Differential composition of vaginal microbiome, but not of seminal microbiome, is associated with successful intrauterine insemination in couples with idiopathic infertility: A prospective observational study

Background Vaginal and seminal microbiomes have gained increasing interest for their involvement in reproductive health and fertility. However, their role in reproductive outcome is not fully understood yet. In this study, we aimed to correlate the vaginal and the seminal microbiome of 23 couples with idiopathic infertility to the clinical pregnancy rate after intrauterine insemination (IUI). Methods Vaginal swabs and seminal fluids were collected on the day of IUI procedure and analyzed through polymerase chain reaction amplification of variable regions 3 and 4 (V3–V4) of 16S ribosomal ribonucleic acid genes and Illumina MiSeq sequencing. The taxonomic data were then correlated to IUI success. Results Idiopathic infertile women showed a different average composition of vaginal microbiome compared with control sequences, whereas for seminal counterpart no relevant differences were observed. Furthermore, among idiopathic infertile women, different patterns of Lactobacillus species dominations were observed, with a predominance either of Lactobacillus crispatus, a marker of a healthy vaginal ecosystem, or of Lactobacillus iners and Lactobacillus gasseri, associated with a more dysbiosis-prone environment. More important, considering all investigated variables, vaginal L crispatus domination was the only factor strongly associated to IUI success (P = .0002). Conclusions Our results strengthen the potential role of L crispatus in promoting a favorable environment for pregnancy and suggest that microbiome characterization could be useful, together with standard clinical and laboratory assessments, in the pre-IUI evaluation of infertile couples

Recombinant FSH improves sperm DNA damage in male infertility: A phase II clinical trial

Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets. Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test. Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis. Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40 years). Intervention(s) Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH â¥15 pmol/L: 0.10â0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.publishedVersionPeer reviewe

È sufficiente la sola supplementazione di ferro nel trattamento dell’anemia sideropenica?

La carenza di ferro è la causa più comune di anemia sia in Italia che nel mondo; circa il 30% della popolazione mondiale è affetta da anemia e in almeno la metà dei casi è conseguenza di una carenza marziale. Le condizioni che favoriscono l'insorgenza della carenza di ferro sono conseguenza di uno o più dei seguenti tre meccanismi: aumentato fabbisogno (gravidanza, puerperio, infanzia), diminuito assorbimento intestinale (carenza dietetica, malattie intestinali che compromettono l'assorbimento del ferro, soprattutto la celiachia), aumentata perdita di sangue (mestruazioni, gastrite, tumori intestinali benigni e maligni, ecc.). Il deficit di ferro si manifesta attraverso tre stadi. Il primo stadio - deplezione di ferro - si verifica quando il contenuto in ferro non è sufficiente a soddisfare le richieste corporee. Se il bilancio negativo persiste, inizia il secondo stadio - deficit di ferro nell’eritropoiesi - caratterizzato da una riduzione del ferro sierico, con una saturazione della transferrina al di sotto del 16%. Nel terzo stadio - anemia da deficit di ferro - l’emoglobina è al di sotto degli standard secondo l’età ed il sesso. La stadio è caratterizzato dallo sviluppo di microcitosi e ipocromia. Quando la deplezione di ferro riguarda solo quello dei depositi, ed i valori degli eritrociti e dell’emoglobina sono nella norma, l’obiettivo terapeutico principale e rappresentato dal ripristino di tali depositi tramite preparati a base di solo ferro. Quando invece gli effetti progressivi della carenza di ferro influiscono sulla produzione di eritrociti, occorre ristabilire un’ adeguata eritropoiesi. La normale produzione di globuli rossi richiede la presenza di un’adeguata e costante disponibilità non solo di ferro, ma anche di varie vitamine (tra le quali, la cianocobalamina e gli acidi folici) e di alcuni oligoelementi (quali il rame, lo zinco, il cobalto) necessari per una totale globalizzazione della terapia antianemica, fondamentale in gravidanza laddove il “sistema ferro” è particolarmente sotto pressione per le richieste materne e fetali

SlowReq: A Weapon for Cyberwarfare Operations. Characteristics, Limits, Performance, Remediations

In the last years, with the advent of the Internet, cyberwarfare opera- tions moved from the battlefield to the cyberspace, locally or remotely execut- ing sabotage or espionage operations in order to weaken the enemy. Among the technologies and methods used during cyberwarfare actions, Denial of Service attacks are executed to reduce the availability of a particular service on a net- work. In this paper we present a Denial of Service tool that belongs to the Slow DoS Attacks category. We describe in detail the attack functioning and we compare the proposed threat with a similar one known as slowloris, showing the enhancements provided by the proposed tool

Taxonomy of Slow DoS Attacks to Web Applications

In the last years, Denial of Service (DoS) attacks have been widely spreaded becoming a more than ever relevant threat to network security. DoS attacks evolved from flood to low bandwidth rate based, making a host unreachable through the usage of a small amount of bandwidth and eluding an Intrusion Detection System more easily. In this paper, we analyze the most common slow Denial of Service attacks to web applications, proposing a taxonomy to categorize such attacks. The proposal of our work is to make an overview and to classify slow DoS attacks for a better understanding of their action strategy, thus helping developers and network administrators to design proper defense methodologies

SlowDroid: Turning a Smartphone into a Mobile Attack Vector

Nowadays, last generation of smartphones are comparable to desktop computers in terms of computational capabilities. Such characteristics can turn a smartphone into a mobile attack vector. In this paper we analyze the use of mobile devices to perpetrate cyber attacks. We present a mobile threat, SlowDroid, running on Android operating system. Such menace implements a Denial of Service attack and it is particularly suitable to a mobile execution, since it makes use of low amounts of computational and bandwidth resources. We present in detail SlowDroid implementation and our choices in terms of design, graphical user interface, and system architecture

Tyrosinase immobilized reactor as a fast tool for polyphenolic index of tea

A new approach for the determination of polyphenolic index of black and green teas has been developed employing a bioreactor with mushroom tyrosinase immobilized on aminopropyl-controlled pore glass (AMP-CPG). Initially a linear correlation (r2 = 0.997) of catechin content between the Folin-Ciocalteu (FC) and the enzymatic assays is obtained. Our method appears to be more specific and rapid. Successively the inhibition of the enzymatic oxidation of catechin by some tea components like gallic acid (GA), epigallocatechin (EGC), epigallocatechingallate (EGCG) and epicatechin (EC) is investigated. Finally when tea samples are analyzed by using the new method it appears that green tea is the strongest inhibitor followed by black tea and flavored tea. The level of polyphenols, which is correlated to the extent of inhibition, is reported as epigallocatechin equivalents and the results are compared with those obtained using the FC assay and the vanillin index. The differences in phenol content found by applying the three methods are discussed in terms of the different specificities of the analytical basis. © 2009 Elsevier Inc. All rights reserved