The relBE2Spn Toxin-Antitoxin System of Streptococcus pneumoniae: Role in Antibiotic Tolerance and Functional Conservation in Clinical Isolates

Type II (proteic) chromosomal toxin-antitoxin systems (TAS) are widespread in Bacteria and Archaea but their precise function is known only for a limited number of them. Out of the many TAS described, the relBE family is one of the most abundant, being present in the three first sequenced strains of Streptococcus pneumoniae (D39, TIGR4 and R6). To address the function of the pneumococcal relBE2Spn TAS in the bacterial physiology, we have compared the response of the R6-relBE2Spn wild type strain with that of an isogenic derivative, ΔrelB2Spn under different stress conditions such as carbon and amino acid starvation and antibiotic exposure. Differences on viability between the wild type and mutant strains were found only when treatment directly impaired protein synthesis. As a criterion for the permanence of this locus in a variety of clinical strains, we checked whether the relBE2Spn locus was conserved in around 100 pneumococcal strains, including clinical isolates and strains with known genomes. All strains, although having various types of polymorphisms at the vicinity of the TA region, contained a functional relBE2Spn locus and the type of its structure correlated with the multilocus sequence type. Functionality of this TAS was maintained even in cases where severe rearrangements around the relBE2Spn region were found. We conclude that even though the relBE2Spn TAS is not essential for pneumococcus, it may provide additional advantages to the bacteria for colonization and/or infection

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS)

Objective: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. Method: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. Results: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. Conclusion: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.The Berlin Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy is financially supported by the German Federal Institute for Drugs and Medical Devices (BfArM); included German study cases were obtained from the Embryotox cohort. The UK Teratology Information Service is funded by the UK Health Security Agency. The Dutch Teratology Information Service is funded by the Ministerie van Volksgezondheid, Welzijnen Sport Research Unit on Congenital Anomalies-UIAC & Spanish Teratology Information Services SITTE and SITE are financially supported by Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, of Spain.S

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation

Management of Priapism: Results of a Nationwide Survey and Comparison with International Guidelines

Objective: The aim of this study is to evaluate current urologic practice regarding the management of priapism in Turkey and compare with international guidelines. Methods: Urologists and urology residents were invited to an online survey consisting of 30 multiple-choice questions on priapism-related clinical practices that were considered most important and relevant to practices by using Google Forms. Results: Total number of responses was 340. Respondents reported that they recorded a detailed patient’s medical history and physical examination findings (n = 340, 100%) and laboratory testing, which includes corporal blood gas analysis (n = 323, 95%). Participants announced that they performed Doppler ultrasound for 1/4 cases (n = 106, 31%), but 22% of the participants (n = 75) replied that they performed in >75% of cases. Participants (n = 311, 91%) responded that the first-line treatment of ischemic priapism is decompression of the corpus cavernosum. Moreover, most respondents (n = 320, 94%) stated that sympathomimetic injection drugs should be applied as the second step. About three-quarters of respondents (n = 247, 73%) indicated adrenaline as their drug of choice. Phosphodiesterase type 5 inhibitors seems to be the most preferred drug for stuttering priapism (n = 141, 41%). Participants (n = 284, 84%) replied that corpora-glanular shunts should be preferred as the first. A large number of participants (n = 239, 70%) declared that magnetic resonance imaging can be performed in cases with delayed (>24 hours) priapism to diagnose corporal necrosis. Most of the participants (84%) responded that penile prosthesis should be preferred to shunts in cases with delayed (>48 hours) priapism. Conclusion: It would be appropriate to improve the training offered by professional associations and to give more training time to the management of priapism during residency