Versatile and Remotely Controllable Light-Induced Coagulation of Particles Under Flow in a 2D Channel.

On-demand switch on/off blood clogging is of paramount importance for the survival of mammals, for example as a quick response to seal damage wounds to minimize their bleeding rate. This mechanism is a complex chain process from initiated red blood cell aggregation at the target location (open wound) that quickly seals on a macroscopic scale the damaged flash. Inspired by nature an on-demand switchable particle clogging mechanism is developed with high spatial resolution down to micrometer size using light as an external non-invasive stimulation. Particle clogging can be adjusted on demand strong enough to even withstand pressure-driven fluid flow, additionally building up walls of aggregated particles, which stop the momentum of big particles under shear. The principle relies on a photosensitive surfactant, which induces under light illumination a long-ranged lateral attractive phoretic-osmotic activity of silica microparticles forcing them to aggregate. The strength of aggregation and therefore motion reduction or even stop of the particles against the fluid flow depends on the ratio between the aggregation strength and the velocity of the particles. The aggregation strength can be precisely controlled by the applied light intensity and adjusted particle concentration. Increasing both parameters results in a stronger aggregation tendency.

Light-Induced Material Motion Fingerprint - A Tool Toward Selective Interfacial Sensitive Fractioning of Microparticles via Microfluidic Methods.

In this article, a novel strategy is presented to selectively separate a mixture of equally sized microparticles but differences in material composition and surface properties. The principle relies on a photosensitive surfactant, which makes particles under light illumination phoretically active. The latter hovers microparticles from a planar interface and together with a superimposed fluid flow, particles experience a drift motion characteristic to its interfacial properties. The drift motion is investigated as a function of applied wavelength, demonstrating that particles composed of different material show a unique spectrally resolved light-induced motion profile. Differences in those motion profile allow a selective fractioning of a desired particle from a complex particle mixture made out of more than two equally sized different particle types. Besides that, the influence of applied wavelength is systematically studied, and discussed the origin of the spectrally resolved chemical activity of microparticles from measured photo-isomerization rates.

Identification and characterization of sugar-regulated promoters in Chaetomium thermophilum.

The thermophilic fungus Chaetomium thermophilum has been used extensively for biochemical and high-resolution structural studies of protein complexes. However, subsequent functional analyses of these assemblies have been hindered owing to the lack of genetic tools compatible with this thermophile, which are typically suited to other mesophilic eukaryotic model organisms, in particular the yeast Saccharomyces cerevisiae. Hence, we aimed to find genes from C. thermophilum that are expressed under the control of different sugars and examine their associated 5' untranslated regions as promoters responsible for sugar-regulated gene expression. To identify sugar-regulated promoters in C. thermophilum, we performed comparative xylose- versus glucose-dependent gene expression studies, which uncovered a number of enzymes with induced expression in the presence of xylose but repressed expression in glucose-supplemented media. Subsequently, we cloned the promoters of the two most stringently regulated genes, the xylosidase-like gene (XYL) and xylitol dehydrogenase (XDH), obtained from this genome-wide analysis in front of a thermostable yellow fluorescent protein (YFP) reporter. With this, we demonstrated xylose-dependent YFP expression by both Western blotting and live-cell imaging fluorescence microscopy. Prompted by these results, we expressed the C. thermophilum orthologue of a well-characterized dominant-negative ribosome assembly factor mutant, under the control of the XDH promoter, which allowed us to induce a nuclear export defect on the pre-60S subunit when C. thermophilum cells were grown in xylose- but not glucose-containing medium. Altogether, our study identified xylose-regulatable promoters in C. thermophilum, which might facilitate functional studies of genes of interest in this thermophilic eukaryotic model organism.

Toward incorporating epigenetics into regulation of gene expression in the parasite Trichomonas vaginalis.

Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract, causing a highly prevalent sexually transmitted infection. The parasite must change its transcriptional profile in order to establish and maintain infection. However, few core regulatory elements and transcription factors have been identified to date and little is known about other mechanisms that may control these rapid changes in gene expression during parasite infection. In the last years, epigenetic mechanisms involved in the regulation of gene expression have been gaining major attention in this parasite. In this review, we summarize and discuss the major advances of the last few years with regard to epigenetics (DNA methylation, post-translational histone modifications, and histone variants) in the parasite T. vaginalis. These studies can shed light into our current understanding of this parasite's biology with far-reaching implications for the prognosis and treatment of trichomoniasis.

Von Economo neurons: Cellular specialization of human limbic cortices?

Von Economo neurons (VENs) have been mentioned in the medical literature since the second half of the 19th century; however, it was not until the second decade of the 20th century that their cytomorphology was described in detail. To date, VENs have been found in limbic sectors of the frontal, temporal and insular lobes. In humans, their density seems to decrease in the caudo-rostral and ventro-dorsal direction; that is, from the anterior regions of the cingulate and insular cortices towards the frontal pole and the superior frontal gyrus. Several studies have provided similar descriptions of the shape of the VEN soma, but the size of the soma varies from one cortical region to another. There is consensus among different authors about the selective vulnerability of VENs in certain pathologies, in which a deterioration of the capacities involved in social behaviour is observed. In this review, we propose that the restriction of VENs towards the sectors linked to limbic information processing in Homo sapiens gives them a possible functional role in relation to the structures in which they are located. However, given the divergence in characteristics such as location, density, size and biochemical profile among VENs of different cortical sectors, the activities in which they participate could allow them to partake in a wide spectrum of neurological functions, including autonomic responses and executive functions.

Ischemic stroke in young patients in Medellín, Colombia.

BACKGROUND: There is scarce information about ischemic stroke in young patients in Colombia. To get insights about this phenomenon, this study describes the etiologies and risk factors of ischemic stroke in young patients in a third level complexity referral hospital in Medellin, Colombia. METHODS: A retrospective observational cross-sectional study was carried out reviewing the medical records of patients between 18 to 49 years old admitted for the first time for ischemic stroke, from January 2009 to December 2019. The sociodemographic characteristics, risk factors, and etiological classification of ischemic stroke according to the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) were described. RESULTS: Two hundred thirty-seven cases were found. The most frequent risk factors were arterial hypertension (31.7%), smoking (29.5%) and alcohol intake (23.2%). There was a greater number of traditional cardiovascular risk factors at older ages. The TOAST classification was large-artery atherosclerosis (6.8%), cardioembolism (17.7%), small-vessel disease (7.6%), other determined etiology (25.7%) and undetermined (42.2%). Within cardioembolism, the most common high-risk source was valve replacement, and the most common moderate-risk source was patent foramen ovale. Craniocervical arterial dissection (11.4%) and substance abuse (2.9%) were the two most frequent sources within other determined etiologies. The most common compromised vascular territory was the anterior (55.7%). CONCLUSIONS: The high frequency of traditional risk factors in young patients highlights the need to optimize primary and secondary prevention plans. This study provides new insights about the relevance of illicit substance abuse in Colombia as a cause of stroke in young patients, unlike the previous one conducted in Bogotá. Infectious causes were other peculiarities found. It is necessary to investigate the reasons for the high proportion of undetermined causes.

Retrospective and Predictive Investigation of Fish Kill Events.

Fish kill investigations are critical to understanding threats to aquatic ecosystems and can serve as a measure of environmental disruption as well as an early indicator of emerging disease. The goal of this study was to analyze historical data related to such events among wild fish populations in Minnesota in order to assess the quality and completeness of the data and potential trends in fish kills. After excluding events with incomplete data (e.g., in which the location was not reported), we analyzed 225 unique fish kills from 2003 to 2013 that were recorded in two Minnesota Department of Natural Resources databases. The most reported fish kills occurred during 2007 (n = 41) and during the month of June (n = 81) across all years. Centrarchid species were present in the most fish kills (138), followed by cyprinid and ictalurid species, which were present in 53 and 40 events, respectively. Environmental factors were the most common cause of death reported. Models of environmental factors revealed that the maximum nighttime land surface temperature was the most critical factor in fish mortality, followed by changes in primary productivity and human disturbances. During the course of this study, data gaps were identified, including underreporting, inconsistent investigation, and the lack of definitive diagnoses, making interpretation of our results challenging. Even so, understanding these historical trends and data gaps can be useful in generating hypotheses and advancing data collection systems for investigating future fish kills. Our study is a primer investigation of fish kills providing information on the plausible areas, seasons, and fish groups at risk that can guide active environmental monitoring and epidemiological surveillance of fishes.

Cysteine Desulfurase IscS2 Plays a Role in Oxygen Resistance in Clostridium difficile.

Clostridium difficile is an anaerobic, spore-forming bacterium capable of colonizing the gastrointestinal tract of humans following disruption of the normal microbiota, typically from antibiotic therapy for an unrelated infection. With approximately 500,000 confirmed infections leading to 29,000 deaths per year in the United States, C. difficile infection (CDI) is an urgent public health threat. We previously determined that C. difficile survives in up to 3% oxygen. Low levels of oxygen are present in the intestinal tract, with the higher concentrations being associated with the epithelial cell surface. Additionally, antibiotic treatment, the greatest risk factor for CDI, increases the intestinal oxygen concentration. Therefore, we hypothesized that the C. difficile genome encodes mechanisms for survival during oxidative stress. Previous data have shown that cysteine desulfurases involved in iron-sulfur cluster assembly are involved in protecting bacteria from oxidative stress. In this study, deletion of a putative cysteine desulfurase (Cd630_12790/IscS2) involved in the iron-sulfur cluster (Isc) system caused a severe growth defect in the presence of 2% oxygen. Additionally, this mutant delayed colonization in a conventional mouse model of CDI and failed to colonize in a germfree model, which has higher intestinal oxygen levels. These data imply an undefined role for this cysteine desulfurase in protecting C. difficile from low levels of oxygen in the gut.

Distributional ecology of Andes hantavirus: a macroecological approach.

BACKGROUND: Hantavirus pulmonary syndrome (HPS) is an infection endemic in Chile and Argentina, caused by Andes hantavirus (ANDV). The rodent Oligoryzomys longicaudatus is suggested as the main reservoir, although several other species of Sigmodontinae are known hosts of ANDV. Here, we explore potential ANDV transmission risk to humans in southern South America, based on eco-epidemiological associations among: six rodent host species, seropositive rodents, and human HPS cases. METHODS: We used ecological niche modeling and macroecological approaches to determine potential geographic distributions and assess environmental similarity among rodents and human HPS cases. RESULTS: Highest numbers of rodent species (five) were in Chile between 35° and 41°S latitude. Background similarity tests showed niche similarity in 14 of the 56 possible comparisons: similarity between human HPS cases and the background of all species and seropositive rodents was supported (except for Abrothrix sanborni). Of interest among the results is the likely role of O. longicaudatus, Loxodontomys micropus, Abrothrix olivaceus, and Abrothrix longipilis in HPS transmission to humans. CONCLUSIONS: Our results support a role of rodent species' distributions as a risk factor for human HPS at coarse scales, and suggest that the role of the main reservoir (O. longicaudatus) may be supported by the broader rodent host community in some areas.

Evaluation of an Oral Health Promotion and Preventive Programme: A Case-Control Study.

PURPOSE: To evaluate the oral health of children who were beneficiaries of a promotion and preventive programme for more than 6 years and to estimate the factors relating to their oral condition. MATERIALS AND METHODS: In this case-control study, the total population comprised all 7- to 13-year-old children who attended the Paediatric Dentistry Centre of Reference Simón Bolívar (CROSB), a programme for students of the community of Viña del Mar, Chile. The case group was treated from the age of 7 to 13 years and controls were only seen at the age of 13 (had not been previously enrolled in the programme). The compilation of data was carried out through examination of clinical records. Statistical analysis included Fisher's Exact Test, the chi-square and Mantel-Haenszel tests to determine odds ratios, log-linear models to study some types of relationships between the different qualitative variables and Mood's Median Test for quantitative variables. Finally, a logit-type generalised linear model (GLM) was adjusted to estimate the probability of a caries-free child according to the different variables under study. RESULTS: The main finding is that this programme does not successfully control the local risk factors of caries. The factors that jointly explain the presence of caries-free children were: non-participation in the programme, attending public school and the presence of sealed teeth. CONCLUSION: Even though the evaluated programme creates equity in the indicators of oral health among its beneficiaries, it does not reach the levels of oral health of the non-vulnerable population. It is recommended that this programme seek more effective tools.

Deep genome-wide measurement of meiotic gene conversion using tetrad analysis in Arabidopsis thaliana.

Gene conversion, the non-reciprocal exchange of genetic information, is one of the potential products of meiotic recombination. It can shape genome structure by acting on repetitive DNA elements, influence allele frequencies at the population level, and is known to be implicated in human disease. But gene conversion is hard to detect directly except in organisms, like fungi, that group their gametes following meiosis. We have developed a novel visual assay that enables us to detect gene conversion events directly in the gametes of the flowering plant Arabidopsis thaliana. Using this assay we measured gene conversion events across the genome of more than one million meioses and determined that the genome-wide average frequency is 3.5×10(-4) conversions per locus per meiosis. We also detected significant locus-to-locus variation in conversion frequency but no intra-locus variation. Significantly, we found one locus on the short arm of chromosome 4 that experienced 3-fold to 6-fold more gene conversions than the other loci tested. Finally, we demonstrated that we could modulate conversion frequency by varying experimental conditions.

Versatile Microfluidics Separation of Colloids by Combining External Flow with Light-Induced Chemical Activity.

Separation of particles by size, morphology, or material identity is of paramount importance in fields such as filtration or bioanalytics. Up to now separation of particles distinguished solely by surface properties or bulk/surface morphology remains a very challenging process. Here a combination of pressure-driven microfluidic flow and local self-phoresis/osmosis are proposed via the light-induced chemical activity of a photoactive azobenzene-surfactant solution. This process induces a vertical displacement of the sedimented particles, which depends on their size and surface properties . Consequently, different colloidal components experience different regions of the ambient microfluidic shear flow. Accordingly, a simple, versatile method for the separation of such can be achieved by elution times in a sense of particle chromatography. The concepts are illustrated via experimental studies, complemented by theoretical analysis, which include the separation of bulk-porous from bulk-compact colloidal particles and the separation of particles distinguished solely by slight differences in their surface physico-chemical properties.

Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness.

Through regulation of DNA packaging, histone proteins are fundamental to a wide array of biological processes. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed histone code that is interpreted by "reader" proteins to modulate chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity. The protozoan parasite Toxoplasma gondii is unique among eukaryotes in possessing a novel variant of H2B designated H2B.Z. The combination of PTMs and the use of histone variants is important for gene regulation in T. gondii, offering new targets for drug development. In this work, T. gondii parasites were generated in which the 5 N-terminal acetylatable lysines in H2B.Z were mutated to either alanine (c-Myc-A) or arginine (c-Myc-R). c-Myc-A mutant only displayed a mild effect in its ability to kill mice. c-Myc-R mutant presented an impaired ability to grow and an increase in differentiation to latent bradyzoites. This mutant line was also more sensitive to DNA damage, displayed no virulence in mice, and provided protective immunity against future infection. While nucleosome composition was unaltered, key genes were abnormally expressed during in vitro bradyzoite differentiation. Our results show that the N-terminal positive charge patch of H2B.Z is important for these procceses. Pull down assays with acetylated N-terminal H2B.Z peptide and unacetylated one retrieved common and differential interactors. Acetylated peptide pulled down proteins associated with chromosome maintenance/segregation and cell cycle, opening the question of a possible link between H2B.Z acetylation status and mitosis.

Histone variant H2B.Z acetylation is necessary for maintenance of Toxoplasma gondii biological fitness.

Through regulation of DNA packaging, histone proteins are fundamental to a wide array of biological processes. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed histone code that is interpreted by "reader" proteins to modulate chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity. The protozoan parasite Toxoplasma gondii is unique among eukaryotes in possessing a novel variant of H2B designated H2B.Z. The combination of PTMs and the use of histone variants are important for gene regulation in T. gondii, offering new targets for drug development. In this work, T. gondii parasites were generated in which the 5 N-terminal acetylatable lysines in H2B.Z were mutated to either alanine (c-Myc-A) or arginine (c-Myc-R). The c-Myc-A mutant displayed no phenotype over than a mild defect in its ability to kill mice. The c-Myc-R mutant presented an impaired ability to grow and an increase in differentiation to latent bradyzoites. The c-Myc-R mutant was also more sensitive to DNA damage, displayed no virulence in mice, and provided protective immunity against future infection. While nucleosome composition was unaltered, key genes were abnormally expressed during in vitro bradyzoite differentiation. Our results show that regulation of the N-terminal positive charge patch of H2B.Z is important for these processes. We also show that acetylated N-terminal H2B.Z interacts with some unique proteins compared to its unacetylated counterpart; the acetylated peptide pulled down proteins associated with chromosome maintenance/segregation and cell cycle, suggesting a link between H2B.Z acetylation status and mitosis.

Physician practices and attitudes towards atopic dermatitis in Latin America: A cross-sectional study.

Background: The prevalence of atopic dermatitis (AD) is increasing in developing countries. Different worldwide guidelines have been proposed, but their applicability for AD specialists in Latin American (LA) countries is unknown. Objective: The objective of this study was to explore the medical approach to treating AD in LA countries. Methods: The study population comprised AD specialists (allergists and dermatologists). They completed an electronic survey containing questions about the health system, diagnostic criteria, and pharmacotherapy approach to treating AD. The survey was constructed and validated by the Atopic Dermatitis Committee of the Latin American Society of Allergy Asthma and Immunology (SLAAI) in Spanish and Portuguese. Each member was responsible for distributing the questionnaire through different networks in their respective countries. Results: A total of 284 AD specialists from 13 LA countries completed the questionnaire; among them, 67% were allergists and 33% were dermatologists. Less than 50% of the AD specialists strictly followed guideline recommendations. Among the AD specialists, the European and North American guidelines were more frequently used, and only 16% followed LA guidelines. Dermatologists used the local guidelines less frequently than allergists. Most physicians did not routinely use AD assessment tools (55%). The frequency of the diagnostic tests depends on symptom severity. The availability of some systemic treatments, such as biologics and Janus Kinase (JAK) inhibitors, is not universal in all LA countries. Conclusion: There were marked differences between the specialists, and these differences seemed to be affected by their specialty and each country's healthcare system. New AD education strategies that consider the particularities of the region could allow patients to be more accurately managed. AD assessment tools may provide a way to enhance AD treatment and allow for shared decision-making, patient empowerment, and standardized care.

Transitional Care for Young People with Movement Disorders: Consensus-Based Recommendations from the MDS Task Force on Pediatrics.

Background: The International Parkinson and Movement Disorders Society (MDS) set up a working group on pediatric movement disorders (MDS Task Force on Pediatrics) to generate recommendations to guide the transition process from pediatrics to adult health care systems in patients with childhood-onset movement disorders. Methods: To develop recommendations for transitional care for childhood onset movement disorders, we used a formal consensus development process, using a multi-round, web-based Delphi survey. The Delphi survey was based on the results of the scoping review of the literature and the results of a survey of MDS members on transition practices. Through iterative discussions, we generated the recommendations included in the survey. The MDS Task Force on Pediatrics were the voting members for the Delphi survey. The task force members comprise 23 child and adult neurologists with expertise in the field of movement disorders and from all regions of the world. Results: Fifteen recommendations divided across four different areas were made pertaining to: (1) team composition and structure, (2) planning and readiness, (3) goals of care, and (4) administration and research. All recommendations achieved consensus with a median score of 7 or greater. Conclusion: Recommendations on providing transitional care for patients with childhood onset movement disorders are provided. Nevertheless several challenges remain in the implementation of these recommendations, related to health infrastructure and the distribution of health resources, and the availability of knowledgeable and interested practitioners. Research on the influence of transitional care programs on outcomes in childhood onset movement disorders is much needed.

Lip competence in Class III patients undergoing orthognathic surgery: an electromyographic study.

PURPOSE: The aim of this study was to compare the presurgical and postsurgical electromyographic (EMG) activities of the lips in patients with skeletal Class III treated with combined orthognathic surgery and contrast these data with those obtained from a control group with skeletal Class I. PATIENTS AND METHODS: Ten patients with skeletal Class III underwent the registration of EMG activity before an orthognathic surgical procedure and 4 months after surgery. The results were compared with a control group of 11 healthy patients with skeletal Class I and clinical and EMG lip competence. EMG activity was recorded from the upper orbicularis oris and mentalis muscles during swallowing, lips in contact (LC), and lips apart (LA) using bipolar surface electrodes. The competence condition was assessed by determining the difference in the EMG activity of the mentalis muscle (LC-LA ≤0 for lip competence). RESULTS: Patients with skeletal Class III showed greater EMG activity than the control group before and after surgery. Patients with skeletal Class III showed a significantly greater difference in LC-LA than the control group before surgery for the 2 muscles (P < .05). No significant difference was found between the skeletal Class III group after surgery and the control group for the mentalis muscle (P > .05). CONCLUSIONS: Four months after treatment with orthognathic surgery, patients with skeletal Class III and an initial muscle activity pattern of lip incompetence different from the control group (P < .05) showed EMG values compatible with lip competence. These values were similar to the control group.

EEG Evaluation in a Neuropsychological Intervention Program Based on Virtual Reality in Adults with Parkinson's Disease.

Nowadays, several strategies for treating neuropsychologic function loss in Parkinson's disease (PD) have been proposed, such as physical activity performance and developing games to exercise the mind. However, few studies illustrate the incidence of these therapies in neuronal activity. This work aims to study the feasibility of a virtual reality-based program oriented to the cognitive functions' rehabilitation of PD patients. For this, the study was divided into intervention with the program, acquisition of signals, data processing, and results analysis. The alpha and beta bands' power behavior was determined by evaluating the electroencephalography (EEG) signals obtained during the execution of control tests and games of the "Hand Physics Lab" Software, from which five games related to attention, planning, and sequencing, concentration, and coordination were taken. Results showed the characteristic performance of the cerebral bands during resting states and activity states. In addition, it was determined that the beta band increased its activity in all the cerebral lobes in all the tested games (p-value < 0.05). On the contrary, just one game exhibited an adequate performance of the alpha band activity of the temporal and frontal lobes (p-value < 0.02). Furthermore, the visual attention and the capacity to process and interpret the information given by the surroundings was favored during the execution of trials (p-value < 0.05); thus, the efficacy of the virtual reality program to recover cognitive functions was verified. The study highlights implementing new technologies to rehabilitate people with neurodegenerative diseases.

Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa.

ABSTRACT: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition in which mutations in the type VII collagen gene ( COL7A1 ) lead to decreased expression of this anchoring protein of the skin, causing the loss of stability at the dermo-epidermal junction. Most patients with RDEB experience neuropathic pain and itch due to the development of a small fibre neuropathy, characterised by decreased intraepidermal innervation and thermal hypoaesthesia. To understand the physiopathology of this neuropathy, we used a mouse model of RDEB (Col7a1 flNeo/flNeo ) and performed a detailed characterisation of the somatosensory system. Col7a1 flNeo/flNeo mice showed a decrease in heat sensitivity, an increase in spontaneous scratching, and a significant decrease in intraepidermal nerve fibre density in the hindpaw; these changes were distal because there was no significant loss of unmyelinated or myelinated fibres in the nerve trunk. Of interest, we observed a decrease in axon diameter in both myelinated and unmyelinated fibres. This axonal damage was not associated with inflammation of the dorsal root ganglion or central projection targets at the time of assessment. These results suggest that in RDEB, there is a distal degeneration of axons produced by exclusive damage of small fibres in the epidermis, and in contrast with traumatic and acute neuropathies, it does not induce sustained neuroinflammation. Thus, this animal model emphasizes the importance of a healthy cutaneous environment for maintenance of epidermal innervation and faithfully replicates the pathology in humans, offering the opportunity to use this model in the development of treatments for pain for patients with RDEB.