbar. PTX führte bereits in der Periphe-rie (Lymphknoten und Milz) zu einer rascheren Expansion PLP-spezifischer CD4+ T-Zellen und zu einer früheren und verstärkten Expression von Aktivierungsmerkmalen wie CD69 (very early activation marker) und dem Zelladhäsionsmolekül CD44 (pgp-1, homing cell adhesion molecule). Unter den in das ZNS eingewanderten Zellen stellten die in der Tetramerfärbung nachweisbaren PLP139-151-spezifischen T-Zellen mit etwa 15.000 Zellen nur eine Minderheit von etwa 5% aller CD4+ T-Zellen im ZNS dar. Alle Zellen im ZNS exprimierten den homing rezeptor CD44 und nach Durchtritt durch die Blut-Hirnschranke verstärkt das Merkmal CD69 als Hinweis für einen erneuten Anti-genkontakt. Parallel zum Anstieg der Aktivierungsparameter wurde eine verstärkte Ex-pression der Apoptose-induzierenden Moleküle Fas und Fas-Ligand auf der Zellmemb-ran von CD4+ T-Lymphozyten gefunden. Der Nachweis AnnexinV-positiver T-Zellen wies darauf hin, dass die infiltrierten T-Zellen im Verlauf der EAE den Weg der Apop-tose einschlagen und autoreaktive T-Zellen somit nach Auslösung eines Krankheits-schubes im ZNS wieder eliminiert werden. Dieses als „activation induced cell death“ bezeichnete Phänomen wurde unter den PLP139-151-spezifischen T-Zellen lediglich im ZNS, nicht aber in den Lymphknoten oder in der Milz beobachtet. Diese Untersuchungen zur Dynamik einer autoreaktiven T-Zell-Population im Krank-heitsverlauf der EAE sollten therapeutisch relevante Schlüsselpositionen identifizieren und zur Entwicklung neuer Therapiestrategien bei Autoimmunkrankheiten wie der Mu-tiplen Sklerose beitragen.The experimental autoimmune encephalomyelitis (EAE), an animal model disease for multiple sclerosis, forms a scientific basis to analyze mechanisms of organ specific autoimmune diseases. SJL mice develop a chronic EAE, very similar to the disease course of a relapsing-remitting multiple sclerosis, after immunization with a peptide of the proteolipid protein (PLP 139-151), a part of the central nervous system (CNS) myelin. The activation and expansion of pre-existing PLP 139-151 specific T-cells in the immune repertoire is responsible for the EAE development. By the use of recombinant, oligomeric MHC-class II molecules, loaded with PLP 139-151 (so-called MHC-class II tetramers), antigen-specific CD4+ T-cells could be identified without former manipulation ex vivo in tissue samples and in the circulating blood. Detailed examinations of the population dynamics of antigen specific CD4+ helper T-cells in lymph nodes, spleen and CNS were carried out and phenotype changes of CD4+ helper T-cells in the CNS after the transition of the blood brain barrier were noted quantitatively. Finally the elimination process of helper T-cells after the completion of their effector functions were investigated. After the immunization with PLP 139-151 only mice received pertussis toxin (PTX) additionally developed disease symptoms. Without PTX only isolated CD4+ T-cells were found in the CNS. PTX-administration during immunization resulted in a fast expansion of PLP-specific CD4+ T-cells in the periphery (lymph nodes and spleen) – also an early and strong expression of activation markers like CD69 (very early activation antigen) and the cell adhesion molecule CD44 (pgp-1, homing cell adhesion molecule) was noticed. Demonstrated by tetramer staining PLP 139-151 specific T-cells represented with 15.000 cells only a subset of 5% of all CD4+ helper T-cells after the entrance into the CNS. The homing receptor CD44 was presented on all CD4+ T-cells in the CNS and the molecule CD69 was upregulated after the transition of the blood brain barrier as a sign for a secondary antigen contact. Contemporaneously to the rise of activation markers an increased expression of the apoptosis-inducing molecules Fas and Fas-ligand on the cell membrane of CD4+ T-lymphocytes was noted. The identification of Annexin-V positive T-cells showed that CNS infiltrating T-cells were directed into apoptosis during the course of the EAE. Autoreactive T-cells were eliminated after a disease relapse in the CNS. The “activation induced cell death” phenomenon was found among the PLP 139-151 specific T-cells entirely in the CNS – the behaviour in lymph nodes and spleen was unsuspicious concerning this way of cell degradation. These findings of dynamics of autoreactive T-cell populations during the disease course of the EAE might identify relevant therapeutic key positions and should support the development of new treatment strategies of autoimmune diseases like the multiple sclerosis