Recovery of menses after functional hypothalamic amenorrhoea: if, when and why

BACKGROUND Prolonged amenorrhoea occurs as a consequence of functional hypothalamic amenorrhoea (FHA) which is most often induced by weight loss, vigorous exercise or emotional stress. Unfortunately, removal of these triggers does not always result in the return of menses. The prevalence and conditions underlying the timing of return of menses vary strongly and some women report amenorrhoea several years after having achieved and maintained normal weight and/or energy balance. A better understanding of these factors would also allow improved counselling in the context of infertility. Although BMI, percentage body fat and hormonal parameters are known to be involved in the initiation of the menstrual cycle, their role in the physiology of return of menses is currently poorly understood. We summarise here the current knowledge on the epidemiology and physiology of return of menses. OBJECTIVE AND RATIONALE The aim of this review was to provide an overview of (i) factors determining the recovery of menses and its timing, (ii) how such factors may exert their physiological effects and (iii) whether there are useful therapeutic options to induce recovery. SEARCH METHODS We searched articles published in English, French or German language containing keywords related to return of menses after FHA published in PubMed between 1966 and February 2020. Manuscripts reporting data on either the epidemiology or the physiology of recovery of menses were included and bibliographies were reviewed for further relevant literature. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria served to assess quality of observational studies. OUTCOMES Few studies investigate return of menses and most of them have serious qualitative and methodological limitations. These include (i) the lack of precise definitions for FHA or resumption of menses, (ii) the use of short observation periods with unsatisfactory descriptions and (iii) the inclusion of poorly characterised small study groups. The comparison of studies is further hampered by very inhomogeneous study designs. Consequently, the exact prevalence of resumption of menses after FHA is unknown. Also, the timepoint of return of menses varies strongly and reliable prediction models are lacking. While weight, body fat and energy availability are associated with the return of menses, psychological factors also have a strong impact on the menstrual cycle and on behaviour known to increase the risk of FHA. Drug therapies with metreleptin or naltrexone might represent further opportunities to increase the chances of return of menses, but these require further evaluation

Sequences of acetyl CoA carboxylase promoter for tumour necrosis factor action

Tumour necrosis factor (TNF) inhibits the accumulation of acetyl CoA carboxylase (ACC) mRNA by decreasing the rate of ACC gene transcription. The ACC mRNA species found in 30A5 cells are generated from promoter II and TNF inhibits the accumulation of class 2 type mRNAs. By using 5' deletion mutants of promoter II fused to the bacterial chloramphenicol acetyltransferase (CAT) gene, the DNA mobility shift assay and the DNase I footprinting assay, the authors have identified the 30 bp from −389 to −359 as the TNF responsive element in promoter II. TNF treatment causes a decrease in the binding activity of nuclear protein(s) specific to the TNF responsive element. When the fragment containing the TNF responsive element was incorporated into the thymidine kinase promoter, the chimeric gene exhibited TNF induced inhibition of expression

Biodiversity and function of nematodes in contrasting southern European deep-sea environments = Biodiversiteit en functie van nematoden in contrasterende zuid-Europese diepzeegebieden

Until around 150 years ago, the deep sea was regarded as a relatively uniform and stable habitat, and owing to the extreme abiotic conditions (lack of sunlight, high atmospheric pressure and low temperature), it was thought to contain no life. However, expeditions in the 1960s and 1970s revealed remarkably high biodiversity in the deep-sea realm; later, state-of-the-art technology (such as manned or autonomous submersibles) evidenced an unexpectedly high habitat heterogeneity and temporal variability. Although the deep sea (the pelagic and the benthic zone) constitutes the most extensive biome on Earth, it is still largely under-sampled and new habitats and species are still being discovered. There is a growing awareness of the global significance of this ecosystem since it hosts a large fraction of the Earth’s biodiversity, contains a large reservoir of mineral and biological resources, regulates the climate (by taking up carbon dioxide, which is a greenhouse gas) and is an important player in the recycling of nutrients. Human activities (e.g. waste disposal, extraction of fish, minerals and hydrocarbons, global warming) have been shown to alter deep-sea ecosystem properties and processes. Hence, it is of the utmost importance that we advance our knowledge on the functioning of the deep-sea ecosystem to underpin its sustainable management. International, collaborative research projects like HERMES (“Hotspot Ecosystem Research on the Margins of European Seas”, 2005-2009)/HERMIONE (“Hotspot Ecosystem Research and Man's Impact ON European Seas”, 2009-2012) and BIOFUN (“BIOdiversity and ecosystem FUNctioning in Southern European Deep-sea environments: from viruses to megafauna”, 2007-2011), which provided the frame for this doctoral research, were set up to gather more information on the structure, functioning and dynamics of deep-sea ecosystems.Nematodes, which constitute the predominant meiofaunal phylum, are the most abundant,speciose and ubiquitous metazoan organisms residing in deep-sea sediments. Consequently, they represent the ideal organisms to evaluate macro-ecological patterns and to examine the link between diversity and ecosystem functioning. Because of their high standing stock, high metabolic and reproductive rates, and their presumed intermediate trophic position (between detritus and/or bacteria, and predatory meiofauna and/or macro- or megafauna) these roundworms are thought to have an important role in the benthic carbon cycle in coastal habitats. Whether this also applies to nematodes living in the deep sea is unknown, since information on their life history strategies in this extreme environment is completely lacking. So far, we have not succeeded in characterizing the feeding behaviour and preferences of nematodes, and also the functional importance of nematode activities that are unrelated to foraging, remains a big unknown. An overview of the general characteristics of the deep-sea environment, the concept of biodiversity and the effect on ecosystem functioning, as well as the applicability to deep-sea nematodes are presented

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Testing for Network and Spatial Autocorrelation

Testing for dependence has been a well-established component of spatial statistical analyses for decades. In particular, several popular test statistics have desirable properties for testing for the presence of spatial autocorrelation in continuous variables. In this paper we propose two contributions to the literature on tests for autocorrelation. First, we propose a new test for autocorrelation in categorical variables. While some methods currently exist for assessing spatial autocorrelation in categorical variables, the most popular method is unwieldy, somewhat ad hoc, and fails to provide grounds for a single omnibus test. Second, we discuss the importance of testing for autocorrelation in network, rather than spatial, data, motivated by applications in social network data. We demonstrate that existing tests for autocorrelation in spatial data for continuous variables and our new test for categorical variables can both be used in the network setting

Tips and tricks to avoid implant failure in proximal femur fractures treated with cephalomedullary nails: a review of the literature

Objective: To describe the surgical aspects potentially contributing to hardware failure of cephalomedullary nails. Data Sources: A search of the Embase, PubMed (MEDLINE), Web of Science, and the Cochrane library for reports of hardware failures after intramedullary fixation of proximal femur fractures. Issues of cut out and cut through phenomena related to technique were excluded. Expert opinion of 3 surgeons, each trained on several fixation systems at Level | trauma centers is reported. Data Extraction: Three authors extracted data using a predesigned form. Implant type, reported failure mechanism, and associated factors with implant failure were recorded as well as potential bias. Results: Of 2182 search results screened, 64 articles were deemed relevant for our research question and were included. The authors identified factors associated with implant failure: preoperative patient and fracture characteristics, intraoperative reduction, implant handling, and postoperative nonunion. Issues were identified as independent modifiable intraoperative risk factors: inadequate fracture reduction, varus position of femoral neck, direct damage of the cephalomedullary nail aperture by eccentric drilling related to guide sleeve handling, and implant design mechanism failures. Conclusions: Multiple factors associated with intraoperative handling can influence the healing of proximal femur fractures. Although many of these have been well described and are taught in fracture courses, surgeons should be aware of subtle intraoperative complications reported in the literature that can weaken implants and add to the likelihood of early failure