Histomorphological analysis of the urogenital diaphragm in elderly women: a cadaver study

The objective of this study was to describe the histomorphological structure of the urogenital diaphragm in elderly women using a modern morphometric procedure. Biopsies were taken from the posterior margin of the urogenital diaphragm of 22 female cadavers (mean age, 87years) using a 60-mm punch. Hematoxylin/eosin and Goldner sections were analyzed with the Cavalieri estimator. The mean thickness of the urogenital diaphragm was 5.5mm. The main component was connective tissue. All biopsies contained smooth muscle. Eighteen biopsies contained more smooth muscle than striated muscle. In six of 22 biopsies, no striated muscle was found. The ratio of striated to smooth muscle to connective tissue was 1:2.3:13.3. Muscle fibers were dispersed in all parts of the urogenital diaphragm. The urogenital diaphragm of elderly women mainly consists of connective tissue. Smooth muscle was also found but to a lesser extent. The frequently used English term "perineal membrane” for the urogenital diaphragm is justified and well describes our findings in elderly wome

Nr. 3: Die Behandlung bei Belastungsinkontinenz

Sobald die Diagnose Belastungsinkontinenz gesichert ist, kann diese heute mit etablierten Behandlungsmethoden erfolgreich angegangen werden. Im Folgenden werden konservative und chirurgische Massnahmen nach heutigem Goldstandard erläutert

Histomorphological analysis of the urogenital diaphragm in elderly women: a cadaver study

The objective of this study was to describe the histomorphological structure of the urogenital diaphragm in elderly women using a modern morphometric procedure. Biopsies were taken from the posterior margin of the urogenital diaphragm of 22 female cadavers (mean age, 87 years) using a 60-mm punch. Hematoxylin/eosin and Goldner sections were analyzed with the Cavalieri estimator. The mean thickness of the urogenital diaphragm was 5.5 mm. The main component was connective tissue. All biopsies contained smooth muscle. Eighteen biopsies contained more smooth muscle than striated muscle. In six of 22 biopsies, no striated muscle was found. The ratio of striated to smooth muscle to connective tissue was 1:2.3:13.3. Muscle fibers were dispersed in all parts of the urogenital diaphragm. The urogenital diaphragm of elderly women mainly consists of connective tissue. Smooth muscle was also found but to a lesser extent. The frequently used English term "perineal membrane" for the urogenital diaphragm is justified and well describes our findings in elderly women

The Long Pentraxin PTX3 Controls Klebsiella Pneumoniae Severe Infection

Klebsiella pneumoniae is a common pathogen in human sepsis. The emergence of multidrug-resistant K. pneumoniae strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against K. pneumoniae infections using Ptx3-/- mice and mouse models of severe K. pneumoniae infections. Local and systemic PTX3 expression was induced following K. pneumoniae pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of K. pneumoniae infection revealed that PTX3 did not interact with K. pneumoniae, or promote opsonophagocytosis. The comparison of susceptibility of wild-type, Ptx3-/-, C3-/- and Ptx3-/-/C3-/- mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in Ptx3-/- mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of K. pneumoniae infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections

Association analysis of PRNP gene region with chronic wasting disease in Rocky Mountain elk

<p>Abstract</p> <p>Background</p> <p>Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of cervids including white-tailed (<it>Odocoileus virginianus</it>) and mule deer (<it>Odocoileus hemionus</it>), Rocky Mountain elk (<it>Cervus elaphus nelsoni</it>), and moose (<it>Alces alces</it>). A leucine variant at position 132 (132L) in prion protein of Rocky Mountain elk confers a long incubation time with CWD, but not complete resistance. However, variants in regulatory regions outside the open reading frame of <it>PRNP </it>have been associated with varying degrees of susceptibility to prion disease in other species, and some variants have been observed in similar regions of Rocky Mountain elk <it>PRNP</it>. Thus, additional genetic variants might provide increased protection, either alone or in combination with 132L.</p> <p>Findings</p> <p>This study provided genomic sequence of all exons for <it>PRNP </it>of Rocky Mountain elk. Many functional sites in and around the <it>PRNP </it>gene region were sequenced, and this report approximately doubled (to 75) the number of known variants in this region. A haplotype-tagging approach was used to reduce the number of genetic variants required to survey this variation in the <it>PRNP </it>gene region of 559 Rocky Mountain elk. Eight haplotypes were observed with frequencies over 1.0%, and one haplotype was present at 71.2% frequency, reflecting limited genetic diversity in the <it>PRNP </it>gene region.</p> <p>Conclusions</p> <p>The presence of 132L cut odds of CWD by more than half (Odds Ratio = 0.43; P = 0.0031), which was similar to a previous report. However after accounting for 132L, no association with CWD was found for any additional variants in the <it>PRNP </it>region (P > 0.05).</p

Pelvic floor muscle function in a general female population in relation with age and parity and the relation between voluntary and involuntary contractions of the pelvic floor musculature

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Functional Anatomy of the Female Pelvic Floor

The anatomic structures in the female that prevent incontinence and genital organ prolapse on increases in abdominal pressure during daily activities include sphincteric and supportive systems. In the urethra, the action of the vesical neck and urethral sphincteric mechanisms maintains urethral closure pressure above bladder pressure. Decreases in the number of striated muscle fibers of the sphincter occur with age and parity. A supportive hammock under the urethra and vesical neck provides a firm backstop against which the urethra is compressed during increases in abdominal pressure to maintain urethral closure pressures above the rapidly increasing bladder pressure. This supporting layer consists of the anterior vaginal wall and the connective tissue that attaches it to the pelvic bones through the pubovaginal portion of the levator ani muscle, and the uterosacral and cardinal ligaments comprising the tendinous arch of the pelvic fascia. At rest the levator ani maintains closure of the urogenital hiatus. They are additionally recruited to maintain hiatal closure in the face of inertial loads related to visceral accelerations as well as abdominal pressurization in daily activities involving recruitment of the abdominal wall musculature and diaphragm. Vaginal birth is associated with an increased risk of levator ani defects, as well as genital organ prolapse and urinary incontinence. Computer models indicate that vaginal birth places the levator ani under tissue stretch ratios of up to 3.3 and the pudendal nerve under strains of up to 33%, respectively. Research is needed to better identify the pathomechanics of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72597/1/annals.1389.034.pd

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started

Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors

Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4- CD8- unconventional αβ T cells (UTCαβ). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCαβ associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTCαβ polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors