Spatially clustered type I interferon responses at injury borderzones.

Sterile inflammation after myocardial infarction is classically credited to myeloid cells interacting with dead cell debris in the infarct zone1,2. Here we show that cardiomyocytes are the dominant initiators of a previously undescribed type I interferon response in the infarct borderzone. Using spatial transcriptomics analysis in mice and humans, we find that myocardial infarction induces colonies of interferon-induced cells (IFNICs) expressing interferon-stimulated genes decorating the borderzone, where cardiomyocytes experience mechanical stress, nuclear rupture and escape of chromosomal DNA. Cardiomyocyte-selective deletion of Irf3 abrogated IFNIC colonies, whereas mice lacking Irf3 in fibroblasts, macrophages, neutrophils or endothelial cells, Ccr2-deficient mice or plasmacytoid-dendritic-cell-depleted mice did not. Interferons blunted the protective matricellular programs and contractile function of borderzone fibroblasts, and increased vulnerability to pathological remodelling. In mice that died after myocardial infarction, IFNIC colonies were immediately adjacent to sites of ventricular rupture, while mice lacking IFNICs were protected from rupture and exhibited improved survival3. Together, these results reveal a pathological borderzone niche characterized by a cardiomyocyte-initiated innate immune response. We suggest that selective inhibition of IRF3 activation in non-immune cells could limit ischaemic cardiomyopathy while avoiding broad immunosuppression.

From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.

Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.

Effect of particle concentration on the microstructural and macromechanical properties of biocompatible magnetic hydrogels.

We analyze the effect of nanoparticle concentration on the physical properties of magnetic hydrogels consisting of polymer networks of the human fibrin biopolymer with embedded magnetic particles, swollen by a water-based solution. We prepared these magnetic hydrogels by polymerization of mixtures consisting mainly of human plasma and magnetic nanoparticles with OH- functionalization. Microscopic observations revealed that magnetic hydrogels presented some cluster-like knots that were connected by several fibrin threads. By contrast, nonmagnetic hydrogels presented a homogeneous net-like structure with only individual connections between pairs of fibers. The rheological analysis demonstrated that the rigidity modulus, as well as the viscoelastic moduli, increased quadratically with nanoparticle content following a square-like function. Furthermore, we found that time for gel point was shorter in the presence of magnetic nanoparticles. Thus, we can conclude that nanoparticles favor the cross-linking process, serving as nucleation sites for the attachment of the fibrin polymer. Attraction between the positive groups of the fibrinogen, from which the fibrin is polymerized, and the negative OH- groups of the magnetic particle surface qualitatively justifies the positive role of the nanoparticles in the enhancement of the mechanical properties of the magnetic hydrogels. Indeed, we developed a theoretical model that semiquantitatively explains the experimental results by assuming the indirect attraction of the fibrinogen through the attached nanoparticles. Due to this attraction the monomers condense into nuclei of the dense phase and by the end of the polymerization process the nuclei (knots) of the dense phase cross-link the fibrin threads, which enhances their mechanical properties.

Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease.

Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X2  = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X2  = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X2  = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS.

Early spermatogenesis changes in traumatic complete spinal cord-injured adult patients.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on the spermatogenesis of patients studied in the early subacute stage and ensuing months. SETTING: National hospital for SCI patients. METHODS: A prospective follow-up study was conducted on 28 male patients with complete SCI who were evaluated in the early subacute phase (~1 month), and 3 and 6 months after the injury. At each time point, fine needle aspiration biopsy samples were taken from the testes for cytological assessment, and serum levels of relevant hormones were measured. At the end of the study period, ejaculation was attempted for standard semen analyses. RESULTS: Cytological patterns indicative of defective spermatogenesis were found in 61%, 52% and 20% of the patients at 1, 3 and 6 months after SCI, respectively, suggesting an improvement over time. Serum hormone analyses showed a steady elevation of estradiol levels above the reference range, and increasing levels of testosterone, inhibin B and prolactin throughout the study period. Prolactin levels were above the reference range at all time points. Only 2 out of the 10 patients who were able to ejaculate at 6 months post injury showed normal sperm parameters. CONCLUSION: A majority of the patients showed impaired spermatogenesis soon after the injury, which in most cases recovered over time. That was accompanied by parallel increases in serum levels of inhibin B, testosterone and prolactin, possibly driving or reflecting the spermatogenesis recovery. Further studies are needed to elucidate the biological mechanisms underlying these changes.

IVIVC approach based on carbamazepine bioequivalence studies combination.

The aim of the present study was to explore the feasibility of obtaining an IVIVC by combination of data from two bioequivalence (BE) studies of carbamazepine (CBZ) in order to assess if the previously published dissolution media and conditions could be applicable to any other oral immediate release (IR) CBZ products with conventional excipients. Twenty-four healthy male subjects from two BE study received one IR dose of the test (test 1 or 2) or the reference formulation (Tegretol, 400 mg). Dissolution studies of the IR CBZ tablets were performed in two different laboratories. In order to develop IVIVC, individual or average data analysis were considered. A level C, level B and level A correlation have been successfully developed by combining data from different BE studies of CBZ immediate release drug products. A level A IVIVC was developed with all four datasets with a good R2 for all the combinations of in vivo and in vitro data. A dissolution medium containing 1% SLS has demonstrated its suitability as the universal biopredictive dissolution medium, even if different batches and in vivo/in vitro studies were combined.

Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region.

The increasing human presence in Antarctica and the waste it generates is causing an impact on the environment at local and border scale. The main sources of anthropic pollution have a mainly local effect, and include the burning of fossil fuels, waste incineration, accidental spillage and wastewater effluents, even when treated. The aim of this work is to determine the presence and origin of 30 substances of anthropogenic origin considered to be, or suspected of being, endocrine disruptors in the continental waters of the Antarctic Peninsula region. We also studied a group of toxic metals, metalloids and other elements with possible endocrine activity. Ten water samples were analyzed from a wide range of sources, including streams, ponds, glacier drain, and an urban wastewater discharge into the sea. Surprisingly, the concentrations detected are generally similar to those found in other studies on continental waters in other parts of the world. The highest concentrations of micropollutants found correspond to the group of organophosphate flame retardants (19.60-9209ngL(-1)) and alkylphenols (1.14-7225ngL(-1)); and among toxic elements the presence of aluminum (a possible hormonal modifier) (1.7-127µgL(-1)) is significant. The concentrations detected are very low and insufficient to cause acute or subacute toxicity in aquatic organisms. However, little is known as yet of the potential sublethal and chronic effects of this type of pollutants and their capacity for bioaccumulation. These results point to the need for an ongoing system of environmental monitoring of these substances in Antarctic continental waters, and the advisability of regulating at least the most environmentally hazardous of these in the Antarctic legislation.

[Treatment of postpartum hemorrhage with intrauterine hydrostatic condom]. / Tratamiento de la hemorragia posparto con condón hidrostático intrauterine.

OBJECTIVE: To report of experience of intrauterine hydrostatic condom to control obstetric hemorrhage. MATERIAL AND METHOD: Descriptive, retro-prospective study. The method was use in patients who had obstetric hemorrhage and do not responded to medical management during the period from March 1st to August27, 2015 in a rural facility. RESULTS: 955 patients that had a vaginal delivery were identified, 40 (4.1%) of which needed the application of the method. The method was unsuccessful in 2 of 40 patients (5%), one requiring emergency obstetric hysterectomy and other exploratory laparotomy with conservative measures. 11 of 40 patients (2 7.5%) required at least 1-3 globular packs transfusion. None of the 38 patients (95%) who responded to the method presented endometritis in the postpartum follow up or complications associated with the use of hydrostatic condom. CONCLUSION: The use of intrauterine hydrostatic condom is an effective method to control postpartum obstetric hemorrhage secondary to uterine atony unresponsive to medical management.

Feeding practices of low-income mothers: how do they compare to current recommendations?

BACKGROUND: Despite a growing consensus on the feeding practices associated with healthy eating patterns, few observational studies of maternal feeding practices with young children have been conducted, especially in low-income populations. The aim of this study was to provide such data on a low income sample to determine the degree to which observed maternal feeding practices compare with current recommendations. METHODS: Eighty low-income mothers and their preschool children were videotaped at dinner in their homes. Mothers were chosen from a larger study to create a 2 X 2 X 2 design: maternal ethnicity (African American vs. Latina) by child gender by child weight status (healthy weight vs. overweight/obese). Observers coded videotapes for a range of maternal feeding strategies and other behaviors. RESULTS: Many mothers spent considerable time encouraging eating--often in spite of the child's insistence that he or she was finished. Mothers talked little about food characteristics, rarely referred to feelings of hunger and fullness, and made more attempts to enforce table manners than to teach eating skills. Latina mothers showed higher levels of teaching eating skills and encouraging their children to eat; African American mothers showed higher levels of enforcing table manners and getting children to clear their plates. Mothers of boys used more unelaborated commands and less questions/suggestions than mothers of girls. Finally, compared to mothers of overweight/obese children, mothers of healthy weight children showed higher levels of encouraging eating and lower levels of discouraging eating. CONCLUSIONS: Most of the mothers in this study did not engage in feeding practices that are consistent with current recommendations. They did this, despite the fact that they knew they were being observed. These results should be used to inform future research about the motivations behind mothers' feeding practices and the development of interventions by helping identify areas in greatest need of change.

Inverse magnetorheological fluids.

We report a new kind of field-responsive fluid consisting of suspensions of diamagnetic (DM) and ferromagnetic (FM) microparticles in ferrofluids. We designate them as inverse magnetorheological (IMR) fluids for analogy with inverse ferrofluids (IFFs). Observations on the particle self-assembly in IMR fluids upon magnetic field application showed that DM and FM microparticles were assembled into alternating chains oriented along the field direction. We explain such assembly on the basis of the dipolar interaction energy between particles. We also present results on the rheological properties of IMR fluids and, for comparison, those of IFFs and bidispersed magnetorheological (MR) fluids. Interestingly, we found that upon magnetic field application, the rheological properties of IMR fluids were enhanced with respect to bidispersed MR fluids with the same FM particle concentration, by an amount greater than the sum of the isolated contribution of DM particles. Furthermore, the field-induced yield stress was moderately increased when up to 30% of the total FM particle content was replaced with DM particles. Beyond this point, the dependence of the yield stress on the DM content was non-monotonic, as expected for FM concentrations decreasing to zero. We explain these synergistic results by two separate phenomena: the formation of exclusion areas for FM particles due to the perturbation of the magnetic field by DM particles and the dipole-dipole interaction between DM and FM particles, which enhances the field-induced structures. Based on the second phenomenon, we present a theoretical model for the yield stress that semi-quantitatively predicts the experimental results.

Taguchi optimisation of the synthesis of vine-pruning-waste hydrochar as potential adsorbent for pesticides in water.

This research aimed to synthesise an effective hydrochar adsorbent from vineyard pruning wastes to remove emerging contaminants as a potential valorisation product. The adsorption capacity of the hydrochar was optimised using the Taguchi method. Four synthesis variables were evaluated: hydrothermal reaction temperature, use of H3PO4 as a catalyst, number of acetone washes, and type of chemical cold activation. The simultaneous adsorption of five model pesticides (clothianidin (CTD), acetamiprid (ACE), 2,4-D, metalaxyl (MET), and atrazine (ATZ)) at an initial pH of 7 was studied. At optimum conditions, the hydrochar presented a total adsorption capacity of 22.7 µmol/g, representing a 2.7-fold improvement with respect to pristine hydrochar performance. High percentage removals were achieved for all pollutants (85 % CTD, 94 % ACE, 86 % MET, and 95 % ATZ) except for 2,4-D (4 %). This research provides a valuable reference for developing hydrochar adsorbents for pollution control and the valorisation of biomass wastes.

Impact of malnutrition on the quality of life in older patients with advanced heart failure: a cohort study.

OBJECTIVES: The aim of this study was to assess the prevalence of malnutrition, the clinical characteristics associated with malnutrition and the impact of nutritional status on mortality, quality of life, self-care abilities, and activities of daily living in the older patients with advanced heart failure. METHODS: A prospective multicentre cohort study including 260 community-dwelling elderly patients with advanced HF was conducted between June 2017 and December 2019. The study was carried out in 22 primary healthcare centres, three university hospitals, one acute-care hospital, and one geriatric rehabilitation unit in the city of Barcelona (Spain). Nutritional status was assessed at baseline using the Mini Nutritional Assessment questionnaire. Patient-reported outcome measures included quality of life (EQ-5D-3L), self-care behaviour (European Heart Failure Self-care Behaviour Scale) and impact on activities of daily living (Barthel Index). RESULTS: Using the MNA-SF, 126 (48.5%) patients were identified as being at risk of malnutrition and 33 (12.7%) patients as having confirmed malnutrition. Compared to HF patients with normal nutritional status, patients with confirmed malnutrition were significantly older, with a lower BMI, and with reduced haemoglobin levels. During follow-up (median 14.9 months, Interquartile Range; 4.9-26.9), 133 (51.2%) of the included participants died, and mortality was significantly higher among patients identified as having malnutrition (p < 0.001). Better Barthel index and quality of life scores were inversely related to the risk of malnutrition, [Odds Ratio (OR) 0.97 (95% Confidence interval 0.96; 0.98) and OR 0.98 (95% Confidence interval, 0.96; 0.99)], respectively. Higher scores in the European Heart Failure Self-care Behaviour Scale, which implies worse self care, were related to higher malnutrition risk, OR 1.05 (95% Confidence interval, 1.02; 1.09. Adjusted multivariate logistic model found that malnutrition was significantly associated with poor quality of life, and adverse impacts on daily activities and self-care. CONCLUSIONS: In community-dwelling older patients with advanced HF, malnutrition was associated with worse patient reported outcome measures related to poor quality of life, and adverse impacts on self-care and daily activities. Nutritional status must be systematically addressed by primary care nurses and family doctors to improve survival rates in these patients. It would be helpful the incorporation of expert professionals in nutrition in the primary health care centres.

Single radio frequency bucket injection in the 88-Inch Cyclotron using a pulsed high voltage chopper.

A single radio frequency bucket of the 88-Inch Cyclotron is filled using a fast chopper located in the axial line. The bucket then accelerates until it reaches the deflector, at which point, it is extracted as a train of bunches. This phenomenon can be attributed to the characteristic multi-turn extraction of the cyclotron and, by simplifying the complex dynamics of a cyclotron, corresponds to the conceptual transfer function of the cyclotron. The confirmation of the single radio frequency bucket injection was achieved by operating the cyclotron in the third harmonic mode and observing the absence of intermediate bunches during the multiple-bunch extraction.

Towards establishing MS prevalence in Latin America and the Caribbean.

A very high prevalence of multiple sclerosis (MS) has been reported in some Western European and North American countries. The few surveys of MS epidemiology in South America reveal lower prevalence rates, implying that susceptibility varies between distinct ethnic groups, thus forming an important determinant of the geographic distribution of the disease. The objective of this study is to review MS prevalence estimates in different Latin American and Caribbean countries. We reviewed surveys of regional MS prevalence from 1991 to 2011. Sources included an online database, authors' reports and proceedings or specific lectures from regional conferences. We obtained a total of 30 prevalence surveys from 15 countries, showing low/medium MS prevalence rates. Both the number and the quality of prevalence surveys have greatly improved in this region over recent decades. This is the first collaborative study to map the regional frequency of MS. Establishment of standardized methods and joint epidemiological studies will advance future MS research in Latin America and the Caribbean.

Eczema herpeticum with herpetic folliculitis after bone marrow transplant under prophylactic acyclovir: are patients with underlying dermatologic disorders at higher risk?

We present an unreported coexistence: eczema herpeticum (EH) with histopathological findings of herpetic folliculitis (HF) after allogeneic bone marrow transplantation (BMT). A patient with atopic dermatitis (AD) underwent allogeneic BMT for idiopathic acquired aplastic anemia. She had been receiving cyclosporine (150 mg/12 h) and acyclovir (400 mg/12 h) for 6 months. A facial rash was observed, composed of monotonous erythematous, umbilicated papulo-vesicles and papulo-crusts <4 mm in size. The histopathological study showed herpetic cytopathic changes within the epidermis that extended into the hair follicle epithelium. Interestingly, microscopic HF has not previously been associated with post-transplant patients or EH. However, it is reasonable to hypothesize that the coexistence of these herpes simplex virus-related events may be underreported in the literature. Although further studies are necessary, we suggest that the prophylactic antiviral dose after BMT be enhanced in patients with underlying dermatologic diseases, especially in those with AD.

Prevalence of verotoxigenic Escherichia coli O157 (VTEC O157) and compliance with microbiological safety standards in bovine carcasses from an industrial beef slaughter plant.

UNLABELLED: The presence of Salmonella spp. and levels of Enterobacteriaceae and aerobic plate count were determined in 300 bovine carcasses randomly collected in an industrial cattle slaughterhouse in Catalonia (Spain) as part of a control programme to validate good slaughter practices according to Commission Regulation No 2073/2005. The verotoxigenic Escherichia coli O157 (VTEC O157), although not currently legislated, was also investigated in the same carcasses due to the importance of bovines as a reservoir for this micro-organism. Virulence genes (vtx1, vtx2 and eae), the presence of fliCH 7 and antimicrobial susceptibility were studied in E. coli O157 isolates. Levels of Enterobacteriaceae and aerobic colonies and the presence of Salmonella were within the admissible range stipulated by current legislation. However, VTEC O157 was detected in 14·7% of carcasses. Among the VTEC O157 strains tested for antimicrobial susceptibility, 65% were multiresistant. Overall, the results of this study indicate that even with good manufacturing practices, contamination with VTEC O157 can occur and cattle meat can pose a risk to human health. These results confirm the need for a review of the appropriateness of introducing antimicrobial treatments in the processing of cattle carcasses in Europe. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the prevalence of verotoxigenic and multidrug-resistant E. coli O157 strains in bovine carcasses. These results suggest that despite the good manufacturing practices used in the slaughterhouse studied (the largest in Catalonia slaughtering over 81 000 cattle per year), the absence of verotoxigenic E. coli O157 in bovine carcasses cannot be guaranteed.

Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis.

The purpose of this investigation was to analyze the clinical and epidemiological aspects of all cases of erysipelas and infectious cellulitis admitted to a tertiary hospital during a period of five years. All patients admitted with the main diagnosis of erysipelas or cellulitis to the Department of Dermatology of the author's institution from January 2005 to May 2010 were included. Seventy patients were identified and their medical records were retrospectively reviewed so as to record the epidemiological and clinical data. Univariate and multivariable analyses were performed to analyze variables that predicted longer length of stay. The frequency of cellulitis in the lower limbs was higher in men and patients older than 65 years. Moderate/severe cellulitis in patients with basal comorbidity followed by a poor response to oral antibiotic therapy for 48 h were the most common reasons for admission. At arrival, four patients had abscessed areas. Fourteen patients developed local complications and 18 cases developed general in-hospital complications. Most patients improved or were healed with intravenous amoxicillin-clavulanate 1 g-200 mg/8 h. Intravenous amoxicillin-clavulanate 1 g-200 mg/8 h may be a good choice for empiric treatment in our setting. The development of in-hospital complications and the need for changing empiric antibiotic therapy were significant and independent variables associated with longer length of stay.

Behavioral effects of environmental enrichment on male and female wistar rats with early life stress experiences.

Exposure to adverse childhood experiences or early life stress experiences (ELSs) increase the risk of non-adaptive behaviors and psychopathology in adulthood. Environmental enrichment (EE) has been proposed to minimize these effects. The vast number of methodological variations in animal studies underscores the lack of systematicity in the studies and the need for a detailed understanding of how enrichment interacts with other variables. Here we evaluate the effects of environmental enrichment in male and female Wistar rats exposed to adverse early life experiences (prenatal, postnatal, and combined) on emotional (elevated plus maze), social (social interaction chamber), memory (Morris water maze) and flexibility tasks. Our results-collected from PND 51 to 64-confirmed: 1) the positive effect of environmental enrichment (PND 28-49) on anxiety-like behaviors in animals submitted to ELSs. These effects depended on type of experience and type of enrichment: foraging enrichment reduced anxiety-like behaviors in animals with prenatal and postnatal stress but increased them in animals without ELSs. This effect was sex-dependent: females showed lower anxiety compared to males. Our data also indicated that females exposed to prenatal and postnatal stress had lower anxious responses than males in the same conditions; 2) no differences were found for social interactions; 3) concerning memory, there was a significant interaction between the three factors: A significant interaction for males with prenatal stress was observed for foraging enrichment, while physical enrichment was positive for males with postnatal stress; d) regarding cognitive flexibility, a positive effect of EE was found in animals exposed to adverse ELSs: animals with combined stress and exposed to physical enrichment showed a higher index of cognitive flexibility than those not exposed to enrichment. Yet, within animals with no EE, those exposed to combined stress showed lower flexibility than those exposed to both prenatal stress and no stress. On the other hand, animals with prenatal stress and exposed to foraging-type enrichment showed lower cognitive flexibility than those with no EE. The prenatal stress-inducing conditions used here 5) did not induced fetal or maternal problems and 6) did not induced changes in the volume of the dentate gyrus of the hippocampus.