Background: Patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of cerebral reperfusion injury after prolonged hypoperfusion and immediate restoration of systemic blood flow. We aimed to examine the impact of mild hypothermia during the first 24 hours post-ECMO on neurological outcome in VA-ECMO patients. Methods: This was a retrospective study of adult VA-ECMO patients from a tertiary care center. Mild hypothermia was defined as 32-36°C during the first 24 hours post-ECMO. Primary outcome was good neurological function at discharge measured by a modified Rankin Scale ≤3. Multivariable logistic regression analysis was performed for primary outcome adjusting for pre-specified covariates. Results: Overall, 128 consecutive patients with VA-ECMO support (median age: 60 years and 63% males) were included. Within the first 24 hours of VA-ECMO cannulation, we found a median of 71 readings per patient (interquartile range 45-88). Eighty-eight patients (68.8%) experienced mild hypothermia within the first 24 hours while 18 of those 88 patients (14.2%) had a mean temperature<36°C. ECMO indications included post-cardiotomy shock (39.8%), cardiac arrest (29.7%), and cardiogenic shock (26.6%). Duration of mild hypothermia, but not mean temperature, was independently associated with increased odds of good neurological outcome at discharge (Odds Ratio [OR]=1.16, 95% Confidence Interval [CI]=1.04-1.31, p=0.01) after adjusting for age, severity of illness, post-ECMO systemic hemorrhage, post-cardiotomy shock, acute brain injury, and mean 24-hour PaO 2. Neither duration of mild hypothermia (OR=0.93, CI=0.84-1.03, p=0.17) nor mean temperature (OR=0.78, CI=0.29-2.08, p=0.62) was significantly associated with mortality. Similarly, duration of mild hypothermia (p=0.47) and mean 24-hour temperature (p=0.76) were not significantly associated with frequency of systemic hemorrhages. Conclusions: In this single center study, longer duration of mild hypothermia during the first 24 hours of ECMO support was significantly associated with improved neurological outcome. Mild hypothermia was not associated with an increased risk of systemic hemorrhage or improved survival.

Osteopoikilosis(OPK) is one of the rare genetic musculoskeletal, non inflammatory disorders that we should increase awareness towards. We report a case of a patient diagnosed with psoriatic arthritis with incidental imaging findings of lesions suggestive of osteopoikilosis.

Population dynamics are functions of several demographic processes including survival, reproduction, somatic growth, and maturation. The rates or probabilities for these processes can vary by time, by location, and by individual. These processes can co-vary and interact to varying degrees, e.g., an animal can only reproduce when it is in a particular maturation state. Population dynamics models that treat the processes as independent may yield somewhat biased or imprecise parameter estimates, as well as predictions of population abundances or densities. However, commonly used integral projection models (IPMs) typically assume independence across these demographic processes. We examine several approaches for modelling between process dependence in IPMs, and include cases where the processes co-vary as a function of time (temporal variation), co-vary within each individual (individual heterogeneity), and combinations of these (temporal variation and individual heterogeneity). We compare our methods to conventional IPMs, which treat vital rates independent, using simulations and a case study of Soay sheep (Ovis aries). In particular, our results indicate that correlation between vital rates can moderately affect variability of some population-level statistics. Therefore, including such dependent structures is generally advisable when fitting IPMs to ascertain whether or not such between vital rate dependencies exist, which in turn can have subsequent impact on population management or life-history evolution.

A centroid- and covariance-invariant deterministic mapping of sets of discrete data points to nonlinear models is introduced. Conditions for bijectivity of this mapping are developed. Since the mapping can be accomplished by look-up tables for the special case of equally-spaced data, the resulting mapping algorithm is considered computationally fast. This could be attractive for real-time operations.

Non-steroidal anti-inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti-inflammatory, antipyretic and analgesic effects are applied against symptoms of respiratory infections, including SARS-CoV-2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID-19 also revealed the gaps in our understanding of their mechanism of action, selectivity and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs-exacerbated respiratory disease (NERD). In this context, the consensus report summarises currently available knowledge, novel discoveries and controversies regarding the use of NSAIDs in COVID-19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID-19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarise the major knowledge gaps and unmet needs in current eicosanoid research.

Concern about potential deleterious effects of pharmaceuticals in the environment is growing fast. From wiping out vulture populations in Asia, to feminization of fish, pharmaceuticals have shown to provoke important consequences albeit at very low concentrations. A recent article addresses the environmental impact of metered-dose inhalers for asthma in the United Kingdom due to the greenhouse effects hydrofluorocarbons they contain. Since 2005, it is mandatory for all new drugs in Europe to be assessed for their environmental impact. Crucially, this regulation solely refers to the active pharmaceutical ingredient, not the “whole medicine” or finished medical product. This can sometimes lead to incongruences. For instance, it does not consider the environmental impact of the hydrofluorocarbons contained in MDIs. Another example is Adasuve®, an antipsychotic (loxapine) aimed at the rapid control of agitation in patients suffering from psychotic disorders. The device was developed as a rapid systemic delivery of loxapine by inhalation of a thermally generated aerosol for single use. Apart from the active substance it holds a medical-grade plastic housing and a lithium battery. Therefore, after every single use, a lithium battery waste is produced. We envision that we are on a brink of a new era in pharmacotherapy, in which environmental aspects of drugs are taken into account. In definitive, we agree with Wilkinson & Woodcock. When considering the environmental impact of pharmaceuticals, we need to take into account the whole package.

Chronic liver diseases comprises a broad spectrum of burdensome diseases that still lack effective pharmacological therapies. Our research group focuses on Fibrosis which is a major precursor of liver cirrhosis. Fibrosis consists in a progressive disturbance of liver sinusoidal architecture characterised by connective tissue deposition as a reparative response to tissue injury. Multifactorial events and several types of cells, participate in fibrosis initiation and progression and the process still needs to be completely understood. The development of experimental models of liver fibrosis alongside the identification of critical factors progressing fibrosis to cirrhosis will facilitate the development of more effective therapeutic approaches for such condition. This review provides an overlook of the main process leading to hepatic fibrosis and therapeutic approaches that have emerged from a deep knowledge of the molecular regulation of fibrogenesis in the liver.

Comprehensive clinical and imaging-based surveillance represents a fundamental aspect in the management of thoracic aortic aneurysms (TAAs), affording the opportunity to identify intermediate-sized TAAs before the onset of worrying symptoms or devastating acute aortic dissection/rupture. Currently, size-based indices are favoured as the major determinants driving patient selection for surgery, as supported by aortic guidelines, although it is recognised that smaller sub-threshold TAAs may still confer substantial risks. Prophylactic aortic surgery can be offered within set timeframes at dedicated aortic centres with excellent outcomes, to mitigate the threat of acute aortic complications associated with repeatedly deferred intervention. In this commentary, we discuss a recent article from the Journal of Cardiac Surgery which highlights important socio-economic disparities in TAA surveillance and follow-up.

Although the process of species formation is notoriously idiosyncratic, the observation of pervasive patterns of reproductive isolation across species pairs suggests that generalities, or “rules”, underlie species formation in all animals. Haldane’s rule states that whenever a sex is absent, rare or sterile in a cross between two taxa, that sex is usually the heterogametic sex. Yet, understanding how Haldane’s rule first evolves and whether it is associated to genome wide barriers to gene flow remains a challenging task because this rule is usually studied in highly divergent taxa that no longer hybridize in nature. Here, we address these questions using the meadow grasshopper Pseudochorthippus parallelus where populations that readily hybridize in two natural hybrid zones show hybrid male sterility in laboratorial crosses. Using mitochondrial data, we infer that such populations have diverged some 100,000 years ago, surviving multiple glacial periods in isolated Pleistocenic refugia. Nuclear data shows that secondary contact has led to extensive introgression throughout the species range, including between populations showing hybrid male sterility. We find repeatable patterns of genomic differentiation across the two hybrid zones, yet such patterns are consistent with shared genomic constraints across taxa rather than their role in reproductive isolation. Together, our results suggest that Haldane’s rule can evolve relatively quickly within species, particularly when associated to strong demographic changes. At such early stages of species formation, hybrid male sterility still permits extensive gene flow, allowing future studies to identify genomic regions associated with reproductive barriers.

Anomalies of the appendix are rare, and one of the rarest is the double appendixes. Most anomalies of the appendix are observed in adults and are discovered incidentally during surgery that does not primarily involve the appendix. It is usually missed, often with life-threatening consequences.

We introduce a new approach—acoustic restoration—focusing on the applied utility of soundscapes for restoration, recognizing the rich ecological and social values they encapsulate. Broadcasting soundscapes in disturbed areas can accelerate recolonization of animals and the microbes and propagules they carry; long duration recordings are also ideal sources of data for benchmarking restoration initiatives and evocative engagement tools.

The arboreal marsupial Monito del Monte (genus Dromiciops, with two recognized species) is a paradigmatic mammal. It is the sole living representative of the order Microbiotheria, the ancestor lineage of Australian marsupials. Also, this marsupial is the unique frugivorous mammal in the temperate rainforest, being the main seed disperser of several endemic plants of this ecosystem, thus acting as keystone species. Dromiciops is also one of the few hibernating mammals in South America, spending half of the year in a physiological dormancy where metabolism is reduced to 10% of normal levels. This capacity to reduce energy expenditure in winter contrasts with the enormous energy turnover rate they experience in spring and summer. The unique life-history strategies of this living Microbiotheria, characterized by an alternation of life in the slow and fast lanes, putatively represent ancestral traits that permitted these cold-adapted mammals to survive in this environment. Here we describe the ecological role of this emblematic marsupial, summarizing the ecophysiology of hibernation and sociality, actualized phylogeographic relationships, reproductive cycle, trophic relationships, mutualisms, conservation and threats. This marsupial shows high densities, despite presenting slow reproductive rates, a paradox that is explained by the unique characteristics of its three-dimensional habitat. We finally suggest immediate actions to protect these locally abundant but globally threatened species.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1 % of cases and can be differentiated from infectious etiologies based on fluid cytology.

Bangladesh recently faced large outbreaks of both COVID-19 and Dengue fever. A 28-year-old woman suffered from symptoms including hemoptysis as first presentation followed by high-grade fever, sore throat, and fatigue. SARS-CoV-2 was confirmed by RT-PCR and also diagnosed dengue later on.COVID-19 and dengue fever could be a harmful combination.

Interspecific interactions within biofilms determine relative species abundance, growth dynamics, community resilience, and success or failure of invasion by an extraneous organism. However, deciphering interspecific interactions and assessing their contribution to biofilm properties and function remain a challenge. Here, we describe the constitution of a model biofilm composed of four bacterial species belonging to four different genera (Rhodocyclus sp., Pseudomonas fluorescens, Kocuria varians, and Bacillus cereus), derived from a biofilm isolated from an industrial milk pasteurization unit. We demonstrate that the growth dynamics and equilibrium composition of this biofilm are highly reproducible. Based on its equilibrium composition, we show that the establishment of this 4-species biofilm is highly robust against initial, transient perturbations but less so towards continuous perturbations. By comparing biofilms formed from different numbers and combinations of the constituent species and by fitting a growth model to the experimental data, we reveal a network of dynamic, positive, and negative interactions that determine the final composition of the biofilm. Furthermore, we reveal that the molecular determinant of one negative interaction is the thiocillin I synthesized by the B. cereus strain, and demonstrate its importance for species distribution and its impact on robustness by mutational analysis of the biofilm ecosystem.

Functional regulation via conformational dynamics is well known in structured proteins, but less well characterized in intrinsically disordered proteins and their complexes. Using NMR spectroscopy we have identified a dynamic regulatory mechanism in the human insulin-like growth factor (IGF) system involving the central, intrinsically disordered linker domain of human IGF-binding protein-2 ( hIGFBP2). The bioavailability of IGFs is regulated by the proteolysis of IGF-binding proteins. In the case of hIGFBP2, the linker domain (L- hIGFBP2) retains its intrinsic disorder upon binding IGF-1 but its dynamics are significantly altered, both in the IGF binding region and distantly located protease cleavage sites. The increase in flexibility of the linker domain upon IGF-1 binding may explain the IGF-dependent modulation of proteolysis of IGFBP2 in this domain. As IGF homeostasis is important for cell growth and function, and its dysregulation is a key contributor to several cancers, our findings open up new avenues for the design of IGFBP analogs inhibiting IGF-dependent tumors.

Increased surface temperatures (0.7℃ per decade) in the Arctic affects polar ecosystems by reducing the extent and duration of annual snow cover. Monitoring of these important ecosystems needs detailed information on snow cover properties (depth and density) at resolutions (< 100 m) that influence ecological habitats and permafrost thaw. As arctic snow is strongly influenced by vegetation, an ecotype map at 10 m resolution was added to a method with the Random Forest (RF) algorithm previously developed for alpine environments and applied here over an arctic landscape for the first time. The topographic parameters used in the RF algorithm were Topographic Position Index (TPI) and up-wind slope index (Sx), which were estimated from the freely available Arctic DEM at 2 m resolution. Ecotypes with taller vegetation with moister soils were found to have deeper snow because of the trapping effect. Using feature importance with RF, snow depth distributions were predicted from topographic and ecosystem parameters with a root mean square error = 8 cm (23%) (R² = 0.79) at 10 m resolution for an arctic watershed (1 500 km²) in western Nunavut, Canada.

The mRNA COVID-19 vaccine and COVID-19 infection caused by the SARS-CoV-2 virus may be immunologic triggers for the development of thrombotic thrombocytopenic purpura (TTP). There is not yet literature that discusses TTP induced by COVID-19 vaccination or infection in pediatric or adolescent patients. We describe 4 adolescents presenting with TTP (both de novo and relapsed disease) following administration of the Pfizer COVID-19 vaccine or after COVID-19 infection. Our observations demonstrate that the Pfizer-BioNTech mRNA vaccine and COVID-19 infection can act as triggers for the development/relapse of both congenital and acquired TTP.