Genetic Algorithm for Feature Selection Applied to Financial Time Series Monotonicity Prediction: Experimental Cases in Cryptocurrencies and Brazilian Assets.

Since financial assets on stock exchanges were created, investors have sought to predict their future values. Currently, cryptocurrencies are also seen as assets. Machine learning is increasingly adopted to assist and automate investments. The main objective of this paper is to make daily predictions about the movement direction of financial time series through classification models, financial time series preprocessing methods, and feature selection with genetic algorithms. The target time series are Bitcoin, Ibovespa, and Vale. The methodology of this paper includes the following steps: collecting time series of financial assets; data preprocessing; feature selection with genetic algorithms; and the training and testing of machine learning models. The results were obtained by evaluating the models with the area under the ROC curve metric. For the best prediction models for Bitcoin, Ibovespa, and Vale, values of 0.61, 0.62, and 0.58 were obtained, respectively. In conclusion, the feature selection allowed the improvement of performance in most models, and the input series in the form of percentage variation obtained a good performance, although it was composed of fewer attributes in relation to the other sets tested.

Alterations in CD39/CD73 axis of T cells associated with COVID-19 severity.

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+ CD25+ CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27- CD28- ) CD8+ T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4+ CD39+ , CD4+ CD25- CD39+ (memory T effector cell), and high-differentiated CD8+ T cells (CD27- CD28- ), and diminished frequencies of CD4+ CD73+ , CD4+ CD25+ CD39+ mTreg cell, CD8+ CD73+ , and low-differentiated CD8+ T cells (CD27+ CD28+ ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+ Annexin-V+ and CD8+ Annexin-V+ T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.

O3 concentration and duration of exposure are factors influencing the environmental health risk of exercising in Rio Grande, Brazil.

Ozone (O3) represents a great threat to human health, contributing to respiratory diseases and premature mortality. This pollutant is often considered a critical pollutant in regions of southern Brazil. Exposure to this pollutant during vigorous physical activity should be the subject of thorough investigations due to the increased ventilation rate and altered breathing pattern present during vigorous physical activity that result in greater inhalation of O3. Thus, this study aimed to evaluate the health risk of exposure to low, mean, and high concentrations of O3 during different durations of exercise in the city of Rio Grande (southern Brazil). Healthy young men (n = 45) performed cardiopulmonary exercise testing, and ventilation rate data were collected to predict total ventilation and pollutant inhalation during a 5 km running session. The O3 concentration in the city of Rio Grande was obtained from data reported by the Copernicus Atmosphere Monitoring Service (CAMS). The environmental health risk was calculated based on the potential intake dose. The lowest, mean, and highest concentrations of O3 detected during the monitoring period were 32.5, 64.9, and 115.2 µg/m3, respectively. In all evaluated scenarios, there was a toxicological risk (RQ > 1), except when exercising when the O3 concentration was lowest for the shortest length of time (p < 0.001). As the concentration of O3 and the duration of the exposure increase, the health risk is increased. Therefore, O3 concentration and duration of exposure are factors influencing the health risk of exercising. These findings are extremely relevant in cities that have high levels of O3, such as the city of Rio Grande.

Bacillus thuringiensis Cry1Ab Domain III ß-16 Is Involved in Binding to Prohibitin, Which Correlates with Toxicity against Helicoverpa armigera (Lepidoptera: Noctuidae).

Helicoverpa armigera is a major insect pest of several crops worldwide. This insect is susceptible to some Bacillus thuringiensis (Bt) Cry insecticidal proteins expressed in transgenic crops or used in biopesticides. Previously, we identified H. armigera prohibitin (HaPHB) as a Cry1Ac-binding protein. Here, we further analyzed the potential role of PHB as a Cry toxin receptor in comparison to cadherin (CAD), well recognized as a Cry1Ac receptor. HaPHB-2 midgut protein and HaCAD toxin-binding region (TBR) fragment from H. armigera were expressed in Escherichia coli cells, and binding assays with different Cry1 toxins were performed. We demonstrated that Cry1Ab, Cry1Ac, and Cry1Fa toxins bound to HaPHB-2 in a manner similar to that seen with HaCAD-TBR. Different Cry1Ab mutant toxins located in domain II (Cry1AbF371A and Cry1AbG439D) or domain III (Cry1AbL511A and Cry1AbN514A), which were previously characterized and found to be affected in receptor binding, were analyzed regarding their binding interaction with HaPHB-2 and toxicity against H. armigera One ß-16 mutant (Cry1AbN514A) showed increased binding to HaPHB-2 that correlated with 6-fold-higher toxicity against H. armigera, whereas the other ß-16 mutant (Cry1AbL511A) was affected in binding to HaPHB-2 and lost toxicity against H. armigera Our data indicate that ß-16 from domain III of Cry1Ab is involved in interactions with HaPHB-2 and in toxicity. This report identifies a region of Cry1Ab involved in binding to HaPHB-2 from a Lepidoptera insect, suggesting that this protein may participate as a novel receptor in the mechanism of action of the Cry1 toxins in H. armigeraIMPORTANCEHelicoverpa armigera is a polyphagous pest that feeds on important crops worldwide. This insect pest is sensitive to different Cry1 toxins from Bacillus thuringiensis In this study, we analyzed the potential role of PHB-2 as a Cry1 toxin receptor in comparison to CAD. We show that different Cry1 toxins bound to HaPHB-2 and HaCAD-TBR similarly and identify ß-16 from domain III of Cry1Ab as a binding region involved in the interaction with HaPHB-2 and in toxicity. This report characterized HaPHB-Cry1 binding interaction, providing novel insights into potential target sites for improving Cry1 toxicity against H. armigera.

Differential effects of whole blood heat treatment on the ex vivo inflammatory profile of untrained and trained men.

This study evaluated the effects of heat stress on the ex vivo inflammatory profile in untrained and trained men. Whole blood samples from untrained (UT) and trained (TR) individuals were incubated for 2 h at 37 °C or 40 °C. The whole blood of a subsample of the participants (n = 5 in both TR and UT groups) were stimulated with lipopolysaccharide (LPS, 10 ng/mL) concomitant to heat treatment (37 °C versus 40 °C). Flow cytometry was used to assess the intracellular NF-κB activation in CD4+ T cells and CD14+ monocytes, the expression of Toll-Like Receptor-4 (TLR-4), the frequencies of CD4+CD25-CD39+ and CD4+CD25+CD39+ T cells and monocyte subsets (CD14+CD16-; CD14+CD16+; CD14-CD16+), the mitochondrial membrane potential (MMP) and the reactive oxygen species (ROS) production by lymphocytes and monocytes. The production of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) by LPS-stimulated whole blood were also evaluated. Heat treatment (40 °C) increased the proportions of CD14+CD16- and CD14+CD16+ monocytes and the lymphocyte MMP in the UT group. The frequencies of CD14-CD16+ monocytes and the activation of NF-κB in CD14+ monocytes decreased in UT and TR groups after heat treatment, while a reduction in CD4+CD25-CD39+ T-cells was observed only in the UT group. Higher TLR-4 and NF-κB activation were found in LPS-stimulated monocytes of UT men concomitant with higher TNF-α production and diminished IL-10 production after heat treatment. TR individuals presented lower NF- κB activation in LPS-stimulated monocytes after heat treatment. Our data suggest that the training status of individuals may impact on the anti-inflammatory response of heat treatment.

Association of Visceral and Subcutaneous Fat Mass With Bone Density and Vertebral Fractures in Women With Severe Obesity.

INTRODUCTION: The aim of this study was to evaluate the association of visceral and subcutaneous adipose tissue with bone mineral density (BMD), geometric indices of femoral neck strength and vertebral fractures in pre- and postmenopausal women with severe obesity. METHODS: A cross-sectional study was conducted with pre- (n = 37) and postmenopausal (n = 21) women with body mass index higher than 40 kg/cm2. BMD at total body, lumbar spine, hip and forearm, presence of vertebral fractures, lean mass, visceral, and subcutaneous adipose tissue were assessed by DXA. Geometric indices of femoral neck strength were calculated by DXA. Serum bone turnover markers (CTX and osteocalcin) and 25(OH)D were also measured. RESULTS: BMD at all studied sites was similar in pre- and postmenopausal women. In postmenopausal women, total subcutaneous adipose tissue was inversely associated with BMD at total femur (ß = -0.009; 95% confidence interval [CI] -0.017; -0.002) and with strength index (ß = -0.03; 95% CI -0.04; -0.01). In premenopausal women, visceral adipose tissue was inversely associated with cross-sectional moment of inertia (ß = -0.95; 95%CI -1.89; -0.01). Vertebral fractures were highly prevalent in premenopausal (32%), and even more frequent among postmenopausal women (55%). CONCLUSION: Taken together, our results suggest that both visceral and subcutaneous fat may be detrimental for bone health in pre- and postmenopausal women, and that severe obesity may increase the risk of vertebral fractures, even in young women.

Profile and costs associated with the use of osteosynthesis materials in victims of traffic accidents.

BACKGROUND/AIMS: Facial trauma arising from traffic accidents is one of the most prevalent injuries in urban trauma centers. The aim of this study was to evaluate the frequency, types, and costs associated with osteosynthesis material used in facial fractures of traffic accident victims seen at the Hospital da Restauração, Recife/PE, Brazil, from January to December 2014. MATERIALS AND METHODS: Data were collected from the medical records of hospitalized patients submitted to surgery under general anesthesia for the treatment of facial fractures during the period. The data were analyzed descriptively by calculating absolute frequencies, percentages, and means. Statistical analysis was performed using SPSS v.21.0. RESULTS: Among the patients, 73.1% were victims of motorcycle accidents that led to higher costs as they were the most prevalent injuries. Mandibular fractures were the most prevalent injury (53.5%). A total of 477 osteosynthesis materials were used, of which 76.51% were a 2.0-mm plate system, 15.51% were a 1.5-mm plate system, 3.14% were a 2.4-mm plate system, 3.77% titanium meshes, 0.83% lag screws, and 0.2% steel wires. The use of these materials for the treatment of facial fractures resulted in a cost of US $51.285,00 for the Brazilian public health system. CONCLUSION: The increase in the number of traffic accidents implies significant numbers of victims with facial fractures, as well as considerable costs associated with the use of osteosynthesis materials for public health services.

Physical fitness modulates the expression of CD39 and CD73 on CD4+ CD25- and CD4+ CD25+ T cells following high intensity interval exercise.

AIM: To investigate the impact of physical fitness on the mobilization of CD4+ CD25 - CD39 + and CD4 + CD25 + CD39 + T cells in response to acute exercise. METHODS: Fifteen high physical fitness (25.3 ± 1.4 years) and 15 low physical fitness (26.1 ± 1.9 years) men performed a single bout of high-intensity interval exercise (HIIE, 10 bouts of 60 seconds at 85% HRmax intercepted by 75 seconds of recovery at 50% HRmax). Blood lymphocytes were isolated before, immediately after and 1 hour after exercise for assessment of cell surface expression of CD25, CD39, and CD73 on CD4+ T cells. Effector memory T cells (mTeff) were identified by CD4 + CD25 - CD39 + coexpression, and memory regulatory T cells (mTReg) were defined as CD4 + CD25 + CD39 + T cells. RESULTS: Exercise increased CD4+ and CD4 + CD25 + T cell frequencies immediately after followed by a decrease bellow to baseline values at 1 hour after the bout in both low and high physical fitness groups. At baseline, the proportions of mTeff were higher, while mTreg were lower in low physical fitness individuals. The frequency of mTreg increased immediately after HIIE in both groups, and remained higher 1 hour after the bout. However, high physical fitness individuals presented higher mTreg frequency in all periods evaluated. A significantly mobilization of mTeff cells was identified in both groups immediately after HIIE. High physical fitness individuals displayed a decrease in mTeff cells bellow to baseline, while the frequency of mTeff remained higher in low physical fitness group 1 hour after the bout. The peripheral frequency of CD4 + CD25 + CD73 + T cells increased in a similar way immediately after the bout in both groups, returning to the baseline values 1 hour after exercise. No differences in CD4 + CD25 - CD73 + T cells were observed after HIIE in both groups. CONCLUSION: Our results highlight the impact of physical activity status in the redistribution of CD4+ T cells expressing ectonucleotidases in response to HIIE.

Cardiorespiratory fitness modulates the proportions of monocytes and T helper subsets in lean and obese men.

This study investigated the peripheral frequency of monocytes, CD4 + T cell subsets and the systemic levels of cytokines in lean and obese men with different levels of cardiorespiratory fitness (CRF). Mononuclear cells were obtained from 45 lean and 45 obese men who were assigned into six groups according to their body mass index and CRF (low, moderate, or high VO2Peak ) to analyze the frequency of monocyte subsets and subpopulations of CD4 + T cells (Treg cells, CD4 + CD25high CD127low ; mTeff, CD4 + CD25-CD39+; mTreg, CD4 + CD25+CD39+). The systemic levels of interleukin (IL)-6, IL-10, IL-17a, IL-33, leptin, and tumor necrosis factor-alpha (TNF-α) were also evaluated. Seven sedentary obese men performed one week of high-intensity interval training (HIIT, 3 sessions/week), and blood samples were collected before and 24 hours after the last session for phenotypic analysis of T cells and monocytes. Obese individuals presented an inflammatory profile characterized by lower frequencies of Treg and mTreg cells and higher proportions of proinflammatory monocytes. However, higher CRF status increased the frequencies of Treg cells and mTreg cells and decreased the percentage of CD4 + mTeff cells and intermediate and non-classical monocytes in the peripheral blood from lean and obese men. Systemic lower levels of proinflammatory (IL-6 and TNF-) cytokines and higher concentrations of IL-10 and IL-33 were observed in moderate and higher CRF in all subjects. HIIT increased the proportions of circulating mTreg and Treg cells in sedentary obese individuals. The immunoregulatory role of CRF contributes to the maintenance of low levels of inflammatory mediators.

Excess of children's outpatient consultations due to asthma and bronchitis and the association between meteorological variables in Canoas City, Southern Brazil.

The southern Brazilian city of Canoas, situated in the metropolitan region of Porto Alegre, is subject to several annual meteorological phenomena, such as cold fronts and squall lines. Here, we assess the relationship between meteorological conditions and outpatient consultations for asthma or bronchitis in children from Canoas City. Data from outpatient consultations of children (below 9 years), between January/2005 and September/2008, were combined with daily meteorological data from 12UTC (morning) and 18UTC (afternoon). We identified 42 days with an excess of outpatient consultations (peaks). Consultations were negatively correlated with temperature and human thermal comfort index (HTCI) from the 3 previous days based on consultation data at 12 and 18UTC, and positively correlated with atmospheric pressure. A positive correlation with relative humidity was significant only at 12UTC. The highest correlations occurred on the day of consultation (12UTC) with temperature, relative humidity, and atmospheric pressure, as well as 2 days previous to the HTCI. The sensation of cold was associated with about 55% of the days of the period at 12UTC: considering only the peaks of consultations, this association exceeds 90% of days. The highest frequencies of respiratory complications (June, July, and August) were associated with negative temperature anomalies, wind speed and direction, and positive anomalies in relative humidity and atmospheric pressure. Nearly half (45%) of the air masses associated with respiratory complications arrived at Canoas from a SW direction, 19% from the south and 14% from the west. In summary, observed increases in respiratory complications were mainly associated with the presence of cold and humid air (and/or falling temperature with increasing humidity) in the morning.

Effects of the extracorporeal shock wave therapy on the skin: an experimental study.

Extracorporeal shock wave therapy (ESWT) has been extensively studied for its multiple biological properties, and although it is widely applied in esthetical procedures, little is known about its effects on the epidermis and dermis. In this study, a histological and immunohistochemical study of the effects of ESWT was performed on rat skin. Forty-five female rats were treated with one or two sessions of ESWT and sacrificed on days 1, 7, 14, and 21 after treatment. The samples were histologically processed and then morphometric analyses were performed to assess the epidermis, dermis, and subcutaneous fat tissue thickness. Immunohistochemical reactions were also performed against the antibodies: basic fibroblastic growth factor (FGF2), its receptor (FGFR1), and α-smooth muscle actin. Slides were scanned and digitally assessed, to determine the microvessel density (MVD) and digital scoring of the immunohistochemical staining. The results showed that ESWT produced a significantly higher collagen content, MVD, and epidermis and dermis thickness than the control, non-treated group. Both in epidermis and dermis, FGF2 was overexpressed in the ESWT-treated groups, whereas FGFR1 was increased only in the group treated with two ESWT sessions at 21-days post-treatment. The ESWT-treated groups have also shown diminished thickness of subcutaneous fat tissue. In conclusion, ESWT induces neocollagenesis and neoangiogenesis, and upregulates the FGF2 expression, particularly in the groups treated with two sessions. Furthermore, it was demonstrated that overexpression of FGF2 on skins treated with ESWT seems to be a key role on its mechanism of action.

18-Des-hydroxy Cytochalasin: an antiparasitic compound of Diaporthe phaseolorum-92C, an endophytic fungus isolated from Combretum lanceolatum Pohl ex Eichler.

Chemical investigation of the ethyl acetate extract from the endophytic fungus Diaporthe phaseolorum-92C (92C) isolated from the roots of Combretum lanceolatum led to the isolation of 18-des-hydroxy Cytochalasin H (compound 1). The trypanocidal and schistosomicidal activity and cytotoxicity of the extract from 92C were evaluated. The schistosomicidal, leishmanicidal, antimicrobial, and antioxidant actions, as well as the antitumor activity against the breast cancer cells MDA-MB-231 and MCF-7, and the cytotoxicity towards normal human lung fibroblasts GM07492A of compound 1 was tested. The extract from 92C (20 µg/mL) exerted potent trypanocidal activity, reducing 82% of the number of amastigotes and trypomastigotes of Trypanosoma cruzi. Compound 1 at 50 µg/mL killed 50% of Schistosoma mansoni adult worms. Compound 1 reduced the viability of Leishmania amazonenses promastigotes (IC50 = 9.2 µg/mL) and of the cancer cells MDA-MB-231 and MCF-7 (IC50 = 17.5 and 8.88 µg/mL, respectively), presented moderate antioxidant activity, and gave IC50 of 2049.7 ± 39.9 µg/mL for the cytotoxicity towards normal cells GM07492A. This knowledge is highly relevant to the search for new promising compounds for therapeutic purposes.

Bioactive compounds of Aspergillus terreus-F7, an endophytic fungus from Hyptis suaveolens (L.) Poit.

The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus-F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC50 ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC50 of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC50 of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC50 of 15.3 × 103, 3.4 × 103, and 5.8 × 103 µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus-F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.

Sensing hydrocarbons with interband cascade lasers and substrate-integrated hollow waveguides.

Tunable diode laser absorption spectroscopy (TDLAS) is an excellent analytical technique for gas sensing applications. In situ sensing of relevant hydrocarbon gases is of substantial interest for a variety of in-field scenarios including environmental monitoring and process analysis, ideally providing accurate, molecule specific, and rapid information with minimal sampling requirements. Substrate-integrated hollow waveguides (iHWGs) have demonstrated superior properties for gas sensing applications owing to minimal sample volumes required while simultaneously serving as efficient photon conduits. Interband cascade lasers (ICLs) are recently emerging as mid-infrared light sources operating at room temperature, with low power consumption, and providing excellent potential for integration. Thereby, portable and handheld mid-infrared sensing devices are facilitated. Methane (CH4) is among the most frequently occurring, and thus, highly relevant hydrocarbons requiring in situ emission monitoring by taking advantage of its distinct molecular absorption around 3 µm. Here, an efficient combination of iHWGs with ICLs is presented providing a methane sensor calibrated in the range of 100 to 2000 ppmv with a limit of detection at 38 ppmv at the current stage of development. Furthermore, a measurement precision of 0.62 ppbv during only 1 s of averaging time has been demonstrated, thereby rendering this sensor concept useful for in-line and on-site emission monitoring and process control applications.

Dural Closure Training With Prototyped Model.

INTRODUCTION: The hermetic closure of the dura mater is a critical step in neurosurgical training, often undervalued but crucial to preventing serious complications such as cerebrospinal fluid (CSF) leaks leading to meningitis and death. Inadequate closure, often due to insufficient training, can result in challenging complications, including prolonged hospitalization and reoperation. OBJECTIVE: To address the deficiencies in dural closure training, this study aims to describe a 3D prototype for simulating post-craniotomy dura mater suturing. The objective is to reduce the incidence of CSF leaks and improve the training of neurosurgery residents. DESIGN: The study involves the creation of a 3D prototype based on magnetic resonance imaging and computed tomography scans. The additive manufacturing of structures is performed using ABS filament, and a silicone rubber membrane is used to simulate the meningeal dura mater. Neurosurgery residents undergo training using this model, and the effectiveness is evaluated. SETTING: The study is conducted at the Institute of Neurology of Curitiba (Hospital INC), focusing on neurosurgery residents from the first to fifth year of residency. PARTICIPANTS: Seven residents participate in the study, with varying levels of experience in dural closure procedures. The training involves a simulated surgical environment using the 3D prototype. RESULTS: After training, residents show improvements in confidence and theoretical knowledge related to dural closure. Binary questions indicate a strong desire for more practical training on dural closure, with 85.7% believing in the essential role of 3D molds in their neurosurgery training. CONCLUSION: The study highlights the importance of adequate training for dural closure to prevent serious complications in neurosurgery. The use of 3D simulation models, despite some limitations, proves to be an effective educational strategy. The emerging technology of bioprinting holds promise for further enhancing simulation materials, bringing medical education closer to realistic tissue replication.

Anatomical Vascular Differences and Leishmania-Induced Vascular Morphological Changes Are Associated with a High Parasite Load in the Skin of Dogs Infected with Leishmania infantum.

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite-host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs.

Obesity aggravates acute kidney injury resulting from ischemia and reperfusion in mice.

In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia-reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed mice a standard or high-fat diet for eight weeks. The mice were divided into four groups and submitted to sham surgery or IRI: obese, normal, normal + IRI, obese, and obese + IRI. All studies were performed 48 h after the procedures. Serum glucose, cholesterol, and creatinine clearance did not differ among the groups. Survival and urinary osmolality were lower in the obese + IRI group than in the normal + IRI group, whereas urinary neutrophil gelatinase-associated lipocalin levels, tubular injury scores, and caspase 3 expression were higher. Proliferating cell nuclear antigen expression was highest in the obese + IRI group, as were the levels of oxidative stress (urinary levels of thiobarbituric acid-reactive substances and renal heme oxygenase-1 protein expression), whereas renal Klotho protein expression was lowest in that group. Expression of glutathione peroxidase 4 and peroxiredoxin 6, proteins that induce lipid peroxidation, a hallmark of ferroptosis, was lower in the obese + IRI group. Notably, among the mice not induced to AKI, macrophage infiltration was greater in the obese group. In conclusion, greater oxidative stress and ferroptosis might aggravate IRI in obese individuals, and Klotho could be a therapeutic target in those with AKI.

BJ-PI2, a non-hemorrhagic metalloproteinase from Bothrops jararaca snake venom.

BACKGROUND: Envenoming by Bothrops jararaca can result in local pain, edema, hemorrhage and necrosis, partially mediated by snake venom metalloproteinases (SVMPs). Here, we describe the characterization of BJ-PI2, a P-I class SVMP from B. jararaca venom, and its local tissue actions. METHODS: BJ-PI2 was purified by a combination of gel filtration, anion-exchange chromatography and reverse phase HPLC, and identified by mass spectrometry. Clotting and fibrin(ogen)olytic activities were assayed using conventional methods. Hemorrhagic activity and changes in vascular permeability were examined in rat dorsal skin. Myonecrosis and inflammatory activity were examined in mouse gastrocnemius muscle. RESULTS: BJ-PI2 was a 23.08kDa single-chain polypeptide. Tryptic fragments showed highest homology with SVMP insularinase A from Bothrops insularis, but also with B. jararaca SVMP bothrojaractivase; less similarity was observed with B. jararaca SVMPs BJ-PI and jararafibrases II and IV. BJ-PI2 did not clot fibrinogen or rat citrated plasma but had α- and ß-fibrinogenolytic activity (inhibited by EDTA and 1,10-phenanthroline but not by PMSF) and attenuated coagulation after plasma recalcification. BJ-PI2 had fibrinolytic activity. BJ-PI2 increased the vascular permeability of rat dorsal skin (inhibited by 1,10-phenanthroline). BJ-PI2 was not hemorrhagic or myonecrotic but caused migration of inflammatory cells. In contrast, venom was strongly hemorrhagic and myonecrotic but caused less infiltration of inflammatory cells. CONCLUSIONS: BJ-PI2 is a non-hemorrhagic, non-myonecrotic, non-coagulant P-I class SVMP that may enhance vascular permeability and inflammatory cell migration in vivo. GENERAL SIGNIFICANCE: BJ-PI2 contributes to enhanced vascular permeability and inflammatory cell migration after envenoming, but not to venom-induced hemorrhage and necrosis.

Trigeminal Neuralgia Due to Unilateral Early Bifurcated Superior Cerebellar Artery: Case Report and Literature Review.

Trigeminal neuralgia (TN) is considered a debilitating pain syndrome resulting from a neurovascular conflict in the prepontine cistern, usually through compression of the trigeminal nerve by the superior cerebellar artery (SCA), resulting in neural pathology at the root entry zone. This is a case report of a patient whose TN symptoms were attributed to an anatomical variant of the SCA, managed successfully through conservative treatment. Anatomical variants of the SCA have been related to TN. However, this is the first reported case in the PubMed literature of primary TN due to an unilateral early bifurcated SCA treated conservatively with first-line sodium channel blockers with a good outcome.

Use of Doppler ultrasonography for selection of recipients in embryo transfer programs in horses.

We aimed to evaluate the impact of corpus luteum (CL) and uterine characteristics accessed by B-mode and Color-Doppler ultrasonography in recipient mares at the time of embryo transfer (ET) on pregnancy outcomes. Recipient mares (n = 110), between days 3-9 after spontaneous ovulation, received a fresh embryo. Immediately before ET, the reproductive system was assessed by transrectal palpation for the following parameters: uterine tone (0-3), CL echogenicity (0-6), CL type (homogeneous, trabecular or anechoic center), luteal area (cm2), uterine echogenicity (0-3), uterine edema (0-3), luteal blood perfusion (0-100%) and uterine blood perfusion (1-4). Additionally, a blood sample was collected by puncture of the jugular vein for plasma P4 dosage. Retrospectively, recipients were classified according to the luteal area (small [≤ 6 cm2] or large [> 6 cm2]), luteal blood perfusion (low [≤ 55%] or high [> 55%]), and plasma concentration of P4 (low ≤ 9.98 ng/mL or high > 9.98 ng/mL). Pregnancy diagnosis was performed at 12 and 30 days of gestation. Luteal blood perfusion was significantly higher (P = 0.04) in pregnant recipients (n = 83) than in non-pregnant recipients (n = 27). Overall P/ET was higher (P ≤ 0.02) in mares with high luteal blood perfusion and high P4. Luteal blood perfusion was the most adequate significant (P = 0.01) predictor of pregnancy compared with the luteal area and plasma P4 concentration. Only luteal blood perfusion showed a linear (P = 0.03) and cubic (P = 0.004) effect on P/ET. In conclusion, CL blood perfusion determined by color-Doppler can be used in real-time to select recipients with the greatest chance of maintaining pregnancy in equine ET programs.