Abnormal hippocampal melatoninergic system: a potential link between absence epilepsy and depression-like behavior in WAG/Rij rats?

Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings. However, neither pinealectomy nor melatonin administration had any effect on SWD incidence, suggesting that the melatoninergic system was not involved in the pathophysiology of absence-like seizures. Endogenous melatonin levels were lower in the hippocampus of WAG/Rij rats as compared to non-epileptic control rats, and this was associated with higher levels of melatonin receptors in the hippocampus, but not in the thalamus. In line with the reduced melatonin levels, cell density was lower in the hippocampus ofWAG/Rij rats and was further reduced by pinealectomy. As expected, WAG/Rij rats showed an increased depression-like behaviour in the sucrose preference and forced swim tests, as compared to non-epileptic controls. Pinealectomy abolished the difference between the two strains of rats by enhancing depression-like behaviour in non-epileptic controls. Melatonin replacement displayed a significant antidepressant-like effect in bothWAG/Rij and control rats. These findings suggest that a defect of hippocampal melatoninergic system may be one of the mechanisms underlying the depression-like phenotype inWAG/Rij rats and that activation of melatonin receptors might represent a valuable strategy in the treatment of depression associated with absence epilepsy

Treatment of Non-Union and Bone Loss of Tibial Pilon

Non-union is a fracture with no healing potential without a further surgical procedure. Diagnosis of non-union can be done in case of healing failure from 6 to 9 months after the first fracture. We consider appropriate to keep the attention of the reader on the relevance that more frequent traumatic mechanisms have in relationship with evolution and eventual failure of healing processes. In literature, non-union mean rate for tibial pilon fractures is around 5% independently from the synthesis technique used; as main causes we can recognize a significant fracture’s comminution ad eventual bone loss, vascular damage, and local infection. Risk factors can be divided into two big groups: factors proper of the patient at the moment of injury (age, diseases, drugs, smoke, etc.) and characteristics of the trauma itself (comminution and dislocation of fragments, involvement of soft tissues, topography, distance between fragments). Tibial pilon fractures are mainly caused by high-energy trauma. This kind of dynamic determines not only more serious damage to the bone, but often cause damage of the surrounding tissues. Following important lesions of the periosteum and of the vascular network and after a suboptimal synthesis caused by comminution and dislocation of fragments is frequent with the evolution toward a bad bone healing process. Bone healing was, in the last 50 years, argument of intense research activity. The incidence of non-union is growing steadily, although principles and materials of synthesys are well standardized. Recently it has been codified the “diamond concept,” which clarified different appliances mechanical and biological, these distinguished between cells, scaffolds, and growth factors. Under the mechanical profile, it must be restored the spectrum of stability that consider the set of bone and synthesis implanted. The spectrum of stability interprets Wolf’s law providing indications on the need to modulate the rigidity of the synthesis in reason of the level of instability of the pseudoarthrosis itself. During the years several kinds of non-union classifications have been proposed. The most widespread until now is the one proposed by Weber–Cech in 1976, which distinguishes vital forms (hypertrophic and oligotrophic) from non-vital forms (atrophic). In 2007 a new score classification system has been processed, which is the “Non-Union Scoring System (NUSS),” which divides patients in four big groups by score awarded based on the real non-healing risk. The NUSS represents an innovative approach to the problem because it understand the multifactorial reasons of failure, explains why in a variable percentage of cases (depending from de district affected), the healing is not obtained, even with a correct treatment and above all make possible the drafting of a therapeutic choice algorithm. Biotechnologies at our disposal are synthetic growth factors, the autologous growth factors and platelet-rich plasma, mesenchymal stem cells, and scaffolds or bone substitute. The biologic chamber represent the ideal site for bone regeneration; it is a bio-reactor in which are present all those elements at the base of the concept of diamond. The chamber needs to be aseptic, vital, mechanically stable, and sealed but selectively permeable. Thanks to the use of megaprosthesis not only in oncologic orthopaedics, but also it is now possible to avoid the amputation or long and often inconclusive treatment of lengthening or ankle arthrodesis. The new frontier in treatment of non-unions will be genetic therapy, that is, the possibility to transport to the patient those genes that con drive to the formation of good bone callus and his maturation toward strong bone

Gestational Diabetes and Thyroid Autoimmunity

Background. About 10% of pregnancies are complicated by previously unknown impairment of glucose metabolism, which is defined as gestational diabetes. There are little data available on prevalence of thyroid disorders in patients affected by gestational diabetes, and about their postgestational thyroid function and autoimmunity. We therefore investigated pancreatic and thyroid autoimmunity in gestational diabetic patients and in women who had had a previous gestational diabetic pregnancy. Methods. We investigated 126 pregnant women at the time of a 100-g oral glucose tolerance test: 91 were classified as gestational diabetics, and 35 were negative (controls). We also studied 69 women who had delivered a baby 18–120 months prior to this investigation and who were classified at that time gestational diabetics (38 women) or normally pregnant (31 women; controls). Results. Our data show no differences for both thyroid function and prevalence of autoimmune disorders during pregnancy; however, a significant increase in thyroid autoimmunity was seen in women previously affected by gestational diabetes. This increased prevalence of thyroid autoimmunity was not associated with the development of impaired glucose metabolism after pregnancy. Conclusions. Our data suggest that maternal hyperglycemia is a risk factor for the development of thyroid autoimmunity, a conclusion that should now be confirmed in a larger cohort of patients

Adrenal Modulation & Perceived Distress of BC Survivors

Background: Distress and adrenal balance of breast cancer survivors (BCS) are key elements of their psychophysical health, and increasing evidence has shown both physical exercise and the natural environment are effective for their modulation. The aim of the study was to evaluate the acute effects of the environment and type of light intensity workouts, on distress, salivary cortisol and dehydroepiandrosterone sulfate (DHEA-S) in BCS.Methods: Twenty-four BCS participated in six different workouts, each with the same duration and intensity. Three of them were conducted in natural environments – walking (Wnature), canoeing with assistance (Cnature) and a mix of myofascial and yoga exercises (MYnature). The others were conducted in an urban environment, namely walking (Wurban), or an indoor environment, namely mobilisation and light upper body exercises (MCgym) and a mix of myofascial and yoga exercises (MYgym). Before and after each workout, the Distress Thermometer was completed and saliva was collected.Results: Workouts practised in natural environments elicited a higher reduction in cortisol and the cortisol to DHEA-S ratio and a greater DHEA-S increase compared with workouts practised in urban and indoor environments. Overall, Cnature and MYnature were the best activities; among those practised in urban and indoor environments, MYgym elicited the best results. Distress was not acutely reduced after Wurban and MCgym. Conclusion: Natural environments seem to provide the best management of distress, cortisol, DHEA-S and their balance when working out at light intensities. The simultaneous presence of forests and rivers seems to be the key element of the observed results

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Data quality of Aeolus wind measurements

The European Space Agency (ESA)'s Earth Explorer Aeolus was launched in August 2018 carrying the world's first spaceborne wind lidar, the Atmospheric Laser Doppler Instrument (ALADIN). ALADIN uses a high spectral resolution Doppler wind lidar operating at 355nm to determine profiles of line-of-sight wind components in near-real-time (NRT). ALADIN samples the atmosphere from 30km altitude down to the Earth's surface or to the level where the lidar signal is attenuated by optically thick clouds. The global wind profiles provided by ALADIN help to improve weather forecasting and the understanding of atmospheric dynamics as they fill observational gaps in vertically resolved wind profiles mainly in the tropics, southern hemisphere, and over the northern hemisphere oceans. Since 2020, multiple national and international weather centres (e.g. ECMWF, DWD, Météo France, MetOffice) assimilate Aeolus observations in their operational forecasting. Additionally, the scientific exploitation of the Aeolus dataset has started. A main prerequisite for beneficial impact and scientific exploitation is data of sufficient quality. Such high data quality has been achieved through close collaboration of all involved parties within the Aeolus Data Innovation and Science Cluster (DISC), which was established after launch to study and improve the data quality of Aeolus products. The tasks of the Aeolus DISC include the instrument and platform monitoring, calibration, characterization, retrieval algorithm refinement, processor evolution, quality monitoring, product validation, and impact assessment for NWP. The achievements of the Aeolus DISC for the NRT data quality and the one currently available reprocessed dataset will be presented. The data quality of the Aeolus wind measurements will be described and an outlook on planned improvements of the dataset and processors will be provided

The Aeolus Data Innovation and Science Cluster

The Data Innovation and Science Cluster (DISC) is a core element of ESA's data quality strategy for the Aeolus mission, which was launched in August 2018. Aeolus provides for the first-time global observations of vertical profiles of horizontal wind information by using the first Doppler wind lidar in space. The Aeolus DISC is responsible for monitoring and improving the quality of the Aeolus aerosol and wind products, for the upgrade of the operational processors as well as for impact studies and support of data usage. It has been responsible for multiple significant processor upgrades which reduced the systematic error of the Aeolus observations drastically. Only due to the efforts of the Aeolus DISC team members prior to and after launch, the systematic error of the Aeolus wind products could be reduced to a global average below 1 m/s which was an important pre-requisite for making the data available to the public in May 2020 and for its use in operational weather prediction. In 2020, the reprocessing of earlier acquired Aeolus data, another important task of the Aeolus DISC, also started. In this way, also observations from June to December 2019 with significantly better quality could be made available to the public, and more data will follow this and next year. Without the thorough preparations and close collaboration between ESA and the Aeolus DISC over the past decade, many of these achievements would not have been possible

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Contributions from the DISC to accomplish the Aeolus mission objectives

The Aeolus Data Innovation and Science Cluster (DISC) supports the Aeolus mission with a wide range of activities from instrument and product quality monitoring over retrieval algorithm improvements to numerical weather prediction (NWP) impact assessments for wind and aerosols. The Aeolus DISC provides support to ESA, Cal/Val teams, numerical weather prediction (NWP) centers, and scientific users for instrument special operations and calibration, for the re-processing of Aeolus products from the past and through the provision of bi-annual updates of the L1A, L1B, L2A and L2B operational processors. The Aeolus DISC is coordinated by DLR with partners from ECMWF, KNMI, Météo-France, TROPOS, DoRIT, ABB, s&t, serco, OLA, Physics Solutions, IB Reissig and Les Myriades involving more than 40 scientists and engineers. The presentation will highlight the Aeolus DISC activities with a focus for the year 2021 and early 2022 since the last Aeolus workshop in November 2020. This covers the evolution of the instrument performance including investigations of the cause of the on-going signal loss and the achieved improvement via dedicated laser tests in 2021. In addition, refinements of algorithms and correction of the wind bias will be discussed - including a known remaining seasonal bias in October and March as encountered during the re-processing campaigns. Finally, the strategy for the on-going and future re-processing campaigns will be addressed to inform the scientific community about the availability and quality of the re-processed data products. The Aeolus mission has fully achieved its mission objectives including the unprecedented demonstration of direct-detection Doppler wind lidar technology and high-power laser operation in space in the ultraviolet spectral region over its planned full mission lifetime of 3 years and 3 months. Aeolus wind products have clearly demonstrated positive impact on forecasts using several NWP models. Since early 2020, and thus only 1.5 years after launch, the Aeolus wind products are used in operation at various NWP centers worldwide. This was achieved even despite the larger than expected wind random errors due to lower initial atmospheric signal levels and the observed signal losses during the operation of the first and second laser. In addition to this incredible success, first scientific studies demonstrated the use of Aeolus for atmospheric dynamics research in the stratosphere and for the analysis of aerosol transport. These achievements of the Aeolus mission and its success were only possible with the essential and critical contributions from the Aeolus DISC. This demonstrates the need and potential for setting up such scientific consortia covering a wide range of expertise from instrument, processors, and scientific use of products for Earth Explorer type missions. The invaluable experience gained by the Aeolus DISC during the more then 3 years of Aeolus mission in orbit (preceded by a period of 20 years before launch by a similar study team) is a pre-requisite for a successful preparation of an operational follow-on Aeolus-2 mission

The Role of the Transcription Factor Nuclear Factor-kappa B in Thyroid Autoimmunity and Cancer

Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor that is involved in inflammatory and immune responses, as well as in regulation of expression of many other genes related to cell survival, proliferation, and differentiation. In mammals, NF-κB comprises five subunits that can bind to promoter regions of target genes as homodimers or heterodimers. The most common dimer is the p50/p65 heterodimer. The several combinations of dimers that can be formed contribute to the heterogeneous regulation of NF-κB target genes, and this heterogeneity is further increased by interactions of the NF-κB dimers with other transcription factors, such as steroid hormone receptors, activator protein-1 (AP-1), and cAMP response element binding protein (CREB). In the thyroid, several studies have demonstrated the involvement of NF-κB in thyroid autoimmunity, thyroid cancer, and thyroid-specific gene regulation. The role of NF-κB in thyroid autoimmunity was hypothesized more than 20 years ago, after the finding that the binding of distinct NF-κB heterodimers to the major histocompatibility complex class I gene is hormonally regulated. Further studies have shown increased activity of NF-κB in thyroid autoimmune diseases and in thyroid orbitopathy. Increased activity of NF-κB has also been observed in thyroid cancer, where it correlates with a more aggressive pattern. Of particular interest, mutation of some oncogenes or tumor suppressor genes involved in thyroid carcinogenesis results in constitutive activation of the NF-κB pathway. More recently, it has been shown that NF-κB also has a role in thyroid physiology, as it is fundamental for the expression of the main thyroid-specific genes, such as sodium iodide symporter, thyroid peroxidase, thyroglobulin, Pax8, and TTF-1 (NKX2-1)