Genetic control strategies for population suppression in the Anopheles gambiae complex: a review of current technologies.

Malaria continues to pose a critical public health threat, with mosquitoes from the Anopheles gambiae complex acting as the main vectors of the disease in sub-Saharan Africa, where approximately 95% of malaria-related deaths occur. Despite significant advancements in vector control, such as insecticide-treated bed nets and indoor spraying, the effectiveness of these interventions is increasingly compromised by various challenges, including rising levels of insecticide and pathogen resistance, mosquito behavioural adaptations, and persistent funding gaps. In this context, genetic vector control strategies have shown considerable promise, primarily based on findings from controlled laboratory studies.

Feasibility of single step hysteroscopic myomectomy: fibroid size is the most significant factor based on data from a single centre and surgeon.

Background: Uterine fibroids are the most common benign solid neoplasms of the uterus. Hysteroscopy represents the gold standard treatment for submucosal fibroids.

Objectives: The aim of this study was to retrospectively analyse all consecutive symptomatic patients diagnosed with the International Federation of Gynecology and Obstetrics G0-G3 fibroids who underwent hysteroscopic myomectomy, to identify factors that may influence the feasibility of single step myomectomy.

A total endoscopic levonorgestrel-releasing intrauterine system (LNG-IUS) placement: a novel approach for obese patients with early-stage endometrial cancer.

Background: Endometrioid adenocarcinoma is a common endometrial cancer, linked to excess oestrogen exposure. Obesity, a major risk factor, can lead to unopposed oestrogen and endometrial cancer. Surgery is the standard treatment for early-stage disease.

Complete uterine septum, cervical septum and longitudinal vaginal septum: a challenging differential diagnosis with double cervix.

Background: The presence of complete uterine septum, cervical septum and longitudinal vaginal septum (class U2bC1V1 according European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy classification) is a rare congenital anomaly of the female genital tract. The diagnosis of this anomaly is very challenging, significantly influencing the type of treatment to be performed.

Objectives: We propose a one-stop diagnosis through the combined use of 2D-3D ultrasound (US) and hysteroscopy and the minimally invasive endoscopic treatment of this anomaly, emphasising the diagnostic and therapeutic differences compared to U2bC2V1 anomaly.

Efficacy of Neoadjuvant Chemotherapy as pre-habilitation program in advanced epithelial ovarian cancer.

Introduction: Approximately 70 % of ovarian cancer patients present at diagnosis with advanced disease(AOC) and impaired clinical conditions, making them not ideal surgical candidates. We aimed to investigate whether neoadjuvant chemotherapy(NACT) can modify pre-operative characteristics of patients at high risk(HR) of perioperative complications, as defined in the Mayo Clinic Algorithm. We also compared their morbidity and survival outcomes with comparable HR women undergoing primary surgery (PCS).

A Y chromosome-linked genome editor for efficient population suppression in the malaria vector Anopheles gambiae.

Genetic control - the deliberate introduction of genetic traits to control a pest or vector population - offers a powerful tool to augment conventional mosquito control tools that have been successful in reducing malaria burden but that are compromised by a range of operational challenges. Self-sustaining genetic control strategies have shown great potential in laboratory settings, but hesitancy due to their invasive and persistent nature may delay their implementation. Here, instead, we describe a self-limiting strategy, designed to have geographically and temporally restricted effect, based on a Y chromosome-linked genome editor (YLE).

Y chromosome shredding in Anopheles gambiae: Insight into the cellular dynamics of a novel synthetic sex ratio distorter.

Despite efforts to explore the genome of the malaria vector Anopheles gambiae, the Y chromosome of this species remains enigmatic. The large number of repetitive and heterochromatic DNA sequences makes the Y chromosome exceptionally difficult to fully assemble, hampering the progress of gene editing techniques and functional studies for this chromosome. In this study, we made use of a bioinformatic platform to identify Y-specific repetitive DNA sequences that served as a target site for a CRISPR/Cas9 system.

Hormone Replacement Therapy in Post-Menopause Hormone-Dependent Gynecological Cancer Patients: A Narrative Review.

Background: Advances in the treatment of gynecological cancer have led to improvements in survival but also an increase in menopausal symptoms, especially in young women with premature iatrogenic menopause.

Methods: A narrative review was performed to clarify the possibility of prescribing hormone replacement therapy (HRT) after hormone-dependent gynecological cancers (ovarian cancer [OC], cervical adenocarcinoma [AC], and endometrial cancer [EC]).

Results: HRT can be prescribed to patients with early-stage, grade I-II OC who experience bothersome menopausal symptoms non-responsive to alternative non-hormone therapy after optimal surgery.

Relative expression of key genes involved in nucleic acids methylation in Anopheles gambiae sensu stricto.

In vertebrates, enzymes responsible for DNA methylation, one of the epigenetic mechanisms, are encoded by genes falling into the cytosine methyltransferases genes family (Dnmt1, Dnmt3a,b and Dnmt3L). However, in Diptera, only the methyltransferase Dnmt2 was found, suggesting that DNA methylation might act differently for species in this order. Moreover, genes involved in epigenetic dynamics, such as Ten-eleven Translocation dioxygenases (TET) and Methyl-CpG-binding domain (MBDs), present in vertebrates, might play a role in insects.

Whole-Mount Fluorescence In Situ Hybridization to Study Spermatogenesis in the Anopheles Mosquito.

Spermatogenesis is a complex biological process during which diploid cells undergo successive mitotic and meiotic division followed by large structural changes to form haploid spermatozoa. Besides the biological aspect, studying spermatogenesis is of paramount importance for understanding and developing genetic technologies such as gene drive and synthetic sex ratio distorters, which, by altering Mendelian inheritance and the sperm sex ratio, respectively, could be used to control pest insect populations. These technologies have proven to be very promising in lab settings and could potentially be used to control wild populations of Anopheles mosquitoes, which are vectors of malaria.

Driving down malaria transmission with engineered gene drives.

The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs.

Neoadjuvant Chemotherapy in Pregnant Patients with Cervical Cancer: A Monocentric Retrospective Study.

Background: To date, little and discordant data still exists on the management of cervical cancer (CC) during pregnancy. In this paper, we report our experience of the treatment of these patients analyzing the oncologic, obstetric, and neonatal outcomes.

Methods: Between January 2010 and December 2021, 13 patients were diagnosed with CC during pregnancy.

Comprehensive characterization of a transgene insertion in a highly repetitive, centromeric region of mosquitoes.

The availability of the genomic sequence of the malaria mosquito has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection.

Hyperthermic intraperitoneal chemotherapy (HIPEC) after primary debulking surgery in advanced epithelial ovarian cancer: Is BRCA mutational status making the difference?

Introduction: The role of a molecular pattern predictive of hyperthermic intraperitoneal chemotherapy (HIPEC) efficacy in advanced ovarian cancer (AOC) patients has been poorly investigated. We aimed to assess the effect of HIPEC after primary debulking surgery (PDS) in AOC according to patient's Breast Cancer Gene (BRCA) mutational status.

Methods: This is a retrospective, single center, case-control study.

The Potential for a Released Autosomal X-Shredder Becoming a Driving-Y Chromosome and Invasively Suppressing Wild Populations of Malaria Mosquitoes.

Sex-ratio distorters based on X-chromosome shredding are more efficient than sterile male releases for population suppression. X-shredding is a form of sex distortion that skews spermatogenesis of XY males towards the preferential transmission of Y-bearing gametes, resulting in a higher fraction of sons than daughters. Strains harboring X-shredders on autosomes were first developed in the malaria mosquito , resulting in strong sex-ratio distortion.

Genome Conservation as a Resource for Rational Gene Drive Target Site Selection.

The increase in molecular tools for the genetic engineering of insect pests and disease vectors, such as mosquitoes that transmit malaria, has led to an unprecedented investigation of the genomic landscape of these organisms. The understanding of genome variability in wild mosquito populations is of primary importance for vector control strategies. This is particularly the case for gene drive systems, which look to introduce genetic traits into a population by targeting specific genomic regions.

Incidence, predictors and clinical outcome of pancreatic fistula in patients receiving splenectomy for advanced or recurrent ovarian cancer: a large multicentric experience.

Purpose: To evaluate the incidence, predictors and clinical outcome of pancreatic fistulas in patients receiving splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancer.

Methods: Data of women who underwent splenectomy during cytoreduction for advanced or recurrent ovarian cancer from December 2012 to May 2018 were retrospectively retrieved from the oncological databases of five institutions. Surgical, post-operative and follow-up data were analysed.

High-resolution transcriptional profiling of Anopheles gambiae spermatogenesis reveals mechanisms of sex chromosome regulation.

Although of high priority for the development of genetic tools to control malaria-transmitting mosquitoes, only a few germline-specific regulatory regions have been characterised to date and the presence of global regulatory mechanisms, such as dosage compensation and meiotic sex chromosome inactivation (MSCI), are mostly assumed from transcriptomic analyses of reproductive tissues or whole gonads. In such studies, samples include a significant portion of somatic tissues inevitably complicating the reconstruction of a defined transcriptional map of gametogenesis. By exploiting recent advances in transgenic technologies and gene editing tools, combined with fluorescence-activated cell sorting and RNA sequencing, we have separated four distinct cell lineages from the Anopheles gambiae male gonads: premeiotic, meiotic (primary and secondary spermatocytes) and postmeiotic.

Publisher Correction: Introgression of a synthetic sex ratio distortion system from Anopheles gambiae into Anopheles arabiensis.

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Introgression of a synthetic sex ratio distortion system from Anopheles gambiae into Anopheles arabiensis.

I-PpoI is a homing endonuclease that has a high cleavage activity and specificity for a conserved sequence within the ribosomal rDNA repeats, located in a single cluster on the Anopheles gambiae X chromosome. This property has been exploited to develop a synthetic sex ratio distortion system in this mosquito species. When I-PpoI is expressed from a transgene during spermatogenesis in mosquitoes, the paternal X chromosome is shredded and only Y chromosome-bearing sperm are viable, resulting in a male-biased sex ratio of >95% in the progeny.

Molecular tools and genetic markers for the generation of transgenic sexing strains in Anopheline mosquitoes.

Malaria is a serious global health burden, affecting more than 200 million people each year in over 90 countries, predominantly in Africa, Asia and the Americas. Since the year 2000, a concerted effort to combat malaria has reduced its incidence by more than 40%, primarily due to the use of insecticide-treated bednets, indoor residual spraying and artemisinin-based combination drug therapies. Nevertheless, the cost of control is expected to nearly triple over the next decade and the current downward trend in disease transmission is threatened by the rise of resistance to drugs and insecticides.

Cross-Species Y Chromosome Function Between Malaria Vectors of the Species Complex.

Y chromosome function, structure and evolution is poorly understood in many species, including the genus of mosquitoes-an emerging model system for studying speciation that also represents the major vectors of malaria. While the Anopheline Y had previously been implicated in male mating behavior, recent data from the complex suggests that, apart from the putative primary sex-determiner, no other genes are conserved on the Y. Studying the functional basis of the evolutionary divergence of the Y chromosome in the gambiae complex is complicated by complete F1 male hybrid sterility.