Teaching the distribution of pulmonary blood flow using a Starling resistor model and turbine flowmeters.

The distribution of pulmonary blood flow is uneven and can be described as a three-zone model, the West zones: zone 1 occurs whenever alveolar pressure exceeds arterial pressure; zone 2 when the arterial pressure is greater than alveolar but the alveolar pressure exceeds the venous pressure; and finally zone 3 when both arterial and venous pressures exceed alveolar pressure. Consequently, the blood flow is almost determined by the difference between the arterial and venous pressures in zone 3 and between arterial and alveolar pressures in zone 2 and ceases in zone 1. The understanding of this subject may be difficult to some medical students. Therefore, to improve the learning of this topic in our physiology course, we used a didactic model to demonstrate the core concept of flow down gradients and its application to pulmonary blood flow. We modeled a Starling resistor by placing a collapsible tube inside a hermetic chamber of variable pressure. Transparent turbine flowmeters were connected to the upstream and downstream extremities of the Starling resistor, and we generated a constant airflow with a brushless motor. By maintaining the input (arterial) pressure constant and varying the chamber (alveolar) pressure, we could simulate the three zones and demonstrate the resulting flow through the turbines. In conclusion, our demonstration using a Starling resistor model combined with visible turbine flowmeters can be used to facilitate comprehension of important concepts in physiology involving flow down gradients, such as pulmonary blood flow.NEW & NOTEWORTHY The understanding of respiratory physiology is a challenge to medical students. To improve the learning of pulmonary blood flow distribution through lung vessels in our physiology course, we modeled a Starling resistor model combined with visible turbine flowmeters. Our model can significantly improve the core concept of flow down gradients teaching and its application to West zones.

Carcass traits and morphometry, typification of the Longissimus dorsi muscle and non-carcass components of hair lambs: can biscuit bran completely replace corn? A machine learning approach.

Biscuit bran (BB) is a co-product with worldwide distribution, with Brazil as the second largest cookie producer in the world with 1,157,051 tons. We evaluate the impact of completely replacing corn with BB on the characteristics and morphometry of carcass of purebred and crossbred Morada Nova lambs using machine learning techniques as an auxiliary method. Twenty male lambs from two genetic groups (GG) were used: purebred red-coated Morada Nova (MNR) and crossbred MNR × white-coated Morada Nova (MNF1). Supervised and unsupervised machine learning techniques were used. No interaction (P > 0.05) was observed between diets (D) and genetic groups (GG) and no simple isolated effect was observed for carcass characteristics, qualitative-quantitative typification of the Longissimus dorsi muscle, weight of non-carcass components, weight and yield of commercial cuts and carcass morphometric measurements. The formation of two horizontal clusters was verified: (i) crossed lambs with corn and BB and (ii) purebred lambs fed corn and BB. Vertically, three clusters were formed based on carcass and meat characteristics of native lambs: (i) thermal insulation, body capacity, true yield, and commercial cuts; (ii) choice, performance, physical carcass traits, and palatability; and (iii) yield cuts and non-carcass components. The heatmap also allowed us to observe that pure MN lambs had a greater body capacity when fed BB, while those fed corn showed superiority in commercial cuts, true yields, and non-carcass components. Crossbred lambs, regardless of diet, showed a greater association of physical characteristics of the carcass, performance, palatability, and less noble cuts. Crossbred lambs, regardless of diet, showed a greater association of physical characteristics of the carcass, performance, palatability, and less noble cuts. BB can be considered an alternative energy source in total replacement of corn. Integrating of machine learning techniques is a useful statistical tool for studies with large numbers of variables, especially when it comes to analyzing complex data with multiple effects in the search for data patterns and insights in decision-making on the farm.

Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up.

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

Remote sensing environmental indicators for monitoring spatial and temporal dynamics of weather and vegetation conditions: applications for Brazilian biomes.

The SAFER (Simple Algorithm for Evapotranspiration Retrieving) algorithm and the radiation use efficiency (RUE) model were coupled to test large-scale remote sensing environmental indicators in Brazilian biomes. MODIS MOD13Q1 reflectance product and gridded weather data for the year 2016 were used to demonstrate the suitability of the algorithm to monitor the dynamics of environmental remote sensing indicators along a year in the Brazilian biomes, Amazon, Caatinga, Cerrado, Pantanal, Atlantic Forest, and Pampa. Significant spatial and temporal variations in precipitation (P), actual evapotranspiration (ET), and biomass production (BIO) yielded differences on water balance (WB = P-ET) and water productivity (WP = ET/BIO). The highest WB and WP differences were detected in the wettest biomes, Amazon, Atlantic Forest, and Pampa, when compared with the driest biome, Caatinga. Rainfall distribution along the year affected the magnitude of the evaporative fraction (ETf), i.e., the ET to reference evapotranspiration (ET0) ratio. However, there was a gap between ETf and WB, which may be related to the time needed for recovering good soil moisture conditions after rainfalls. For some biomes, BIO related most to the levels of absorbed photosynthetically active radiation (Amazon and Atlantic Forest), while for others, BIO followed most the soil moisture levels, depicted by ETf (Caatinga, Cerrado, Pantanal, and Pampa). The large-scale modeling showed suitability for monitoring the water and vegetation conditions, making way to detect anomalies for specific periods along the year by using historical images and weather data, with strong potential to support public policies for management and conservation of natural resources and with possibilities for replication of the methods in other countries.

Stabilization of oil-water emulsions with protein concentrates from the microalga Tetradesmus obliquus.

The present work used water-soluble protein concentrates from the microalga Tetradesmus obliquus to stabilize sunflower oil emulsions. Microalgal cells were disrupted by sonication, and proteins were separated from the biomass using two methods, isoelectric and solvent precipitations. The protein extracts were concentrated by lyophilization, and the concentrates were used to produce emulsions with three amounts of Tetradesmus obliquus protein concentrate (TobPC) (0.1, 0.5, and 1.0% w/v). Emulsions were homogenized through sonication and characterized for creaming index, optical microscopy, size distribution, ζ-potential, and rheology. Isoelectric precipitation resulted in TobPC with a high protein content (51.46 ± 2.37%) and a better dispersibility profile. Emulsion stability was higher for both the isoelectric TobPC and control systems than for the TobPC solvent. Solvent TobPC does not efficiently stabilize emulsions at low protein concentrations that showed microscopically larger oil droplets and flocculation spots. A high phase separation velocity was observed for solvent TobPC, probably due to the higher hydrodynamic droplet diameters. The increase in TobPC content in the emulsions resulted in more stable emulsions for all samples. Therefore, Tetradesmus obliquus protein concentrates are a potential emulsifying agent.

Rheology of dispersions and emulsions composed of chia mucilage and the application of chia in food.

Chia mucilage (CM) is an emerging resource in food applications. However, the mechanism of this biopolymer as a stabilizer/emulsifier ingredient has not yet been well defined. A non-uniform viscoelastic tridimensional network was observed on emulsions with CM, while the surface activity of the CM ingredient has been associated with its protein content. To understand its functionality in food, this review focused on discussing and summarizing the rheological properties of dispersions and emulsions composed of CM under different conditions, such as pH, temperature, salt content, and mucilage content. For example, emulsions and dispersions with CM showed pseudoplastic behavior. An increase in the CM concentration increased the viscosity and the consistency index and decreased the behavior index. The consistency index of dispersions with CM increased with pH. The future evaluation of emulsions and dispersions properties, such as viscoelastic properties and microstructure, is particularly important for the successful use of CM in the food industry. The principal studies have evaluated the use of CM in dairy and meat systems as an emulsifier, stabilizer, or lipid replacer. The nutritional quality of the products with CM was maintained or improved, but sometimes an undesirable darkening was observed. Future evaluation of the cold extraction method of CM might improve the color and overall sensory acceptability of food products with CM. Integrated chia seed processing, including mucilage, oil, and protein extraction could be carried out to make chia seed industrial processing viable. © 2022 Society of Chemical Industry.

Nisin resistance in Gram-positive bacteria and approaches to circumvent resistance for successful therapeutic use.

Antibiotic resistance among bacterial pathogens is one of the most worrying problems in health systems today. To solve this problem, bacteriocins from lactic acid bacteria, especially nisin, have been proposed as an alternative for controlling multidrug-resistant bacteria. Bacteriocins are antimicrobial peptides that have activity mainly against Gram-positive strains. Nisin is one of the most studied bacteriocins and is already approved for use in food preservation. Nisin is still not approved for human clinical use, but many in vitro studies have shown its therapeutic effectiveness, especially for the control of antibiotic-resistant strains. Results from in vitro studies show the emergence of nisin-resistant bacteria after exposure to nisin. Considering that nisin has shown promising results for clinical use, studies to elucidate nisin-resistant mechanisms and the development of approaches to circumvent nisin-resistance are important. Thus, the objectives of this review are to identify the Gram-positive bacterial strains that have shown resistance to nisin, describe their resistance mechanisms and propose ways to overcome the development of nisin-resistance for its successful clinical application.

Effect of dexamethasone on experimental enteritis produced by Giardia lamblia in a Meriones unguiculatus model.

Our aim was to evaluate the impact of immunosuppression on the development of giardiasis. Thirty-six gerbils (4-6 weeks old) were distributed in four groups containing nine animals each: Control (CT); Control-Infected by Giardia lamblia (CTIn), Immunosuppressed (IS), and Immunosuppressed-Infected by G. lamblia (ISIn). Animals in the IS and ISIn groups received intramuscular dexamethasone solution for 25 days. On the 11th day, the animals in the CTIn and ISIn groups were inoculated with G. lamblia. After 14 days of infection, the 25th day of the experiment, all groups were euthanized. Four hours after euthanasia, the intestinal permeability was evaluated and sections of the duodenum and spleen were harvested for morphometric and histopathological analyses. Immunosuppressed groups showed a significant increase in intestinal permeability compared to control and infected groups. Considering that the infection can become chronic in immunosuppressed groups, we should be alert to the possibilities of chronic inflammatory changes, both locally and systemically, due to the loss of the intestinal barrier. Lesions were observed in the duodenal mucosa of the gerbils of the CTIn group, with reduced villi size, crypt hyperplasia, edema, and the presence of inflammatory infiltrate in the lamina propria. In the ISIn group, we observed no inflammation, long and intact villi, and a significant increase in the area of intestinal mucins, despite the large number of trophozoites identified. Our results suggest that exacerbation of the immune response has a direct relationship with the appearance of lesions during enteritis produced by G. lamblia in the assessed model.

In Vitro Effects of 2-{4-[Methylthio(methylsulfonyl)]phenyl}-3-substitutedthiazolidin-4-ones on the Acetylcholinesterase Activity in Rat Brain and Lymphocytes: Isoform Selectivity, Kinetic Analysis, and Molecular Docking.

This work evaluated the in vitro effect of thiazolidin-4-ones on the activity of AChE (total and isoforms) isolated from the cerebral cortex, hippocampus, and lymphocytes. Kinetic parameters were evaluated and molecular docking was performed. Our results showed that thiazolidinones derived from 4-(methylthio)benzaldehyde (1) and from 4-(methylsulfonyl)benzaldehyde (2) were capable of inhibiting the AChE activity in vitro. Three compounds, two with a propylpiperidine (1b and 2b) moiety and one with a 3-(diethylamino)propyl (1c) moiety showed IC50 values of 13.81 µM, and 3.13 µM (1b), 55.36 µM and 44.33 µM (1c) for cerebral cortex and hippocampus, respectively, and 3.11 µM for both (2b). Enzyme kinetics revealed that the type of AChE inhibition was mixed. Compound 1b inhibited the G1 and G4 AChE isoforms, while compounds 1c and 2b selectively inhibited the G4 isoform. Molecular docking showed a possible three-dimensional fit into the enzyme. Our findings showed that these thiazolidin-4-ones, especially those containing the propylpiperidine core, have a potential cholinesterase inhibitory activity and can be considered good candidates for future Alzheimer's therapy.

Antileishmanial activity of 4-phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) derivative on Leishmania amazonensis and Leishmania braziliensis: In silico ADMET, in vitro activity, docking and molecular dynamic simulations.

Organic compounds obtained by click chemistry reactions have demonstrated a broad spectrum of biological activities being widely applied for the development of molecules against pathogens of medical and veterinary importance. Cutaneous leishmaniasis (CL), caused by intracellular protozoa parasite of genus Leishmania, comprises a complex of clinical manifestations that affect the skin and mucous membranes. The available drugs for the treatment are toxic and costly, with long periods of treatment, and the emergence of resistant strains has been reported. In this study we investigated the in vitro effects of a phthalimide-1,2,3-triazole derivative, the 4-Phenyl-1-[2-(phthalimido-2-yl)ethyl]-1H-1,2,3-triazole (PT4) obtained by click chemistry, on mammalian cells and on L. amazonensis and L. braziliensis, the causative agents of CL in Brazil. In silico ADMET evaluation of PT4 showed that this molecule has good pharmacokinetic properties with no violation of Lipinski's rules. The in vitro assays showed that PT4 was more selective for both Leishmania species than to mammalian cells. This compound also presented low cytotoxicity to mammalian cells with CC50 > 500 µM. Treatment of promastigote forms with different concentrations of PT4 resulted in ultrastructural alterations, such as plasma membrane wrinkling, shortening of cell body, increased cell volume and cell rupture. The molecular dynamic simulations showed that PT4 interacts with Lanosterol 14 α-demethylase from Leishmania, an essential enzyme of lipid synthesis pathway in this parasite. Our results demonstrated PT4 was effective against both species of Leishmania. PT4 caused a decrease of mitochondrial membrane potential and increased production of reactive oxygen species, which may lead to parasite death. Taken together, our results pointed PT4 as promissing therapeutic agent against CL.

Comparison of two pharmacological prophylaxis strategies for venous thromboembolism in spinal cord injury patients: a retrospective study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare the cost and incidence of venous thromboembolism (VTE) and bleeding between two different VTE pharmacological prophylaxis strategies in individuals with spinal cord injury: one based on motor impairment (Protocol 1) and the other based on time from the lesion and presence of associated risk factors for VTE (Protocol 2). SETTING: A tertiary rehabilitation hospital in Brazil. METHODS: We retrospectively reviewed a total of 1475 charts of individual admissions: 814 individuals received pharmacological prophylaxis according to Protocol 1 and 661 according to protocol 2. These cohorts were compared with respect to age, time and level of injury, length of stay, AIS classification, type of injury, and occurrence of VTE and major bleeding. The number of prescribed doses of enoxaparin and expenditures associated with enoxaparin during each period were evaluated. RESULTS: The median lesion time was 3 years. The risk-based strategy drastically reduced the average monthly use of enoxaparin by 75% and the 12-month enoxaparin expenditure by $119,930.33, without increasing the risk of VTE. The incidence density of thromboembolic events was 0.55/10,000 patient-days, and all events occurred in individuals receiving prophylaxis according to Protocol 1. CONCLUSIONS: Time from injury and risk of VTE-based protocol for indication of pharmacological prophylaxis drastically reduced costs. No difference in occurrence of VTE was observed.

Color stability of a bis-acryl composite resin subjected to polishing, thermocycling, intercalated baths, and immersion in different beverages.

OBJECTIVE: To evaluate the color of a bis-acryl resin after polishing, aging, and colorants. MATERIALS AND METHODS: From the 140 disks obtained, 35 were not polished (NP), 35 were polished with 3-µm (3P), 35 with 3- and 1-µm (1P), and 35 with 3-, 1-, and 0.5-µm sized particles (05P). Five disks of each group were thermocycled for 20, 100, and 200 cycles. Sixty disks were thermocycled and kept in beverages (tea, wine, and coffee) after four cycles. Sixty disks were immersed in the beverages for 24 hours, a week, and a month. The coordinates L*a*b* were measured and the color differences were analyzed by ANOVA. The lightness, chroma, and hue differences were evaluated by repeated measures ANOVA. Comparisons were made with Tukey's test (α = 0.05). RESULTS: Similar behaviors were observed between 3P and 05P groups (1.53 and 1.95ΔE00 ) (P < .05). The NP group submitted to 200 cycles showed the biggest color differences (3.02) (P = .003). The greatest color differences were observed in the NP group submitted to immersion in coffee (8.30) and wine (7.93) (P < .05). CONCLUSIONS: The polished surfaces were the least stained. Coffee and wine provided the greatest color changes, both for baths and immersions. CLINICAL SIGNIFICANCE: Polishing of provisional surfaces restorations made of bis-acrylic resin is essential to minimize staining caused by aging and use of colorants, regardless of the particle size present in the polishing paste. The contact with coffee and red wine should be avoided, especially for clinical times greater than 1 week.

Microparticles derived from obese adipose tissue elicit a pro-inflammatory phenotype of CD16+, CCR5+ and TLR8+ monocytes.

Macrophage infiltration into adipose tissue (AT) is a hallmark of the chronic inflammatory response in obesity and is supported by an intense monocyte migration towards AT. Although it has been detected an increased proportion of circulating CD16+ monocyte subsets in obese subjects, the mechanisms underlying this effect and the contribution of these cells to the inflamed profile of obese AT are still poorly understood. We investigated whether factors secreted by human obese omental AT could polarize monocytes to CD16+ enriched phenotype, and how these changes could modify their migratory capacity towards adipose tissue itself. We show that explants of human obese omental AT, obtained during bariatric surgery, released higher levels of MIP1-α, TNFα, leptin and also VEGF, together with increasing amounts of microparticles (MP), when compared to explants of lean subcutaneous AT. A higher content of circulating MP derived from preadipocytes and leukocytes was also detected in plasma of obese subjects. Conditioned media or MP released from obese omental AT increased CD16 and CCR5 expression on CD14+CD16- monocytes and augmented their migratory capacity towards the conditioned media from obese omental AT, itself. This effect was inhibited when MIP1-α was neutralized. Additionally, we demonstrate that MP derived from obese omental AT carry and transfer TLR8 to monocytes, thus triggering an increase in CD16 expression in those cells. Our data shows a positive feedback loop between blood monocytes and obese omental AT, which releases chemotactic mediators and TLR8-enriched MP, thus inducing an up-regulation of CD16+ monocytes, favoring leukocyte infiltration in the obese omental AT.

P2X7 from j774 murine macrophages acts as a scavenger receptor for bacteria but not yeast.

We studied the effects of extracellular ATP and Ca2+ on uptake of bacteria (Staphylococcus aureus or Escherichia coli) and live yeast (Candida glabrata) by J774 macrophages to determine the role of endogenous P2X7 receptors in phagocytosis. Our findings show that phagocytosis of bio-particles coated with S. aureus or E. coli was blocked by ATP and the P2X7 receptor agonist BzATP, while yeast phagocytosis was not. A438079, an antagonist of P2X7 receptors, partially reverted the effects of ATP on bacterial phagocytosis. To determine if P2X7-mediated Ca2+ entry into macrophages was blocking the engulfment of bacteria, we measured phagocytic activity in the absence or presence of 2 mM extracellular Ca2+ with or without ATP. Ca2+, in the absence of ATP, was required for engulfment of E. coli and C. glabrata but not S. aureus. Adding ATP inhibited phagocytosis of S. aureus and E. coli regardless of Ca2+, suggesting that Ca2+ entry was not important for inhibiting phagocytosis. On the other hand, phagocytosis of normal or hyper-adherent C. glabrata mutants had an absolute requirement for extracellular Ca2+ due to yeast adhesion to macrophages mediated by Ca2+-dependent adhesion proteins. We conclude that unstimulated P2X7 from J774 cells act as scavenger receptor for the uptake of S. aureus and E. coli but not of yeast; Ca2+ entry via P2X7 receptors play no role in phagocytosis of S. aureus and E. coli; while the effect of Ca2+ on C. glabrata phagocytosis was mediated by the adhesins Epa1, Epa6 and Epa7.

Diaphragm and genioglossus corticomotor excitability in patients with obstructive sleep apnea and control subjects.

Corticomotor excitability of peripheral muscles appears to be altered in patients with obstructive sleep apnea. However, there is no evidence of such alteration for upper airway/respiratory muscles that are involved in the pathophysiology of this disease. The aim of this study was to compare the effects of hypercapnic stimulation on diaphragm and genioglossus corticomotor excitability in awake healthy subjects versus patients with obstructive sleep apnea. Corticomotor excitability was assessed by transcranial magnetic stimulation in 12 untreated apneic men (48 ± 10 years; body mass index = 28.9 ± 4.7 kg m(-2); apnea-hypopnoea index = 41 ± 23 events per hour) and nine control men (45 ± 10 years; body mass index = 27.3 ± 3.3 kg m(-2); apnea-hypopnoea index = 7 ± 4 events per hour). Assessments included diaphragm and genioglossus expiratory motor thresholds, and transcranial magnetic stimulation-induced motor-evoked potential characteristics obtained while breathing room air or 5% CO2 (random order) and then 7% CO2 both balanced with pure O2. Transcranial magnetic stimulation twitches were applied during early inspiration and end expiration. Diaphragm motor-evoked potential amplitudes increased and expiratory diaphragm motor-evoked potential latencies decreased during CO2-induced increase in ventilatory drive, with no difference in these responses between patients with obstructive sleep apnea and control subjects. Expiratory genioglossus motor-evoked potential amplitudes were significantly lower in patients with obstructive sleep apnea than in control subjects. Baseline activity of the genioglossus increased with increasing FiCO2, this effect being significantly higher in patients with obstructive sleep apnea than in control subjects. However, neither genioglossus motor-evoked potential amplitudes nor latencies were significantly modified with increasing FiCO2 both in patients with obstructive sleep apnea and in control subjects. Corticomotor excitability of genioglossus and diaphragm are not altered during CO2-induced increase in ventilatory drive in patients with obstructive sleep apnea.

Mechanical effects of repetitive transcranial magnetic stimulation of upper airway muscles in awake obstructive sleep apnoea subjects.

NEW FINDINGS: What is the central question of this study? Can repetitive transcranial magnetic stimulation (rTMS) of the genioglossus enhance the beneficial effects observed with transcranial magnetic stimulation single twitches on upper airway mechanical properties? What is the main finding and its importance? We found that both inspiratory and expiratory rTMS protocols induce a different activation pattern of upper airway muscles, with evidence for an increase in genioglossus corticomotor excitability in response to rTMS. This is of major importance because it might open the door for rTMS protocols with the goal of increasing corticomotor excitability and, thus, possibly increasing the tonic genioglossus activity, which is known to be diminished during sleep in subjects with sleep apnoea. ABSTRACT: Stimulation of upper airway (UA) muscles during sleep by isolated transcranial magnetic stimulation (TMS) twitch can improve airflow dynamics without arousal, but the effect of repetitive TMS (rTMS) on UA dynamics is unknown. Phrenic nerve magnetic stimulation (PNMS) can be used to produce painless experimental twitch-induced flow limitation during wakefulness. The aim of this study was to quantify the effects of rTMS applied during wakefulness on UA mechanical properties using PNMS in subjects with obstructive sleep apnoea (OSA). Phrenic nerve magnetic stimulation was applied to 10 subjects, with and without simultaneous rTMS, during inspiration and expiration. Flow-limitation characteristics and UA obstruction level were determined [maximal (V̇I,max)and minimal inspiratory airflow (V̇I,min),V̇I,max-V̇I,min flow drop (ΔV̇I),oropharyngeal (POro,peak ) and velopharyngeal peak pressures, oropharyngeal k1 /k2 ratios with k1 and k2 determined by the polynomial regression model between instantaneous flow and pharyngeal pressure and UA resistance]. Both genioglossus and diaphragm root mean squares and motor-evoked potential amplitudes (geniolossus, GGAmp ) and latencies were computed. A flow-limitation pattern always occurred after PNMS. A decrease in V̇I,max and an increase in ΔV̇I occurred following rTMS applied during inspiration, and POro,peak values were more negative with both inspiratory and expiratory rTMS. The GGAmp also increased significantly from the second to the last rTMS expiratory train twitch. All other parameters remained unchanged. These results suggest the following conclusions: (i) rTMS does not improve UA mechanical properties in awake subjects with OSA; (ii) the activation pattern of UA muscles differs following isolated twitch and repetitive cortical stimulation of the genioglossus; and (iii) rTMS applied during expiration induces corticomotor facilitation.

Effects of anti-inflammatory drugs in primary kidney cell culture of a freshwater fish.

The non-steroidal anti-inflammatory drugs are emerging contaminants in aquatic ecosystems. This study aimed to evaluate toxic effects of some representative drugs of this pharmaceutical group on primary culture of monocytic lineage of Hoplias malabaricus anterior kidney. The effects of diclofenac, acetaminophen and ibuprofen in cell viability, lipopolysaccharide (LPS)-induced NO production and genotoxicity were evaluated. Cytometry analysis CD11b(+) cells showed 71.5% of stem cells, 19.5% of macrophages and 9% of monocytes. Cell viability was lower in the ficoll compared to percoll separation. LPS-induced NO production by these cells was blocked after treatment with dexamethasone and NG-Methyl-L-Arginine (L-NMMA). Exposure of the cells to diclofenac (0.2-200 ng/mL), acetaminophen (0.025-250 ng/mL) ibuprofen (10-1000 ng/mL) reduced basal NO production and inhibited LPS-induced NO production at all concentrations after 24 h of exposure. Genotoxicity occurred at the highest concentration of diclofenac and at the intermediary concentration of acetaminophen. Genotoxicity was also observed by ibuprofen. In summary, the pharmaceuticals influenced NO production and caused DNA damage in monocytic cells suggesting that these drugs can induce immunosuppression and genotoxicity in fish.

Scapholunate ligament reconstruction using a flexor carpi radialis tendon graft.

PURPOSE: To review the results of scapholunate ligament reconstruction using a flexor carpi radialis tendon graft. METHODS: We performed a retrospective review of 22 patients with post-traumatic scapholunate instability who were treated with a modification of the Brunelli, a flexor carpi radialis tendon graft. RESULTS: The mean follow-up was 61 months. The average age was 40 years. The average loss of flexion was 23° and of extension was 22° compared with the contralateral side. Grip strength averaged 67% of the nonoperated side. All patients except 2 returned to work. Degenerative changes were seen in 3 patients at the time of revision. Complications occurred in 2 patients and included avascular necrosis of the scaphoid. CONCLUSIONS: Perfect biomechanical reconstruction might not be possible for scapholunate dissociation. Our results show, however, that ligament reconstruction led to satisfactory results from the patient's point of view. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Rare earth elements as tracers of iron ore tailings on the Brazilian eastern continental shelf.

Iron ore tailings are stored in large dams and pose risks to the environment around the world. In Brazil, the rupture of these dams has become frequent and has generated environmental and social concern. Rare earth elements are good tracers of sediment sources and our results indicated chronic contamination of the seabed sediment from the marine region affected by the Fundão Dam tailings since 2015, including areas of environmental protection. This research, carried out between November 2018 and September 2021, with a database of 575 samples, showed a greater amount of contaminated material in the marine region adjacent to the Doce River mouth. Although data suggest prior mining contamination of the Doce River basin, the Fundão episode was an empirical and massive example of the environmental damage caused by these human activities over the centuries, showing that the impact remains in the shallow marine environments for years. Integr Environ Assess Manag 2024;20:179-188. © 2023 SETAC.

Os rejeitos de minério de ferro são armazenados em grandes barragens que trazem riscos ao meio ambiente em todo o mundo. No Brasil, o rompimento dessas barragens tem se tornado frequente e gerado preocupação ambiental e social. Elementos terras raras são bons marcadores de fontes sedimentares e nossos resultados indicaram uma contaminação crônica da região marinha afetada pelos rejeitos da barragem de Fundão, incluindo áreas de proteção ambiental. Esta pesquisa teve com 575 amostras analisadas entre os meses de novembro de 2018 e outubro de 2021, com a região marinha adjacente a foz do Rio Doce apresentando o maior grau de impacto. Embora os dados ressaltem a contaminação histórica da mineração na bacia do Rio Doce, o episódio do Fundão foi um exemplo empírico e massivo dos danos ambientais causados por essas atividades ao longo dos séculos, mostrando que o impacto permanece nos ambientes marinhos rasos por anos. Integr Environ Assess Manag 2024;20:179-188.