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Sex differences are often observed in psychiatric patients, especially major depressive disorders (MDD), schizophrenia, and developmental disorders, including autism spectrum disorders (ASDs). The prevalence rates between males and females seem variate according to the clinical condition. Although the findings are still incipient, it is suggested that these differences can involve neuroanatomical, neurochemical, and physiological sex differences. In this context, the microbiota-gut-brain axis hypothesis arises to explain some aspects of the complex pathophysiology of neuropsychiatric disorders. The microbiota composition is host-specific and can change conforming to age, sex, diet, medication, exercise, and others. The communication between the brain and the gut is bidirectional and may impact the entire system homeostasis. Many pathways appear to be involved, including neuroanatomic communication, neuroendocrine pathways, immune system, bacteria-derived metabolites, hormones, neurotransmitters, and neurotrophic factors. Although the clinical and preclinical studies are sparse and not very consistent, they suggest that sex differences in the gut microbiota may play an essential role in some neuropsychiatric conditions. Thus, this narrative review has as a mainly aim to show the points sex-related patterns associated to the gut-microbiota-brain axis in the MDD, ASDs, and schizophrenia.In this work, nanocomposites that combine mucopenetrating and mucoadhesive properties in a single system are proposed as innovative strategy to increase drug residence time in the intestine following oral administration. To this aim, novel mucoadhesive chitosan (CH) sponges loaded with mucopenetrating nanoemulsions (NE) were developed via freeze-casting technique. The NE mucopenetration ability was determined studying the surface affinity and thermodynamic binding of the nanosystem with mucins. The ability of nanoparticles to penetrate across a preformed mucins layer was validated by 3D-time laps Confocal Laser Scanning Microscopy imaging. Microscopy observations (Scanning Electron Microscopy and Optical Microscopy) showed that NE participated in the structure of the sponge affecting its stability and in vitro release kinetics. When incubated with HCT 116 and Caco-2 cell lines, the NE proved to be cytocompatible over a wide concentration range. Finally, the in vivo biodistribution of the nanocomposite was evaluated after oral gavage in healthy mice. The intestinal retention of NE was highly enhanced when loaded in the sponge compared to the NE suspension. Overall, our results demonstrated that the developed nanocomposite sponge is a promising system for sustained drug intestinal delivery.Magic tricks have enjoyed an increasing interest by scientists. However, most research in magic focused on isolated aspects of it and a conceptual understanding of magic, encompassing its distinct components and varieties, is missing. Here, we present an account of magic within the theory of Bayesian predictive coding. We present the "wow" effect of magic as an increase in surprise evoked by the prediction error between expected and observed data. We take into account prior knowledge of the observer, attention, and (mis-)direction of perception and beliefs by the magician to bias the observer's predictions and present a simple example for the modelling of the evoked surprise. The role of misdirection is described as everything that aims to maximize the surprise a trick evokes by the generation of novel beliefs, the exploitation of background knowledge and attentional control of the incoming information. Understanding magic within Bayesian predictive coding allows unifying all aspects of magic tricks within one framework, making it tractable, comparable and unifiable with other models in psychology and neuroscience.The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades. The three dimensions of the tumor, including its cellular and extracellular microenvironment, are recreated by combining co-cultures of cancer and stromal cells in 3D hydrogel-based growth factors-inclusive scaffolds. More complex 3D cultures, containing functional blood vasculature, can integrate in the system external stimuli (e.g. oxygen and nutrient deprivation, cytokines, growth factors) along with drugs, or other therapeutic compounds. In this scenario, cell signaling pathways, metastatic cascade steps, cell differentiation and self-renewal, tumor-microenvironment interactions, and precision and personalized medicine, are among the wide range of biological applications that can be studied. Here, we discuss a broad variety of strategies exploited by scientists to create in vitro 3D cancer models that resemble as much as possible the biology and patho-physiology of in vivo tumors and predict faithfully the treatment outcome.
Congenital heart disease (CHD) is the most common live birth defect and a proportion of these patients have chronic hypoxia. Chronic hypoxia leads to secondary erythrocytosis resulting in microvascular dysfunction and increased thrombosis risk. The conjunctival microcirculation is easily accessible for imaging and quantitative assessment. It has not previously been studied in adult CHD patients with cyanosis (CCHD).
We assessed the conjunctival microcirculation and compared CCHD patients and matched healthy controls to determine if there were differences in measured microcirculatory parameters. We acquired images using an iPhone 6s and slit-lamp biomicroscope. Parameters measured included diameter, axial velocity, wall shear rate and blood volume flow. The axial velocity was estimated by applying the 1D+T continuous wavelet transform (CWT). Results are for all vessels as they were not sub-classified into arterioles or venules.
11 CCHD patients and 14 healthy controls were recruited to the study. selleck chemical CCHD patients were markedly more hypoxic compared to the healthy controls (84% vs 98%, p=0.
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