Different types of microsatellite instability in ovarian carcinoma

Microsatellite instability at mono- and dinucleotide repeats is the hallmark of the hereditary non-polyposis cancer syndrome (HNPCC) and is related to deficient DNA mismatch repair. In contrast, a distinct form of microsatellite instability at selective tetranucleotide repeats (EMAST or elevated microsatellite alterations at selected tetranucleotides) was described in several non-HNPCC cancer types. EMAST is probably unrelated to mismatch repair defects. We investigated the frequency of microsatellite instability at mononucleotide, dinucleotide and tetranucleotide repeats in a series of 75 ovarian carcinomas (53 serous and 22 non-serous). Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel and 6 tetranucleotide markers, which have been reported as frequently unstable in the literature. High frequency of microsatellite instability (MSI-H) at mono- and dinucleotide repeats was observed in 9% and a low frequency (MSI-L) in 21% of serous carcinomas. MSI-H was detected in 4% and MSI-L in 18% of non-serous carcinomas. Nine percent of serous carcinomas showed instability at multiple and 9% at single tetranucleotide loci. All non-serous carcinomas were stable at tetranucleotide loci. In summary, EMAST (e.g., tumors with tetranucleotide instability without concomitant MSI-H) was observed in 13% of ovarian serous carcinomas. All EMAST positive tumors were of advanced stage. We conclude that EMAST occurs as a distinct form of microsatellite instability in ovarian cancer. EMAST seems to be particularly frequent in advanced serous carcinomas. Its clinical significance needs to be investigated.     

Increase of white matter string vessels in Alzheimer's disease

String vessels are collagenous structures connected to capillaries. They have no endothelial cells or lumen. We assessed collagen IV-labeled string vessels in the white matter (WM) of subjects with Alzheimer's disease (AD) (n = 12) and non-AD controls (n = 11) using 100 microm celloidin sections. Ten standard fields were digitally captured and the number and length of normal vessels and string vessels were quantified by computerized image analysis. The WM of the AD-diagnosed individuals contained more strings per mm2 (3.95 +/- 0.49) than comparable WM from controls (1.36 +/- 0.39) (p = 0.0005) and had increased total string vessel length in mm/mm2 (AD = 0.29 +/- 0.04; control = 0.10 +/- 0.03; p = 0.0015). There was a 25% increase (not statistically significant) in vessel density in mm/mm2 in AD subjects (AD = 11.88 +/- 0.87; control = 9.53 +/- 0.78; p = 0.06), presumably due to brain atrophy in the white matter. Although vessel length was slightly increased in AD subjects, they still had more than double the string length per total vessel length (AD = 2.88 +/- 0.38) compared to controls (1.36 +/- 0.27) (p = 0.0057). This increase in string vessels in the white matter of AD subjects suggests a decrease in vascular supply in this disease.     

Anatomical analysis of the developing cerebral vasculature in premature neonates: absence of precapillary arteriole-to-venous shunts

Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) commonly affects premature neonates. The gravity of the consequences associated with GMH-IVH makes it a major concern in their care. GMH-IVH begins in the germinal matrix tissue and is, most commonly, the result of venous rupture. Arteriole-to-venous precapillary shunts in the cerebrum of premature neonates could, if present, lead to elevated venous pressure in the germinal matrix and, thus, would be an important etiological factor. We report an autopsy study, involving 33 cases of premature neonates, designed to determine whether precapillary arteriole-to-venous shunts are present in the cerebral vasculature. Brain tissue was embedded in celloidin, sectioned into 100- micro m-thick slices and stained using alkaline phosphatase enzyme histochemistry, a method that distinguishes afferent from efferent vessels. Our sections, which are ideal for tracing vessels over long distances and for displaying patterns of branching and connections with other vessels, indicate that precapillary arteriole-to-venous shunts are not a major influence on cerebral blood flow in babies born at 23 wk gestation or later. The cerebral vasculature in one baby, who died at 24 wk postconception, included shunt-like connections, whereas in 34 babies shunts were not identified. We conclude that precapillary arteriole-to-venous shunts are not a significant factor leading to GMH.     

Hypoxia and PDGF have a synergistic effect that increases the expression of the angiogenetic peptide vascular endothelial growth factor in Achilles tendon fibroblasts

BACKGROUND: Angiogenesis, the formation of new blood vessels from pre-existing vessels, is an essential step in the process of tendon healing and tendon graft remodelling, e.g. after anterior cruciate ligament reconstruction. To address the question of whether platelet-derived growth factor (PDGF) could influence vascular endothelial growth factor (VEGF) expression in tenocytes, we challenged primary cultures of rat tenocytes with different stimulators (hypoxia, PDGF) and measured their VEGF secretion. METHODS: To measure the VEGF secretion and the effect of PDGF, we used cell culture and stimulation of rat tenocytes (2-5 days old), immunohistochemistry as well as enzyme-linked immunosorbent assay (ELISA). RESULTS: Tenocytes cultivated under normal oxygen pressure released measurable amounts of VEGF into their culture supernatants. Stimulation with PDGF, a cytokine that activates mitogen-activated protein kinases, raised VEGF secretion 2-fold. Hypoxic conditions alone (5% O(2)) raised VEGF secretion only 2-fold. However, the combination of cytokines and hypoxia increased VEGF production 5-fold, apparently a synergistic effect. CONCLUSION: These data are useful to further our understanding of angiogenesis in tendon healing and tendon graft remodelling after ACL reconstruction.     

Anatomie des hinteren Kreuzbandes sowie der posterolateralen und posteromedialen Strukturen

The posterior cruciate ligament (PCL) is the strongest ligament of the human knee joint and the primary restraint against posterior tibial translation. It originates at the lateral wall of the medial femoral condyle and inserts into the posterior aspect of the tibial eminence approximately 10 mm below the joint surface. The quadriceps muscle is the functional agonist for the PCL, whereas the hamstrings act as an antagonist pulling the tibia back in 90° of flexion. There are two functional bundles: the strong anterolateral bundle which tightens in flexion and a thin posteromedial bundle which becomes tense in maximal flexion and in extension. The AL bundle originates in the superior aspect of the femoral PCL origin. Under arthroscopic visualization in 90° of flexion the PM bundle originates in the inferior aspect of the PCL origin. When the knee is extended the PM origin rotates backwards. The PM bundle inserts into the posterior aspect of the tibial insertion. The AL bundle inserts into the anterior aspect of the tibial insertion. When creating a tunnel for a PCL reconstruction one should be aware of the proximity of the nerves and vessels within the fossa poplitea. The PCL forms a functional unit with the posteromedial and posterolateral structures. The posteromedial structures are the medial collateral ligament, the posteromedial capsule with its muscular insertions (m. semimembranosus and m. gastrocnemius). The most important structures of the posterolateral corner are the fibular collateral ligament, the lateral m. gastrocnemius, the oblique popliteal ligament, the arcuate popliteal ligament, the popliteofibular ligament, and the tendon of the m. popliteus. The popliteofibular ligament has an important role for the passive stabilization against rotation. It is highly recommended that concomitant injuries of these structures be addressed when treating PCL injuries.     

Corona and Reproduction,or Why the Corona Vaccination Does Not Result in Infertility

Background As the COVID-19 pandemic persists and new vaccines are developed, concerns among the general public are growing that both infection with the SARS-CoV-2 virus and vaccinations against the coronavirus (mRNA vaccines) could lead to infertility or higher miscarriage rates. These fears are voiced particularly often by young adults of reproductive age. This review summarizes the current data on the impact of SARS-CoV-2 infection and corona vaccinations on female and male fertility, based on both animal models and human data. Method A systematic literature search (PubMed, Embase, Web of Science) was carried out using the search terms “COVID 19, SARS-CoV-2, fertility, semen, sperm, oocyte, male fertility, female fertility, infertility”. After the search, original articles published between October 2019 and October 2021 were selected and reviewed. Results Despite the use of very high vaccine doses in animal models, no negative impacts on fertility, the course of pregnancy, or fetal development were detected. In humans, no SARS-CoV-2 RNA was found in the oocytes/follicular fluid of infected women; similarly, no differences with regard to pregnancy rates or percentages of healthy children were found between persons who had recovered from the disease, vaccinated persons, and controls. Vaccination also had no impact on live-birth rates after assisted reproductive treatment. No viral RNA was detected in the semen of the majority of infected or still infectious men; however, a significant deterioration of semen parameters was found during semen analysis, especially after severe viral disease. None of the studies found that corona vaccines had any impact on male fertility. Discussion Neither the animal models nor the human data presented in recent studies provide any indications that fertility decreases after being vaccinated against coronavirus. However, there is a growing body of evidence that severe SARS-CoV-2 infection has a negative impact on male fertility and there is clear evidence of an increased risk of complications among pregnant women with SARS-CoV-2 infection. The counseling offered to young adults should therefore take their fears and concerns seriously as well as providing a structured discussion of the current data. Key words: COVID-19, corona vaccine, SARS-CoV-2, reproduction, sperm, oocyte, embryo, infertility     

Prevalence of apical periodontitis, crowned teeth and teeth with posts in a Swedish population

Abstract A longitudinal radiological study was carried out of 200 consecutive patients in a Swedish population. The aims of the investigation were to study the prevalences of crowned teeth, pontics and posts on two occasions with an interval of 5–7 years and, furthermore, to study apical periodontitis in connection with teeth with crowns and posts to see if such treatments affected this prevalence. 417 (mean 2.1) teeth were crowned at the first examination and 529 (mean 2.6) at the second. For pontics, the corresponding figures were 93 (mean 0.5) and 141 (mean 0.7). Crowns and pontics were more common in the upper jaw. 59.4% of the endodontically treated teeth had posts at the first examination and 64.4% at the second. 34.5% of the 255 teeth with apical periodontitis found at the first examination and 41.0% of the 268 at the second were in connection with posts. It was concluded that both crowns and pontics were common treatment procedures in the studied population. Crown therapy did not seem to impair the apical status while teeth with posts more often had apical periodontitis than other teeth and, furthermore, teeth with screw posts were lost more frequently than other teeth.     

Comparative Evaluation of Five Chromogenic Media for Detection, Enumeration and Identification of Urinary Tract Pathogens

 Five chromogenic agar plates – CPS ID2 medium (bioMérieux, France), CHROMagar Orientation medium (Becton Dickinson, France), UriSelect3 medium (Sanofi Diagnostics Pasteur, France), Rainbow Agar UTI medium (Biolog, USA) and Chromogenic UTI medium (Oxoid, Germany) – for the detection, enumeration and direct identification of urinary tract pathogens were compared using 443 urine specimens at two hospital laboratories. The enumeration of microorganisms was consistent on the five media for 403 of the 477 (84.5%) microorganisms. Chromogenic UTI, CPS ID2, UriSelect3, CHROMagar Orientation and Rainbow UTI gave detection rates of 98.3%, 97.9%, 97.3%, 96.9% and 94.1%, respectively, with some problems in yeast growth occurring on Rainbow UTI agar and problems in Staphylococcus spp. growth occurring on UriSelect3. For the direct identification of Escherichia coli, sensitivities were 93.8%, 88.5%, 86.1% and 82.2% for CHROMagar Orientation, CPS ID2, UriSelect3 and Rainbow UTI, respectively. Chromogenic UTI medium did not allow the accurate identification of Escherichia coli, since the indole reaction cannot be applied to this medium. Depending on the media, Enterococcus spp. could be identified at the genus or the species level. Slight differences were detected in the presumptive identification of the Proteus-Morganella-Providencia group and the Klebsiella-Enterobacter-Serratia group. Additionally, on Rainbow UTI agar, 12 of 20 Klebsiella pneumoniae strains and two of nine Pseudomonas aeruginosa strains were correctly identified.In conclusion, CPS ID2 medium and CHROMagar Orientation medium showed similar performance overall, while the UriSelect3, Rainbow UTI and Chromogenic UTI media require some improvement.