Stroke is a leading cause of death and disability throughout the world. Although physical and cognitive impairments after stroke have been well studied, little is known about sexual functioning and ...satisfaction in these patients, despite being crucial aspects of quality of life. Post-stroke sexual dysfunctions seem to be common; in men affected by stroke, a decline in libido and poor or curtailed erection and ejaculation are frequently observed. Sexual disorders after stroke are thought to be due to multiple etiologies, including both organic (e.g., lesion localization, premorbid medical conditions, medications) and psychosocial (e.g., fear of recurrences, loss of self-esteem, role changes, anxiety and depression) etiologies. Thus, the exploration of sexual dysfunction and sexual counseling by trained professionals should be part of stroke rehabilitation.
The purpose of this paper is to assess the influence of a novel type of vortex creation device called the leading-edge vortex controller (LEVCON) on the aerodynamic characteristics of a fighter jet. ...LEVCON has become a trending term in modern military aircraft in recent years and is a continuation of an existing and widely used aerodynamic solution called the leading-edge root extension (LERX). LEVCON is designed to operate on the same principles as LERX, but its aim is to generate lift-augmenting vortices, i.e., vortex lift, at higher angles of attack than LERX. To demonstrate the methodology, a custom delta wing fighter aircraft is introduced, and details about its aerodynamic configuration are provided. The LEVCON geometry is designed and then incorporated into an existing three-dimensional (3D) model of the aircraft in question. The research is conducted using OpenFOAM 8, a high-fidelity computational fluid dynamics (CFD) open-source software. The computational cases are designed to simulate the aircraft’s flight at stall velocities within a high range of angles of attack. The results are assessed and discussed in terms of aerodynamic characteristics. A conclusion is drawn from the analysis regarding the perceived improvements in fighter jet aerodynamics. The analysis reveals that both lift and critical angle of attack can be manipulated positively. With the addition of LEVCON, the average lift gain in the high angle of attack (α) range is between 8.5% and 10%, while the peak gain reaches 19.4%. The critical angle of attack has also increased by 2°, and a flatter stall characteristic has been achieved.
What models can and cannot tell us about COVID-19 Siegenfeld, Alexander F.; Taleb, Nassim N.; Bar-Yam, Yaneer
Proceedings of the National Academy of Sciences - PNAS,
07/2020, Letnik:
117, Številka:
28
Journal Article
The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in ...prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.
Rosacea: New Concepts in Classification and Treatment van Zuuren, Esther J.; Arents, Bernd W. M.; van der Linden, Mireille M. D. ...
American journal of clinical dermatology,
07/2021, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Rosacea is a chronic inflammatory dermatosis mainly affecting the cheeks, nose, chin, and forehead. Rosacea is characterized by recurrent episodes of flushing or transient erythema, persistent ...erythema, phymatous changes, papules, pustules, and telangiectasia. The eyes may also be involved. Due to rosacea affecting the face, it has a profound negative impact on quality of life, self-esteem, and well-being. In addition to general skin care, there are several approved treatment options available for addressing these features, both topical and systemic. For some features, intense pulse light, laser, and surgery are of value. Recent advances in fundamental scientific research have underscored the roles of the innate and adaptive immune systems as well as neurovascular dysregulation underlying the spectrum of clinical features of rosacea. Endogenous and exogenous stimuli may initiate and aggravate several pathways in patients with rosacea. This review covers the new phenotype-based diagnosis and classification system reflecting pathophysiology, and new and emerging treatment options and approaches. We address new topical and systemic formulations, as well as recent evidence on treatment combinations. In addition, ongoing studies investigating novel therapeutic interventions will be summarized.
Sustainable development must account for pandemic risk Di Marco, Moreno; Baker, Michelle L.; Daszak, Peter ...
Proceedings of the National Academy of Sciences - PNAS,
02/2020, Letnik:
117, Številka:
8
Journal Article
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are glucose-lowering drugs that reduce plasma glucose levels by inhibiting glucose and sodium reabsorption in the kidneys, thus resulting in ...glucosuria. Their effects consequently include reductions in HbA1c, blood glucose levels, and blood pressure, but also reductions in body weight and adiposity. The ability to reduce body weight is consistently observed in individuals taking SGLT2 inhibitors, but this weight loss is moderate due to counter-regulatory mechanisms striving to maintain body weight. This has prompted exploration of SGLT2 inhibitors in combination with other agents acting via decreased food intake, e.g., glucagon-like peptide 1 receptor agonists (GLP1-RAs). The bodyweight effects are promising, and together with the signs of prevention of cardiovascular and renal events, such combinations including SGLT2 inhibitors are appealing. The weight loss is clinically important, as most individuals with type 2 diabetes are overweight or obese, but also because there is an unmet need for safe, effective, and durable weight loss interventions in obese individuals without diabetes.
•This leading opinion paper highlights the additive benefit of multiaxial load bioreactors in cartilage preclinical research.•It emphasizes that mechanical activation of endogenous TGFβ may be a key ...event in early cartilage repair after injury.•There is a need to implement kinematic load during in vitro/ex vivo studies to better align data obtained with that from in vivo studies.
Novel cartilage regeneration therapies often look promising in-vitro but fail when implanted in vivo. One of the possible reasons for this discrepancy is the simplified, static in-vitro chondrogenesis models typically used. Complex mechanical stimulation plays a key role in physiological cartilage and chondrogenic cell metabolism, including the development of cartilage structure, yet it is routinely lacking during in-vitro studies. Multiaxial load bioreactors are becoming more widespread and offer advantages over more simple loading devices. Within this article, we highlight some of the important findings from in-vitro assays and key aspects relating to tribological loading of cartilage and chondrogenic cells.
The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The ...cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
The ‘centre–periphery hypothesis’ (CPH) is a long‐standing postulate in ecology that states that genetic variation and demographic performance of a species decrease from the centre to the edge of its ...geographic range. This hypothesis is based on an assumed concordance between geographical peripherality and ecological marginality such that environmental conditions become harsher towards the limits of a species range. In this way, the CPH sets the stage for understanding the causes of distribution limits. To date, no study has examined conjointly the consistency of these postulates. In an extensive literature review we discuss the birth and development of the CPH and provide an assessment of the CPH by reviewing 248 empirical studies in the context of three main themes. First, a decrease in species occurrence towards their range limits was observed in 81% of studies, while only 51% demonstrated reduced abundance of individuals. A decline in genetic variation, increased differentiation among populations and higher rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and 48%, respectively). However, demographic rates, size and population performance less often followed CPH expectations (20–30% of studies). We highlight the impact of important methodological, taxonomic, and biogeographical biases on such validation rates. Second, we found that geographic and ecological marginality gradients are not systematically concordant, which casts doubt on the reliability of a main assumption of the CPH. Finally, we attempt to disentangle the relative contribution of geographical, ecological and historical processes on the spatial distribution of genetic and demographic parameters. While ecological marginality gradients explain variation in species' demographic performance better than geographic gradients, contemporary and historical factors may contribute interactively to spatial patterns of genetic variation. We thereby propose a framework that integrates species' ecological niche characteristics together with current and past range structure to investigate spatial patterns of genetic and demographic variation across species ranges.
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