Effectiveness of the etonogestrel subdermal implant in users with overweight and obesity: a systematic literature review.

Background: The etonogestrel (ENG) subdermal implant is considered a well-tolerated and effective contraception option to avoid unintended pregnancies. However, it is unclear whether being affected by overweight or obesity diminishes the effectiveness of the implant.

Objectives: To systematically assess the published evidence on implant contraceptive effectiveness in women with overweight or obesity, and in women who underwent bariatric surgery.

Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics-A Systematic Literature Review.

Background: Endometriosis diagnosis reportedly faces delays of up to 10 years. Despite growing awareness and improved guidelines, information on the current status is limited.

Objectives: To systematically assess the published evidence on the status of time to diagnosis in individuals with endometriosis, with respect to the definition of time to diagnosis, geographical location and patient characteristics.

Activation of Ca phosphatase Calcineurin regulates Parkin translocation to mitochondria and mitophagy in flies.

Selective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance of cellular homeostasis. This event is initiated by the translocation of the E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires the Serine/Threonine-protein kinase PINK1. In a coordinated set of events, PINK1 operates upstream of Parkin in a linear pathway that leads to the phosphorylation of Parkin, Ubiquitin, and Parkin mitochondrial substrates, to promote ubiquitination of outer mitochondrial membrane proteins.

Venous Thromboembolic Risk of Estradiol Valerate-Dienogest Compared with Ethinyl Estradiol-Levonorgestrel Combined Oral Contraceptives.

This pooled analysis compared the risk of venous thromboembolism (VTE) associated with combined oral contraceptives (COCs) containing estradiol (E2) valerate-dienogest with those containing ethinyl E2-levonorgestrel. Data were retrieved from two large, prospective, observational cohort studies. Propensity score subclassification was applied to balance baseline parameters between the COC user cohorts.

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study.

Objective: To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40.

Methods: In this large, observational study, new users of NOMAC-E2 and COC were recruited in Europe, Australia, and Latin America and followed-up questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/10 women-years [WY]).

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study.

To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COC) users under 25 years. In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COC were recruited in 12 countries in Europe, Australia, and Latin America and followed up questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years).

Thromboembolic safety of norethisterone vs levonorgestrel in combined oral contraceptive users: a pooled analysis of 4 large prospective cohort studies.

Background: Norethisterone (acetate) and levonorgestrel are marketed globally as components of combined oral contraceptives. Although guidelines recommend both as first-line combined oral contraceptives, no direct, comparative safety studies are available.

Objective: We directly compared the thromboembolic event risk associated with the use of norethisterone acetate-containing and levonorgestrel-containing combined oral contraceptives.

Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila.

Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms.

Risk of depression and anemia in users of hormonal endometriosis treatments: Results from the VIPOS study.

Objective: Dienogest (DNG) 2 mg (Visanne) was launched for endometriosis treatment in Europe in 2010. The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of DNG 2 mg/day compared to other hormonal endometriosis treatments, focusing especially on clinically relevant depression and anemia.

Study Design: Large, prospective, non-interventional, active surveillance study in six European countries.

Comprehensive Genetic Characterization of Mitochondrial Ca Uniporter Components Reveals Their Different Physiological Requirements In Vivo.

Mitochondrial Ca uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca uniporter has opened it up to genetic analysis in model organisms. Here, we report a comprehensive genetic characterization of all known uniporter components conserved in Drosophila.

Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction.

Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic and pharmacological inhibition of USP8 normalized the elevated MFN protein levels observed in PINK1 and Parkin-deficient models.

Purification of Functional F-ATP Synthase from Blue Native PAGE.

In the presence of Ca, F-ATP synthase preparations eluted from Blue Native gels generate electrophysiological currents that are typical of an inner mitochondrial membrane mega-channel, the permeability transition pore. Here we describe an experimental protocol for purification of F-ATP synthase that allows to maintain the enzyme assembly and activity that are essential for catalysis and channel formation.

USP14 inhibition corrects an model of impaired mitophagy.

Mitochondrial autophagy or mitophagy is a key process that allows selective sequestration and degradation of dysfunctional mitochondria to prevent excessive reactive oxygen species, and activation of cell death. Recent studies revealed that ubiquitin-proteasome complex activity and mitochondrial membrane rupture are key steps preceding mitophagy, in combination with the ubiquitination of specific outer mitochondrial membrane (OMM) proteins. The deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14) has been shown to modulate both proteasome activity and autophagy.

Regulation of ER-mitochondria contacts by Parkin via Mfn2.

Parkin, an E3 ubiquitin ligase and a Parkinson's disease (PD) related gene, translocates to impaired mitochondria and drives their elimination via autophagy, a process known as mitophagy. Mitochondrial pro-fusion protein Mitofusins (Mfn1 and Mfn2) were found to be a target for Parkin mediated ubiquitination. Mfns are transmembrane GTPase embedded in the outer membrane of mitochondria, which are required on adjacent mitochondria to mediate fusion.

Mitochondrial dynamics and mitophagy in Parkinson's disease: A fly point of view.

Mitochondria are double membrane-bounded organelles residing in the cytoplasm of almost all eukaryotic cells, which convert energy from the disposal of organic substrates into an electrochemical gradient that is in turn converted into ATP. However, the ion gradient that is generated through the oxidation of nutrients, may lead to the production of reactive oxygen species (ROS), which can generate free radicals, damaging cells and contributing to disease. Originally described as static structures, to date they are considered extremely plastic and dynamic organelles.

F-ATPase of Drosophila melanogaster forms 53-picosiemen (53-pS) channels responsible for mitochondrial Ca2+-induced Ca2+ release.

Mitochondria of Drosophila melanogaster undergo Ca(2+)-induced Ca(2+) release through a putative channel (mCrC) that has several regulatory features of the permeability transition pore (PTP). The PTP is an inner membrane channel that forms from F-ATPase, possessing a conductance of 500 picosiemens (pS) in mammals and of 300 pS in yeast. In contrast to the PTP, the mCrC of Drosophila is not permeable to sucrose and appears to be selective for Ca(2+) and H(+).

Leigh syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing.

Leigh Syndrome (LS) is the most common early-onset, progressive mitochondrial encephalopathy usually leading to early death. The single most prevalent cause of LS is occurrence of mutations in the SURF1 gene, and LS(Surf1) patients show a ubiquitous and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). SURF1 encodes an inner membrane mitochondrial protein involved in COX assembly.

Dimers of mitochondrial ATP synthase form the permeability transition pore.

Here we define the molecular nature of the mitochondrial permeability transition pore (PTP), a key effector of cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase. We show that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), that Bz-423 sensitizes the PTP to Ca(2+) like CyPD itself, and that decreasing oligomycin sensitivity-conferring protein expression by RNAi increases the sensitivity of the PTP to Ca(2+).

The permeability transition pore as a Ca(2+) release channel: new answers to an old question.

Mitochondria possess a sophisticated array of Ca(2+) transport systems reflecting their key role in physiological Ca(2+) homeostasis. With the exception of most yeast strains, energized organelles are endowed with a very fast and efficient mechanism for Ca(2+) uptake, the ruthenium red (RR)-sensitive mitochondrial Ca(2+) uniporter (MCU); and one main mechanism for Ca(2+) release, the RR-insensitive 3Na(+)-Ca(2+) antiporter. An additional mechanism for Ca(2+) release is provided by a Na(+) and RR-insensitive release mechanism, the putative 3H(+)-Ca(2+) antiporter.

Properties of Ca(2+) transport in mitochondria of Drosophila melanogaster.

We have studied the pathways for Ca(2+) transport in mitochondria of the fruit fly Drosophila melanogaster. We demonstrate the presence of ruthenium red (RR)-sensitive Ca(2+) uptake, of RR-insensitive Ca(2+) release, and of Na(+)-stimulated Ca(2+) release in energized mitochondria, which match well characterized Ca(2+) transport pathways of mammalian mitochondria. Following larger matrix Ca(2+) loading Drosophila mitochondria underwent spontaneous RR-insensitive Ca(2+) release, an event that in mammals is due to opening of the permeability transition pore (PTP).

The mitochondrial permeability transition from yeast to mammals.

Regulated permeability changes have been detected in mitochondria across species. We review here their key features, with the goal of assessing whether a "permeability transition" similar to that observed in higher eukaryotes is present in other species. The recent discoveries (i) that treatment with cyclosporin A (CsA) unmasks an inhibitory site for inorganic phosphate (Pi) [Basso, E.