Efficacy of combined oral contraceptives for depressive symptoms and overall symptomatology in premenstrual syndrome:pairwise and network meta-analysis of randomized trials

OBJECTIVE: Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) also seeking contraception, but evidence for this treatment is scarce. We aimed to determine 1) the level of evidence for the efficacy of combined oral contraceptives in managing premenstrual depressive symptoms and overall premenstrual symptomatology, and 2) the comparative efficacy of combined oral contraceptives (PROSPERO registration number CRD42020205510). DATA SOURCES: We searched Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, Emcare, and EMBASE from inception to June 3rd, 2021. STUDY ELIGIBILITY: All randomized clinical trials that evaluated efficacy of combined oral contraceptives in women with PMS or PMDD were considered eligible for inclusion in the present meta-analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A random effect Bayesian pairwise and network meta-analysis was conducted with change in premenstrual depressive symptoms and overall premenstrual symptomatology between baseline and 3 cycles as outcome. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 3664 records, nine eligible trials were included that studied 1205 women with PMS or PMDD (mean age per study range: 24.6-36.5 years). The pairwise meta-analysis revealed that combined oral contraceptives were more efficacious than placebo in treating overall premenstrual symptomatology (standardized mean difference SMD [95%CrI], 0.41 [0.17, 0.67]), but not premenstrual depressive symptoms specifically (SMD [95%CrI], 0.22 [-0.06, 0.47]). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology. CONCLUSIONS: Combined oral contraceptives may improve overall premenstrual symptomatology in women with PMS or PMDD, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other

CT colonography with minimal bowel preparation: evaluation of tagging quality, patient acceptance and diagnostic accuracy in two iodine-based preparation schemes

PURPOSE: The aim of this study was to compare a 1-day with a 2-day iodine bowel preparation for CT colonography in a positive faecal occult blood test (FOBT) screening population. MATERIALS AND METHODS: One hundred consecutive patients underwent CT colonography and colonoscopy with segmental unblinding. The first 50 patients (group 1) ingested 7 50 ml iodinated contrast starting 2 days before CT colonography. The latter 50 patients (group 2) ingested 4 50 ml iodinated contrast starting 1 day before CT colonography. Per colonic segment measurements of residual stool attenuation and homogeneity were performed, and a subjective evaluation of tagging quality (grade 1-5) was done. Independently, two reviewers performed polyp and carcinoma detection. RESULTS: The tagging density was 638 and 618 HU (p = 0.458) and homogeneity 91 and 86 HU for groups 1 and 2, respectively (p = 0.145). The tagging quality was graded 5 (excellent) in 90% of all segments in group 1 and 91% in group 2 (p = 0.749). Mean per-polyp sensitivity for lesions >or=10 mm was 86% in group 1 and 97% in group 2 (p = 0.355). Patient burden from diarrhoea significantly decreased for patients in group 2. CONCLUSIONS: One-day preparation with meglumine ioxithalamate results in an improved patient acceptability compared with 2-day preparation and has a comparable, excellent image quality and good diagnostic performanc

Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination

In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2-Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra ?-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion

Serum Kisspeptin Levels in Korean Girls with Central Precocious Puberty

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 ± 1.78 vs 2.15 ± 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity

A Mycobacterium tuberculosis cluster demonstrating the use of genotyping in urban tuberculosis control

Background: DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries. Methods: A medium-sized molecular cluster of TB cases with identical DNA fingerprints was used for the development of a visual presentation of epidemiologic links between cases. Results: Of 32 cases, 17 (53%) were linked to the index case, and 11 (34%) to a secondary case. The remaining four (13%) could not be linked and were classified as possibly caused by the index patient. Of the 21 cases related to the index case, TB developed within one year of the index diagnosis in 11 patients (52%), within one to two years in four patients (19%), and within two to five years in six patients (29%). Conclusion: Cluster analysis underscored several issues for TB control in an urban setting, such as the recognition of the outbreak, the importance of reinfections, the impact of delayed diagnosis, the contribution of pub-related transmissions and its value for decision-making to extend contact investigations. Visualising cases in a cluster diagram was particularly useful in finding transmission locations and the similarities and links between patients