Anammox with alternative electron acceptors: perspectives for nitrogen removal from wastewaters.

In the context of the anaerobic ammonium oxidation process (anammox), great scientific advances have been made over the past two decades, making anammox a consolidated technology widely used worldwide for nitrogen removal from wastewaters. This review provides a detailed and comprehensive description of the anammox process, the microorganisms involved and their metabolism. In addition, recent research on the application of the anammox process with alternative electron acceptors is described, highlighting the biochemical reactions involved, its advantages and potential applications for specific wastewaters. An updated description is also given of studies reporting the ability of microorganisms to couple the anammox process to extracellular electron transfer to insoluble electron acceptors; particularly iron, carbon-based materials and electrodes in bioelectrochemical systems (BES). The latter, also referred to as anodic anammox, is a promising strategy to combine the ammonium removal from wastewater with bioelectricity production, which is discussed here in terms of its efficiency, economic feasibility, and energetic aspects. Therefore, the information provided in this review is relevant for future applications.

The COVID-19 pandemic and non-COVID-19 healthcare utilization in Mexico.

OBJECTIVES: This study aimed to analyze the effects of the COVID-19 pandemic on non-COVID-19 healthcare utilization in Mexico, including oral health, mental health, communicable disease visits, health checkups, chronic degenerative disease visits, postpartum care, prenatal care, and family planning visits. STUDY DESIGN: This was a retrospective ecological analysis during the COVID-19 pandemic. During the pandemic, the Mexican government recommended non-essential consultations be suspended or rescheduled to accommodate the new demand for healthcare services from COVID-19 patients. METHODS: This study uses administrative data from Mexico's Ministry of Health from January 2017 to December 2022. These data cover 14,299 consultation units and 775 hospitals from the 32 Mexican States, all of which are public institutions. A difference-in-differences strategy and an event study specification are used to study the impacts of the pandemic on non-COVID-19 healthcare utilization. RESULTS: The findings reveal a decrease in the utilization of all healthcare services: oral health (69%), mental health (27%), communicable diseases (46%), chronic degenerative diseases (36%), health checkups (62%), family planning (45%), prenatal care (36%), and postpartum care (44%). Furthermore, the event study indicates that most services follow a U-shaped trend, although only mental health services clearly return to prepandemic levels. The remainder of services remain below prepandemic levels at the end of 2022. CONCLUSIONS: The 2020 pandemic had detrimental effects on non-COVID-19 healthcare utilization. The healthcare interruptions will likely impact short- and long-term morbidity and mortality. Programs intended to remediate these negative consequences may be of interest to public health policymakers.

RNA-Based Therapy for Cryptosporidium parvum Infection: Proof-of-Concept Studies.

Cryptosporidium is a leading cause of moderate-to-severe diarrhea in children, which is one of the major causes of death in children under 5 years old. Nitazoxanide is the only FDA-approved treatment for cryptosporidiosis. However, it has limited efficacy in immunosuppressed patients and malnourished children. Therefore, it is urgent to develop novel therapies against this parasite. RNA interference-mediated therapies are emerging as novel approaches for the treatment of infectious diseases. We have developed a novel method to silence essential genes in Cryptosporidium using single-stranded RNA (ssRNA)/Argonaute (Ago) complexes. In this work we conducted proof-of-concept studies to test the anticryptosporidial activity of these complexes by silencing Cryptosporidium parvum nucleoside diphosphate kinase (NDK) using in vitro and in vivo models. We demonstrated that a 3-day treatment with anti-sense NDK ssRNA/Ago decreased parasite burden by ~98% on infected cells. In vivo studies showed that ssRNA/Ago complexes encapsulated in lipid nanoparticles can be delivered onto intestinal epithelial cells of mice treated orally. In addition a cryptosporidiosis-mouse model showed that treatment with NDK ssRNA/Ago complexes reduced oocyst shedding in 4/5 SCID/beige mice during the acute phase of the infection. Our findings highlight the potential use of antisense RNA-based therapy as an alternative approach to cryptosporidiosis treatment.

Enhanced anaerobic treatment of synthetic protein-rich wastewater promoted by organic xerogels.

Carbon-based materials have been shown to enhance anaerobic digestion processes by promoting direct interspecies electron transfer in methanogenic consortia. However, little is known on their effects during the treatment of complex substrates, such as those derived from protein-rich wastewaters. Here, organic xerogels (OX) are tested, for the first time, as accelerators of the methanogenic activity of an anaerobic consortium treating a synthetic protein-rich wastewater. Three OX with distinct pore size distribution (10 and 1000 nm for OX-10 and OX-1000, respectively) and structural conformation (graphene oxide integration into OX-10-GO polymeric matrix) were synthesized. OX-1000 promoted the highest methane production rate (5.21 mL/g*h, 13.5% increase with respect to the control incubated without OX) among the synthesized OX. Additionally, batch bioreactors amended with OX achieved higher chemical oxygen demand (COD) removal (up to 88%) as compared to the control, which only showed 50% of COD removal. Interestingly, amendment of bioreactors with OX also triggered the production of medium-chain fatty acids, including caprylate and caproate. Moreover, OX decreased the accumulation of ammonium, derived from proteins hydrolysis, partly explained by their adsorption capacities, and probably involving their electron-accepting capacity promoting anaerobic ammonium oxidation. This is the first time that OX were successfully applied as methanogenic accelerators for the anaerobic treatment of synthetic protein-rich wastewater, increasing the methane production rate and COD removal as well as triggering the production of medium chain fatty acids and attenuating the accumulation of ammonium. Therefore, OX are proposed as suitable materials to boost the efficiency of anaerobic systems to treat complex industrial wastewaters.

Calpain Participates in Cortical Cytoskeleton Modification and DNA Release during Neutrophil Extracellular Trap Formation.

INTRODUCTION: The formation of neutrophil extracellular traps (NETs) is a process in which several kinds of enzymes participate generating posttranslational modifications of proteins. NETs have been associated with infectious, autoimmune, and inflammatory diseases. Inhibition of several proteases reduces the formation of NETs. In the present work, we analyzed the role of several broad-acting and specific inhibitors of proteases in the formation of NETs. METHODS: Neutrophils were isolated from peripheral blood of healthy individuals by density gradient. The neutrophils were quantified and seeded into cell culture plates. Phorbol myristate acetate and A23187 were used as NETs inducers, and several specific inhibitors of proteases were used. The cells were stained for cytoskeleton or DNA. The cell-free supernatants were used to assess DNA release. Statistical analysis was carried out by a Kruskal-Wallis or ANOVA test. RESULTS: We observed marked changes in actin organization after the induction of NETs, suggesting that the cytoskeleton is being actively regulated. When we used protease inhibitors, the release of DNA was reduced, suggesting the participation of actin remodeling in the process. Further characterization of the specific proteases revealed that calpain modulates the reorganization of actin cytoskeleton and DNA release. Preservation of part of the actin cytoskeleton suggests that DNA release is not only a mechanic process associated to the chromatin decondensation; rather the process is highly regulated by active proteases that promote cytoskeleton reorganization and chromatin decondensation that culminates in DNA release. CONCLUSION: Calpain mediates the DNA release in the NET formation process by the modification of cortical actin cytoskeleton in a calcium-dependent manner.

Realized genetic selection differentials in Canadian Ayrshire, Jersey, and Brown Swiss dairy cattle populations.

Estimated breeding values of a selection index, production, durability, health, and fertility traits from Canadian Ayrshire, Jersey, and Brown Swiss bulls and cows were used to study genetic selection differentials (GSD). The bulls and cows were born from 1950 and 1960, respectively. The GSD for the 3 Canadian dairy populations were studied along the 4-path selection model: sire-to-bull (SB), dam-to-bull (DB), sire-to-cow (SC), and dam-to-cow (DC) pathways. We also determined the variations in realized GSD due to herd and herd × year of conception in addition to the effects of some environmental factors on realized GSD of the SC and DC paths. The mean realized GSD of the DB were higher than those of other paths and were increasing for lifetime performance index, 305-d milk yield, 305-d fat yield, and 305-d protein yield in all 3 dairy cattle populations. We observed no clear trends in realized GSD for type traits in all 3 dairy cattle breeds except for the apparent increasing trends in realized GSD of mammary system, dairy strength, and feet and legs in the DB and SC paths of the Ayrshire breed. No clear patterns were observed in the realized GSD of daughter fertility in the SB, DB, and SC paths of all dairy cattle breeds. Realized GSD for somatic cell score showed increasing and favorable trends in the 3 most influential selection paths (SB, DB, and SC). Year of conception influenced realized GSD of artificial insemination bulls in Ayrshire, Jersey, and Brown Swiss dairy populations. Selection emphases for the SC path generally increased with time. There was considerable variation among herds in selection pressures applied in the SC and DC pathways but no clear association with housing system or region. This study demonstrates that variations exist among herds of minor dairy cattle breeds in their selection for economically important traits. These variations offer opportunities for further improvements in these populations.

Toward a dissection of ß-Amyloid localized effects on glutamatergic hippocampal repertoire: An Editorial Highlight for "Amyloid-beta1-42 induced glutamatergic receptor and transporter expression changes in the mouse hippocampus"on https://doi.org/10.1111/jnc.15099.

Hippocampal excitatory glutamatergic transmission is critically involved in cognitive functions such as learning and memory. A severe impairment of spatial memory is associated with the Alzheimer's disease characteristic augmentation of soluble Amyloid-beta1-42 which in turn leads to glutamatergic neurotransmission dysfunction. As the molecular basis of such correlations has not been completely understood, this Editorial highlights a study in the current issue of the Journal of Neurochemistry in which Yeung and coworkers provide an elegant anatomical study that sheds light into this problematic. Through a rigorous immunohistochemical approach, a sub-regional expression pattern of ionotropic glutamate receptors and vesicular transporters was determined in control and beta amyloid-injected mouse hippocampus. The selected areas participate in information processing and thus, in memory formation. Furthermore, the authors discuss their findings in the context of cognitive deficits present in Alzheimer's disease patients delivering an intuitive analysis of plausible molecular events that disturb proper glutamate signaling. This study takes an important step toward a better understanding of the complexity of Amyloid-beta1-42 and glutamatergic neurotransmission interactions.

Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.

Leptospirosis in an asplenic patient -case report.

BACKGROUND: The presentation of clinical leptospirosis has been historically associated with animal workers, slaughterhouse workers and medical veterinarians. This association has shifted to be related to flooding events and outdoor activities; few cases are related to high-risk factors found in immunosuppressed patients. Scarcely a handful of cases have serological evidence of immune response against Leptospira serovar Bratislava representing serogroup Australis, a serovar associated with poor reproductive performance in swine and horses, and recently with cats. CASE PRESENTATION: Herein, we describe a rare clinical presentation of disseminated Leptospira infection in an immunosuppressed 65-year-old woman. She was admitted to the emergency room with fever, bacteraemia, bilateral uveitis and pulmonary involvement. The patient denied outdoor activities; she only had wide exposure to faeces and urine from cats living in her home. Her medical history included idiopathic thrombocytopenic purpura (ITP) diagnosed at the age of 18. She did not respond to medical treatment, and a splenectomy was performed. At age 60, she was diagnosed with Chronic Myeloid Leukemia (CML), and was treated with a tyrosine kinase inhibitor (TKI) -Imatinib. The patient voluntarily discontinued the treatment for the last 6 months. After extensive workup, no microorganisms were identified by the commonly used stains in microbiology. The diagnosis was performed through dark-field microscopy, microagglutination test (MAT), Leptospira genus-specific PCR, the IS1500 PCR for identification of pathogenic species, and 16S based sequencing for the genus identification. CONCLUSION: Immunosuppressed patients may acquire uncommon infections from ubiquitous microorganisms. In this case, serology evidence of exposure to Leptospira serovar Bratislava by MAT and the presence of the Leptospira genus were identified. It should be on mind for the diagnosis in otherwise healthy patients, and thoroughly search on splenectomised patients exposed to animals. Additionally, this report highlights the usefulness of PCR for diagnosis of this potentially life-threatening illness.

Effects of graphene oxide and reduced graphene oxide on acetoclastic, hydrogenotrophic and methylotrophic methanogenesis.

This study describes the effects of graphene oxide (GO) and reduced graphene oxide (rGO) on the acetoclastic, hydrogenotrophic and methylotrophic pathways of methanogenesis by an anaerobic consortium. The results showed that GO negatively affected the hydrogenotrophic and acetoclastic pathways at a concentration of 300 mg/L, causing a decrease of ~ 38% on the maximum specific methanogenic activity (MMA) with respect to the controls lacking GO. However, the presence of rGO (300 mg/L) promoted an improvement of the MMA (> 45%) achieved with all substrates, except for the hydrogenotrophic pathway, which was relatively insensitive to rGO. The presence of either rGO or GO enhanced the methylotrophic pathway and resulted in an increase of the MMA of up to 55%. X-ray photoelectron spectroscopy (XPS) analysis revealed that GO underwent microbial reduction during the incubation period. Electrons derived from substrates oxidation were deviated from methanogenesis towards the reduction of GO, which may explain the MMA decreased observed in the presence of GO. Furthermore, XPS evidence indicated that the extent of GO reduction depended on the metabolic pathway triggered by a given substrate.

Realized genetic selection differentials in Canadian Holstein dairy herds.

Estimated breeding values for a selection index, production, durability, health, and fertility traits for Canadian Holstein bulls and cows born from 1950 and 1960, respectively, were used to define and determine realized genetic selection differentials (GSD) and generation intervals along the 4-path model of genetic improvement and the variability among herds in realized GSD. The effects of some non-genetic factors on realized GSD were also determined. The mean generation intervals of the sire-to-bull (SB), dam-to-bull (DB), sire-to-cow (SC), and dam-to-cow (DC) pathways reduced, respectively, from 9.7, 7.5, 7.7, and 4.7 years in 1980 to 2.3, 2.5, 4.8, and 3.6 years in 2016. The realized GSD of lifetime performance index and 305-d milk, fat, and protein yields for the SB and DB paths were greater than those of the SC and DC, and realized GSD for DB were increasing for all production traits and the index after 2009. With the exception of daughter fertility (DF), we found zero to negative selection in the DC path for all the traits studied, due to the minimal opportunity for selection in that path. No clear trends were observed in realized GSD of SB, DB, or SC paths for mammary system, dairy strength, feet and legs, or herd life. The realized GSD for DF in the SB, DB, and SC remained largely negative, except after the early 2000s when positive realized GSD were observed in the SB and DB paths. The realized GSD for DF in the DC path remained positive throughout the period of the study, though mostly non-significantly different from zero, except for 2014 and 2015. Realized GSD for somatic cell score in the SB, DB, and SC paths showed increasing and favorable trends. Year of conception, housing system, agricultural region, and their interactions had significant effects on realized GSD of some traits in the SC and DC paths. We also observed considerable variations in realized GSD among herds. The population mean realized GSD and those of the top and bottom 10% of herds could serve as benchmarks that individual herds could use to monitor their past selection and make changes if they are not moving in the intended direction.

Pillared graphene oxide composite as an adsorbent of soluble hydrocarbons in water: pH and organic matter effects.

Graphene oxide (GO) is a single-atom-thick sheet of carbon with oxygen-containing functional groups decorating its basal plane and edge sites. Most of its high surface area can be lost due to restacking of individual layers during the synthesis and drying of GO-based bulk sorbents. There is great interest to increase the specific surface area of graphene-based sorbents by introducing organic molecules as "pillaring agents" between GO sheets to hinder the stacking process and create sorbents with elevated surface area. This work synthesizes pillared GO by introducing chitosan (CS), a linear polysaccharide with various molecular weights. A composite of low molecular weight CS at a CS/GO ratio of 0.1 is shown to have the highest specific surface area (up to 70.5 m2/g) in comparison to the medium and high CS molecular weight, pristine GO, and the CS/GO composite materials. The affinity of the optimized GO/CS composites towards benzene, toluene, and naphthalene was evaluated at 19.3 mg/L of organic matter content while altering pH. Sips and Langmuir adsorption isotherm models well described the adsorption behavior, and benzene adsorption performance was reduced at low pH. Related to the presence of dissolved organic matter (DOM) in solution, lower diffusivity constants (k1) in hydrocarbon systems were recorded. Our results demonstrate the feasibility of CS as a potential pillaring agent in CS/GO composites to increase specific surface area and enhance the capture of soluble hydrocarbons from aqueous solutions.

AMPA receptors modulate the reorganization of F-actin in Bergmann glia cells through the activation of RhoA.

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors have been shown to modulate the morphology of the lamelar processes of Bergmann glia cells in the molecular layer of the cerebellum. Here we suggest that reorganization of F-actin may underlay the changes in the morphology of the lamelar processes. Using the fluorescent staining of F-actin with Phalloidin and the quantification of RhoA activation through immunoprecipitation or pull-down assays, we show that RhoA is activated after stimulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors and leads to the reorganization of the actin cytoskeleton of Bergmann fibers. This reorganization of the actin cytoskeleton is reflected in the form of an increase in the intensity of the F-actin staining as well as in the loss of the number of Bergmann fibers stained with Phalloidin. Moreover, using a pharmacological approach, we show that activation of RhoA and the change in the intensity of the F-actin staining depends on the activation of PI3-K, focal adhesion kinase, and protein kinase C, whereas changes in the number of Bergmann fibers depend on external calcium in a RhoA independent manner. Our findings show that glutamate may induce a form of structural plasticity in Bergmann glia cells through the reorganization of the actin cytoskeleton. This may have implications in the way the synaptic transmission is processed in the cerebellum.

Biofilm microbial composition changes due to different surface chemical modifications of activated carbon cloths in the biotransformation of 4-nitrophenol.

Activated carbon cloths (ACCs) were used as biofilms supports in the anaerobic biotransformation of 4-nitrophenol (4NP). As received ACC material (AW) was oxidized with HNO3 (OX) and then functionalized with anthraquinone-2,6-disulfonate (AQ). The three ACCs were packed in hybrid UASB reactors and seeded with anaerobic granular sludge for biotransformation experiments. The results indicated that ACC-packed bioreactors improved the biotransformation of 4NP by twofold as compared to the control reactor without support materials. However, the biotransformation effciency of AW, OX and AQ was very similar (59%), indicating the role of ACC as biofilm support and not as redox mediator. After 4NP biotransformation several physicochemical and biological changes were observed like (1) the point of zero charge (pHPZC) shift from acidic values (AW = 5.0, OX = 3.4, AQ = 3.1) to neutral values (pHPZC = 7.6 on average), (2) increase in the concentration of acidic and basic surface functional groups over ACC materials and the amount of supported biomass on ACCs due to biofilm formation, and (3) enrichment of exoelectrogenic microorganisms belonging to the genera Geobacter over carbonyl-rich ACC surface as revealed by 16S rRNA amplicon sequencing. Overall, the results suggest that chemical modifications of ACCs changed the microbial composition of the biofilm, but the higher concentration of carbonyl groups on ACC did not affect the biotransformation of 4NP.

Evaluation of Nanomechanical Properties of Tomato Root by Atomic Force Microscopy.

Here, different tissue surfaces of tomato root were characterized employing atomic force microscopy on day 7 and day 21 of growth through Young's modulus and plasticity index. These parameters provide quantitative information regarding the mechanical behavior of the tomato root under fresh conditions in different locations of the cross-section of root [cell surface of the epidermis, parenchyma (Pa), and vascular bundles (Vb)]. The results show that the mechanical parameters depend on the indented region, tissue type, and growth time. Thereby, the stiffness increases in the cell surface of epidermal tissue with increasing growth time (from 9.19 ± 0.68 to 13.90 ± 1.68 MPa) and the cell surface of Pa tissue displays the opposite behavior (from 1.74 ± 0.49 to 0.48 ± 0.55); the stiffness of cell surfaces of Vb tissue changes from 10.60 ± 0.58 to 6.37 ± 0.53 MPa, all cases showed a statistical difference (p < 0.05). Viscoelastic behavior dominates the mechanical forces in the tomato root. The current study is a contribution to a better understanding of the cell mechanics behavior of different tomato root tissues during growth.

Improved reductive transformation of iopromide by magnetite containing reduced graphene oxide nanosacks as electron shuttles.

The novel application of magnetite containing reduced graphene oxide nanosacks (MrGO-N) as electron shuttles to improve the reductive degradation of pharmaceutical pollutant, iopromide (IOP), was evaluated. The MrGO-N were synthesized by ultrasonicated nebulization process, and their physicochemical characterization was performed by potentiometric titrations, zeta potential, high resolution transmission electron microscopy (HR-TEM), X-ray diffraction, as well as by Raman and Fourier transform infrared spectroscopies. Results demonstrated the thermal reduction of precursor graphene oxide sheets, the removal of different oxygenated groups, and the successful assembly of magnetite nanoparticles (MNP) in the graphene sacks. Also, reduction experiments revealed 72 % of IOP removal efficiency and up to 2.5-fold faster degradation of this pollutant performed with MrGO-N as redox catalysts in batch assays and with sulfide as electron donor. Chemical transformation pathway of IOP provides evidence of complete dehalogenation and further transformation of aromatic ring substituents. Greater redox-mediating ability of MrGO-N was observed, which was reflected in the catalytic activity of these nanomaterials during the reductive degradation of IOP. Transformation byproducts with simpler chemical structure were identified, which could lead to complete degradation by conventional methodologies in a complementary treatment process. Redox-mediating activity of MrGO-N could potentially be applied in wastewater treatment systems in order to facilitate the biodegradation of priority contaminants.

Evaluation of the Applicability of 3d Models as Perceived by the Students of Health Sciences.

The methodology and style of teaching anatomy in the faculties of Health Sciences is evolving due to the changes being introduced as a result of the application of new technologies. This brings a more positive attitude in the students, enabling an active participation during the lessons. One of these new technologies is the creation of 3D models that reliably recreates the anatomical details of real bone pieces and allow access of anatomy students to bone pieces that are not damaged and possess easily identifiable anatomical details. In our work, we have presented previously created 3D models of skull and jaw to the students of anatomy in the Faculties of Health Sciences of the University of Salamanca, Spain. The faculties included were odontology, medicine, occupational therapy nursing, health sciences and physiotherapy. A survey was carried out to assess the usefulness of these 3D models in the practical study of anatomy. The total number of students included in the survey was 280.The analysis of the results presents a positive evaluation about the use of 3D models by the students studying anatomy in different Faculties of Health Sciences.

Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort.

Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post-treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2 . In conclusion, eGFR slightly declines during therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR.

Mechanisms of Neuronal Silencing After Cortical Spreading Depression.

Cortical spreading depression (CSD) is associated with migraine, stroke, and traumatic brain injury, but its mechanisms remain poorly understood. One of the major features of CSD is an hour-long silencing of neuronal activity. Though this silencing has clear ramifications for CSD-associated disease, it has not been fully explained. We used in vivo whole-cell recordings to examine the effects of CSD on layer 2/3 pyramidal neurons in mouse somatosensory cortex and used in vitro recordings to examine their mechanism. We found that CSD caused a reduction in spontaneous synaptic activity and action potential (AP) firing that lasted over an hour. Both pre- and postsynaptic mechanisms contributed to this silencing. Reductions in frequency of postsynaptic potentials were due to a reduction in presynaptic transmitter release probability as well as reduced AP activity. Decreases in postsynaptic potential amplitude were due to an inhibitory shift in the ratio of excitatory and inhibitory postsynaptic currents. This inhibitory shift in turn contributed to the reduced frequency of APs. Thus, distinct but complementary mechanisms generate the long neuronal silence that follows CSD. These cellular changes could contribute to wider network dysfunction in CSD-associated disease, while the pre- and postsynaptic mechanisms offer separate targets for therapy.

Novel application of magnetic nano-carbon composite as redox mediator in the reductive biodegradation of iopromide in anaerobic continuous systems.

The redox-mediating capacity of magnetic reduced graphene oxide nanosacks (MNS) to promote the reductive biodegradation of the halogenated pollutant, iopromide (IOP), was tested. Experiments were performed using glucose as electron donor in an upflow anaerobic sludge blanket (UASB) reactor under methanogenic conditions. Higher removal efficiency of IOP in the UASB reactor supplied with MNS as redox mediator was observed as compared with the control reactor lacking MNS. Results showed 82% of IOP removal efficiency under steady state conditions in the UASB reactor enriched with MNS, while the reactor control showed IOP removal efficiency of 51%. The precise microbial transformation pathway of IOP was elucidated by high-performance liquid chromatography coupled to mass spectroscopy (HPLC-MS) analysis. Biotransformation by-products with lower molecular weight than IOP molecule were identified in the reactor supplied with MNS, which were not detected in the reactor control, indicating the contribution of these magnetic nano-carbon composites in the redox conversion of this halogenated pollutant. Reductive reactions of IOP favored by MNS led to complete dehalogenation of the benzene ring and partial rupture of side chains of this pollutant, which is the first step towards its complete biodegradation. Possible reductive mechanisms that took place in the biodegradation of IOP were stated. Finally, the novel and successful application of magnetic graphene composites in a continuous bioreactor to enhance the microbial transformation of IOP was demonstrated.